Podcasts about qed therapeutics

Erin joins David Rintell, Head of Patient Advocacy at BridgeBio, and Mandy Rohrig, Director of Patient Advocacy at BridgeBio Gene Therapy, to share her experience living with hypochondroplasia. Erin also has two sons living with hypochondroplasia and one son of average height. Raised in a loving and supportive family with a can-do attitude, her father told her that she may be of short stature but that she could do everything she wanted to do, just maybe in a slightly different way. Erin shares her diagnostic journey with hypochondroplasia in the third grade. Even though her diagnosis was upsetting to her, her friends and family never treated her any differently. She describes her decision to undergo limb-lengthening surgery, how she manages her condition, and discusses how her two sons navigate living with hypochondroplasia in very different ways. While there were times when Erin would have preferred to be just like everyone else, she has learned the value of embracing individuality and the importance of family and finding fulfillment in life. Elena Muslimova, Medical Director of the hypochondroplasia program at QED Therapeutics, a BridgeBio affiliate, provides a medical overview. She explains that hypochondroplasia is a rare genetic bone condition causing short stature with an average-sized trunk but shorter arms and legs. It often arises from de novo (spontaneous) mutations, yet it can also be inherited. Hypochondroplasia is typically diagnosed in children aged 2 to 5 years old. While short stature is the primary characteristic, individuals may experience other complications although the severity of these issues varies greatly among individuals.  

Dr. Shaalan Beg and Dr.Mohamed Salem discuss key abstracts that will be presented at the 2024 ASCO Annual Meeting, including hypoxia-response CAR T- cell therapy for solid tumors, GPC3-specific CAR T- cell therapy in hepatocellular carcinoma, and the promising efficacy of targeted therapies in GI cancers.  TRANSCRIPT Dr. Shaalan Beg: Hello and welcome to the ASCO Daily News Podcast. I am Dr. Shaalan Beg, your guest host of the podcast today. I'm an adjunct associate professor at UT Southwestern's Simmons Comprehensive Cancer Center. In today's episode, we'll be discussing some key abstracts in GI cancers that will be presented at the 2024 ASCO Annual Meeting. I'm delighted to welcome Dr. Mohammed Salem, a GI medical oncologist at the Levine Cancer Institute at Atrium Health, for this discussion. Our full disclosures are available in the transcript of this episode. Mohammed, it's great to have you back on the podcast. Dr. Mohamed Salem: Thank you, Dr. Beg. It's always a pleasure to be here. Thanks for having me.  Dr. Shaalan Beg: So we're seeing more and more exciting data emerge on the role of ctDNA in GI cancers. And that's a topic that we've covered fairly extensively on the podcast. This year, in Abstract 3513, investigators used a novel, highly sensitive HPV ctDNA assay to evaluate the clinical outcomes of HPV ctDNA status in people with localized anal cancer treated with chemoradiation. And we know that prior HPV infection is associated with 90% of anal cancers. Can you give us a summary of the study and why it's so important to the clinical care we're giving our patients today?  Dr. Mohamed Salem: Sure. So, as you already alluded to, in the current era of precision oncology or precision medicine in general, there is an effort to try to maximize treatment efficacy and minimize the side effects. We're trying to understand how to do that by developing more biomarkers. I think this was a very interesting study that was led by Dr. Morris of MD Anderson. As you mentioned, he tried to determine the correlation between that circulating tumor DNA at different timelines and also associated that with the relapse. Obviously, as we all know, HPV infection is linked to about over 90% of anal cancers, and anal cancer is increasingly common in the U.S.  The study design includes patients from stage 1, 2, and 3 anal cancer treated with curative intent concurrent chemo radiation and the plot sample to collect circulating DNA was taken at five weeks of treatment and then at various intervals, including 3months, 6  months, 9 months and 12 months, to detect the HPV circulating DNA. And the analysis was done to correlate detection of circulating DNA with a relapse.  So what they observed is after collecting the samples at the end of the treatment, which is 5 weeks, followed by 3 months, 6 months, 9 months, and 12 months following treatment using the correlation between the detection of circulating tumor DNA as well as the recurrence rate, they were able to identify that about 22% was seen at 5 weeks, 13% was seen at three months, then 10% was seen at 6 months, and 0% actually was seen at 12 months. In the final analysis, they concluded that detection of circulating DNA at 3 months was significantly associated with a relapse rate of those patients. And also, they looked at the baseline stage, T stage, end stage, age and other perhaps prognostic factors. But the clinical implication of that trial is this finding supports the potential of integrating now the circulating DNA analysis and routine post-treatment surveillance, which hopefully will help us identify those patients with high risk of relapse and whether they can be treated with adjuvant therapy  in context-free drug trial or even like more close surveillance. Obviously, this is a very novel study, so it needs validation. Also, we need to understand more about the platform used because with the immersion technology and how fast this field is moving, I think it's important to look at this platform or other platforms. I think as a concept it's very interesting and hopefully will help us to identify patients with higher risk. So, I'm looking forward to hearing the full presentation. Dr. Shaalan Beg: Moving on to colorectal cancer, Abstract 3514 is a trial of hypoxia-responsive CEA CAR T-cell therapy for people with heavily pretreated solid tumors where this was administered intraperitoneally or intravenously. And you know, as a solid tumor oncologist or GI oncologist, we've been watching the hematologic space evolve so dramatically in the last five years with cellular therapies that it's exciting to see these CAR T-cell approaches being applied in solid tumors with some results. So can you talk about this study and whether you think it will influence clinical practice?  Dr. Mohamed Salem: Of course, I'm actually very excited to see this study because as you mentioned, CAR T-cell therapy has been utilized in hematological malignancies for the last several years and in fact it's becoming a center of care. As you know, it's very effective in certain tumors. Unfortunately, we did not see a similar result in solid tumors thus far. I know we are trying to make progress, but we are definitely not seeing the same efficacy in solid tumors. And also, of course, in CRC and many other tumors, we need more target options, so I was very excited to see this abstract. And I want to give a little bit of background why this abstract is important. Many solid tumors have a low oxygen level environment, hypoxia obviously, which can impact the effectiveness of CAR T therapy. So hypoxia can suppress the immune response, leading to poor performance of the immune cells like the T cell within the tumor. The investigators, to overcome that challenge, meaning hypoxia impacting the efficacy of the T cell, they were actually able to engineer a CAR T cell to be hypoxia responsive. And what does that mean? That the cells are designed to become more active in low oxygen conditions, which is more difficult in many of the solid tumors. The reason that's very interesting is because, one, it reduces exhaustion of the T cell, meaning like when you have the T cell active all the time, they get exhausted. So when you have the T cell in the resting state, until they reach the tumor environment and they get activated by the hypoxia status, now you reduce the expulsion of the T cell. But also that one overcomes the resistance. So once activated in the tumor hypoxic environment, this CAR T cell shows increased efficacy in targeting and killing the cancer cell.  Based on that concept, the investigators conducted a phase 1 dose escalation study in solid tumors. So this was a phase 1 open label group escalation study involving patients with tumor suppressed CEA and also had relapsed refractory second line treatment. The trial actually included 2 routes of administration, which I think was very interesting – IV versus intraperitoneal, IP, way of administration. And they enrolled about 40 patients between June of 2022 and January 2023. And 35 patients had colorectal cancer, 3 patients had gastric cancer, and 2 patients had non-small cell lung cancer. Overall, there was no surprising safety data. In terms of side effects, it was largely macrocystis, colitis. Unfortunately, they had 1 treatment that did not finish. But the interesting feature was the efficacy of that concept was demonstrated and in fact they were able to see more disease response and control at this rate with IP infusion, which I think is a very novel approach. I would look forward to trying and looking into this kind of delivery, especially in CRC and other tumors. Dr. Shaalan Beg: Because we've known that historically managing disease intraperitoneally has been challenging with cytotoxic chemotherapies and even surgical approaches that have been deployed can be fairly morbid as well. So looking at novel delivery mechanisms can help us understand, maybe be able to manage side effects of treatments in different ways and open doors for treatment in diseases that otherwise we couldn't manage. So definitely a very novel and exciting approach on this study.  Dr. Mohamed Salem: I agree. I think the idea of administering an IP route is a very interesting idea.   Well, Shaalan, there is another study in CRC, Abstract 3515. This is the first human study of ABBV-400, cMET–targeting antibody-drug conjugate in advanced solid tumors. Can you tell us about this promising data? Dr. Shaalan Beg: Yeah, so we've known that cMET is a very relevant biomarker across many cancers, particularly colorectal cancer, and it is overexpressed in a fairly large proportion of multiple diseases. But there hasn't been an effective regimen that has been found to be tolerable to target this specific biomarker. In this study, the investigators are evaluating an antibody drug conjugate, which takes the cMET targeting antibody telisotuzumab and conjugates it to a novel topoisomerase one inhibitor payload. And there's a phase one study that enrolled people across multiple different tumor types. This was presented at ASCO 2023. And this year, the investigators are coming in and giving the results of a colorectal cancer cohort within that study. Patients were enrolled in the dose escalation phase, and in the dose expansion phase, there were 122 colorectal cancer cases; so a fairly healthy size colorectal cancer population. And the median number of prior lines of therapy was 4, which is fairly consistent with what we would expect in our clinical population for people with colorectal cancer. So what they found in terms of efficacy is that the response rates, the confirmed overall response rates, were between 15 and 20%, depending on what dose of the medication the patients had received. They enrolled people regardless of cMET expression and then evaluated the response based on a higher or lower cMET expression. And those with higher cMET expression had an overall response rate of >30%, while those with lower cMET expression had a response rate of 10 to 15%. So they still had a response rate, which for fifth-line colorectal cancer is something to be aware of and it could be a marker of more significant clinical activity than other treatments that are out there.  And with the antibody drug conjugates, it's also important for us to keep an eye on the side effect profiles because a lot of these agents can have distinct side effect profiles that otherwise we wouldn't be familiar with. And in this study, 64% of participants had a grade 3 or above treatment emergent adverse events, and 41% had serious adverse events. So definitely something to think about. And most of these were hematologic toxicities, 30% had grade 3 or worse anemia. Neutropenia was seen, in grade three and above, was seen in 25%, leukopenia or grade three and above was seen in 12%, and thrombocytopenia again around 12%. And the non-hematologic toxicities were nausea, fatigue, vomiting and diarrhea. There was some interstitial lung disease, pneumonitis, which was seen in 7% of the total population, of which 2% had grade three or above. So definitely something to think about. From my perspective, I really am excited about this presentation because we're seeing evidence of clinical activity focused on cMET for refractory colorectal cancer compared to other agents that are out in the market. If this pans out in future studies, it could definitely change the way we deliver our treatments. Dr. Mohamed Salem: I totally agree that we actually need more therapy for those patients. And I'm not surprised that the myelosuppression, as you mentioned, was in fifth-line treatment. So this patient had large exposure to cytotoxic agents before.   So, looking at CAR T once more, there is a very interesting Abstract 4019, which is a study of C-CAR031, a GPC3-specific TGFβRIIDN armored autologous CAR T, in patients with advanced hepatocellular carcinoma (HCC). What are your key takeaways from this study, Shaalan? Dr. Shaalan Beg: This is a first-in-human study. It enrolled people with advanced HCC who failed on one or more lines of prior therapy and they were given one single infusion of C-CAR031 after standard lymphodepletion and they enrolled 24 patients across 4 dose levels. If we look at the overall response rate, 50% of the 22 people who were eligible for response assessments had a partial response. This response rate varies based on the dose level itself and the investigators claim a 90% disease control rate. So definitely when we think about standard treatments for hepatocellular cancer after first line therapy, this is something which will catch a lot of people's attention. Again, with CAR T-cell therapy, we need to be aware of the risk of potential toxicities. There were no dose limiting toxicities and CRS or cytokine release syndrome was observed in 91% of patients, while a very small proportion, about less than 5%, had grade three CRS. Most of the side effects here were, again, lymphocytopenia, neutropenia, thrombocytopenia, and some transaminitis in 16% of patients. They did see tumor reduction in 90%, not only in the intrahepatic disease, but also in the extrahepatic disease. And again, these are people who had BCLC stage C disease. So this included people with hepatic and extrahepatic metastases. And in terms of prior lines of therapy, 96% of patients had either received immune checkpoint inhibitors and TKIs.  If we think about how some other immune therapy regimens are being developed in the GI cancer space, there is some indication that liver lesions may respond differently compared to extra hepatic disease. So in this case, they saw responses in both scenarios, which makes it very exciting, because even though we've seen many approvals of TKIs and immunotherapy, anti-androgenic therapy in hepatocellular cancer, the treatment of these patients is still extremely difficult because of their underlying hepatic dysfunction. And it'll be very interesting to see how this treatment unfolds.  Dr. Mohamed Salem: You summarized it very well, Shaalan. I echo your thoughts. What is also interesting about that study, it's actually targeted at the GPC strain, which is prevalent in HCC but not normal tissue, which goes back to your comment about the toxicity, and hopefully we can also manage treatment in the context of underlying liver disease.  Dr. Shaalan Beg: I guess it's fair to say that we're both very excited to see what's ahead in GI cancers at the Annual Meeting.   Mohamed, thanks as always for sharing your great insights with us on the ASCO Daily News Podcast.  Dr. Mohamed Salem: Thank you all for having me, and I'm looking forward to meeting you and all our colleagues in Chicago in a couple of weeks. Dr. Shaalan Beg: And thank you to our listeners for your time today. You'll find links to the abstracts discussed today in the transcripts of this episode. I'll be back to cover late breaking abstracts and other key advances in GI oncology after the annual meeting, so please join me for more key insights from ASCO24 and on the ASCO Daily News Podcast. Finally, if you value the insights that you hear on the podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Find out more about today's speakers:  Dr. Shaalan Beg  @ShaalanBeg  Dr. Mohamed Salem  @SalemGIOncDoc    Follow ASCO on social media:  @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn   Disclosures: Dr. Shaalan Beg:  Consulting or Advisory Role: Ispen, Cancer Commons, Foundation Medicine, Genmab/Seagen  Speakers' Bureau: Sirtex  Research Funding (An Immediate Family Member): ImmuneSensor Therapeutics  Research Funding (Institution): Bristol-Myers Squibb, Tolero Pharmaceuticals, Delfi Diagnostics, Merck, Merck Serono, AstraZeneca/MedImmune    Dr. Mohamed Salem: Consulting or Advisory Role: Taiho Pharmaceutical, Exelixis, Bristol-Myers Squibb, Exelixis, QED Therapeutics, Novartis, Pfizer, Daiichi Sankyo/Astra Zeneca  Speakers' Bureau: Genentech/Roche, Taiho Pharmaceutical, Daiichi Sankyo/Astra Zeneca, BMS, Merck 

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/JSQ865. CME/MOC/AAPA/IPCE credit will be available until February 26, 2025.Making an Impact in Bladder Cancer Care: Integrating the Latest Evidence and Modern Therapeutic Advances Across the Disease Continuum In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Bladder Cancer Advocacy Network. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported through independent educational grants from AstraZeneca; Bristol Myers Squibb; Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC; Merck & Co., Inc.; and Seagen and Astellas.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerMatthew D. Galsky, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie; AstraZeneca; Bicycle Therapeutics; Bristol Myers Squibb; Curis, Inc.; Daiichi Sankyo, Inc.; EMD Serono Inc.; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Pfizer and Seagen Inc.Grant/Research Support from Bristol Myers Squibb and Merck & Co., Inc.Faculty/PlannerShilpa Gupta, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Bristol Myers Squibb; EMD Serono Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Pfizer; and Seattle Genetics (Seagen Inc.).Grant/Research Support from Bristol Myers Squibb; EMD Serono Inc.; Exelixis, Inc.; F. Hoffmann-La Roche Ltd; Gilead Sciences, Inc.; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Pfizer; QED Therapeutics, Inc.; and Seattle Genetics (Seagen Inc.).Speaker for Bristol Myers Squibb; Gilead Sciences, Inc.; and Seattle Genetics (Seagen Inc.).Faculty/PlannerAndrea Necchi, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Astellas Pharma Inc.; AstraZeneca; Bristol Myers Squibb; CatalYm; F. Hoffmann-La Roche Ltd; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Merck & Co., Inc.; Pfizer; and Seagen Inc.Grant/Research Support from Bristol Myers Squibb; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; and Merck & Co., Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/JSQ865. CME/MOC/AAPA/IPCE credit will be available until February 26, 2025.Making an Impact in Bladder Cancer Care: Integrating the Latest Evidence and Modern Therapeutic Advances Across the Disease Continuum In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Bladder Cancer Advocacy Network. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported through independent educational grants from AstraZeneca; Bristol Myers Squibb; Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC; Merck & Co., Inc.; and Seagen and Astellas.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerMatthew D. Galsky, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie; AstraZeneca; Bicycle Therapeutics; Bristol Myers Squibb; Curis, Inc.; Daiichi Sankyo, Inc.; EMD Serono Inc.; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Pfizer and Seagen Inc.Grant/Research Support from Bristol Myers Squibb and Merck & Co., Inc.Faculty/PlannerShilpa Gupta, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Bristol Myers Squibb; EMD Serono Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Pfizer; and Seattle Genetics (Seagen Inc.).Grant/Research Support from Bristol Myers Squibb; EMD Serono Inc.; Exelixis, Inc.; F. Hoffmann-La Roche Ltd; Gilead Sciences, Inc.; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Pfizer; QED Therapeutics, Inc.; and Seattle Genetics (Seagen Inc.).Speaker for Bristol Myers Squibb; Gilead Sciences, Inc.; and Seattle Genetics (Seagen Inc.).Faculty/PlannerAndrea Necchi, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Astellas Pharma Inc.; AstraZeneca; Bristol Myers Squibb; CatalYm; F. Hoffmann-La Roche Ltd; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Merck & Co., Inc.; Pfizer; and Seagen Inc.Grant/Research Support from Bristol Myers Squibb; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; and Merck & Co., Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/JSQ865. CME/MOC/AAPA/IPCE credit will be available until February 26, 2025.Making an Impact in Bladder Cancer Care: Integrating the Latest Evidence and Modern Therapeutic Advances Across the Disease Continuum In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Bladder Cancer Advocacy Network. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported through independent educational grants from AstraZeneca; Bristol Myers Squibb; Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC; Merck & Co., Inc.; and Seagen and Astellas.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerMatthew D. Galsky, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie; AstraZeneca; Bicycle Therapeutics; Bristol Myers Squibb; Curis, Inc.; Daiichi Sankyo, Inc.; EMD Serono Inc.; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Pfizer and Seagen Inc.Grant/Research Support from Bristol Myers Squibb and Merck & Co., Inc.Faculty/PlannerShilpa Gupta, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Bristol Myers Squibb; EMD Serono Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Pfizer; and Seattle Genetics (Seagen Inc.).Grant/Research Support from Bristol Myers Squibb; EMD Serono Inc.; Exelixis, Inc.; F. Hoffmann-La Roche Ltd; Gilead Sciences, Inc.; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Pfizer; QED Therapeutics, Inc.; and Seattle Genetics (Seagen Inc.).Speaker for Bristol Myers Squibb; Gilead Sciences, Inc.; and Seattle Genetics (Seagen Inc.).Faculty/PlannerAndrea Necchi, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Astellas Pharma Inc.; AstraZeneca; Bristol Myers Squibb; CatalYm; F. Hoffmann-La Roche Ltd; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Merck & Co., Inc.; Pfizer; and Seagen Inc.Grant/Research Support from Bristol Myers Squibb; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; and Merck & Co., Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/JSQ865. CME/MOC/AAPA/IPCE credit will be available until February 26, 2025.Making an Impact in Bladder Cancer Care: Integrating the Latest Evidence and Modern Therapeutic Advances Across the Disease Continuum In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Bladder Cancer Advocacy Network. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported through independent educational grants from AstraZeneca; Bristol Myers Squibb; Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC; Merck & Co., Inc.; and Seagen and Astellas.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerMatthew D. Galsky, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie; AstraZeneca; Bicycle Therapeutics; Bristol Myers Squibb; Curis, Inc.; Daiichi Sankyo, Inc.; EMD Serono Inc.; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Pfizer and Seagen Inc.Grant/Research Support from Bristol Myers Squibb and Merck & Co., Inc.Faculty/PlannerShilpa Gupta, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Bristol Myers Squibb; EMD Serono Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Pfizer; and Seattle Genetics (Seagen Inc.).Grant/Research Support from Bristol Myers Squibb; EMD Serono Inc.; Exelixis, Inc.; F. Hoffmann-La Roche Ltd; Gilead Sciences, Inc.; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Pfizer; QED Therapeutics, Inc.; and Seattle Genetics (Seagen Inc.).Speaker for Bristol Myers Squibb; Gilead Sciences, Inc.; and Seattle Genetics (Seagen Inc.).Faculty/PlannerAndrea Necchi, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Astellas Pharma Inc.; AstraZeneca; Bristol Myers Squibb; CatalYm; F. Hoffmann-La Roche Ltd; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Merck & Co., Inc.; Pfizer; and Seagen Inc.Grant/Research Support from Bristol Myers Squibb; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; and Merck & Co., Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/JSQ865. CME/MOC/AAPA/IPCE credit will be available until February 26, 2025.Making an Impact in Bladder Cancer Care: Integrating the Latest Evidence and Modern Therapeutic Advances Across the Disease Continuum In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Bladder Cancer Advocacy Network. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported through independent educational grants from AstraZeneca; Bristol Myers Squibb; Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC; Merck & Co., Inc.; and Seagen and Astellas.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerMatthew D. Galsky, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie; AstraZeneca; Bicycle Therapeutics; Bristol Myers Squibb; Curis, Inc.; Daiichi Sankyo, Inc.; EMD Serono Inc.; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Pfizer and Seagen Inc.Grant/Research Support from Bristol Myers Squibb and Merck & Co., Inc.Faculty/PlannerShilpa Gupta, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Bristol Myers Squibb; EMD Serono Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Pfizer; and Seattle Genetics (Seagen Inc.).Grant/Research Support from Bristol Myers Squibb; EMD Serono Inc.; Exelixis, Inc.; F. Hoffmann-La Roche Ltd; Gilead Sciences, Inc.; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Pfizer; QED Therapeutics, Inc.; and Seattle Genetics (Seagen Inc.).Speaker for Bristol Myers Squibb; Gilead Sciences, Inc.; and Seattle Genetics (Seagen Inc.).Faculty/PlannerAndrea Necchi, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Astellas Pharma Inc.; AstraZeneca; Bristol Myers Squibb; CatalYm; F. Hoffmann-La Roche Ltd; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Merck & Co., Inc.; Pfizer; and Seagen Inc.Grant/Research Support from Bristol Myers Squibb; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; and Merck & Co., Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/JSQ865. CME/MOC/AAPA/IPCE credit will be available until February 26, 2025.Making an Impact in Bladder Cancer Care: Integrating the Latest Evidence and Modern Therapeutic Advances Across the Disease Continuum In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Bladder Cancer Advocacy Network. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported through independent educational grants from AstraZeneca; Bristol Myers Squibb; Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC; Merck & Co., Inc.; and Seagen and Astellas.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerMatthew D. Galsky, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie; AstraZeneca; Bicycle Therapeutics; Bristol Myers Squibb; Curis, Inc.; Daiichi Sankyo, Inc.; EMD Serono Inc.; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Pfizer and Seagen Inc.Grant/Research Support from Bristol Myers Squibb and Merck & Co., Inc.Faculty/PlannerShilpa Gupta, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Bristol Myers Squibb; EMD Serono Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Pfizer; and Seattle Genetics (Seagen Inc.).Grant/Research Support from Bristol Myers Squibb; EMD Serono Inc.; Exelixis, Inc.; F. Hoffmann-La Roche Ltd; Gilead Sciences, Inc.; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Pfizer; QED Therapeutics, Inc.; and Seattle Genetics (Seagen Inc.).Speaker for Bristol Myers Squibb; Gilead Sciences, Inc.; and Seattle Genetics (Seagen Inc.).Faculty/PlannerAndrea Necchi, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Astellas Pharma Inc.; AstraZeneca; Bristol Myers Squibb; CatalYm; F. Hoffmann-La Roche Ltd; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Merck & Co., Inc.; Pfizer; and Seagen Inc.Grant/Research Support from Bristol Myers Squibb; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; and Merck & Co., Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/THZ865. CME/MOC/AAPA/IPCE credit will be available until February 26, 2025.Synergizing for Success in HCC: Immunotherapy Advances and the Role of the Interventional Radiologist-Oncologist Collaboration Across the Disease Continuum In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerLipika Goyal, MD, MPhil, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Alentis Therapeutics AG; Basilea Pharmaceutica; Black Diamond Therapeutics, Inc.; Blueprint Medicines Corporation; Eisai Inc./H3Biomedicine; Exelixis, Inc.; Genentech, Inc.; Incyte Corporation; Kinnate Biopharma Inc.; Merck & Co., Inc.; QED Therapeutics; Relay Therapeutics; Servier Pharmaceuticals; Sirtex Medical Ltd; Surface Oncology; Taiho Oncology, Inc.; and TransThera Biosciences.Data Safety Monitoring Board for AstraZeneca.Co-Chair/PlannerRiad Salem, MD, MBA, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bard Pharmaceuticals; Boston Scientific Corporation; Cook Medical; Eisai Inc./Merck & Co., Inc.; and Genentech, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/THZ865. CME/MOC/AAPA/IPCE credit will be available until February 26, 2025.Synergizing for Success in HCC: Immunotherapy Advances and the Role of the Interventional Radiologist-Oncologist Collaboration Across the Disease Continuum In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerLipika Goyal, MD, MPhil, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Alentis Therapeutics AG; Basilea Pharmaceutica; Black Diamond Therapeutics, Inc.; Blueprint Medicines Corporation; Eisai Inc./H3Biomedicine; Exelixis, Inc.; Genentech, Inc.; Incyte Corporation; Kinnate Biopharma Inc.; Merck & Co., Inc.; QED Therapeutics; Relay Therapeutics; Servier Pharmaceuticals; Sirtex Medical Ltd; Surface Oncology; Taiho Oncology, Inc.; and TransThera Biosciences.Data Safety Monitoring Board for AstraZeneca.Co-Chair/PlannerRiad Salem, MD, MBA, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bard Pharmaceuticals; Boston Scientific Corporation; Cook Medical; Eisai Inc./Merck & Co., Inc.; and Genentech, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/THZ865. CME/MOC/AAPA/IPCE credit will be available until February 26, 2025.Synergizing for Success in HCC: Immunotherapy Advances and the Role of the Interventional Radiologist-Oncologist Collaboration Across the Disease Continuum In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerLipika Goyal, MD, MPhil, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Alentis Therapeutics AG; Basilea Pharmaceutica; Black Diamond Therapeutics, Inc.; Blueprint Medicines Corporation; Eisai Inc./H3Biomedicine; Exelixis, Inc.; Genentech, Inc.; Incyte Corporation; Kinnate Biopharma Inc.; Merck & Co., Inc.; QED Therapeutics; Relay Therapeutics; Servier Pharmaceuticals; Sirtex Medical Ltd; Surface Oncology; Taiho Oncology, Inc.; and TransThera Biosciences.Data Safety Monitoring Board for AstraZeneca.Co-Chair/PlannerRiad Salem, MD, MBA, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bard Pharmaceuticals; Boston Scientific Corporation; Cook Medical; Eisai Inc./Merck & Co., Inc.; and Genentech, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/THZ865. CME/MOC/AAPA/IPCE credit will be available until February 26, 2025.Synergizing for Success in HCC: Immunotherapy Advances and the Role of the Interventional Radiologist-Oncologist Collaboration Across the Disease Continuum In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerLipika Goyal, MD, MPhil, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Alentis Therapeutics AG; Basilea Pharmaceutica; Black Diamond Therapeutics, Inc.; Blueprint Medicines Corporation; Eisai Inc./H3Biomedicine; Exelixis, Inc.; Genentech, Inc.; Incyte Corporation; Kinnate Biopharma Inc.; Merck & Co., Inc.; QED Therapeutics; Relay Therapeutics; Servier Pharmaceuticals; Sirtex Medical Ltd; Surface Oncology; Taiho Oncology, Inc.; and TransThera Biosciences.Data Safety Monitoring Board for AstraZeneca.Co-Chair/PlannerRiad Salem, MD, MBA, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bard Pharmaceuticals; Boston Scientific Corporation; Cook Medical; Eisai Inc./Merck & Co., Inc.; and Genentech, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/THZ865. CME/MOC/AAPA/IPCE credit will be available until February 26, 2025.Synergizing for Success in HCC: Immunotherapy Advances and the Role of the Interventional Radiologist-Oncologist Collaboration Across the Disease Continuum In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerLipika Goyal, MD, MPhil, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Alentis Therapeutics AG; Basilea Pharmaceutica; Black Diamond Therapeutics, Inc.; Blueprint Medicines Corporation; Eisai Inc./H3Biomedicine; Exelixis, Inc.; Genentech, Inc.; Incyte Corporation; Kinnate Biopharma Inc.; Merck & Co., Inc.; QED Therapeutics; Relay Therapeutics; Servier Pharmaceuticals; Sirtex Medical Ltd; Surface Oncology; Taiho Oncology, Inc.; and TransThera Biosciences.Data Safety Monitoring Board for AstraZeneca.Co-Chair/PlannerRiad Salem, MD, MBA, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bard Pharmaceuticals; Boston Scientific Corporation; Cook Medical; Eisai Inc./Merck & Co., Inc.; and Genentech, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/THZ865. CME/MOC/AAPA/IPCE credit will be available until February 26, 2025.Synergizing for Success in HCC: Immunotherapy Advances and the Role of the Interventional Radiologist-Oncologist Collaboration Across the Disease Continuum In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerLipika Goyal, MD, MPhil, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Alentis Therapeutics AG; Basilea Pharmaceutica; Black Diamond Therapeutics, Inc.; Blueprint Medicines Corporation; Eisai Inc./H3Biomedicine; Exelixis, Inc.; Genentech, Inc.; Incyte Corporation; Kinnate Biopharma Inc.; Merck & Co., Inc.; QED Therapeutics; Relay Therapeutics; Servier Pharmaceuticals; Sirtex Medical Ltd; Surface Oncology; Taiho Oncology, Inc.; and TransThera Biosciences.Data Safety Monitoring Board for AstraZeneca.Co-Chair/PlannerRiad Salem, MD, MBA, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bard Pharmaceuticals; Boston Scientific Corporation; Cook Medical; Eisai Inc./Merck & Co., Inc.; and Genentech, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/THZ865. CME/MOC/AAPA/IPCE credit will be available until February 26, 2025.Synergizing for Success in HCC: Immunotherapy Advances and the Role of the Interventional Radiologist-Oncologist Collaboration Across the Disease Continuum In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerLipika Goyal, MD, MPhil, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Alentis Therapeutics AG; Basilea Pharmaceutica; Black Diamond Therapeutics, Inc.; Blueprint Medicines Corporation; Eisai Inc./H3Biomedicine; Exelixis, Inc.; Genentech, Inc.; Incyte Corporation; Kinnate Biopharma Inc.; Merck & Co., Inc.; QED Therapeutics; Relay Therapeutics; Servier Pharmaceuticals; Sirtex Medical Ltd; Surface Oncology; Taiho Oncology, Inc.; and TransThera Biosciences.Data Safety Monitoring Board for AstraZeneca.Co-Chair/PlannerRiad Salem, MD, MBA, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bard Pharmaceuticals; Boston Scientific Corporation; Cook Medical; Eisai Inc./Merck & Co., Inc.; and Genentech, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/THZ865. CME/MOC/AAPA/IPCE credit will be available until February 26, 2025.Synergizing for Success in HCC: Immunotherapy Advances and the Role of the Interventional Radiologist-Oncologist Collaboration Across the Disease Continuum In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerLipika Goyal, MD, MPhil, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Alentis Therapeutics AG; Basilea Pharmaceutica; Black Diamond Therapeutics, Inc.; Blueprint Medicines Corporation; Eisai Inc./H3Biomedicine; Exelixis, Inc.; Genentech, Inc.; Incyte Corporation; Kinnate Biopharma Inc.; Merck & Co., Inc.; QED Therapeutics; Relay Therapeutics; Servier Pharmaceuticals; Sirtex Medical Ltd; Surface Oncology; Taiho Oncology, Inc.; and TransThera Biosciences.Data Safety Monitoring Board for AstraZeneca.Co-Chair/PlannerRiad Salem, MD, MBA, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bard Pharmaceuticals; Boston Scientific Corporation; Cook Medical; Eisai Inc./Merck & Co., Inc.; and Genentech, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/GUS865. CME/MOC/AAPA/IPCE credit will be available until February 18, 2025.Empowering Providers and Patients to Battle Advanced Biliary Tract Cancers: Expert Guidance on Integrating the Latest Evidence on Immunotherapy and Targeted Agents in Real-World Practice In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Cholangiocarcinoma Foundation. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through independent educational grants from AstraZeneca and Incyte Corporation.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerMilind Javle, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie; Agios Pharmaceuticals Inc.; Array BioPharma Inc.; Astellas Pharma Inc.; AstraZeneca; Bayer Corporation; BeiGene; Biocartis; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo Co., Ltd.; EMD Serono Inc.; GlaxoSmithKline; Halozyme Therapeutics; Helsinn; Incyte Corporation; Ipsen; Janssen Pharmaceuticals, Inc.; Lilly; Merck Sharp & Dohme; Novartis Pharmaceuticals Corporation; OncoSil Medical Ltd; QED Therapeutics, Inc.; Servier Laboratories; Taiho Oncology, Inc.; and TransThera Biosciences Co. Ltd.Faculty/PlannerTanios Bekaii-Saab, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for (to self) AbbVie; Artiva Biotherapeutics; Aptitude Health; AstraZeneca; BeiGene; Blueprint Medicines; Boehringer Ingelheim Pharmaceuticals, Inc.; Caladrius Biosciences; Celularity Inc.; Daiichi Sankyo Co., Ltd.; Deciphera Pharmaceuticals, Inc.; Exact Sciences Corporation; Exelixis, Inc.; Foundation Medicine, Inc.; GlaxoSmithKline; Immuneering Corporation; Illumina, Inc.; Imugene Ltd.; Janssen Pharmaceuticals, Inc.; KANAPH Therapeutics Inc.; Natera, Inc.; Replimune Group Inc.; Sanofi; Sobi; Stemline Therapeutics, Inc.; Treos Bio Limited; Xilis, Inc; and Zai Lab. To institution: Arcus Biosciences, Inc.; Bayer Corporation; Eisai Co., Ltd.; Genentech, Inc.; Incyte Corporation; Ipsen Biopharmaceuticals, Inc.; Merck & Co., Inc.; Merck KGaA; Merus; Pfizer; Seattle Genetics; and Servier Laboratories.Grant/Research Support from AbGenomics Corporation; Agios Pharmaceuticals, Inc.; Arcus Biosciences, Inc.; Arys; Atreca, Inc.; Bayer Corporation; Boston Biomedical Inc.; Bristol Myers Squibb; Celgene Corporation; Clovis Oncology; Eisai Co., Ltd.; Genentech, Inc.; Incyte Corporation; Ipsen Biopharmaceuticals, Inc.; Lilly; Merus N.V.; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Pfizer; and Seattle Genetics. Research funding to Institution.Data Safety Monitoring Board for 1Globe Health Institute; AstraZeneca; Exelixis, Inc.; FibroGen, Inc.; Lilly; Merck & Co., Inc./Eisai Co., Ltd.; Pancreatic Cancer Action Network; Suzhou Kintor Pharmaceuticals, Inc.; and The Valley Hospital.Other Financial or Material Support from holding patents WO/2018/183488: HUMAN PD1 PEPTIDE VACCINES AND USES THEREOF – Licensed to Imugene. WO/2019/055687 METHODS AND COMPOSITIONS FOR THE TREATMENT OF CANCER CACHEXIA – Licensed to Recursion.Faculty/PlannerRachna Shroff, MD, MS, FASCO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Boehringer Ingelheim; Clovis Oncology; Genentech, Inc.; Incyte Corporation; Merck & Co., Inc.; QED Therapeutics; Servier Laboratories; Syros Pharmaceuticals, Inc.; and Zymeworks Inc.Grant/Research Support from Bayer; Bristol Myers Squibb; Exelixis, Inc.; IMV Inc.; Loxo Oncology, Inc.; Merck & Co., Inc.; Novocure, Inc.; NuCana; Pieris Pharmaceuticals, Inc.; QED Therapeutics; Rafael Pharmaceuticals, Inc.; Seagen; and Taiho Oncology, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/GUS865. CME/MOC/AAPA/IPCE credit will be available until February 18, 2025.Empowering Providers and Patients to Battle Advanced Biliary Tract Cancers: Expert Guidance on Integrating the Latest Evidence on Immunotherapy and Targeted Agents in Real-World Practice In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Cholangiocarcinoma Foundation. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through independent educational grants from AstraZeneca and Incyte Corporation.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerMilind Javle, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie; Agios Pharmaceuticals Inc.; Array BioPharma Inc.; Astellas Pharma Inc.; AstraZeneca; Bayer Corporation; BeiGene; Biocartis; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo Co., Ltd.; EMD Serono Inc.; GlaxoSmithKline; Halozyme Therapeutics; Helsinn; Incyte Corporation; Ipsen; Janssen Pharmaceuticals, Inc.; Lilly; Merck Sharp & Dohme; Novartis Pharmaceuticals Corporation; OncoSil Medical Ltd; QED Therapeutics, Inc.; Servier Laboratories; Taiho Oncology, Inc.; and TransThera Biosciences Co. Ltd.Faculty/PlannerTanios Bekaii-Saab, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for (to self) AbbVie; Artiva Biotherapeutics; Aptitude Health; AstraZeneca; BeiGene; Blueprint Medicines; Boehringer Ingelheim Pharmaceuticals, Inc.; Caladrius Biosciences; Celularity Inc.; Daiichi Sankyo Co., Ltd.; Deciphera Pharmaceuticals, Inc.; Exact Sciences Corporation; Exelixis, Inc.; Foundation Medicine, Inc.; GlaxoSmithKline; Immuneering Corporation; Illumina, Inc.; Imugene Ltd.; Janssen Pharmaceuticals, Inc.; KANAPH Therapeutics Inc.; Natera, Inc.; Replimune Group Inc.; Sanofi; Sobi; Stemline Therapeutics, Inc.; Treos Bio Limited; Xilis, Inc; and Zai Lab. To institution: Arcus Biosciences, Inc.; Bayer Corporation; Eisai Co., Ltd.; Genentech, Inc.; Incyte Corporation; Ipsen Biopharmaceuticals, Inc.; Merck & Co., Inc.; Merck KGaA; Merus; Pfizer; Seattle Genetics; and Servier Laboratories.Grant/Research Support from AbGenomics Corporation; Agios Pharmaceuticals, Inc.; Arcus Biosciences, Inc.; Arys; Atreca, Inc.; Bayer Corporation; Boston Biomedical Inc.; Bristol Myers Squibb; Celgene Corporation; Clovis Oncology; Eisai Co., Ltd.; Genentech, Inc.; Incyte Corporation; Ipsen Biopharmaceuticals, Inc.; Lilly; Merus N.V.; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Pfizer; and Seattle Genetics. Research funding to Institution.Data Safety Monitoring Board for 1Globe Health Institute; AstraZeneca; Exelixis, Inc.; FibroGen, Inc.; Lilly; Merck & Co., Inc./Eisai Co., Ltd.; Pancreatic Cancer Action Network; Suzhou Kintor Pharmaceuticals, Inc.; and The Valley Hospital.Other Financial or Material Support from holding patents WO/2018/183488: HUMAN PD1 PEPTIDE VACCINES AND USES THEREOF – Licensed to Imugene. WO/2019/055687 METHODS AND COMPOSITIONS FOR THE TREATMENT OF CANCER CACHEXIA – Licensed to Recursion.Faculty/PlannerRachna Shroff, MD, MS, FASCO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Boehringer Ingelheim; Clovis Oncology; Genentech, Inc.; Incyte Corporation; Merck & Co., Inc.; QED Therapeutics; Servier Laboratories; Syros Pharmaceuticals, Inc.; and Zymeworks Inc.Grant/Research Support from Bayer; Bristol Myers Squibb; Exelixis, Inc.; IMV Inc.; Loxo Oncology, Inc.; Merck & Co., Inc.; Novocure, Inc.; NuCana; Pieris Pharmaceuticals, Inc.; QED Therapeutics; Rafael Pharmaceuticals, Inc.; Seagen; and Taiho Oncology, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/GUS865. CME/MOC/AAPA/IPCE credit will be available until February 18, 2025.Empowering Providers and Patients to Battle Advanced Biliary Tract Cancers: Expert Guidance on Integrating the Latest Evidence on Immunotherapy and Targeted Agents in Real-World Practice In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Cholangiocarcinoma Foundation. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through independent educational grants from AstraZeneca and Incyte Corporation.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerMilind Javle, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie; Agios Pharmaceuticals Inc.; Array BioPharma Inc.; Astellas Pharma Inc.; AstraZeneca; Bayer Corporation; BeiGene; Biocartis; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo Co., Ltd.; EMD Serono Inc.; GlaxoSmithKline; Halozyme Therapeutics; Helsinn; Incyte Corporation; Ipsen; Janssen Pharmaceuticals, Inc.; Lilly; Merck Sharp & Dohme; Novartis Pharmaceuticals Corporation; OncoSil Medical Ltd; QED Therapeutics, Inc.; Servier Laboratories; Taiho Oncology, Inc.; and TransThera Biosciences Co. Ltd.Faculty/PlannerTanios Bekaii-Saab, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for (to self) AbbVie; Artiva Biotherapeutics; Aptitude Health; AstraZeneca; BeiGene; Blueprint Medicines; Boehringer Ingelheim Pharmaceuticals, Inc.; Caladrius Biosciences; Celularity Inc.; Daiichi Sankyo Co., Ltd.; Deciphera Pharmaceuticals, Inc.; Exact Sciences Corporation; Exelixis, Inc.; Foundation Medicine, Inc.; GlaxoSmithKline; Immuneering Corporation; Illumina, Inc.; Imugene Ltd.; Janssen Pharmaceuticals, Inc.; KANAPH Therapeutics Inc.; Natera, Inc.; Replimune Group Inc.; Sanofi; Sobi; Stemline Therapeutics, Inc.; Treos Bio Limited; Xilis, Inc; and Zai Lab. To institution: Arcus Biosciences, Inc.; Bayer Corporation; Eisai Co., Ltd.; Genentech, Inc.; Incyte Corporation; Ipsen Biopharmaceuticals, Inc.; Merck & Co., Inc.; Merck KGaA; Merus; Pfizer; Seattle Genetics; and Servier Laboratories.Grant/Research Support from AbGenomics Corporation; Agios Pharmaceuticals, Inc.; Arcus Biosciences, Inc.; Arys; Atreca, Inc.; Bayer Corporation; Boston Biomedical Inc.; Bristol Myers Squibb; Celgene Corporation; Clovis Oncology; Eisai Co., Ltd.; Genentech, Inc.; Incyte Corporation; Ipsen Biopharmaceuticals, Inc.; Lilly; Merus N.V.; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Pfizer; and Seattle Genetics. Research funding to Institution.Data Safety Monitoring Board for 1Globe Health Institute; AstraZeneca; Exelixis, Inc.; FibroGen, Inc.; Lilly; Merck & Co., Inc./Eisai Co., Ltd.; Pancreatic Cancer Action Network; Suzhou Kintor Pharmaceuticals, Inc.; and The Valley Hospital.Other Financial or Material Support from holding patents WO/2018/183488: HUMAN PD1 PEPTIDE VACCINES AND USES THEREOF – Licensed to Imugene. WO/2019/055687 METHODS AND COMPOSITIONS FOR THE TREATMENT OF CANCER CACHEXIA – Licensed to Recursion.Faculty/PlannerRachna Shroff, MD, MS, FASCO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Boehringer Ingelheim; Clovis Oncology; Genentech, Inc.; Incyte Corporation; Merck & Co., Inc.; QED Therapeutics; Servier Laboratories; Syros Pharmaceuticals, Inc.; and Zymeworks Inc.Grant/Research Support from Bayer; Bristol Myers Squibb; Exelixis, Inc.; IMV Inc.; Loxo Oncology, Inc.; Merck & Co., Inc.; Novocure, Inc.; NuCana; Pieris Pharmaceuticals, Inc.; QED Therapeutics; Rafael Pharmaceuticals, Inc.; Seagen; and Taiho Oncology, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/GUS865. CME/MOC/AAPA/IPCE credit will be available until February 18, 2025.Empowering Providers and Patients to Battle Advanced Biliary Tract Cancers: Expert Guidance on Integrating the Latest Evidence on Immunotherapy and Targeted Agents in Real-World Practice In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Cholangiocarcinoma Foundation. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through independent educational grants from AstraZeneca and Incyte Corporation.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerMilind Javle, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie; Agios Pharmaceuticals Inc.; Array BioPharma Inc.; Astellas Pharma Inc.; AstraZeneca; Bayer Corporation; BeiGene; Biocartis; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo Co., Ltd.; EMD Serono Inc.; GlaxoSmithKline; Halozyme Therapeutics; Helsinn; Incyte Corporation; Ipsen; Janssen Pharmaceuticals, Inc.; Lilly; Merck Sharp & Dohme; Novartis Pharmaceuticals Corporation; OncoSil Medical Ltd; QED Therapeutics, Inc.; Servier Laboratories; Taiho Oncology, Inc.; and TransThera Biosciences Co. Ltd.Faculty/PlannerTanios Bekaii-Saab, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for (to self) AbbVie; Artiva Biotherapeutics; Aptitude Health; AstraZeneca; BeiGene; Blueprint Medicines; Boehringer Ingelheim Pharmaceuticals, Inc.; Caladrius Biosciences; Celularity Inc.; Daiichi Sankyo Co., Ltd.; Deciphera Pharmaceuticals, Inc.; Exact Sciences Corporation; Exelixis, Inc.; Foundation Medicine, Inc.; GlaxoSmithKline; Immuneering Corporation; Illumina, Inc.; Imugene Ltd.; Janssen Pharmaceuticals, Inc.; KANAPH Therapeutics Inc.; Natera, Inc.; Replimune Group Inc.; Sanofi; Sobi; Stemline Therapeutics, Inc.; Treos Bio Limited; Xilis, Inc; and Zai Lab. To institution: Arcus Biosciences, Inc.; Bayer Corporation; Eisai Co., Ltd.; Genentech, Inc.; Incyte Corporation; Ipsen Biopharmaceuticals, Inc.; Merck & Co., Inc.; Merck KGaA; Merus; Pfizer; Seattle Genetics; and Servier Laboratories.Grant/Research Support from AbGenomics Corporation; Agios Pharmaceuticals, Inc.; Arcus Biosciences, Inc.; Arys; Atreca, Inc.; Bayer Corporation; Boston Biomedical Inc.; Bristol Myers Squibb; Celgene Corporation; Clovis Oncology; Eisai Co., Ltd.; Genentech, Inc.; Incyte Corporation; Ipsen Biopharmaceuticals, Inc.; Lilly; Merus N.V.; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Pfizer; and Seattle Genetics. Research funding to Institution.Data Safety Monitoring Board for 1Globe Health Institute; AstraZeneca; Exelixis, Inc.; FibroGen, Inc.; Lilly; Merck & Co., Inc./Eisai Co., Ltd.; Pancreatic Cancer Action Network; Suzhou Kintor Pharmaceuticals, Inc.; and The Valley Hospital.Other Financial or Material Support from holding patents WO/2018/183488: HUMAN PD1 PEPTIDE VACCINES AND USES THEREOF – Licensed to Imugene. WO/2019/055687 METHODS AND COMPOSITIONS FOR THE TREATMENT OF CANCER CACHEXIA – Licensed to Recursion.Faculty/PlannerRachna Shroff, MD, MS, FASCO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Boehringer Ingelheim; Clovis Oncology; Genentech, Inc.; Incyte Corporation; Merck & Co., Inc.; QED Therapeutics; Servier Laboratories; Syros Pharmaceuticals, Inc.; and Zymeworks Inc.Grant/Research Support from Bayer; Bristol Myers Squibb; Exelixis, Inc.; IMV Inc.; Loxo Oncology, Inc.; Merck & Co., Inc.; Novocure, Inc.; NuCana; Pieris Pharmaceuticals, Inc.; QED Therapeutics; Rafael Pharmaceuticals, Inc.; Seagen; and Taiho Oncology, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/GUS865. CME/MOC/AAPA/IPCE credit will be available until February 18, 2025.Empowering Providers and Patients to Battle Advanced Biliary Tract Cancers: Expert Guidance on Integrating the Latest Evidence on Immunotherapy and Targeted Agents in Real-World Practice In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Cholangiocarcinoma Foundation. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through independent educational grants from AstraZeneca and Incyte Corporation.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerMilind Javle, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie; Agios Pharmaceuticals Inc.; Array BioPharma Inc.; Astellas Pharma Inc.; AstraZeneca; Bayer Corporation; BeiGene; Biocartis; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo Co., Ltd.; EMD Serono Inc.; GlaxoSmithKline; Halozyme Therapeutics; Helsinn; Incyte Corporation; Ipsen; Janssen Pharmaceuticals, Inc.; Lilly; Merck Sharp & Dohme; Novartis Pharmaceuticals Corporation; OncoSil Medical Ltd; QED Therapeutics, Inc.; Servier Laboratories; Taiho Oncology, Inc.; and TransThera Biosciences Co. Ltd.Faculty/PlannerTanios Bekaii-Saab, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for (to self) AbbVie; Artiva Biotherapeutics; Aptitude Health; AstraZeneca; BeiGene; Blueprint Medicines; Boehringer Ingelheim Pharmaceuticals, Inc.; Caladrius Biosciences; Celularity Inc.; Daiichi Sankyo Co., Ltd.; Deciphera Pharmaceuticals, Inc.; Exact Sciences Corporation; Exelixis, Inc.; Foundation Medicine, Inc.; GlaxoSmithKline; Immuneering Corporation; Illumina, Inc.; Imugene Ltd.; Janssen Pharmaceuticals, Inc.; KANAPH Therapeutics Inc.; Natera, Inc.; Replimune Group Inc.; Sanofi; Sobi; Stemline Therapeutics, Inc.; Treos Bio Limited; Xilis, Inc; and Zai Lab. To institution: Arcus Biosciences, Inc.; Bayer Corporation; Eisai Co., Ltd.; Genentech, Inc.; Incyte Corporation; Ipsen Biopharmaceuticals, Inc.; Merck & Co., Inc.; Merck KGaA; Merus; Pfizer; Seattle Genetics; and Servier Laboratories.Grant/Research Support from AbGenomics Corporation; Agios Pharmaceuticals, Inc.; Arcus Biosciences, Inc.; Arys; Atreca, Inc.; Bayer Corporation; Boston Biomedical Inc.; Bristol Myers Squibb; Celgene Corporation; Clovis Oncology; Eisai Co., Ltd.; Genentech, Inc.; Incyte Corporation; Ipsen Biopharmaceuticals, Inc.; Lilly; Merus N.V.; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Pfizer; and Seattle Genetics. Research funding to Institution.Data Safety Monitoring Board for 1Globe Health Institute; AstraZeneca; Exelixis, Inc.; FibroGen, Inc.; Lilly; Merck & Co., Inc./Eisai Co., Ltd.; Pancreatic Cancer Action Network; Suzhou Kintor Pharmaceuticals, Inc.; and The Valley Hospital.Other Financial or Material Support from holding patents WO/2018/183488: HUMAN PD1 PEPTIDE VACCINES AND USES THEREOF – Licensed to Imugene. WO/2019/055687 METHODS AND COMPOSITIONS FOR THE TREATMENT OF CANCER CACHEXIA – Licensed to Recursion.Faculty/PlannerRachna Shroff, MD, MS, FASCO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Boehringer Ingelheim; Clovis Oncology; Genentech, Inc.; Incyte Corporation; Merck & Co., Inc.; QED Therapeutics; Servier Laboratories; Syros Pharmaceuticals, Inc.; and Zymeworks Inc.Grant/Research Support from Bayer; Bristol Myers Squibb; Exelixis, Inc.; IMV Inc.; Loxo Oncology, Inc.; Merck & Co., Inc.; Novocure, Inc.; NuCana; Pieris Pharmaceuticals, Inc.; QED Therapeutics; Rafael Pharmaceuticals, Inc.; Seagen; and Taiho Oncology, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/GUS865. CME/MOC/AAPA/IPCE credit will be available until February 18, 2025.Empowering Providers and Patients to Battle Advanced Biliary Tract Cancers: Expert Guidance on Integrating the Latest Evidence on Immunotherapy and Targeted Agents in Real-World Practice In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Cholangiocarcinoma Foundation. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through independent educational grants from AstraZeneca and Incyte Corporation.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerMilind Javle, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie; Agios Pharmaceuticals Inc.; Array BioPharma Inc.; Astellas Pharma Inc.; AstraZeneca; Bayer Corporation; BeiGene; Biocartis; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo Co., Ltd.; EMD Serono Inc.; GlaxoSmithKline; Halozyme Therapeutics; Helsinn; Incyte Corporation; Ipsen; Janssen Pharmaceuticals, Inc.; Lilly; Merck Sharp & Dohme; Novartis Pharmaceuticals Corporation; OncoSil Medical Ltd; QED Therapeutics, Inc.; Servier Laboratories; Taiho Oncology, Inc.; and TransThera Biosciences Co. Ltd.Faculty/PlannerTanios Bekaii-Saab, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for (to self) AbbVie; Artiva Biotherapeutics; Aptitude Health; AstraZeneca; BeiGene; Blueprint Medicines; Boehringer Ingelheim Pharmaceuticals, Inc.; Caladrius Biosciences; Celularity Inc.; Daiichi Sankyo Co., Ltd.; Deciphera Pharmaceuticals, Inc.; Exact Sciences Corporation; Exelixis, Inc.; Foundation Medicine, Inc.; GlaxoSmithKline; Immuneering Corporation; Illumina, Inc.; Imugene Ltd.; Janssen Pharmaceuticals, Inc.; KANAPH Therapeutics Inc.; Natera, Inc.; Replimune Group Inc.; Sanofi; Sobi; Stemline Therapeutics, Inc.; Treos Bio Limited; Xilis, Inc; and Zai Lab. To institution: Arcus Biosciences, Inc.; Bayer Corporation; Eisai Co., Ltd.; Genentech, Inc.; Incyte Corporation; Ipsen Biopharmaceuticals, Inc.; Merck & Co., Inc.; Merck KGaA; Merus; Pfizer; Seattle Genetics; and Servier Laboratories.Grant/Research Support from AbGenomics Corporation; Agios Pharmaceuticals, Inc.; Arcus Biosciences, Inc.; Arys; Atreca, Inc.; Bayer Corporation; Boston Biomedical Inc.; Bristol Myers Squibb; Celgene Corporation; Clovis Oncology; Eisai Co., Ltd.; Genentech, Inc.; Incyte Corporation; Ipsen Biopharmaceuticals, Inc.; Lilly; Merus N.V.; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Pfizer; and Seattle Genetics. Research funding to Institution.Data Safety Monitoring Board for 1Globe Health Institute; AstraZeneca; Exelixis, Inc.; FibroGen, Inc.; Lilly; Merck & Co., Inc./Eisai Co., Ltd.; Pancreatic Cancer Action Network; Suzhou Kintor Pharmaceuticals, Inc.; and The Valley Hospital.Other Financial or Material Support from holding patents WO/2018/183488: HUMAN PD1 PEPTIDE VACCINES AND USES THEREOF – Licensed to Imugene. WO/2019/055687 METHODS AND COMPOSITIONS FOR THE TREATMENT OF CANCER CACHEXIA – Licensed to Recursion.Faculty/PlannerRachna Shroff, MD, MS, FASCO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Boehringer Ingelheim; Clovis Oncology; Genentech, Inc.; Incyte Corporation; Merck & Co., Inc.; QED Therapeutics; Servier Laboratories; Syros Pharmaceuticals, Inc.; and Zymeworks Inc.Grant/Research Support from Bayer; Bristol Myers Squibb; Exelixis, Inc.; IMV Inc.; Loxo Oncology, Inc.; Merck & Co., Inc.; Novocure, Inc.; NuCana; Pieris Pharmaceuticals, Inc.; QED Therapeutics; Rafael Pharmaceuticals, Inc.; Seagen; and Taiho Oncology, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/AAU865. CME/MOC/AAPA/IPCE credit will be available until February 18, 2025.Calibrating Care Across the HCC Continuum: Guidance on Delivering Effective Care With Modern Immunotherapy and Targeted Approaches In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Blue Faery: The Adrienne Wilson Liver Cancer Association. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through independent educational grants from AstraZeneca, Eisai Inc., Exelixis, Inc., Merck & Co., Inc., and Novocure, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerGhassan Abou-Alfa, MD, MBA, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Autem Therapeutics; Berry Genomics; BioNTech; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Eisai Inc.; Exelixis, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Incyte; Ipsen Biopharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Neogene Therapeutics; NewBridge Pharmaceuticals; Novartis Pharmaceuticals Corporation; Servier Laboratories; Tempus; Vector; and Yiviva.Grant/Research Support from Agenus Inc.; Arcus Biosciences, Inc.; AstraZeneca; BioNTech; Bristol Myers Squibb; Elicio Therapeutics Inc; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Helsinn Healthcare SA; Parker Institute for Cancer Immunotherapy; Pertzye; Puma Biotechnology, Inc.; QED Therapeutics; and Yiviva.Faculty/PlannerAnthony El-Khoueiry, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Exelixis, Inc.; F. Hoffmann-La Roche AG/Genentech, Inc.; Merck & Co., Inc.; Qurient; and Senti Biosciences.Grant/Research Support from Astex Pharmaceuticals; AstraZeneca; Auransa Inc.; and Fulgent Pharma.Faculty/PlannerAhmed Omar Kaseb, MD, CMQ, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Bristol Myers Squibb; Eisai Inc.; Exelixis, Inc.; Genentech, Inc.; Merck & Co., Inc.; and Pfizer.Grant/Research Support from Bristol Myers Squibb; Eisai Inc.; Exelixis, Inc.; Genentech, Inc.; Merck & Co., Inc.; Pfizer; and Tvardi Therapeutics.Faculty/PlannerStacey M. Stein, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Eisai Inc.; Exelixis, Inc.; and Genentech, Inc.Data Safety Monitoring Board for Aethlon Medical, Inc.and Genentech, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.PlannerAndrea Wilson WoodsPresident & Founder, Blue FaeryAndrea Wilson Woods has a financial interest/relationship or affiliation in the form of:Consultant for AstraZeneca and Humanise Health.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/AAU865. CME/MOC/AAPA/IPCE credit will be available until February 18, 2025.Calibrating Care Across the HCC Continuum: Guidance on Delivering Effective Care With Modern Immunotherapy and Targeted Approaches In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Blue Faery: The Adrienne Wilson Liver Cancer Association. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through independent educational grants from AstraZeneca, Eisai Inc., Exelixis, Inc., Merck & Co., Inc., and Novocure, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerGhassan Abou-Alfa, MD, MBA, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Autem Therapeutics; Berry Genomics; BioNTech; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Eisai Inc.; Exelixis, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Incyte; Ipsen Biopharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Neogene Therapeutics; NewBridge Pharmaceuticals; Novartis Pharmaceuticals Corporation; Servier Laboratories; Tempus; Vector; and Yiviva.Grant/Research Support from Agenus Inc.; Arcus Biosciences, Inc.; AstraZeneca; BioNTech; Bristol Myers Squibb; Elicio Therapeutics Inc; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Helsinn Healthcare SA; Parker Institute for Cancer Immunotherapy; Pertzye; Puma Biotechnology, Inc.; QED Therapeutics; and Yiviva.Faculty/PlannerAnthony El-Khoueiry, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Exelixis, Inc.; F. Hoffmann-La Roche AG/Genentech, Inc.; Merck & Co., Inc.; Qurient; and Senti Biosciences.Grant/Research Support from Astex Pharmaceuticals; AstraZeneca; Auransa Inc.; and Fulgent Pharma.Faculty/PlannerAhmed Omar Kaseb, MD, CMQ, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Bristol Myers Squibb; Eisai Inc.; Exelixis, Inc.; Genentech, Inc.; Merck & Co., Inc.; and Pfizer.Grant/Research Support from Bristol Myers Squibb; Eisai Inc.; Exelixis, Inc.; Genentech, Inc.; Merck & Co., Inc.; Pfizer; and Tvardi Therapeutics.Faculty/PlannerStacey M. Stein, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Eisai Inc.; Exelixis, Inc.; and Genentech, Inc.Data Safety Monitoring Board for Aethlon Medical, Inc.and Genentech, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.PlannerAndrea Wilson WoodsPresident & Founder, Blue FaeryAndrea Wilson Woods has a financial interest/relationship or affiliation in the form of:Consultant for AstraZeneca and Humanise Health.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/AAU865. CME/MOC/AAPA/IPCE credit will be available until February 18, 2025.Calibrating Care Across the HCC Continuum: Guidance on Delivering Effective Care With Modern Immunotherapy and Targeted Approaches In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Blue Faery: The Adrienne Wilson Liver Cancer Association. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through independent educational grants from AstraZeneca, Eisai Inc., Exelixis, Inc., Merck & Co., Inc., and Novocure, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerGhassan Abou-Alfa, MD, MBA, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Autem Therapeutics; Berry Genomics; BioNTech; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Eisai Inc.; Exelixis, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Incyte; Ipsen Biopharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Neogene Therapeutics; NewBridge Pharmaceuticals; Novartis Pharmaceuticals Corporation; Servier Laboratories; Tempus; Vector; and Yiviva.Grant/Research Support from Agenus Inc.; Arcus Biosciences, Inc.; AstraZeneca; BioNTech; Bristol Myers Squibb; Elicio Therapeutics Inc; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Helsinn Healthcare SA; Parker Institute for Cancer Immunotherapy; Pertzye; Puma Biotechnology, Inc.; QED Therapeutics; and Yiviva.Faculty/PlannerAnthony El-Khoueiry, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Exelixis, Inc.; F. Hoffmann-La Roche AG/Genentech, Inc.; Merck & Co., Inc.; Qurient; and Senti Biosciences.Grant/Research Support from Astex Pharmaceuticals; AstraZeneca; Auransa Inc.; and Fulgent Pharma.Faculty/PlannerAhmed Omar Kaseb, MD, CMQ, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Bristol Myers Squibb; Eisai Inc.; Exelixis, Inc.; Genentech, Inc.; Merck & Co., Inc.; and Pfizer.Grant/Research Support from Bristol Myers Squibb; Eisai Inc.; Exelixis, Inc.; Genentech, Inc.; Merck & Co., Inc.; Pfizer; and Tvardi Therapeutics.Faculty/PlannerStacey M. Stein, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Eisai Inc.; Exelixis, Inc.; and Genentech, Inc.Data Safety Monitoring Board for Aethlon Medical, Inc.and Genentech, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.PlannerAndrea Wilson WoodsPresident & Founder, Blue FaeryAndrea Wilson Woods has a financial interest/relationship or affiliation in the form of:Consultant for AstraZeneca and Humanise Health.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/AAU865. CME/MOC/AAPA/IPCE credit will be available until February 18, 2025.Calibrating Care Across the HCC Continuum: Guidance on Delivering Effective Care With Modern Immunotherapy and Targeted Approaches In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Blue Faery: The Adrienne Wilson Liver Cancer Association. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through independent educational grants from AstraZeneca, Eisai Inc., Exelixis, Inc., Merck & Co., Inc., and Novocure, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerGhassan Abou-Alfa, MD, MBA, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Autem Therapeutics; Berry Genomics; BioNTech; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Eisai Inc.; Exelixis, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Incyte; Ipsen Biopharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Neogene Therapeutics; NewBridge Pharmaceuticals; Novartis Pharmaceuticals Corporation; Servier Laboratories; Tempus; Vector; and Yiviva.Grant/Research Support from Agenus Inc.; Arcus Biosciences, Inc.; AstraZeneca; BioNTech; Bristol Myers Squibb; Elicio Therapeutics Inc; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Helsinn Healthcare SA; Parker Institute for Cancer Immunotherapy; Pertzye; Puma Biotechnology, Inc.; QED Therapeutics; and Yiviva.Faculty/PlannerAnthony El-Khoueiry, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Exelixis, Inc.; F. Hoffmann-La Roche AG/Genentech, Inc.; Merck & Co., Inc.; Qurient; and Senti Biosciences.Grant/Research Support from Astex Pharmaceuticals; AstraZeneca; Auransa Inc.; and Fulgent Pharma.Faculty/PlannerAhmed Omar Kaseb, MD, CMQ, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Bristol Myers Squibb; Eisai Inc.; Exelixis, Inc.; Genentech, Inc.; Merck & Co., Inc.; and Pfizer.Grant/Research Support from Bristol Myers Squibb; Eisai Inc.; Exelixis, Inc.; Genentech, Inc.; Merck & Co., Inc.; Pfizer; and Tvardi Therapeutics.Faculty/PlannerStacey M. Stein, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Eisai Inc.; Exelixis, Inc.; and Genentech, Inc.Data Safety Monitoring Board for Aethlon Medical, Inc.and Genentech, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.PlannerAndrea Wilson WoodsPresident & Founder, Blue FaeryAndrea Wilson Woods has a financial interest/relationship or affiliation in the form of:Consultant for AstraZeneca and Humanise Health.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/AAU865. CME/MOC/AAPA/IPCE credit will be available until February 18, 2025.Calibrating Care Across the HCC Continuum: Guidance on Delivering Effective Care With Modern Immunotherapy and Targeted Approaches In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Blue Faery: The Adrienne Wilson Liver Cancer Association. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through independent educational grants from AstraZeneca, Eisai Inc., Exelixis, Inc., Merck & Co., Inc., and Novocure, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerGhassan Abou-Alfa, MD, MBA, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Autem Therapeutics; Berry Genomics; BioNTech; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Eisai Inc.; Exelixis, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Incyte; Ipsen Biopharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Neogene Therapeutics; NewBridge Pharmaceuticals; Novartis Pharmaceuticals Corporation; Servier Laboratories; Tempus; Vector; and Yiviva.Grant/Research Support from Agenus Inc.; Arcus Biosciences, Inc.; AstraZeneca; BioNTech; Bristol Myers Squibb; Elicio Therapeutics Inc; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Helsinn Healthcare SA; Parker Institute for Cancer Immunotherapy; Pertzye; Puma Biotechnology, Inc.; QED Therapeutics; and Yiviva.Faculty/PlannerAnthony El-Khoueiry, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Exelixis, Inc.; F. Hoffmann-La Roche AG/Genentech, Inc.; Merck & Co., Inc.; Qurient; and Senti Biosciences.Grant/Research Support from Astex Pharmaceuticals; AstraZeneca; Auransa Inc.; and Fulgent Pharma.Faculty/PlannerAhmed Omar Kaseb, MD, CMQ, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Bristol Myers Squibb; Eisai Inc.; Exelixis, Inc.; Genentech, Inc.; Merck & Co., Inc.; and Pfizer.Grant/Research Support from Bristol Myers Squibb; Eisai Inc.; Exelixis, Inc.; Genentech, Inc.; Merck & Co., Inc.; Pfizer; and Tvardi Therapeutics.Faculty/PlannerStacey M. Stein, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Eisai Inc.; Exelixis, Inc.; and Genentech, Inc.Data Safety Monitoring Board for Aethlon Medical, Inc.and Genentech, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.PlannerAndrea Wilson WoodsPresident & Founder, Blue FaeryAndrea Wilson Woods has a financial interest/relationship or affiliation in the form of:Consultant for AstraZeneca and Humanise Health.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/AAU865. CME/MOC/AAPA/IPCE credit will be available until February 18, 2025.Calibrating Care Across the HCC Continuum: Guidance on Delivering Effective Care With Modern Immunotherapy and Targeted Approaches In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Blue Faery: The Adrienne Wilson Liver Cancer Association. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through independent educational grants from AstraZeneca, Eisai Inc., Exelixis, Inc., Merck & Co., Inc., and Novocure, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerGhassan Abou-Alfa, MD, MBA, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Autem Therapeutics; Berry Genomics; BioNTech; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Eisai Inc.; Exelixis, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Incyte; Ipsen Biopharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Neogene Therapeutics; NewBridge Pharmaceuticals; Novartis Pharmaceuticals Corporation; Servier Laboratories; Tempus; Vector; and Yiviva.Grant/Research Support from Agenus Inc.; Arcus Biosciences, Inc.; AstraZeneca; BioNTech; Bristol Myers Squibb; Elicio Therapeutics Inc; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Helsinn Healthcare SA; Parker Institute for Cancer Immunotherapy; Pertzye; Puma Biotechnology, Inc.; QED Therapeutics; and Yiviva.Faculty/PlannerAnthony El-Khoueiry, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Exelixis, Inc.; F. Hoffmann-La Roche AG/Genentech, Inc.; Merck & Co., Inc.; Qurient; and Senti Biosciences.Grant/Research Support from Astex Pharmaceuticals; AstraZeneca; Auransa Inc.; and Fulgent Pharma.Faculty/PlannerAhmed Omar Kaseb, MD, CMQ, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Bristol Myers Squibb; Eisai Inc.; Exelixis, Inc.; Genentech, Inc.; Merck & Co., Inc.; and Pfizer.Grant/Research Support from Bristol Myers Squibb; Eisai Inc.; Exelixis, Inc.; Genentech, Inc.; Merck & Co., Inc.; Pfizer; and Tvardi Therapeutics.Faculty/PlannerStacey M. Stein, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Eisai Inc.; Exelixis, Inc.; and Genentech, Inc.Data Safety Monitoring Board for Aethlon Medical, Inc.and Genentech, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.PlannerAndrea Wilson WoodsPresident & Founder, Blue FaeryAndrea Wilson Woods has a financial interest/relationship or affiliation in the form of:Consultant for AstraZeneca and Humanise Health.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/AAU865. CME/MOC/AAPA/IPCE credit will be available until February 18, 2025.Calibrating Care Across the HCC Continuum: Guidance on Delivering Effective Care With Modern Immunotherapy and Targeted Approaches In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Blue Faery: The Adrienne Wilson Liver Cancer Association. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through independent educational grants from AstraZeneca, Eisai Inc., Exelixis, Inc., Merck & Co., Inc., and Novocure, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerGhassan Abou-Alfa, MD, MBA, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Autem Therapeutics; Berry Genomics; BioNTech; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Eisai Inc.; Exelixis, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Incyte; Ipsen Biopharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Neogene Therapeutics; NewBridge Pharmaceuticals; Novartis Pharmaceuticals Corporation; Servier Laboratories; Tempus; Vector; and Yiviva.Grant/Research Support from Agenus Inc.; Arcus Biosciences, Inc.; AstraZeneca; BioNTech; Bristol Myers Squibb; Elicio Therapeutics Inc; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Helsinn Healthcare SA; Parker Institute for Cancer Immunotherapy; Pertzye; Puma Biotechnology, Inc.; QED Therapeutics; and Yiviva.Faculty/PlannerAnthony El-Khoueiry, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Exelixis, Inc.; F. Hoffmann-La Roche AG/Genentech, Inc.; Merck & Co., Inc.; Qurient; and Senti Biosciences.Grant/Research Support from Astex Pharmaceuticals; AstraZeneca; Auransa Inc.; and Fulgent Pharma.Faculty/PlannerAhmed Omar Kaseb, MD, CMQ, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Bristol Myers Squibb; Eisai Inc.; Exelixis, Inc.; Genentech, Inc.; Merck & Co., Inc.; and Pfizer.Grant/Research Support from Bristol Myers Squibb; Eisai Inc.; Exelixis, Inc.; Genentech, Inc.; Merck & Co., Inc.; Pfizer; and Tvardi Therapeutics.Faculty/PlannerStacey M. Stein, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Eisai Inc.; Exelixis, Inc.; and Genentech, Inc.Data Safety Monitoring Board for Aethlon Medical, Inc.and Genentech, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.PlannerAndrea Wilson WoodsPresident & Founder, Blue FaeryAndrea Wilson Woods has a financial interest/relationship or affiliation in the form of:Consultant for AstraZeneca and Humanise Health.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/AAU865. CME/MOC/AAPA/IPCE credit will be available until February 18, 2025.Calibrating Care Across the HCC Continuum: Guidance on Delivering Effective Care With Modern Immunotherapy and Targeted Approaches In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Blue Faery: The Adrienne Wilson Liver Cancer Association. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported through independent educational grants from AstraZeneca, Eisai Inc., Exelixis, Inc., Merck & Co., Inc., and Novocure, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerGhassan Abou-Alfa, MD, MBA, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Autem Therapeutics; Berry Genomics; BioNTech; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Eisai Inc.; Exelixis, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Incyte; Ipsen Biopharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Neogene Therapeutics; NewBridge Pharmaceuticals; Novartis Pharmaceuticals Corporation; Servier Laboratories; Tempus; Vector; and Yiviva.Grant/Research Support from Agenus Inc.; Arcus Biosciences, Inc.; AstraZeneca; BioNTech; Bristol Myers Squibb; Elicio Therapeutics Inc; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Helsinn Healthcare SA; Parker Institute for Cancer Immunotherapy; Pertzye; Puma Biotechnology, Inc.; QED Therapeutics; and Yiviva.Faculty/PlannerAnthony El-Khoueiry, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Exelixis, Inc.; F. Hoffmann-La Roche AG/Genentech, Inc.; Merck & Co., Inc.; Qurient; and Senti Biosciences.Grant/Research Support from Astex Pharmaceuticals; AstraZeneca; Auransa Inc.; and Fulgent Pharma.Faculty/PlannerAhmed Omar Kaseb, MD, CMQ, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Bristol Myers Squibb; Eisai Inc.; Exelixis, Inc.; Genentech, Inc.; Merck & Co., Inc.; and Pfizer.Grant/Research Support from Bristol Myers Squibb; Eisai Inc.; Exelixis, Inc.; Genentech, Inc.; Merck & Co., Inc.; Pfizer; and Tvardi Therapeutics.Faculty/PlannerStacey M. Stein, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Eisai Inc.; Exelixis, Inc.; and Genentech, Inc.Data Safety Monitoring Board for Aethlon Medical, Inc.and Genentech, Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.PlannerAndrea Wilson WoodsPresident & Founder, Blue FaeryAndrea Wilson Woods has a financial interest/relationship or affiliation in the form of:Consultant for AstraZeneca and Humanise Health.

Drs. Shaalan Beg and Rachna Shroff discuss key abstracts on GI cancers that were featured at the 2024 ASCO Gastrointestinal Cancers Symposium, including SKYSCRAPER-08, EMERALD-1, and NEST-1 in esophageal squamous cell carcinoma, hepatocellular carcinoma, and colorectal cancer, respectively. TRANSCRIPT Dr. Shaalan Beg: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Shaalan Beg, your guest host of the podcast today. I'm an adjunct associate professor at UT Southwestern's Simmons Comprehensive Cancer Center and vice president of oncology at Science 37. Today, we'll be discussing key abstracts and other exciting highlights from the 2024 ASCO Gastrointestinal Cancers Symposium. Joining me to discuss some key takeaways from the meeting is the chair of this year's Symposium, Dr. Rachna Shroff. Dr. Shroff is the division chief of Hematology Oncology and chief of GI Medical Oncology at the University of Arizona Cancer Center. She also serves as the associate dean for clinical and translational research at the University of Arizona College of Medicine – Tucson. Our full disclosures are available in the transcript of this episode, and disclosures related to all episodes of the podcast are available at asco.org/DNpod.  Dr. Shroff, welcome back to the ASCO Daily News Podcast, and congratulations on a great Symposium. The scientific advances and innovative, multidisciplinary approaches that were featured throughout the meeting were really inspiring and reflect the incredible strides we're making in GI cancer research. Dr. Rachna Shroff: Thank you so much for having me back. I am delighted to be here.  Dr. Shaalan Beg: Dr. Shroff, the theme of this year's symposium was "Taking Personalized Care to the Next Level." I'd love to hear your reflections on the sessions that you found most exciting and really resonated with the attendees.  Dr. Rachna Shroff: Yes, thank you. We were really excited about this theme because we really felt that “Taking Personalized Care to the Next Level” translated to thinking through personalized approaches to patient care, not just in the traditional ways that we think of with precision oncology and genomics driving our care, but also how we can think through multidisciplinary approaches and an individualized care plan. Thinking through how artificial intelligence and novel clinical trial designs can and should be implemented to meet the needs of our individual patients. And so we really highlighted that in what was a somewhat new reboot of a session called “Intersections,” which were every day and were really more cross-tumor; they were tumor agnostic but were thematic focused. As I mentioned, those themes were really based on feedback that we had from prior attendees, as well as from the program committee's feeling on what are really the questions that we are dealing with and that are burning in the clinic today and that includes the emerging role of artificial intelligence and machine learning and how we integrate that into our clinical care, approaches to oligometastatic disease, and it's not really just something that we think of in colorectal cancer but haven't fully used that paradigm to really apply it to other GI malignancies. And then the art and science of clinical trial design where, again, traditional randomized phase 3 trials might not be the best and most innovative and most expedient way of bringing novel therapeutics to our patients. And so, I thought that all of those sessions were really highlighting different important topics that we deal with day to day. Additionally, we had a really fantastic keynote lecture from Dr. Kimmie Ng of the Dana-Farber Cancer Institute. She is a world-renowned expert in the early-onset colorectal cancer space, and the timing of her keynote was perfect with the new cancer statistics that came out literally days before GI ASCO that demonstrated this just dramatic rise in early onset GI malignancies as a whole, not just colorectal. And she spoke really in a comprehensive manner not just on clinical approaches, screening approaches, and how to find these patients at an earlier stage, but also kind of gave us a call to action, if you will, in terms of public health initiatives, as well as like I said, clinical care and really thinking outside of the box for how to reach these patients.  And then, of course, we always have what I think is one of my favorite aspects of the meeting, which are the networking opportunities that include the Trainee and Early Career Networking Luncheon, the Women's Networking Reception, and the Meet the Experts Luncheon where, especially as junior career investigators, you have an opportunity to meet what we think of as the “big names” in GI cancer. Dr. Shaalan Beg: Absolutely, I remember my first couple of GI ASCO meetings and those were probably the most memorable sessions that I attended as junior faculty as well.   So let's take a deeper dive into some key abstracts from the meeting. I'd like to begin with Abstract 245. This is the SKYSCRAPER-08 study. It's first-line tiragolumab and atezolizumab with chemotherapy in an Asian patient population with esophageal squamous cell carcinoma. What are your key takeaways from this study?  Dr. Rachna Shroff: Yeah. This was an exciting study in my opinion in the sense that thinking through how we can build on immunotherapy backbones is obviously a pressing question across the GI cancer space. So this was a phase 3 randomized, double-blinded, placebo-controlled trial that looked specifically at patients with esophageal squamous cell carcinomas. And the study was enrolled fully with an Asian population. It looked at taking the traditional chemotherapy backbone and adding to it an anti-PD-L1 with atezolizumab and an anti-TIGIT with tiragolumab. Again, that proof of principle of using anti-TIGIT and PD-L1 has been looked at across a lot of different GI cancer spaces and we know that the esophageal squamous cell cancers tend to be very immunotherapy responsive. So this was a really important question.  This involved a number of patients, a little over 460 patients, who were randomized one-to-one to receive the tiragolumab with atezolizumab with the standard paclitaxel and cisplatin, that's used for esophageal squamous versus chemotherapy alone with placebo. And the primary endpoint was independent review of progression-free survival, and overall survival. And so, out of the 461 patients randomized, there was at the primary analysis, a median improvement in progression free survival, from 5.4 months in the control arm to 6.2 months with a tira-paclitaxel plus chemo arm with a hazard ratio of 0.56, highly statistically significant. Similarly the median overall survival was also improved from 11.1 months to 15.7 months again with a hazard ratio of 0.7 and some of the other key efficacy endpoints were also improved with the addition of the anti-TIGIT PD-L1 approach. And importantly, there was not really safety signals that jumped out at us.  And so, to me, what this means is that, in our patients with esophageal squamous cell carcinoma, we really should be thinking about chemotherapy with immunotherapy as a backbone and how we can build on it. And, you know, I would imagine that it's hard to argue with both the PFS and OS endpoint that adding anti-TIGIT won't necessarily be kind of the new approach to these patients. And importantly, I'll point out that it seems to be a benefit across the subgroups, including PD-1 status, which is always our big question here. I think the only thing to keep in mind is this was an all-Asian population and whether or not that kind of immune profile of the immune responsiveness is different in those patients, but regardless, a positive phase 3 trial. Dr. Shaalan Beg: It's really exciting to see immune checkpoint inhibitors or immunotherapy beyond PD-1 targeted, CTLA-4 targeted treatments making their way into GI Cancers.  Dr. Rachna Shroff: Absolutely. Dr. Shaalan Beg: Sticking with the immunotherapy theme, let's focus on hepatocellular carcinoma. So LBA432, the EMERALD-1 study of transarterial chemoembolization combined with durva with or without bevacizumab looked at people with unresectable hepatocellular carcinoma eligible for embolization. So really a highly anticipated study, I'm wondering what your thoughts are and whether it'll be practice-changing for this field.  Dr. Rachna Shroff: I was excited to see the press release when it showed that the study was positive, and I think it's because now that we're using immunotherapy in the advanced HCC space, our obvious question is, can we integrate it into multimodality approaches? There are a lot of smaller studies looking at neoadjuvant IO approaches, and in this intermediate stage, unresectable hepatocellular carcinoma patients. We wanted to know if there was a utility to liver directed therapy with immunotherapy.  So, this was a large study. It was a global study looking at unresectable HCC with preserved Child-Pugh function. But it was Child-Pugh A and up to B7, importantly. And there were 616 patients randomized in a 1:1:1 fashion, with the control arm being just TACE alone. But then, there was also an opportunity for durvalumab with TACE, as well as durvalumab plus bevacizumab with TACE. The patients would receive durvalumab during their TACE treatments and could receive up to four TACE treatments and then subsequently were either continued on durvalumab alone, durvalumab plus bevacizumab, or the placebo. The primary endpoint was progression-free survival, powered specifically to look at TACE versus durvalumab plus TACE. In this study, the primary endpoint was met with a significant improvement in PFS. Median PFS was 15 months versus 8.2 months, with a hazard ratio of 0.77. Most prespecified subgroups demonstrated this benefit.  Importantly, there was a secondary endpoint looking at durvalumab plus TACE versus TACE alone, and that actually did not show a statistically significant improvement in median PFS from 8.2 months in the control arm to 10.0 months. The overall response rates were slightly higher with the durvalumab plus bevacizumab approach at 43.6%. And importantly in these patients, who oftentimes have a higher burden of disease in the liver, median time to progression is a really important and clinically meaningful endpoint. That was 22 months with the durvalumab plus bevacizumab and TACE versus 10 months for TACE alone. I would just point out that the overall concern we always have with bevacizumab is the increased risk of bleeding and the treatment-related adverse event profile. Overall, there were no safety signals that emerged from this, with nothing that really, especially in that bleeding risk category, jumped out at us. Of course, we haven't seen the overall survival data yet because we have not seen enough follow-up to really see that number.  I do think that this is potentially practice-changing, and I think it just demonstrates that there's probably some synergy between anti-VEGF with anti-PD-1, and then the liver-directed treatments. The obvious question for us in the United States is that the vast majority of people are moving away from TACE and towards more radioembolization and what can we extrapolate from this? Does this really tell us much if people are using more of a Y90-based approach? I think those are a lot of the burning questions that most of us have.  Dr. Shaalan Beg: Yeah, and it's a very interesting direction that the HCC space is taking because we heard in previous meetings, the role of PD-1 inhibition as adjuvant therapy after resection. Now, we have data for local-regionally advanced disease over local-regional treatments. And of course, you already mentioned the data for more advanced disease. So it sounds like immunotherapy may be impacting the management of anyone diagnosed with hepatocellular carcinoma.  Let's talk about the MONET trial, Abstract 249, which compared thoracoscopic esophagectomy and open esophagectomy for thoracic esophageal cancer. Do you think this is a study which may influence the treatment of patients with thoracic esophageal cancer? Dr. Rachna Shroff: So, this was, again, I think, a really important question. It was a randomized, controlled phase 3 trial comparing a more minimally invasive approach with TE — thoracoscopic esophagectomy — versus an open approach. This had patients with clinical stage 1-3, excluding T4 thoracic esophageal squamous cell carcinomas. They were randomized 1:1 to the open versus the TE approach, with a primary endpoint of overall survival and an important secondary endpoint of relapse-free survival. 300 patients were randomized, and at the second planned interim analysis, the median follow-up was a little over two and a half years. The 3-year overall survival was 82% in the TE group versus 70.9% in the open group. The DSMC of this trial actually recommended early termination based on the non-inferiority, which is what they were specifically looking at. There was a very statistically significant one-sided p-value for non-inferiority.  Importantly, the 3-year recurrence-free survival was also markedly better in the TE group versus the open group, with no real notable differences in R0 resection, or a large percentage of patients who needed to be converted from a TE to an open approach, and really not any significant difference in overall postoperative morbidity. I think this just supports the concept that minimally invasive approaches for our patients with GI malignancies can and should be considered. Again, esophageal squamous because they tend to be seen a lot more in Asia, this study was conducted in Japan, but I think that being said, a lot of our surgeons in Europe and in the U.S. are also very amenable to minimally invasive approaches. And I think this just supports the fact that an open approach is not necessary. So, I would think again, that this is something that is implementable and I think will affect the field.  Dr. Shaalan Beg: Moving on to metastatic cholangiocarcinoma, there have been many FGFR inhibitors that have shown activity and promise and are approved for the management of cholangiocarcinoma with FGFR alteration. But at this ASCO GI, we heard the results of the safety and efficacy of an FGFR1, 2, and 3 inhibitor, tinengotinib, as monotherapy for advanced metastatic cholangiocarcinoma (Abstract 434). How do you see this fitting into the broad picture? Dr. Rachna Shroff: Yeah, so this was highly anticipated data, primarily because at this point, the FGFR space in cholangiocarcinoma is quite crowded. And so a lot of us were getting sick of the "me-too" drugs. What is really unique about tinengotinib is that, not only is it a selective multikinase inhibitor, but it also, in preclinical models as well as in early phase one trials, demonstrated potent inhibition of patients with FGFR2 fusions and rearrangements who had acquired resistance mutations. So, as we better understand the first generation of FGFR inhibitors and note the resistance mechanisms, these drugs are now being developed to try to circumvent or overcome those.  This study looked at 4 different cohorts: 1 cohort with FGFR2 fusion patients who had primary progression who never responded to FGFR inhibitors, a second cohort with FGFR2 fusion patients who had progression after primary response, so those with acquired resistance, and then there was non-fusion FGFR alterations because we do know that a number of cholangiocarcinoma patients have other FGFR alterations that are not fusions, and then those with FGFR wild-type. The primary endpoint was objective response rate, with a total of 48 patients enrolled across the four cohorts. And so the 40 patients who were evaluable in the group that had primary resistance, which was the first cohort, there was a response rate was 9.1% and that was partial response, and 31% had tumor reduction with tinengotinib. And similarly in those with acquired resistance, 37.5%, 3 out of 8 patients had a partial response and tumor reductions were noted with an overall disease control rate between those patients with FGFR2 fusions of 94.7%, between those with primary and secondary resistance.  In the patients who had FGFR alterations, there was 3 out of 9 patients with a partial response and again, tumor reductions were notable across the board and the disease control rate was 88.9%. The FGFR wild-type group, not surprisingly, did not see any partial responses, but interestingly, 75% of these patients had at least disease control, and the median progression-free survival was 5.26 months, again, kind of most notably impressive in the 2 cohorts that included FGFR2 fusions. The toxicity profiles are what we come to expect for FGFR inhibitors and we've gotten better at managing those and mitigating some of those so there was really nothing to jump out there. So there is now an ongoing randomized phase III trial specifically looking at tinengotinib versus physician's choice in patients with FGFR2-altered cholangiocarcinoma after having received prior FGFR inhibitors. So that's where I think it's in is for those of us who know that there are multiple drugs in the space, our big question is can we sequence through that? Can we offer multiple FGFR inhibitors in these patients? And I think we are all eagerly anticipating this data as well as the subsequent data to really justify the use of these novel second generation FGFR inhibitors.  Dr. Shaalan Beg: It's been fantastic to see the evolution of these compounds in precision medicine, or precision oncology at its finest, in terms of understanding mechanisms of resistance and treating refractory disease.   Let's focus on colorectal cancer. I'll tell you, there has been a lot of discussion, Dr. Shroff, on social media, on insurance companies sometimes rejecting one biologic or the other based on tumor sidedness. We have talked about tumor sidedness predicting response on this podcast based on data from previous studies. But this year in GI ASCO, Abstract 207 explored the role of tumor genomics and tumor sidedness and they said that it's tumor genomics, that tumor genomics better explains the differences on outcomes, and it explains it better than sidedness. What does this mean to the field? Because a lot of professional organizations have guidelines that are asking people to now incorporate sidedness. So how does that change based on these results? Dr. Rachna Shroff: I really commend these authors on leveraging real-world data, and I think we're getting better and better at recognizing that real world data actually informs our clinical decision making, possibly better than sometimes some of these studies that lead to the guidelines and algorithms that we develop. So this is a perfect example of a little bit cart before horse in trying to understand the way that sidedness and genomics may interplay.   So this was a study that basically leveraged both the Foundation Medicine and Flatiron Health clinical genomic database and looked at patients with microsatellite stable metastatic colorectal cancer. There were a total of 3,845 patients included in a kind of two-thirds one-third split between left sided and right-sided colorectal cancer. And they found the typical genomic alterations that historically have been thought of more with left-sided colorectal cancer like APC and then more of the RAS BRAF alterations in the right-sided patients. But I think what they really thought and what I think was remarkable is they really looked at the patients and how they received chemotherapy with anti-EGFR or bevacizumab therapies, and they did a multivariate analysis to really see what is driving outcomes. And like you mentioned, what they found was patients in the RAS pathway, those classified as having alterations in the RAS pathway, had less favorable outcomes, while those with APC altered group had more favorable outcomes. And that was regardless of treatment received and sidedness.  And so when they did an analysis of what was called a “likelihood ratio test,” they found that when genomics was added to the sidedness evaluation, there was an improvement in outcome prediction, but not when sidedness was added to genomics. Like you said, it kind of demonstrates, at least in this mining of real-world data from Flatiron that tumor genomics is probably a better driver and a more important driver in determining outcomes than sidedness.  I totally agree with you. I would push for us to really kind of bring a little bit of noise to this and to make insurance companies and other companies that are looking at this to think through this a little bit more and make sure that we're putting all of the data together in a comprehensive passion before making the treatment plans and determinations. Dr. Shaalan Beg: The last abstract I'd like to ask you about is Abstract 117, the NEST-1 trial. This study looked at neoadjuvant botensilimab and balstilimab for resectable mismatch repair proficient and deficient colorectal cancer, both MSS and MSI. What are your key takeaways from this study?  Dr. Rachna Shroff: This is another study that is demonstrating that there may potentially be a role for immunotherapy in microsatellite stable patients. I will make the caveat that this was a single-arm study that really was looking at feasibility safety, with efficacy as a secondary endpoint. The combination of bot-bal in the neoadjuvant space for colorectal cancer patients, they received one dose of boten and two fixed doses of bal two weeks apart and then were taken to surgery. They limited the number of patients and out of the 12 patients that were enrolled, they limited the number of mismatch repair deficient patients. So to your point, they allowed both, but they wanted to make sure it was not just MSI-high patients. What they basically found is that it was safe and did not delay surgery or increase risks of adverse events. But importantly, there was significant regression of tumor noted. And some interesting spatial biology analyses demonstrated potentially novel mechanisms of action, especially in the MSS population, and that ctDNA reductions correlated with pathologic response. There were a lot of different things that they were looking at, basically suggesting that bot-bal is safe and can be used in both mismatch repair–deficient and proficient patients with colorectal cancer. And now importantly, they've added some additional cohorts and expanding the study. As I mentioned, this is right now just 12 patients, but does definitely have a provocative result.  Dr. Shaalan Beg: Thanks so much, Dr. Shroff.  Finally, the role of cell-free DNA (cfDNA) in GI cancers has been an exciting and important development in our field. There's tremendous data that emerged at the GI meeting, and we have decided to do a separate ASCO Daily News Podcast dedicated to ctDNA. So listeners, please look out for our coverage of key studies on ctDNA in GI cancers very soon here on the ASCO Daily News Podcast.  Many thanks, Dr. Shroff, for sharing your insights with us today and for your great work in building a robust GI meeting this year. Thank you very much. Dr. Rachna Shroff: Thank you so much. Dr. Shaalan Beg: And thank you to all our listeners for your time today. You'll find links to the abstracts discussed on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and inform. It is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Our guests on this podcast express their own opinions, experiences, and conclusions. These statements do not necessarily reflect the views of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an endorsement by ASCO.   Find out more about today's speakers: Dr. Shaalan Beg @ShaalanBeg Dr. Rachna Shroff @rachnatshroff   Follow ASCO on social media:  @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn    Disclosures: Dr. Shaalan Beg: Employment: Science 37 Consulting or Advisory Role: Ipsen, Array BioPharma, AstraZeneca/MedImmune, Cancer Commons, Legend Biotech, Foundation Medicine Research Funding (Inst.): Bristol-Myers Squibb, AstraZeneca/MedImmune, Merck Serono, Five Prime Therapeutics, MedImmune, Genentech, Immunesensor, Tolero Pharmaceuticals   Dr. Rachna Shroff: Consulting or Advisory Role: Exelixis, Merck, QED Therapeutics, Incyte, Astra Zeneca, Taiho Pharmaceutical, Boehringer Ingelheim, SERVIER, Genentech, Basilea Research Funding: Pieris Pharmaceuticals, Taiho Pharmaceutical, Merck, Exelixis, QED Therapeutics, Rafael Pharmaceuticals, Bristol-Myers Squibb, Bayer, Immunovaccine, Seagen, Novocure, Nucana, Loxo/Lilly, Faeth Therapeutics

Drs. Rana McKay and Jonathan Rosenberg highlight key advances in genitourinary cancers featured at the 2023 ASCO Annual Meeting, including the THOR study in mUCC, VESPER in muscle-invasive bladder cancer, CONTACT-03 in mRCC, and TALAPRO-2 in mCRPC. TRANSCRIPT  Dr. Rana McKay: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Rana McKay, your guest host for the podcast today. I'm a GU medical oncologist at the Morris Cancer Center at the University of California in San Diego and an associate professor at the University of California in San Diego School of Medicine. Joining me today is Dr. Jonathan Rosenberg, the chief of the Genitourinary Oncology Service at the Memorial Sloan Kettering Cancer Center in New York. We'll be discussing practice-changing studies and other key advances in genitourinary cancers that were featured at the 2023 ASCO Annual Meeting.   You'll find our full disclosures in the transcript of this episode, and disclosures of all guests featured on the ASCO Daily News Podcast are available on our transcripts at asco.org/DNpod.  Jonathan, it's great to have you with us today. How are you?  Dr. Jonathan Rosenberg: I'm doing very well. Thanks so much for hosting today.  Dr. Rana McKay: Oh, of course. It's always fun to step back from ASCO and reflect on all the practice-changing and practice-informing studies that were presented.  Dr. Jonathan Rosenberg: Absolutely.  Dr. Rana McKay: Maybe we can dive right in with LBA4619. This is the much-talked-about THOR study of erdafitinib versus chemotherapy in patients with advanced or metastatic urothelial cancer with select FGFR alterations. What are your key takeaways from this study?  Dr. Jonathan Rosenberg: It is indeed a study we've been waiting for, for quite some time, to see the results in the confirmatory study after the accelerated approval of erdafitinib. This is half of the THOR trial. There were 2 cohorts of patients. One cohort were patients who previously received a checkpoint inhibitor randomized to chemotherapy or erdafitinib, and those data were reported at ASCO this year. The other cohort was randomized against a checkpoint inhibitor in patients who have not received a checkpoint inhibitor, and we'll see those data in a future meeting.   The bottom line for the THOR study is that FGFR3 inhibition improved overall survival compared with chemotherapy, and the chemotherapy in this study was a taxane. The overall survival was 12.1 months for erdafitinib compared to 7.8 months for chemotherapy with a hazard ratio of 0.64. This led to the DMC to stop the study and blind the data and cross people over. There was also a PFS advantage. There really weren't a lot of new toxicity signals seen; the usual suspects in terms of mucositis, hyperphosphatemia, diarrhea, dry mouth, and onycholysis.  And so, what it tells us ultimately is that in a patient who's progressed on a checkpoint inhibitor, we can feel comfortable about using erdafitinib knowing it provides a survival advantage in patients who've been previously treated for advanced urothelial cancer and have an FGFR alteration, either an FGFR2 or 3. And hopefully, we'll see more data in the future from the study, maybe not too long in the future from the other part of the study, comparing it to checkpoint inhibition.   Dr. Rana McKay: That's really exciting. I think it's exciting to see the data about the positivity of erdafitinib versus chemotherapy in this context. Looking at the phase 3 data is going to be really important. Looking at the data in the IO naive context is going to be really important. I feel like this sort of reaffirms what we've been doing in clinical practice. But how do you feel that the study is practice-changing?   Dr. Jonathan Rosenberg: I think it gives us reassurance that for these patients, erdafitinib is an appropriate option. There's no randomized data between erdafitinib and other choices, such as sacituzumab, which is also based on an accelerated approval, or enfortumab, which is based on randomized phase 3 trial. But it gives us level-1 evidence. I do wonder whether the comparison against the checkpoint inhibitor may turn out differently, but we'll see. Those data aren't in evidence. And I do think it was interesting that the majority of patients who were enrolled on the trial were PDL-1 low. We'll see what the comparison to a checkpoint inhibitor is like and whether those patients have similar characteristics.  Dr. Rana McKay: Yeah, you're almost kind of selecting for people that were not primed to respond.   Dr. Jonathan Rosenberg: Exactly.   Dr. Rana McKay: Well, that's really exciting, I think. Moving on to localized bladder cancer, Dr. Pfister presented the results of the VESPER trial. That's LBA4507. I think this study was really important. This was a trial that explored dose-dense MVAC with methotrexate, vinblastine, doxorubicin, and cisplatin or gemcitabine-cisplatin as a perioperative chemotherapy for muscle-invasive bladder cancer. I think there's always been some discussion around these regimens and how they pair up against one another. Can you tell us about these data?   Dr. Jonathan Rosenberg: It's a very interesting study. It was designed back when it was felt that we could not give patients neoadjuvant therapy. And it was designed as either a neoadjuvant or adjuvant approach. Although, in reality, almost everybody who was enrolled in the study got neoadjuvant chemotherapy, which I think speaks to the shift in practice over the last 10 to 15 years towards neoadjuvant rather than adjuvant therapy. It's an interesting trial in that it used a duration of chemotherapy for the MVAC regimen, the dose-dense MVAC regimen that we don't usually use, which is 6 cycles. And functionally, about 40% of patients couldn't make it to 6 cycles and had to stop sooner, versus 4 cycles of q3-week gemcitabine and cisplatin.   And what the data show is that the progression-free survival for the entire intent-to-treat population didn't reach significance. But if you looked at the neoadjuvant population only, there was an improvement in progression-free survival as well as overall survival. So, it's sort of a negative positive trial. Negative for the primary endpoint, but positive for key secondary endpoints. They did a very interesting analysis looking at the number of cycles that patients received regardless of arm, but looking at it by arm. And it's clear from that analysis that the more chemotherapy they got, the better they did.   Although, the flaw in that analysis is that the healthier patients are, the more chemotherapy they're able to tolerate, and therefore that may translate to an improved overall survival irrespective of the amount of chemotherapy. And this was not necessarily a pre-specified analysis. I think some of the statisticians were clutching their chests during the report of this trial, having talked to several afterward. On the other hand, it does say to me that for a fit, younger patient, it is important to consider dose-dense MVAC instead of gemcitabine and cisplatin.   I'll also note, reading the publication from the first part of the trial, that it appears that nobody over 70 was enrolled from everything I could tell. And so, I question the validity of the tolerability of the results for the average 75-year-old that I see in my practice. Although age is not a bright line cut-off for anybody in terms of cancer treatment. But my own experience has been that dose-dense MVAC has been harder to tolerate for a lot of patients in their 70s, whereas I think we should feel quite comfortable giving it to patients in their sixties. And if you ask me how many cycles I would give, I probably wouldn't say 6, for dose-dense MVAC, I would probably say 4.   Dr. Rana McKay: Was there a predilection that there was a more aggressive disease like nodal disease or other things to prompt the 6 versus 4?  Dr. Jonathan Rosenberg: I think that they stopped primarily for toxicity reasons, but it wasn't clear to me that it was a disease-based issue. And for the neoadjuvant therapy, everyone was supposed to be clinically node-negative on entry, so that probably wouldn't have explained it.  Dr. Rana McKay: Very exciting. I know that the data were quite provocative, but I think it's always difficult to interpret these sorts of subgroup of subgroup analyses, and there's a lot of bias in why people may get more versus less. And I think trying to reduce these data to clinical practice is going to be really important, as you've stated.  Dr. Jonathan Rosenberg: Rana, I'd also like to talk about some key advances in renal cell carcinoma that were reported at ASCO. Dr. Choueiri presented data on LBA4500, the CONTACT-03 study, which really was the first study of its kind in solid tumors because it addressed a major question in the kidney cancer field and in other fields: Is there a role for immunotherapy rechallenge after progression on immunotherapy? Specifically, the study looked at the efficacy and safety of atezolizumab plus cabozantinib versus cabozantinib alone after progression with prior immune checkpoint inhibitor therapy in metastatic RCC. I'd like you to tell me what you think of this study and the results and how they may affect our practice.   Dr. Rana McKay: Absolutely. This was a critically important study looking at the role of IO post-progression on IO. It was a large phase 3 trial that enrolled patients with clear cell and non-clear cell patients. It actually allowed patients with papillary RCC, unclassified RCC, to enroll in the study, whereas most of these studies are excluding patients with non-clear cell disease. Patients had to have progressed on an immune checkpoint inhibitor given either as adjuvant first line or second line, given either as a single agent or in combination with one of the other combos, whether a VEGF or IO. And patients were randomized one-to-one to receive the combination of atezolizumab plus cabozantinib versus cabozantinib alone. And the dosing of the cabozantinib here is at 60 milligrams in the combination, which is the standard dosing of cabozantinib monotherapy. And the primary endpoints for the trial included PFS and OS.   And in essence, this trial was a completely negative study. The primary endpoint, which was centrally reviewed, rPFS, was negative. The hazard ratio there was 1.03. Overall survival was also negative with a hazard ratio of 0.94. And when you look at the subgroup analyses, there really wasn't any specific subgroup that seemed to derive any benefit, potentially those that had a prior response to an immune checkpoint inhibitor, but in essence, a negative study.   And I think these data are really informative because the discussion at ASCO was conducted by Dr. David Braun, and he actually had conducted a very highly scientific Twitter poll to help guide how to interpret the data and what people do. And from that, about 30% of individuals that completed the poll were actually layering on IO therapy, and continuing IO therapy after somebody progressed on therapy layering in a TKI while keeping the IO backbone going.   And I think what this study proves is that we really don't have any really robust data to guide doing that at the present time. And what we may end up doing is compromising the efficacy of the oral TKI or dose-compromising the oral TKI to try to maintain an ineffective IO. And so, I think at the present time these data, while negative, were truly practice-informing. There are other studies that are looking at this strategy as well. I think one of the criticisms here is that atezolizumab really has not had a great track record in renal cell carcinoma in every single context where it was tested, either alone or in combination. It has not met its primary endpoint and it's not utilized as a treatment in RCC. So, there's some discussion that could this be the fact that this is a PDL-1 inhibitor and that it's atezolizumab. And additionally, I think the thing to point out for is that in the modern era if we look at the cabozantinib control arm, cabozantinib in the refractory setting had a PFS of 10.8 months, which is pretty impressive for a later line PFS, if you will. So, there is another study currently ongoing called the TiNivo-2 study that's looking at tivozanib plus nivolumab versus tivozanib alone in a similar patient population. That trial is enrolling only clear cell patients that had progressed on prior IO. So, I think we'll have additional data, but very, I think, informative. I think this question comes up in a lot in other tumor sites as well because of the broad use of checkpoint inhibitors across hematologic and solid tumor malignancies.   Dr. Jonathan Rosenberg: I think this was the most informative negative study and the most negative trial I've seen in a while as well. But it did highlight the importance of asking these questions where people assume they know the answer already, and in fact, we often don't, and our assumptions are wrong. So, I thought that was fascinating and very well described.    Staying in the kidneys arena. I'd like to talk to you also about the phase 2 KEYNOTE-B61, that's Abstract 4518. It looked at first-line lenvatinib and pembrolizumab across non-clear cell carcinomas. Tell me what you thought of the trial and what your takeaways were.   Dr. Rana McKay: This is an important study. I think the treatment of non-clear cell RCC has lagged. I guess the advances have lagged behind clear cell RCC, and really robust phase 3 randomized studies in people with non-clear cell histologies are very limited. This was a single-arm phase 2, so I think we need to kind of take that for what it's worth, that enrolled patients who had non-clear cell RCC per investigator that had received no prior systemic therapy. So, this was a frontline study, and patients received pembrolizumab plus lenvatinib until disease progression or toxicity.   The study enrolled a very robust 158 patients, which is pretty impressive for a modern-day non-clear cell cohort. We've seen data from nivo-cabo that had gotten presented previously by Dr. Lee. That study was a single institution, about 40 patients or so if you will. The primary endpoint of this study was objective response rate, and the bulk of the patients that were enrolled were papillary RCC. As you would imagine, around 60% of patients were papillary. It did include around 18% with chromophobe RCC. And when we break things down by IMDC risk category, about 44% of patients were favorable-risk disease. I think the percentage of patients who were favorable is higher than if we were to take an all-comer metastatic RCC patient population.   But the objective response rate was pretty impressive at 49% with this combination. The CR rate was right around 5.7%. So, I think certainly a pretty solid signal of efficacy. But again, this is a single-arm phase 2 study. I think what's also really interesting, and I think we have to take subset analyses with a grain of salt if you will, but there were responses that were seen across all histologies. And the prior nivo-cabo study that I had shared with you had previously done a futility analysis for patients with chromophobe RCC, and that cohort actually closed down. And in this study, the response rate for the chromophobe patients, though it wasn't a lot of patients, 29 patients with chromophobia RCC, was around 27.6%, so I think these data are certainly informative. If you look at the waterfall plot, there were some deep responses that were certainly observed, and the bulk of patients had some degree of tumor shrinkage with very little patients that had primary PD.   Dr. Jonathan Rosenberg: It's really provocative. So, are we getting to a point where we might start thinking about randomized trials in the non-clear cell population to try to establish the best standard of care?  Dr. Rana McKay: Well, I think PAPMET2 is currently enrolling patients. That study is looking at the combination of cabozantinib with atezolizumab versus cabozantinib alone for frontline papillary. PAPMET1, which was led by Dr. Pal, I mean, these studies are really magnanimous because it takes all hands on deck to get these patients enrolled because they're few and far between. So, I definitely think we need to be moving in that direction. And I think we need to be moving away from lumping all non-clear cells into one bucket because I think what we're seeing is that, one, the biology of these tumors is very distinct and unique, and they don't all behave the same to any one given therapy. So, we really need to move away from just lumping all non-clear cells into one bucket and try to actually conduct studies for each specific subtype.    Dr. Jonathan Rosenberg: Understood and agree. Let's switch gears for a second and talk about prostate cancer. Can you talk about the data from Abstract 5004, the TALAPRO-2 study of talazoparib and enzalutamide compared to placebo and enzalutamide as a first-line treatment with metastatic CRPC that have HR homologous recombination repair gene alterations?    Dr. Rana McKay: Absolutely. So the TALAPRO-2 study is one of three studies that have looked at the combination of PARP inhibitors with an ARSI in the frontline mCRPC setting. And this trial randomized patients to talazoparib and enzalutamide versus placebo enzalutamide. And again, this was first-line mCRPC. Patients were allowed to have received prior docetaxel or prior abiraterone in the castration-sensitive setting, and the primary endpoint was overall survival.  At GU ASCO this year, we saw the top-line data from TALAPRO-2 first get presented. And what was actually presented at this meeting was the subset of patients that were HRR-mutated only. They had two cohorts: an all-comer cohort that was previously presented, and then now they're presenting the subset of the patients that were HRR-mutated. And I think what we've seen across the board is that the efficacy of PARP inhibitors kind of differs by underlying HRR mutations.     When we look at the entire population of HRR-deficient patients, the study was positive, talazoparib plus enzalutamide resulted in an improvement in rPFS compared to enzalutamide placebo. The hazard ratio there was 0.45. And then when we break things down by selected gene groups, they did this subset analysis in patients with only BRCA1, only BRCA2, only PALB2, only CDK12, ATM CHEK2 if you will. The data are most robust for those patients with a BRCA1/2 alteration with hazard ratios of 0.17, 0.19. Again, this is for rPFS.     But then, when we look at some of these other mutations, like ATM CHEK2, hazard ratios are higher, 0.76, 0.90. So, the effect size really kind of drops off for those non-BRCA1/2 altered HRR genes. But if we look across the different subgroup analyses, the interim OS data for the HR deficient, the time to PSA, time to cytotoxic chemo, all of that favored the combination versus placebo enzalutamide for patients that were HR deficient if we just lumped everybody all together.  Dr. Jonathan Rosenberg: How does this fit into the general landscape around this question with selection versus not selecting for HRR alterations?  Dr. Rana McKay: The data that were presented were for the selected patients, and I think that that's not where the controversy is. I think that the selected patients are the ones that seem to derive the most benefit. It's interesting because in looking at the data from PROpel and the final FDA label based off of the PROpel data, the label is only for BRCA1 and 2 patients and not for all comer HRR. It's even a more restricted label than olaporib monotherapy. So, I think it's going to be interesting. I don't know what the right answer is. I think it's going to be interesting to see how this is going to unfold for TALAPRO-2 and even for MAGNITUDE, if you will, like, how select is the selected population going to be. But at the present time, I think the label is what it is for olaparib plus abiraterone in those BRCA1/2 frontline. My hope is that this population is shrinking because everybody should be getting escalated in the metastatic hormone-sensitive setting, and we shouldn't be having people who are naive to an ARSI in frontline mCRPC.  Dr. Jonathan Rosenberg: Understood and agreed.   Dr. Rana Mckay: Well, thank you so much, Jonathan, for joining me today. It's really been a pleasure kind of going through all of the compelling advances in GU cancers from ASCO. I think it was a really exciting meeting, and thanks for your time. Dr. Jonathan Rosenberg: My pleasure. It's been great to talk to you today.     Dr. Rana Mckay: And thank you to our listeners for your time today. You will find links to the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcast.    Disclaimer:   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.    Follow today's speakers:    Dr. Rana McKay  @DrRanaMcKay  Jonathan Rosenberg  @DrRosenbergMSK    Follow ASCO on social media:     @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn      Disclosures:    Dr. Rana McKay:   Consulting or Advisory Role: Janssen, Novartis, Tempus, Exelxis, Pfizer, Bristol-Myers Squibb, Astellas Medivation, Dendreon, Bayer, Sanofi, Merck, Vividion, Calithera, AstraZeneca, Myovant, Caris Life Sciences, Sorrento Therapeutics, AVEO, Seattle Genetics, Telix, Eli Lilly, Pfizer, Bayer, Tempus   Dr. Jonathan Rosenberg:   Honoraria: UpToDate, Medscape, Peerview, Research To Practice, Clinical Care Options, Physician Education Resource, MJH Life Sciences, EMD Serono, Pfizer  Consulting or Advisory Role: Lilly, Merck, Roche/Genentech, AstraZeneca/MedImmune, Bristol-Myers Squibb, Bayer, BioClin Therapeutics, QED Therapeutics, Pharmacyclics, GlaxoSmithKline, Janssen Oncology, Astellas Pharma, Boehringer Ingelheim, Pfizer/EMD Serono, Merck Therapeutics, Immunomedics, Tyra Biosciences, Infinity Pharmaceuticals, Gilead Sciences, Hengrui Pharmamedical, Alligator BioScience, Imvax  Research Funding (Institution): Genentech/Roche, Seattle Genetics, Bayer, AstraZeneca, QED Therapeutics, Astellas Pharma  Patents, Royalties, Other Intellectual Property (Institution): Predictor of platinum sensitivity      

Dr. Shaalan Beg and Dr. Mohamed Salem discuss novel therapies in gastrointestinal cancers, including CAR T therapy and the CodeBreak-101 trial in mCRC, new advances in uHCC in the HIMALAYA trial, and an exciting update from the NAPOLI-3 trial in pancreatic cancer, ahead of the 2023 ASCO Annual Meeting.  TRANSCRIPT Dr. Shaalan Beg: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Shaalan Beg, your guest host of the podcast today. I'm the vice president of oncology at Science 37 and an adjunct associate professor at UT Southwestern Simmons Comprehensive Cancer Center. My guest today is Dr. Mohamed Salem, a GI oncologist at the Levine Cancer Institute at Atrium Health. We'll be discussing key posters and oral abstracts in GI oncology that will be featured at the 2023 ASCO Annual Meeting.  Our full disclosures are available in the transcript of this episode, and disclosures of all guests on the podcast can be found in our transcripts at asco.org/DNpod. Mohamed, thanks for coming on the podcast today.  Dr. Mohamed Salem: Thanks, Shaalan.  Dr. Shaalan Beg: There's some interesting studies in colorectal cancer that I'd like to get us started with today. Abstract 3547 is titled “A Phase I Dose-escalation Study of GCC19 CAR T: A Novel Coupled CAR Therapy for Patients with Metastatic Colorectal Cancer.” What are your thoughts on the study? Dr. Mohamed Salem: Actually, this was a very exciting study to see coming out in GI cancer, especially colorectal cancer. As you know, CAR T made its way to the treatment of lymphoma and other heme malignancies. In fact, we saw a fascinating response and outcome using that technique and that niche in the immunotherapy module. The challenge we had was that we could not replicate this in solid tumors until very recently. I'm sure you had the same thing in your clinic, too. A lot of patients with GI cancer or colorectal cancer come to you and say, "Okay, why can't I have CAR T?" And the response was, "We don't know if it's effective or if it's going to work yet." Here at our center, we had a phase 1 study, I think that was looking also at CAR T and solid tumors, particularly prostate cancer. So that I think was very exciting to see that technology is making its way to the solid tumor. I was very pleased to see this CAR T study coming out from the work of our Chinese colleagues looking into this in the CRC space.  Obviously, as you know, in colorectal cancer, we made a significant advancement, but I don't think we made enough advancement yet, and especially for refractory patients, patients with refractory disease who have underwent multiple lines of therapy. And this study actually addressed the need for those patients. So in this study, that was a phase I escalation dose, very much is we looked at about 13 patients who had metastatic CRC, they had at least two lines of therapy. So in what we say is a "refractory setting," unfortunately for those patients, we don't have large treatment options. And they used two doses, the first dose and the second dose that was a little bit higher. And the interesting part is that they were able to see very nice responses on this patient population. In the lower dose, I think the response was the PFS was about 1.9 months. But when they went up on the dose, actually the PFS was 6.3 months, which I think in the refractory setting is very meaningful.   And also the median overall survival for the first group was 13 months, which in the refractory setting is something we don't see often, and the higher dose was 18 months, which was even better. So there was a trend that higher doses are perhaps more effective or have better efficacies than lower doses, but also in terms of side effects, actually patients were relatively able to tolerate it well, and there were no surprising adverse events. So again, yes, that's 13 patients in total. So it's a very small study, but like everything else, the proof of concept sometimes is the first step and it's very important to see that data to suggest that this technology now can be utilized in solid tumors and CRC, especially now there is an unmet need for those patient populations. I'm sure you and I will see a lot of patients at the clinic with good progress status, and just looking for the next option, and I'm glad to see that. Hopefully, we can continue to build on that work.  Dr. Shaalan Beg: Another key abstract in colorectal cancer is Abstract 3513, the CodeBreak 101 study. This is a phase 1b safety efficacy trial of sotorasib plus panitumumab and chemotherapy with FOLFIRI for previously treated KRAS-G12C mutated colorectal cancer. And this is a really important study because even though KRAS-G12C represents a minority of KRAS mutated colorectal cancer, we know that this treatment can cause meaningful improvement in disease for other cancers like non-small cell lung cancer. And when sotorasib was tested as monotherapy in colorectal cancer, it saw an objective response rate of 9.7% that increased to 30% when added to panitumumab.   So in this trial, they took sotorasib plus panitumumab and added it to chemotherapy to see how it's tolerated and what its effectiveness is going to look like. And they enrolled people who had more than one or more lines of prior therapy for metastatic disease. They treated 33 patients. The most common side effect was dermatologic, which is probably related to EGFR-based therapy, and they saw a confirmed overall response rate of 58%. Side effects are those that we look to expect with this specific regimen. I don't see any additional safety concerns here, but this can be a big step forward for KRAS-G12C-altered colorectal cancer. What do you think? Dr. Mohamed Salem: I totally agree. And again, it was very exciting to see that abstract and that result. I totally believe now, and I'm sure you would agree with me too, Shaalan, that we're moving from an era of one size fits all to a precision oncology and tailored treatment. And the fact now we have a treatment option for patients with a KRAS mutation is very exciting because before, we didn't have much that we can do about that mutation. So now it's not just a proof of concept. Now you're hitting that target with the chemotherapy and you're getting a 50% response rate. That's something interesting also to see for this patient population and as you highlighted as safety also, and the adverse event was not high and patients were able to tolerate it, which makes it more doable for us to use it. Dr. Shaalan Beg: Yeah. And one of the challenges in the precision oncology space, which I'm sure you're experiencing in clinic as well, are the real-world applications of precision oncology and the drop-offs that happen that are preventing us from universal precision oncology - meaning the drop-offs that we see on eligible patients receiving the appropriate genomic testing, those who have genomic testing receiving the appropriate treatment. And we've seen a couple of fairly high-profile studies that are describing this in non-small cell lung cancer where the rates are not as encouraging as we would want it to be, which to me, as a physician, makes me worried that there are people out there who we don't know are carrying these mutations or have these mutations, and it hasn't been acted upon.   And related to that, there is an abstract at ASCO23, which is Abstract 3602, that looked at the real-world rates of FDA-approved targeted therapy and immunotherapy for people with metastatic colorectal cancer. They used the VA's National Precision Oncology Program data to study the prevalence of these mutations and how many of the folks ended up receiving the treatment that would be appropriate for those mutations. And this is a very exciting study. They looked at 908 metastatic colorectal cancer patients who underwent genomic profiling, 81% were colon and the rest were rectal. They found that 34% of patients harbored NRAS, KRAS, BRAF mutations, 9.6% were TMB-high, 7.7% had BRAF V600E, and 5.6% were MSI-high, which kind of puts the overall actionable variant prevalence in colon cancer at 47% and for rectal cancer at 44%.  And then they went down to see amongst those 424 eligible patients, how many ended up on appropriate therapy. And these were their numbers: for MSI-high 70%, TMB-high 47%, NRAS, KRAS, BRAF, wild-type 38%, BRAF V600E 17%. So nearly 30% of patients with MSI-high colorectal cancer did not receive immune checkpoint inhibitor therapy, and again, other aspects in terms of EGFR use, and I know that there are other challenges that may affect the use of EGFR inhibitors in colorectal cancer, but it really begs the point on aspects related to implementation science, on getting the testing and acting on those results. And I'm curious to what you're seeing that's being done on these initiatives nationally.  Dr. Mohamed Salem: I totally agree with you, Shaalan. This is a big problem we're facing day in and day out because we struggle to find treatment options for our patients. And I think if we're missing patient with targetable or actionable mutations and we're not utilizing that, I don't think that's a good situation to be in. And I think that's just a group effort. You have to work with the pathologist, you have to work with your team at the clinic. And as an oncologist treating this patient, we have to pay close attention to those markers. And frankly, just look for them. At least  the ones that you know are going to have therapeutic implications.  I do also think patient advocacy has a huge role here and huge opportunities that they can contribute. I am sure you are familiar with the pancreatic study that was published by our colleague Mike Pishvaian in Lancet a year or two ago. I think he named it the Know Your Tumor Type. I think that should be the way forward now, not just for pancreatic but for any cancer. Patients should ask their oncologists what my tumor is. Is it MSI-high, is it KRAS-G12C, is it BRAF? Because it will affect the treatment. I think it's multi-layer and all of us should work in a cohesive manner to be able to not ever miss those markers which carry therapeutic potential.   Dr. Shaalan Beg: So moving on to hepatocellular carcinoma, Dr. George Lau and colleagues, they'll be sharing data from the phase 3 HIMALAYA study with hepatocellular carcinoma in the Annual Meeting that's Abstract 4004. And he looked at outcomes by occurrence of immune-related events for people who received tremelimumab and durvalumab. What are your thoughts on this study?  Dr. Mohamed Salem: This was a very interesting abstract to see. For a long time, we didn't have many treatment options in hepatocellular carcinoma. So, over the last two or three years now, I think we've made nice advancements in the therapeutic landscape. So, we have multiple options including immunotherapy which is very exciting for all of us to be able to utilize those powerful drugs in that disease. The question that comes out is who actually responds? Obviously, in HCC you don't have a lot of biomarkers like the immune therapy biomarkers like MSI-high and PDL-1, and TMB. It isn't really playing a huge role in HCC. So, as you know, the HIMALAYA study is a phase 3 study and examined the STRIDE regimen which is treme plus durva in the first line of patients with metastatic or unresectable HCC against sorafenib. And the outcome was in favor of the STRIDE regimen with improvement in OS response rate and duration of response and because of that, it became one of the standards of care for that disease. But Abstract 4004 is actually asking a very interesting question - whether immune-related adverse events can predict outcomes. Meaning like those patients who experience immune-related adverse events will likely do better compared to those patients who didn't experience immune-related adverse events or not. The idea of adverse events as a biomarker if you will, for efficacy is not new. I mean we saw that back in the renal carcinoma TKI, hypertension. People who had hypertension were more likely to have a better response. In the GI also there was some data suggesting that rash might be a biomarker in predicting response to EGFR. So the same question we're applying here - immune-related adverse events can function as a biomarker for efficacy for the immune system.  And there are some data out there in other tumors that may be the case, but I think at least to my knowledge in the HCC or GI, this was the first study to address that question. So just to remind our audience that the HIMALAYA was a phase 3 study using the STRIDE regimen as a frontline for patients with hepatocellular carcinoma, either unresectable or metastatic disease. And they compared the STRIDE which is durva-treme compared to the standard of care at that time was sorafenib. The primary endpoint was overall survival and they had secondary endpoint duration of response, response rate, and obviously adverse event.  The study was positive, it met its primary endpoint and OS was in favor of the STRIDE regimen compared to sorafenib. But that part of the abstract now is focusing mainly on those patients who had immune therapy and whether that was a STRIDE regimen or the third arm that durva alone treatment. And they're looking at those patients who had immune-related adverse events, and those who didn't have immune-related adverse events. So basically four groups of patients, the patient who had a STRIDE regimen, about 139 patients had immune-related adverse events, and about 249 didn't have immune-related adverse events. For the cohort who had durva alone, about 64 patients had immune-related adverse events, almost 300 patients had no immune-related adverse events.  And it was very interesting that at least in the STRIDE arm, those patients who experienced immune-related adverse events, their outcome was better than those patients who did not have immune-related adverse events. It's the same trend seen on the durva alone arm, but I think the number was very small to make a statistical value out of it. But I think at least in the STRIDE arm there was a suggestive trend toward the outcome of those patients who experienced immune-related adverse events. So I think this is in a way very interesting because we're always wondering if we give the same dose at least in immunotherapy like for everyone.   What I was wondering is if it's too much, too little, or just right. It's hard to know for sure. But perhaps in my opinion and just me trying to understand why, in my theory, maybe that's just an indication of patients receiving enough drugs and effective drugs that will translate into efficacy. But at the same time, I also wanted to just put a word of caution here because we don't want to see side effects as a good thing. I think we want to make sure that us as oncologists treating these patients and patients also don't see like it's good to have a side effect. Side effects associated with especially those grade 3 or 4 can be associated with significant problems and decreased quality of life. So, definitely should be looking at those side effects and be careful interpreting those data. But I think that is very interesting and I will look for more work on that.   Dr. Shaalan Beg: Let's move on to pancreatic cancer. We heard the results of the NAPOLI-3 clinical trial at GI ASCO and this year in ASCO 2023 we will hear the results of Abstract 4006 by Dr. O'Reilly that are presenting results of the 12 and 18-month survival rates from the study that compared NALIRIFOX or nano-liposomal irinotecan, 5-fluoro/leucovorin, and oxaliplatin versus nab-paclitaxel/gemcitabine for newly diagnosed pancreatic cancer patients. I'm interested to hear what you think about that study. Dr. Mohamed Salem: Thank you, Shaalan. So this also is a very exciting abstract to see, and anyone who treats pancreatic cancer patients realizes that, unfortunately, even in 2023, we don't have a lot of treatment options. And yes, I think over the last decade we're now talking about second-line and third-line, but yet we still don't have a lot of treatment options. So, having more options is always good. But the question now is how do you sequence those chemotherapy options? Most of us obviously use FOLFIRINOX in the first line or gemcitabine and paclitaxel in the first line. Until very recently– because we didn't have a head-to-head comparison– we couldn't tell patients for sure if one is better than the other. I think we had some assumptions, but it wasn't really proven. It was just a cross-trial comparison.  So, the fact is that now we have that phase 3 trial looking at liposomal irinotecan, 5-fluoro/leucovorin and the oxaliplatin comparing to nab-paclitaxel/gemcitabine. To me, that was actually very exciting because now, at least, I can see a triplet chemotherapy drug compared to a doublet chemotherapy drug. And as you mentioned, Shaalan, the first initial read was positive in favor of the triplet regimen compared to the doublet, which I think was an important message to give to our colleagues and all of us that if you can, obviously, the triplet comes with side effects, but if you can deliver the triplet, that's perhaps a better starting point for the treatment. But the study here, we're trying to get more read after more mature or more time-lapsing. So the initial study was initial read was positive. And I think this is good to see, too because it translates that even with a longer follow-up, we're still seeing the same benefit. So the OS rate in 12 months for the triplet was about 45% compared to 39.5% for the doublet, and the 18 months, a year and a half, was 26% compared to 19%. So, definitely, you can see an improvement in every single endpoint. OS in general was 11.1 months compared to 9.2 months, and PFS was also in favor of the triplet. So I think it's a message here to reinforce what we saw a few months ago in the initial presentation that, in fact, the triplet is associated with better outcomes if you can safely manage the toxicity and guide the patient through the process. Dr. Shaalan Beg: Well, thank you very much, Mohamed. This was a lot of fun. Thanks for sharing your valuable insights with us on the ASCO Daily News Podcast. Dr. Mohamed Salem: Thank you for having me and looking forward to the full presentation at the meeting. And please, if you haven't registered for the meeting yet, make sure you attend. It's a wonderful opportunity to learn from an expert in the field and also meet your colleagues and make new friends. I also want to take this opportunity to thank the ASCO Daily News Podcast team for taking the time, and also for our colleagues who reviewed these abstracts. This takes a lot of time and effort, and I think they're doing a wonderful job. So, thank you to all of them, and I'll see you all at ASCO.  Dr. Shaalan Beg: And thank you to our listeners for your time today. You'll find links to the abstracts discussed today in the transcript of this episode. I'll be back to cover late-breaking abstracts and other key advances in GI oncology after the annual meeting, so please join us for more key insights from ASCO 23 on the ASCO Daily News Podcast.  Finally, if you value the insights that you hear on the podcast, please take a moment to rate, review, and subscribe wherever you get your podcast.  Disclaimer:The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experiences, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Find out more about today's speakers: Dr. Shaalan Beg @ShaalanBeg Dr. Mohamed Salem @SalemGIOncDoc   Follow ASCO on social media: @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn   Disclosures:  Dr. Shaalan Beg: Consulting or Advisory Role:  Ispen, Cancer Commons, Foundation Medicine, Genmab/Seagen Speakers' Bureau: Sirtex Research Funding (An Immediate Family Member): ImmuneSensor Therapeutics Research Funding (Institution): Bristol-Myers Squibb, Tolero Pharmaceuticals, Delfi Diagnostics, Merck, Merck Serono, AstraZeneca/MedImmune  Dr. Mohamed Salem: Consulting or Advisory Role: Taiho Pharmaceutical, Exelixis, Bristol-Myers Squibb, Exelixis, QED Therapeutics, Novartis, Pfizer, Daiichi Sankyo/Astra Zeneca Speakers' Bureau: Genentech/Roche, Taiho Pharmaceutical, Daiichi Sankyo/Astra Zeneca, BMS, Merck

Dr. Mohamed Salem, Dr. Myriam Chalabi, and Dr. Andrea Cercek discuss pivotal neoadjuvant immunotherapy clinical trials for patients with MSI-H/dMMR colorectal cancer, focusing on the development of active therapies in the neoadjuvant setting—where patients are treated without surgery, radiation, or chemotherapy—and the importance of patient selection in finding the right target and treatment to improve outcomes. TRANSCRIPT Dr. Mohamed Salem: Hello, and welcome to the ASCO Daily News Podcast. I'm your guest host today, Dr. Mohamed Salem. I'm a GI oncologist at the Levine Cancer Institute at Atrium Health. Today, we will be discussing very promising advancements in the neoadjuvant immunotherapy for patients with MSI-H/dMMR colorectal cancer. And I'm very delighted to welcome two world-renowned oncologists whose research has tremendously helped shape the treatment landscape of colorectal cancer. Dr. Myriam Chalabi is a GI medical oncologist at the Netherlands Cancer Institute, and Dr. Andrea Cercek is a medical oncologist at Memorial Sloan Kettering in the United States.  Our full disclosures are available in the transcript of this episode, and disclosures relating to all episodes of the podcast are available on our transcripts at asco.org/DNpod.  Dr. Chalabi and Dr. Cercek, welcome to the ASCO Daily News Podcast. Dr. Myriam Chalabi: Thank you for having me. Dr. Andrea Cercek: Thank you very much for having me. Dr. Mohamed Salem: It's a pleasure to have two world-renowned stars like you. Thank you for taking the time.  So, before we start going deep into the topic, obviously, now we are seeing emerging data in CRC using immunotherapy as the neoadjuvant approach, which actually can reduce or even eliminate some of the other treatment modalities and potentially save patients from toxicities. Both of you led what I think are landmark studies in this field. I wanted to give you the chance to tell our audience about your studies and why you think they're important. Dr. Cercek? Dr. Andrea Cercek: Sure. Thank you so much. So, our study was a neoadjuvant study in early-stage, locally advanced rectal cancer with tumors that were mismatch repair-deficient or MSI-H. And rectal cancer normally is treated with chemotherapy, chemoradiation, and surgery. And the goal of the trial was to utilize PD-1 blockade alone in this subpopulation and evaluate the response.  Patients received six months of dostarlimab, which is a PD-1 blocking agent, and then were evaluated for response. If there was no residual disease, they were able to avoid radiation and surgery. And what we've seen thus far in the presentation at GI ASCO in 2022 was that all patients who received six months of dostarlimab had a clinical complete response, so no residual tumor, and were able to avoid chemotherapy, radiation, and surgery and are on observation. And the study is ongoing and actively accruing patients. Dr. Mohamed Salem: All of us were very excited seeing that presentation at ASCO. And when we came back to the clinic everyone was talking about it, including patients, obviously. Thank you for this, Dr. Cercek. Dr. Chalabi, you also led a similar study that was actually presented in ESMO in 2022. Can you please give us, like, a brief description of that trial? Dr. Myriam Chalabi: Yeah, sure. So, this is the NICHE trial, and actually the NICHE trial has been ongoing for quite some time now. We recently presented a larger NICHE-2 study, but basically– so what we started out by doing in NICHE is giving patients what we considered back then a window of opportunity study. We treated patients with MMR-deficient tumors, which I'll be focusing on for now, with two cycles of nivolumab and one single cycle of low-dose ipilimumab. And patients all undergo surgery within six weeks of registration within the study. And back in 2020, we published the first data of NICHE-1 showing 100% pathologic responses with 60% pathologic complete responses and decided that this should definitely be a treatment that we need to explore in a larger group of patients. And that's where NICHE-2 was born, which we presented at ESMO last year, where we treated over 100 patients with this neoadjuvant approach of two cycles nivolumab, one single cycle ipilimumab, showing 99% pathologic responses, including 95% major pathologic responses and 67% pathologic complete responses. And this was all within five and a half weeks of the first treatment with immunotherapy, so a very short treatment duration with dual checkpoint blockade. Dr. Mohamed Salem: Amazing results, too. And I know you had a standing ovation when you presented the outcome of the study. And again, congratulations to you, your investigator, and also all the patients participated. Dr. Myriam Chalabi: Thank you so much.  Dr. Mohamed Salem: I guess the first question that comes to my mind - we have two trials, obviously, now we're moving from one size fits all to precision therapy, like getting actually the right treatment for the right patient. But in the NICHE study, it was a checkpoint inhibitor, and the rectal study was a single agent. I want to start with you, Dr. Chalabi. In your opinion, when should we use single agent or double blockade immunotherapy? Dr. Myriam Chalabi: That is a great question. I'm going to start off by saying that I don't know the exact answer. I don't think we know that answer. And Dr. Cercek is going to share also her thoughts on this because we're seeing, of course, fantastic responses with monotherapy as well in Dr. Cercek's study. And we've also seen that in a study by Dr. Overman with monotherapy. So that may suffice in some patients, although what we're seeing is that you need to treat patients longer, probably to achieve that response, at least clinically. And I think that is the difference with dual checkpoint blockade, that we're giving in NICHE where we're seeing these very deep responses in just under six weeks' time.  So, I think it may be more of a question of how long we want to treat patients for to achieve the endpoint that we're aiming for. And, of course, there may be, at some point, patients that need dual checkpoint blockade, but so far, we're seeing great responses in both of our studies. So I think we need more patients, more data to see whether we're going to see non-responders. And hopefully, the studies that are ongoing in the metastatic disease setting will give us at least a little bit of insight into what the differences are in response to mono and dual checkpoint blockade and whether we can tell which patients might benefit more from the combination. But I think there's still a lot of work to be done in that field. Dr. Mohamed Salem: I totally agree. Dr. Cercek, same question to you. What do you think?  Dr. Andrea Cercek: Dr. Chalabi answered beautifully and very comprehensively. I agree completely with what she said. It's hard to argue with the responses that we're seeing with PD-1 blockade alone. But then again, dual checkpoint inhibitors in the NICHE study with just one month of therapy had phenomenal responses as well. So I think it's a question of duration of therapy and, really importantly, what we're trying to achieve. If our goal is organ preservation, then perhaps longer duration is better. The question then becomes, can we do, should we do longer duration with dual checkpoint inhibitors versus single agent? So I think, as she concluded, I couldn't agree more that we just need more information, we need more work to do, basically to answer this question for our patients. Dr. Mohamed Salem: More to come and more studies, which is fascinating.  So, Dr. Chalabi, you created actually a new term on Twitter called ‘Chalabi Plot'. It was amazing to see such a response. But we're curious, among those patients who achieved complete response so far, did you see any relapse? Dr. Myriam Chalabi: Short answer, no.  we're waiting, of course on the disease-free survival data, the three-year DFS data for NICHE-2, and we hope to have that by the end of this year, beginning of next year. But as of now, we showed that data, and so far, we haven't seen any recurrences in, actually, any of the patients treated in NICHE-2. Dr. Mohamed Salem: Fantastic. Dr. Cercek. So I think your slide -- I remember clearly from the ASCO presentation -- was all complete response, every single patient.  Same question, did you see any relapse so far? Dr. Andrea Cercek: So far, no, we have not. Dr. Mohamed Salem: Amazing. So, Dr. Cercek, as you know, and obviously, this is metastatic disease, but in KEYNOTE-177, as you know, about 30% of patients with MSI-high tumors did not respond to checkpoint inhibitors. So that makes some of us feel nervous about using checkpoint inhibitors alone in colorectal cancer, even with MSI-high status. I was curious if you can comment on this and if there is a way we can perhaps sort out who actually is likely to respond and who is likely not going to respond. Dr. Andrea Cercek: I think that's a really important question and an excellent point. And we believe that the difference lies in the fact that in KEYNOTE-177, the patients had metastatic disease, whereas in our neoadjuvant studies that we're discussing, they have early-stage disease. And whether that has to do with the tumor differences, young tumors versus older tumors once they become metastatic, or the microenvironment, remains to be determined. But certainly, there is this pattern of incredible responses with checkpoint inhibitors in early-stage dMMR tumors. And in KEYNOTE-177, as you mentioned, about 30% of patients progressed. And I think we don't know why that is. We are seeing this, about a third of progressors repeatedly in the metastatic setting with checkpoint inhibitors. And so perhaps there is a population. But whether this is driven by genomics or something else, we don't know. Dr. Mohamed Salem: Great. So, along the same lines, especially rectal cancer, obviously, because surgical resection is a key component in the treatment paradigm, do you feel patients who achieve pathological complete response should still go under surgical resection or should go under the ‘watch and wait' approach? Dr. Andrea Cercek: In general, I'm a fan of organ preservation. I think in rectal cancer, the reasons are obvious. It's a challenging surgery. It's very toxic to the patients. It changes their lives forever. In survivorship, 30% of them require a permanent colostomy because of the location of the tumor. So there, the field of rectal cancer, in general, is moving towards non-operative management, even in the MSI-proficient patients, by trying to optimize therapy to increase clinical complete responses and therefore omit surgery. So that's the difference with rectal cancer. In colon cancer, it's a different discussion. I think for many patients, surgery is very straightforward. It's a hemicolectomy. It doesn't alter lifestyle in survivorship, so it's not as morbid as it is in rectal cancer. Of course, I think if a patient is older with MSI-deficient tumor perhaps can undergo surgery, then clinical complete responses become critical because then we can monitor them after just checkpoint blockade, and they don't need surgery.  The challenge there, and I would love to hear Dr. Chalabi's comments on this, too, is just that imaging is challenging. We have a hard time in colon cancer determining whether someone has a clinical complete response or not. It seems to be very different than in rectal cancer, where with endoscopy and with the rectal MRI, we really can't tell whether the tumor is still present or not. This remains a challenge in colon cancer. Dr. Mohamed Salem: Dr. Chalabi, I would like to hear your thoughts and also how you practice in Europe. I don't know if it's the same like here in US or different. Dr. Myriam Chalabi: I completely agree with Dr. Cercek. Well, if we look at the rectal cancer patients, I think this is fantastic. That even though this is a small population achieving this high clinical complete response rate, not having to operate or even give any chemotherapy or radiation therapy to these patients, it is extremely important both in the short term but also in terms of long-term complications and morbidity. When it comes to the colon cancer responses that we're seeing in NICHE, those are all pathologic responses, of course. And we have been evaluating also preoperatively using scans to see whether we can assess these complete responses based on imaging. That doesn't seem to be the case. We do see responses in all patients, so we see these are all very large bulky tumors that we're treating in NICHE-2. And we do see responses in almost all of these patients, but it's not close to complete responses, definitely not in all of the complete responders that we're seeing. So that makes it difficult.  And the question is, what if we would be waiting or treating longer because these bulky tumors need more time to disappear or to be cleared before you're going to see it on the imaging? So that is a question that I don't have an answer to just yet. We may be getting some more data on that with the currently ongoing trials. And as Dr. Cercek pointed out, the endoscopies when you have a right-sided colon tumor are different than doing just a sigmoidoscopy for a rectal tumor. So, we actually do have one patient who hasn't undergone surgery, and that is actually a patient with an MMR-proficient tumor within the NICHE trial who had a complete response. And that patient has a sigmoidal tumor, and he actually had toxicities which prevented him from undergoing timely surgery and now has a complete response after two years, both endoscopically and on imaging. So, he hasn't undergone surgery, and that is a great example of how we may be doing this in the future. It's an interesting case within the trial to follow and see how we can do it in the future. Dr. Mohamed Salem: That's fascinating news. So, was it MMR-proficient? Dr. Myriam Chalabi: Yes, this is an MMR-proficient tumor.  Dr. Mohamed Salem Wow. Any particular biomarkers that you think he or she had to predict that? Dr. Myriam Chalabi: We have treated more patients with MMR-proficient tumors. We have 31 patients, and we have seen actually responses in 9 out of 31 patients in the MMR-proficient tumors with the same combination of two doses of nivolumab and one of ipilimumab. We previously published on half of the cohort approximately on what the possible predictive biomarkers of response could be, and that was a costimulation for CD8 and PD-1. So PD-1 positive CD8 T cells. And we're currently doing the same work for the rest of the cohort. So hopefully, we'll be able to show that soon and see whether this still stands for the completed MMR-proficient cohort. But definitely also very exciting data for the MMR-proficient. Dr. Mohamed Salem: So, this is actually a very good segue to my next question because I know all of us are looking for this. Like, obviously, we're seeing a fascinating response in those patients with MSI-high tumors, but majority of colorectal cancer, as you know, they actually have MSS-proficient tumors. Any thoughts about how we can overcome the primary resistance for this tumor to checkpoint inhibitors? So let me start with you, Dr. Cercek.  Dr. Andrea Cercek: I'm very much looking forward to Dr. Chalabi's data on this because, honestly, we have not seen such amazing responses to immunotherapy in MSS tumors. The initial studies were complete flatline, no responses at all. And here, she just described a patient that had a complete response to just a month of checkpoint inhibitors. So that's phenomenal, and hopefully, we'll learn from the responders.  We believe that there is a subpopulation of MSS colorectal cancer that is more immune sensitive, immune hot, whichever term you like to use. And it's just a matter of appropriately identifying those patients. And personally, I think the answer lies in the neoadjuvant setting in early tumors where they're treatment-naive, not exposed to chemo, not exposed to radiation, younger, have their innate microenvironment. And so, I think it's likely a combination of the above. But obviously, the ultimate goal is to find out who those patients are and then potentially treat them just like this with immunotherapy. And that would be another nice chunk of the pie where we could utilize immunotherapy for our patients. Dr. Mohamed Salem: Very true. Dr. Chalabi, especially with your experience and just showing there is a chance for those people to respond, what are your thoughts about how we can overcome this primary resistance? Dr. Myriam Chalabi: It's great to be here with Dr. Cercek because, obviously, we have very similar interests but it's also good to see that we think the same way because I completely agree with what she just said in terms of neoadjuvant. I think that was one of the most important things that we did here, giving this neoadjuvant treatment in non-metastatic tumors. It's probably a very important driver in the responses that we're seeing. So, we've been seeing data now a bit more in the metastatic disease setting where MSS tumors seem to be responding to new generations of checkpoint blockade. And the question is how those would do in the neoadjuvant setting that would be even different than what we're seeing now. But there's definitely some proof of MSS tumors that can respond to immunotherapy. The question on how to overcome the primary resistance, I think that question is for us: Who are the patients with primary resistant tumors and why are they primarily resistant? And then we can think about how to change that and how to change them into the tumors that are responding. I think these types of data will be key to understand more and know; hopefully, even you said, in the metastatic disease setting, to make these tumors more pliable in response to immunotherapy. Dr. Mohamed Salem: I agree. So, both of you are leading us toward how to choose the right patient with the right target for the right treatment. That's an amazing journey you're taking all of us on.  So, Dr. Cercek, I have to admit that with your data, it created some problems for us in the clinic because all patients the following day came in asking for immunotherapy. We had a hard time trying to explain that maybe this is not the right treatment for them or, like, not the right platform. But I wanted to ask you, if we'll have a patient tomorrow in the clinic with localized rectal cancer and happen to have an MSI-high tumor, what would be your recommendation in terms of how to approach that patient? Dr. Andrea Cercek: I think, ideally, you would discuss clinical trials with the patient. We have opened the study now to not just rectal cancer but colon cancer and, in fact, all solid tumors that are mismatch repair-deficient. So I think at this time, the patients really should be treated on a clinical trial. As we learn more, in particular, until we are more comfortable assessing for a clinical complete response and follow-up. I think the surveillance piece will be critically important. In rectal cancer, it's well established, but it's not in the other tumor types. So my recommendation would be to enroll the patient on a trial. Dr. Mohamed Salem: Just to add to that too, obviously, as you know, there is now the cooperative group trial that's looking at that option and we obviously encourage all centers to participate and open that study to have this option for our patients. Dr. Chalabi, so what do you guys do in Europe for these patients? Dr. Myriam Chalabi: In Europe, it's a very different situation. I would have answered this question differently by saying, well, we don't have that option of treating patients outside of clinical trials. So basically, we have to make sure that we have clinical trials for these patients. And that's something that we've had for colon cancer patients. That is still the case. And we're getting rectal cancer trials also for patients with MMR deficient tumors and have those also for MMR proficient tumors. For us and I agree completely that we should be treating patients within clinical trials, we don't have another option. But still, even if we did, I think it's important to create data within clinical trials to be able to ultimately also show why this should be standard of care and how we can make it standard of care. Because if you're not accumulating that data, then it's going to become very difficult if accrual is lacking. Now, we treat patients either with standard-of-care treatments, but usually, we try to find something within clinical trials.  Dr. Mohamed Salem: I totally agree. And as we always say, the standard of care should be a clinical trial participation. So, I must say, both of you, Dr. Cercek and Dr. Chalabi, you made 2022 a very exciting year for us in GI cancers. You really changed the way we look at how to treat these patients and give them a huge chance of, I would say, actually cure and obviously organ preservation. So, I'm very curious to know what you are both are working on now and what we should expect in 2023 and 2024.  Dr. Andrea Cercek: So, for me, the study is ongoing, as I mentioned, and we've expanded to all mismatch repair-deficient solid tumors with the same approach of six months of dostarlimab and then the option of nonoperative management. And I think that it'll be important for us to learn in terms of responses on the luminal versus some of the other tumor types, like, for example, pancreas cancer, where we don't see these robust responses in the metastatic setting, that will be important to do. We're doing some correlative analysis, as Dr. Chalabi described as well in our patients.  And then, I'm interested in optimizing neoadjuvant approaches to minimize therapy in rectal cancer specifically. So, we have a study now for HER-2 amplified RAS wild-type patients with locally advanced rectal cancer with a similar approach of utilizing HER-2 targeted therapy first and then in combination with chemotherapy. In our case, it's a combination of trastuzumab and tucatinib and then chemotherapy with CAPOX and assessing for response and potential omission of radiation and surgery depending on responders. So, I'm very excited that study is open and actively accruing, and hopefully, we can get similar responses that we did in the MSI population with PD-1 blockade. Dr. Mohamed Salem: Is that only available at MSK? Dr. Andrea Cercek: It is at this time. However, we will likely be expanding, so if there's any interest, let me know. Dr. Mohamed Salem: Great. I'm sure many centers will be. Great. What about you, Dr. Chalabi? Any sneak peek in the future? Dr. Myriam Chalabi: So many sneak peeks, where to begin? I think it's very exciting to be working in this space at this time, and we're very lucky to be in it. So, for NICHE, we're actually accruing now in new cohorts for both MMR-deficient and MMR-proficient tumors. For the patients with MMR-deficient tumors, we're actually testing a new combination of nivolumab plus relatlimab, so anti-LAG-3 plus anti-PD1. And we're testing the same co-formulation in patients with pMMR tumors. In addition to another cohort for the pMMR tumors with nivolumab, all within this window of opportunity, as we did previously in NICHE, and to see if we're going to see more responses if these are going to be different tumors than the ones responding to nivolumab and ipilimumab. And for the MMR deficient tumors, we're treating longer with this combination now. So, we're operating after eight weeks instead of six weeks. We're giving two cycles, four weekly cycles, to see whether we can even improve the PCR rates, even though this is, of course, a different combination treatment. So, very exciting times for NICHE, and we'll have the readout for the DFS at the end of this year, so that's also very exciting. And then, well, it's similar to Dr. Cercek. So again, we're on the same page when it comes to these neoadjuvant treatments. We have actually an ongoing trial for neoadjuvant treatment of patients with MMR proficient rectal cancers, and that is using a combination of radiation therapy followed by a combination of atezolizumab or anti-PDL1 with Bevacizumab with the aim of organ sparing approach in these patients. And we actually presented stage 1 of this trial as a poster at ASCO GI, showing that we achieved 56% complete or near complete responses clinically at 12 weeks. And after at least a year of follow-up for all patients, we have 50% organ preservation. So those are very exciting data as well. Also, in the MMR proficient tumors, I'm very excited to hear about the HER-2-positive tumors and Dr. Cercek's study. So there's definitely a lot going on that we hope to share as soon as the data are available. Dr. Mohamed Salem: We'll be looking forward to your next presentation and seeing that. So again, most of your work showed us that we really have to choose the right patient with the right target for the right treatment to achieve the best possible outcome. So we're getting short on time here. But before we conclude, ASCO Daily News Podcast has a huge audience of oncologists, I wanted to give you the chance to share anything you'd like to share with our audience today before we finish. Dr. Cercek? Dr. Andrea Cercek: I believe this is an incredibly exciting time in colorectal cancer. I think it's finally our turn, which feels really nice, and obviously, we have a lot more work that needs to be done. But my personal belief is to keep trying to chip away at the pie and identify responders and keep working to have better-targeted drugs and better treatment options that will improve responses and improve outcomes for our patients. But I certainly believe that we are well on our way there, and it's very exciting. Dr. Mohamed Salem: I totally agree. Dr. Chalabi, any thoughts? Dr. Myriam Chalabi: I think after 2022 and the data that we've been showing, I think it's important to– and I think by now, maybe it's not even necessary anymore to say it– but I think it's important to really look at the tumors and look at these MMR proteins or MSI, and to make sure that you're treating the patient in the right way, and to consider that. Before, it wasn't as important in the neoadjuvant setting or these localized tumors, but now it's becoming essential.  And I think if you would have looked five years ago and you would say, yeah, these MSI tumors are important to find, it's a very small proportion of patients, in rectal cancer even lower than in colon cancer. But still, it has such a huge impact on what you're doing in these patients and your chances of cure. So I think that would be my most important giveaway to test for MMR deficiency before deciding on a treatment for your patients. And we're working on trials with neoadjuvant immunotherapy. Also in other tumor types, Dr. Cercek is also doing the same. I think those will be very important also outside of the GI field to see whether this approach works for a much larger patient population, despite the low incidence.  Dr. Andrea Cercek: Dr. Chalabi just made a critical point that that is most important is to remember that we do have biomarkers in colorectal cancer that, in the neoadjuvant setting and in the metastatic setting, especially MSI, that we need to test for. And then, just to add from a clinical perspective, in rectal cancer, the large majority of patients that have mismatch-repair deficient or MSI tumors actually have Lynch syndrome. So really, if you identify a patient that's mismatch-repair deficient or MSI-high anywhere, but especially in the rectum, they absolutely should get germline testing. Dr. Mohamed Salem: I echo that and second that. And Dr. Cercek, thank you, and I know you did a lot of work in colorectal cancer in the younger adult population, too, so I think you've had a huge impact on that area too. I would like to thank both of you again for being here today, but more for the great work you and your teams are doing to advance the field. It's really a very exciting time in GI cancers now, and thank you so much for your work and for sharing your insights with us today on the ASCO Daily News Podcast. Dr. Myriam Chalabi: Thank you so much for having me. It's been great. Dr. Andrea Cercek: Thank you for having me. Dr. Mohamed Salem: Of course, and thanks to our listeners for your time today. If you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Thank you very much. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers:     Dr. Mohamed Salem @SalemGIOncDoc   Dr. Myriam Chalabi @MyriamChalabi   Dr. Andrea Cercek @AndreaCercek   Learn about other key advances in GI Oncology: SWOG 1815, PARADIGM, and Other Advances at GI23   Follow ASCO on social media:      @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn      Disclosures:   Dr. Mohamed Salem: Consulting or Advisory Role: Taiho Pharmaceutical, Exelixis, Bristol-Myers Squibb, Exelixis, QED Therapeutics, Novartis, Pfizer, Daiichi Sankyo/Astra Zeneca Speakers' Bureau: Genentech/Roche, Taiho Pharmaceutical, Daiichi Sankyo/Astra Zeneca, BMS, Merck Dr. Myriam Chalabi: Consulting or Advisory Role: MSD, Bristol-Myers Squibb/Celegne, Numab Research Funding (Institution): Bristol-Myers Squibb, Roche/Genentech, MSD Travel, Accommodations, Expenses: Roche/Genentech, Bristol-Myers Squibb Dr. Andrea Cercek: Consulting or Advisory Role: Bayer, GSK, Incyte, Merck, Janssen, Seattle Genetics, G1 Therapeutics Research Funding (Institution): Seattle Genetics, GSK, Rgenix          

JCO PO author Dr. Mohamed Salem shares insights into his JCO PO article, “Landscape of KRASG12C, Associated Genomic Alterations, and Interrelation With Immuno-Oncology Biomarkers in KRAS-Mutated Cancers” and the article's findings of a large-scale, pan-cancer genomic characterization of KRASG12C. Host Dr. Rafeh Naqash and Dr. Salem discuss KRASG12C mutation, KRASG12C -mutated tumors and comutation with STK11 and KEAP1. Click here to read the article!   TRANSCRIPT Dr. Abdul Rafeh Naqash:  Hello and welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I'm your host, Dr. Abdul Rafeh Naqash, Social Media Editor for JCO Precision Oncology and assistant professor of Medical Oncology at the OU Stephenson Cancer Center.  Today I'm thrilled to be joined by Dr. Mohamed Salem, Gastrointestinal Medical Oncologist, and Research Director at the Levine Cancer Institute in Charlotte, North Carolina. Dr. Salem is the lead author of the JCO Precision Oncology article ‘Landscape of KRASG12C, Associated Genomic Alterations, and Interrelation With Immuno-Oncology Biomarkers in KRAS-Mutated Cancers'.  Our guest's disclosures will be linked in the transcript.  Dr. Salem, welcome to our podcast, and thank you for joining us today. Dr. Mohamed Salem: Thank you for having me. A pleasure and honor. Dr. Abdul Rafeh Naqash: For the sake of this podcast, we'll be referring to each other using our first names. So thank you for coming on to our podcast and discussing this very interesting paper. And one of the reasons why we decided to incorporate this is because, as you very well know, KRAS is one of the most common altered genes in cancer, and I'm pretty confident and sure that oncologists, whether it's academic oncologists or community oncologists, have treated patients in different settings having tumors that harbor KRAS alterations. So give us a little bit of a background on where KRAS alterations stand currently and where is drug development in the space of KRAS to give our listeners some idea of why we're interested in this gene. Dr. Mohamed Salem: Sure, thanks again for having me. And as you mentioned, KRAS mutation happens to be, I think, by far the most common oncogenic mutation we see in oncology and solid tumors. The problem with KRAS is that, for a long, long time, there was very much nothing we could do about it; it was, in fact, called an undruggable target. Until recently, we started to realize this might not be true, and, in fact, we start to see successful efforts trying to target KRAS mutation. Currently, there are several KRAS inhibitors. I think it started with G12C. I personally don't think there was anything specific about G12C, but it just happened to be one of the first targets that we were able to approach. And the initial result from using anti-G12C therapy that was published in the New England Journal of Medicine, I think, a year ago now, showed this is feasible and perhaps effective. Dr. Abdul Rafeh Naqash: Thank you so much, Dr. Salem, for that explanation. And being a Phase I trialist, I personally have seen a lot of exciting combination-based approaches in the setting of KRAS-altered tumors, especially KRASG12C.  Now, specifically delving into your paper, given the extensive length and breadth of data that you've covered here, could you tell us a little bit about why you decided to use KRAS as an interesting topic for your study and the kind of data set that you chose to explore this question?  Dr. Mohamed Salem: What happened once we started to realize how important it is to figure out which KRAS mutation we're dealing with because, at least in colorectal cancer, it's a very common mutation, almost like 40-50% of patients with colorectal cancer tumors carry KRAS mutation. Until very recently, we really didn't pay close attention to which variant it is. Is it KRAS G12D, 13, or G12C? And so on and so forth. And the reason we didn't really pay much attention to that is because there was nothing to do about it; whether the patient has this or that variant was really nothing therapeutically wise it really didn't have an impact. But once we started to realize now there is a therapeutic option and, in fact, now there is a change in the way we think about KRAS mutation, there is a proof of concept that we actually can target KRAS mutation, we started to pay closer attention to this.  And I think this was a paradigm shift in our thinking. So for patients who have KRAS mutation, now we have data showing that KRASG12C is something we can target, whether with single agent or with combination therapy. But it was a new era for us because most of us realized it's not going to stop there. It's not going to be just G12C; I think G12C is the tip of the iceberg, and likely the science is going to go forward, try to target the other variants. So one of the obvious questions was what are the other variants and how commonly those exist, and which tumor types also carry those variants. Because as we were talking before the recording for Phase I, now it is not like one approach fits all; it started to kind of like focus on either molecularly driven or disease-type approaches. And it was very important for us to try to figure out, okay, which tumor type carries the most KRAS variants and, within that tumor, which variants are the most common. And this is what we're trying to answer in this paper.  Dr. Abdul Rafeh Naqash: Thank you so much, Mohamed. I looked at your data set that you had access to, very large data set of around 79,000 tumor samples and close to 14,000 KRAS mutated tumors. Could you tell us a little more about this data set and how you started with looking at the distribution of KRAS across different tumors, and what were the kind of interesting results that you came across as far as KRAS distribution is concerned? Dr. Mohamed Salem: It's very obvious to all of us now that the field is moving from one size fits all to a targeted approach or treatment target approach. And this is very important and very interesting because usually, when we do that, we achieve better outcomes and lesser toxicity. But the problem that comes with this is that none of us, as a single, even two centers, will have enough data to ask and answer questions. And when you are talking about something like MSI-high or BRAF or KRAS, usually it becomes very challenging for one single institution, doesn't matter how big they are, to try to answer either prevalent or therapeutic approaches. Because of that, most of us now start to understand that cooperation is very important across centers and also across nations.  So, like as you see here in this paper, there was a global cooperation between investigators in the U.S. and in Europe and Austria, and other countries. And what we did as a group we worked with one of the third-party profiling companies. Our group tried to answer what is the prevalence, just a very simple question, what is the prevalence of KRAS mutation, and what is the prevalence of each variant type in each tumor? And none of us could have answered that question on their own. Because of that, we actually collaborated with one of the third-party companies that do next-generation sequencing for tumors, and we were able to collaborate with them to have access to that database and answer some of those questions.  Dr. Abdul Rafeh Naqash: Excellent. As everybody knows, NGS is a standard of care testing that oncologists do, especially for advanced settings, to identify driver alterations or therapeutic interventions that may be relevant for patients. So in this data set, it seems you had access to NGS data, tumor mutational burden, and PD-L1 data for these tumor types. Could you tell us about the differences in the distribution for KRAS and the KRAS subtypes that you identified in this data set? Dr. Mohamed Salem: Sure. So, as you mentioned, we looked actually at almost 79,000 tumor samples that underwent next-generation sequencing by our collaborator. And it appears that about 17% of the tumors or so had some kind of KRAS mutation. And then, after that, we start to see G12C when we start looking at each variant. G12C were about 11%, 12%, and about 88% of the remaining KRAS mutant tumors harbored some different kind of KRAS mutation.  The next question was, in general, in all tumors, what was the most common KRAS variant seen? I think it mimicked what was already out there. It appears that G12D happened to be perhaps the most frequent mutation seen in KRAS mutation tumors, followed by G12V, followed by G12C, and then G12/13, and then others. What was very interesting, actually, an observation we saw, is that we were able to realize the distribution of KRAS variants varies according to the tumor subtype. So, for example, in pancreatic cancer, we could see patients who had G12R KRAS mutation variants. This was not seen commonly in other tumors. And the reason that's important is because maybe that will be something in pancreatic cancer tumors that will be worth looking at and do therapeutic approach there. But also, I'm sure you're already dealing with this in your clinic quite often. It was interesting, obviously, that non-small cell lung cancer was the most common organ that actually carries G12C, followed by colorectal cancer; followed by a very interesting actual observation that was very interesting for us to see was in appendiceal cancer. As you know, appendiceal cancer is not a common disease; it's a relatively rare disease. And we were surprised to see some of them actually have G12C mutation. And again, the reason that's important is that it just opens the door for possible therapeutic options and in context of clinical trials. Dr. Abdul Rafeh Naqash: Excellent. Definitely, the advantage of having such a rich data set like you did enabled you to look into some of these unique distributions across rare tumors, which makes it very interesting.  Now, one thing that I realized in the paper is that these tumors of unknown origin, where you identified or your group identified that they had a certain percentage of KRAS alterations, suggesting maybe their tumor of origin is perhaps lung or upper diaphragm, which could have therapeutic implications. Could you tell us a little more about this? Dr. Mohamed Salem: Yeah, this was another very interesting observation we saw because it is not uncommon for us in the clinic, we get like a cancer biopsy, but we cannot tell where it's coming from. And there are multiple ongoing efforts to try to identify that for the obvious reasons. But it was very interesting when we looked at those groups that when you had cancer adenocarcinoma but of no identified origin, it was the fourth common tumor that we see G12C. I think if you can just make the assumption - I don't think we have proved that - but since lung cancer was the most common tumor that exhibited G12C mutation, and now we have tumors of unknown origin also, many of them exhibit G12C mutation, we thought this could be a lung primary. As you know, there are also now a few platforms trying to identify the tumor origin based on the agent sequencing, but we didn't try to associate it with that. Dr. Abdul Rafeh Naqash: Thank you for that explanation. Now, one of the other things I observed is you tried to delve into smoking status, very interestingly, and how that correlated with KRAS alterations. And as we know, lung cancer, obviously there is a strong predilection in patients who are smokers, but irrespective of smoking, there can be other alterations that drive lung cancer. But interestingly, in your paper, you identified a unique correlation between smoking and G12C and also found out something on those lines in colorectal cancer, which, to my understanding, has not been described before. What is your understanding of why that happens? What could be the mutational events that lead to something like that, and how could that be potentially therapeutically exploited? Dr. Mohamed Salem: I think this was one of the very interesting findings we observed. And you are right; just because the nature of lung cancer, we know many of patients are either active smokers or former smokers. So it was not a surprise for us to see that there is some kind of association with smoking status and lung cancer. But to your point, what was really surprising and, in a way, interesting for us to see, actually, that association for patients with colorectal cancer. Smoking actually happens to be one of the risk factors, like in colon cancer, but obviously not as high as lung cancer. But when we looked at the data, demographic, and clinical features, it was obvious actually that current smoking status, whether a current smoker or prior smoker, had an association with G12C. And also, with gender as well, females tend to have more G12C, or G12C mutation was more likely to be seen in females than males. So the fact that we were able to identify the smoking status and gender as more likely to harbor G12C mutation was interesting.  I have to tell you, the reviewer, when we submitted the paper for review, the reviewer came back and asked us, did this happen just because you had too many lung cancer, and most lung cancer patients smoke, that's why you're seeing that association? And we went back and looked at the data again and spoke with our biostat team in the study, and we were able to actually run the analysis and show that, no, it is not just because of the enrichment; it's actually a real association between the smoking status and G12C. It's very interesting to see, at least in colorectal cancer, it's following the same trend in lung cancer. Dr. Abdul Rafeh Naqash: Right. And one of the other things I remember when I was reading through your paper and smoking status, I remembered this paper that was published in Science Magazine 2016, looking at how mutational burden changes in patients that have a history of smoking. But when you connect the dots here, interestingly, it seems like, especially in lung cancer, from what you guys have described here, is that the smoking status impacts what kind of KRAS alteration is present. But at the same time, you didn't see a tumor mutational burden that was significantly higher in G12C, mutated non-small cell lung cancer, where you would expect a lot of these G12Cs to be related to smoking. But on the other hand, the tumor mutational burden was not necessarily increased. And I understand you may not have an explanation for that through the data that you've published on, but that was kind of an interesting observation that I had. I don't know if you have any specific comments on that. Dr. Mohamed Salem: No, it's absolutely correct. What we thought is that we should see that because the obvious rationale is just cited, but it wasn't. And until today, we're actually trying to figure out why the disconnect because you have people who smoke usually you expect like PD-L1 is positive, you expect higher tumor burden, but it didn't show at least a statistically significant correlation.  Dr. Abdul Rafeh Naqash: Thank you. And I guess it's notable to mention that you did have some interesting correlations for tumor mutational burden overall, and with PD-L1. Could you tell us about that for different KRAS genetic alterations?  Dr. Mohamed Salem: There were few papers published before by our colleagues trying also to understand the correlation between G12C mutation and immunostatus or immune microenvironment and some biomarkers. And I think, at least to my understanding, there was not one consensus. I think it was different findings to some degree. So, in general, when we actually looked at the entire cohort, regardless of the tumor type, it appears that tumors that carry G12C mutation also happened to have higher PD-L1 expression. What was very interesting was that once we started to look at different tumor types, this was not seen across all tumors. So some tumors did actually carry that, and some other tumor types didn't show that correlation. And to be honest with you, I'm still, until today, I'm not sure why. Is this just a function of number, or actually there is more tumor biology that reflects that? I have to say my own feeling, and that's something we need to study further, is that I think it is tumor biology. One thing was also very interesting to us from the clinical side. You have G12C mutation in lung, and you have G12C mutation in colorectal, and in the New England Phase I study, you could see very clearly that targeted G12C is more effective in the lung compared to colorectal. It's the same target, the same drug, yet the response is different once you start to have two different tumor types. So that just got me to think there must be something with the tumor type and microenvironment of the tumor and also associated co-mutations and other factors that impact that.  Dr. Abdul Rafeh Naqash: I couldn't agree with you more, and I totally have seen that in some of the work that has been published or data that I've been part of where different tumor biology, the tumor microenvironments, even sites of metastasis make a difference in how a certain mutation behaves. So definitely something that needs further validation with perhaps proteomic and transcriptomic data to understand functional characterization of the downstream consequences for some of these mutations. And you pointed out co-mutation status. That's an ever-emerging question for some of the potentially druggable alterations, whether combination approaches targeting some other co-occurring common co-mutation would have more benefit. Could you tell us about some of the unique, interesting commutations that you identified in your cohort that were more common in certain KRAS subtypes? Dr. Mohamed Salem: Sure. I think that's also something we try to look at for the reason I just mentioned. We know that tumor origin and tumor type influence response and sensitivity to therapy. I think the best example we have, at least in colorectal cancer, is the BRAF mutation. When we saw the BRAF inhibitor having very nice response rate and control of BRAF mutant melanoma in colorectal cancer, we saw that it's going to be the same thing, the same drug, the same target, same thing's going to happen. And obviously, it was not the case. And this was a lesson for all of us to understand. Even if it is the same target, even if it's the same drug, tumor origin matters, and that's likely because of the associated co-mutations that will influence the pathway of the tumor and perhaps either the sensitivity to the drug or maybe resistance to the drug.  So it was very important for us to look also at the associated co-mutations. And I think one of the KEAP1, and perhaps you will comment on this more than me, but the KEAP1 gene was likely to be mutated in those tumors who have G12C mutation than others. Another one was STK11. And there were a few other ones, it depends on which tumor type, but KEAP1 was a very interesting finding for us too. Because as you're aware, it's important, at least in lung cancer, and maybe will impact therapeutic approach too. Dr. Abdul Rafeh Naqash: You're definitely right. It is important in lung cancer, and there's data that has shown both the STK11 and KEAP1 tumors have inferior outcomes to checkpoint inhibitors and are partly involved in metabolic reprogramming of the tumors. So there's definitely emerging targets that are trying to see if combination approaches in STK11 mutant lung cancer will demonstrate some level of benefit. But I think the co-mutation status would potentially have some sort of impact. But again, functional studies that help us understand what are the downstream consequences of one mutation versus another need to be further performed to get a better understanding of this space.   But I think this is definitely interesting work and very interesting results. Hopefully, our listeners will feel the same and maybe even try to go through the paper to understand some of the other additional results that you have published as part of this extensive paper.  We thank you on behalf of JCO Precision Oncology for submitting your work to JCO Precision Oncology, and hopefully, you'll consider us for further subsequent work in this space. Thank you so much for being with us today. Dr. Mohamed Salem:  No, thank you for having me, and actually, on behalf of my co-authors, I also wanted to thank JCO Precision Oncology for their interest in our paper. And, of course, for the reviewers, because there was no doubt they actually made our paper a much better one. So thank you for having me today, thank you for the entire team. Dr. Abdul Rafeh Naqash:  Reviewers definitely remain the people hidden behind the scenes who help in getting work refined and eventually published. So thank you again. And thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or a review, and be sure to subscribe, so you never miss an episode. You can find all ASCO shows at asco.org/podcasts   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experiences, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Guest Bio Mohamed E. Salem, MD, is Research Director, Associate Professor of Medicine, and Gastrointestinal Medical Oncologist in the Department of Solid Tumor Oncology at the Levine Cancer Institute.  Guest Disclosures (See also: Landscape of KRASG12C, Associated Genomic Alterations, and Interrelation With Immuno-Oncology Biomarkers in KRAS-Mutated Cancers) Mohamed Salem: Consulting or Advisory Role: Taiho Pharmaceutical, Exelixis, Bristol-Myers Squibb, QED Therapeutics, Novartis, Pfizer, Daiichi Sankyo/Astra Zeneca, Merck  Speakers' Bureau: Taiho Pharmaceutical, Daiichi Sankyo/Astra Zeneca, BMS, Merck, Pfizer 

Dr. Rachna Shroff, chair-elect of the 2023 ASCO GI Cancers Symposium, and guest host Dr. Shaalan Beg discuss new research presented at GI23, including new data from SWOG 1815 in biliary tract cancers, advances in biomarker studies in mCRC such as the PARADIGM trial, and promising updates in ctDNA technology. She also highlights the exciting potential of AI in oncology. TRANSCRIPT Dr. Shaalan Beg:  Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Shaalan Beg, your guest host of the podcast today. I'm an adjunct associate professor at UT Southwestern's Simmons Comprehensive Cancer Center and vice president of Oncology at Science 37. Today we'll be discussing key abstracts and other highlights from the 2023 ASCO Gastrointestinal Cancer Symposium, which celebrated 20 years of transformative care in GI cancers. I'm delighted to welcome Dr. Rachna Shroff, the chair-elect of this milestone meeting. Dr. Shroff is the interim division chief of Hematology Oncology at the University of Arizona Cancer Center. She also serves as the associate dean for Clinical and Translational Research and is the chief of GI Medical Oncology. Our full disclosures are available in the transcript of this episode, and disclosures related to all episodes of the podcast are available on our transcripts at ASCO.org/podcasts. Dr. Shroff, it's great to have you back on the ASCO Daily News podcast. Dr. Rachna Shroff: Thank you so much for having me. I'm so excited to be here. Dr. Shaalan Beg: The ASCO GI Cancers Symposium has been heralded as one of the biggest conferences in the GI cancer space and has occupied this space for the past two decades. Some would say that this year's conference was probably the best GI Cancers Symposium to date. Can you comment on the 20th anniversary milestone and the impact of the symposium on GI cancers? Dr. Rachna Shroff: Absolutely, and that's so great to hear that that's the feedback that you've heard. I have to say GI ASCO is absolutely my favorite meeting of the year, so that is my full disclosure. But I think that this was a tremendous meeting, and I think it was so beautiful that it was also coinciding with the 20th anniversary. It meant so much to us to have Dr. Margaret Tempero open the meeting because she really was the impetus for creating a GI cancer-focused meeting that really brought together multidisciplinary expertise. And so to us, that is what this 20th anniversary represented—20 years of multiple different specialties coming together to discuss how to improve cancer care for patients with gastrointestinal malignancies. And it has been a transformative meeting to see the impact of research presented at this meeting and how it has been implemented over the course of 20 years. And I completely agree that this year in and of itself had some incredible pivotal data that there is no doubt will be practice-changing, and that is absolutely the purpose. I also think that the beauty of this meeting is the networking opportunities for all of us to come out of our individual silos, come together, and discuss cross-cutting care across the spectrum of GI malignancies. And I think that this meeting really did that quite well. Dr. Shaalan Beg: There were many practice-changing studies that made headlines this year, and for me, one of the most anticipated studies was a trial that you led for cholangiocarcinoma and much-anticipated results. The study finished enrollment at a record pace. Can you share your key findings of cholangiocarcinoma? And I'd really like to hear your perspective on cholangiocarcinoma studies. Dr. Rachna Shroff: Yes, it was actually a really big year in the hepatobiliary space, and I was proud to present SWOG 1815, LBA 490, which was the pivotal randomized phase 3 trial looking at gemcitabine, cisplatin, and nab-paclitaxel versus gemcitabine and cisplatin. This was a study that was opened across the entire NCTN and based on a single-arm phase 2 trial that had shown some promising early efficacy of the triplet chemotherapy regimen. As you mentioned, this study accrued 441 patients in two years. And it's really a testament to the fact that the cooperative group mechanism can and should be asking important questions in large, randomized studies and that it is even possible to do in what are historically thought of as, quote-unquote, “rare tumors.” The study was a randomization of two to one to the triplet chemotherapy versus the standard of care for newly diagnosed biliary tract cancer patients. And the primary endpoint was median overall survival. And while the median OS of the triplet regimen was numerically improved at 14 months compared to 12.7 months, this did not meet statistical significance. Other efficacy endpoints, including median progression-free survival and overall response rate, were also numerically improved but not statistically significant, with an overall response rate of 31% with the triplet regimen versus 22%. There were some prespecified stratification factors, including disease site and disease stage, and there may be some interesting signals that bear out of that in terms of perhaps gallbladder cancer and locally advanced patients may be benefiting from the triplet regimen a little bit more, but these are small numbers, and we would really need to explore that in a more rigorous prospective manner. The toxicities were, not surprisingly, there, especially hematologic toxicities. I will say for those of us that use this regimen in practice, we use it a little bit differently than what was done in SWOG 1815, but you can't deny that there were significantly higher grade 3-5 toxicities with anemia neutropenia and thrombocytopenia, though the treatment discontinuation rate did not differ. I think the next steps are really going to be the ongoing biomarker analyses. The study had archival tissue and prospective blood collection and we know that in the space of cholangiocarcinomas and biliary cancers, molecular complexities absolutely play a role in how patients do and how they respond to therapies. So that's going to be an important next step, I think, for this study. Dr. Shaalan Beg: Speaking of biomarkers and an impact on GI cancers, the other malignancy where biomarkers are having a much greater impact than other GI cancers is colon cancer. Another year where we continue to see advances in our understanding of molecularly targeted treatments for colon cancer. What caught your eye? Dr. Rachna Shroff: Well, there were a lot of really interesting studies happening in this space and as a biliary person, one of the first things I got excited about was seeing Abstract 139 that looked at pemigatinib, which is the drug we are very familiar with in cholangiocarcinoma. This was a single-arm phase two study looking at the use of the FGFR inhibitor pemigatinib in metastatic colorectal cancer patients who had FGFR alterations. And so this was a study that was opened through the ACCRU mechanism. It was multicenter with assignment two-stage design and it was specifically for patients with FGF and FGFR-altered metastatic colorectal cancer who had progressed on standard therapies. There was a prespecified interim analysis for futility after 12 evaluable patients and so 14 patients were enrolled in the first stage of the study and evaluated for the primary endpoint of objective response. What was seen and the study was subsequently stopped is that there was really not much efficacy, there was no evidence of safety signals, but this did not seem to be a very active drug in patients with FGFR alterations with no objective response noted. So, the study was stopped with the recognition that perhaps the FGFR translocation or fusion patient population may be something to explore since they did not look at that in this study. The other kind of study that I think is really important was important work of Dr. Raghav and colleagues through SWOG. This was SWOG 1613 Abstract 140. This was the first real study that was investigating targeting HER-2 overexpressed and amplified metastatic colorectal cancer who had RAS wild-type tumors. And it was based on, obviously, some early signals of the effectiveness of HER-2 targeting in metastatic colorectal cancer. And this was a large study looking at pertuzumab and trastuzumab in these patients. They were compared to cetuximab and irinotecan, and the initial plan was for a much larger study. Unfortunately, accrual was really slow so the study was really kind of reformatted and a total of 54 patients were randomized, 26 to the trastuzumab arm and 28 to the CetIri or cetuximab and irinotecan arm. What was seen was that you can absolutely use HER-2 targeting therapies with trastuzumab and pertuzumab in these patients. It was safe and there were some obvious signs of efficacy in terms of overall response rate with an overall response rate of 31% compared to the CetIri arm. Crossover was allowed from the CetIri arm to trastuzumab and pertuzumab. So just that's important to keep in mind when they start to follow out the survival data. But unfortunately, because this study did not accrue, it was stopped early and it's really hard to understand in terms of power calculations the impact of trastuzumab pertuzumab. Of course, we can't talk about this without recognizing that the FDA approval based on the MOUNTAINEER study for tucatinib and trastuzumab came through during GI ASCO. So clearly HER-2 targeting is here to stay in colorectal cancer. Dr. Shaalan Beg: So technology is advancing every year and it's important that we are aware of these advances and how they impact our patients. Probably one of the most exciting technologies in oncology in general is the evolution of ctDNA. And it's been amazing to watch that field unfold as we understand how to use circulating biomarkers for early detection of cancer, for minimal residual disease detection, even as a biomarker of response. What caught your eye when it comes to the use of ctDNA in GI cancers, and how do you see this space develop in the next couple of years? Dr. Rachna Shroff: I completely agree. I think the technology of ctDNA is so incredibly exciting and as somebody who does not actively see and treat colorectal cancer, I'm a little bit envious of my colleagues in that space because the strides that have been made in terms of understanding the utility of ctDNA, especially in colorectal cancer, has just been tremendous and even for the last two to three years. One perfect example of integrating that sort of technology into treatment paradigms is the PARADIGM trial, Abstract 11, which was looking at the concept of hyperselection of patients with RAS wild-type metastatic colorectal cancer who were on the PARADIGM trial which basically looked at frontline FOLFOX with panitumumab versus bevacizumab in patients with RAS wild type left-sided metastatic colorectal cancer. So, you know, the initial data from PARADIGM had demonstrated a longer median overall survival 37.9 months versus 34.3 months, but very smartly, the investigators had also collected baseline plasma ctDNA in the biomarker component of this study and used a custom panel that looked at gene alterations for hyperselection and that included KRAS, NRAS, PTEN, and extracellular domain EGFR mutations HER-2 and MET amplifications, as well as some fusions like ALK, RET, and NTRK. And so out of the 802 patients in the full set, 91% - 733 patients - actually had pretreatment samples for ctDNA, which is really in and of itself, I think, tremendous. And when you break it down, about 28% had at least one gene alteration, and that was across each of those different genes that they were looking at. In the 72% of patients who were defined as hyperselected without any gene alterations, the OS was actually longer with panitumumab versus bev, and that actually was independent of sidedness with hazard ratios that kind of ranged from 0.76 to 0.82. And OS was similar or inferior with panitumumab versus bevacizumab again, regardless of sidedness in patients with any of these gene alterations. And so I think it's a really interesting concept that you can use ctDNA to define negative hyperselection rather than looking at left sided and right sided to really help select patients with frontline therapy in terms of using panitumumab versus bevacizumab. And with the speed with which ctDNA can be obtained, this actually seems like something that could be implemented into clinical practice, which is, I think, really the important component of that. There were a number of other really interesting abstracts. Abstract 5, presented by Dr. Cohen and colleagues, really looked at the kinetics of circulating cell-free DNA and how that kind of relates to minimal residual disease detection rates. And this was in patients with resected stages one through three colorectal cancer. And so, this was a retrospective study, so we have to keep that in mind. And it was multi-institutional in really over 16,000 patients with stages 1 through 3 colorectal cancer. But the complete dataset had about 417 patients and basically the patients' circulating cell-free DNA levels, the total cfDNA, were compared to the ctDNA MRD positivity rates and they looked at very specific time points after surgery. What the authors generally found was that the postoperative cfDNA correlated well with ctDNA positivity and that there was really the ability to see plasma cfDNA levels kind of track and follow with the very specific MRD windows that were being looked at, which really, again, just kind of talks about leveraging this technology in terms of real-world and real-time application and better understanding and informing us of minimal residual disease post what is thought to be curative resection. The last one that I thought was really interesting in relation to ctDNA was actually looking at anal cancer and following ctDNA in patients who were treated with definitive chemoradiation. This was a study that was looking at 31 patients with anal squamous cell carcinoma who were treated with definitive chemo radiation and underwent ctDNA response. The majority of these patients had stage 3 disease and the majority of them received the standard 5-FU Mitomycin with radiation. The patients had ctDNA testing performed in 25 of these patients at baseline and then a smaller number over the course of time, some during chemoradiation. And then they looked again at 30 days post chemoradiation. And at baseline, 88% of patients had detectable ctDNA with those with stage three disease having numerically higher baseline ctDNA levels. And basically what they found was that over the course of treatment, ctDNA levels decreased among the patients with detectable ctDNA. And then ctDNA that tested during chemo radiation showed a drop in decline and were going into molecular remission at a time point in which it was subsequently confirmed that they had a clinical complete response. So, the suggestion here is that the time to molecular ctDNA remission was significantly shorter than being able to see that clinical complete response, which suggests that using surveillance ctDNA monitoring could be an earlier response assessment for patients with anal squamous cell carcinoma who are undergoing definitive therapy. Now, obviously this needs to be confirmed in a larger manner, but again, really suggests that we could be understanding how we're doing with treatment in more of a real-time fashion, which I just think is incredible for those of us who are making sure that we are doing and taking the right approaches for these patients. Dr. Shaalan Beg: One of the major transformative announcements that took place only a couple of months before the GI Cancer Symposium was the announcement of ChatGPT. And we heard a lot of discussion on how it can be used for improving cancer care, improving drug development, and in general, artificial intelligence and machine learning. We've been hearing these buzzwords for such a long time, to the point that a lot of people are probably just filtering it out and then this tool comes up and it makes it real. And we're seeing different people apply these technologies in different ways. But there is tremendous potential in how this technology can improve clinical trials, drug development, and early diagnosis. And luckily, we had already secured a keynote speaker, Dr. Matthew Lundgren from Nuance Communications, and he was invited to talk about artificial intelligence, machine learning, and how it applies to cancer care. I'm really curious to hear what your highlights were from his address and how you see this impacting your day-to-day, or just the ecosystem of which we're all part of. Dr. Rachna Shroff: Yeah, I will say that his keynote was really one of the highlights of the entire meeting for me. And that is coming from somebody who doesn't really know– I know who I'm speaking to, but somebody who does not truly understand the way AI is moving. And so, I was joking with him that it was like AI 101. And I really, really appreciated the way he was able to kind of speak to a crowd that he doesn't normally speak to and help us really understand the way in which artificial intelligence can be integrated into healthcare, and specifically oncology. To me, I think what were the most salient takeaways from his address was really about how this is just a rapidly evolving field and we need to be a little bit ahead of the eight ball when it comes to thinking how we can smartly leverage artificial intelligence like you mentioned, to improve our clinical research efforts, to improve access, and to improve fully integrating AI into our EMR, so that we can really leverage that technology and ensure that we are capturing every potential patient for a clinical trial and be smarter about how we're even approaching things. I mean, I loved him talking about the prior authorizations and that sort of thing, and the ways in which we can decrease the burden on health care providers and really let us focus on the areas that we need to focus on. The one thing that I thought was a really important point, though, and I think a number of people asked him, was about how using this technology has the potential to create more gaps and disparities and how can we be smart to ensure that we don't broaden those gaps. And I think that is a really important point that we all need to think about because we know that especially when we think through clinical trials, there's already underrepresentation of certain populations and certain geographic regions. And so, I think that was a really important takeaway for me is how can we make sure that we work and partner with those who are creating these technologies to ensure that we aren't taking two steps forward and four steps back. Dr. Shaalan Beg: It really calls into question how we define productivity and what our value in the entire delivery system really is. And I think from people who are in middle school or high school to people who are in college and even folks who are in the field as you and I are, it's forcing us to rethink what we bring to the table in a way that we've never been challenged to ask that question ever before. Dr. Rachna Shroff: Absolutely. Dr. Shaalan Beg: So, thank you very much, Dr. Shroff. This was wonderful. Thank you for sharing your insights with us today. And we thank you and Dr. George Chang, the chair of the ASCO GI Cancers Symposium, and everyone who worked so hard to develop a robust program this year.  Dr. Rachna Shroff: Thank you. It was so wonderful to be able to speak about it. And thank you to all of the attendees for making it such a memorable meeting. Dr. Shaalan Beg: And thank you to all our listeners for your time today. You'll find links to the abstracts discussed today on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News podcast, please take a moment to rate, review, and subscribe wherever you get your podcast. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experiences, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers: Dr. Shaalan Beg @ShaalanBeg Dr. Rachna Shroff @rachnatshroff Follow ASCO on social media:  @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn  Disclosures: Dr. Shaalan Beg: Employment: Science 37 Consulting or Advisory Role: Ipsen, Array BioPharma, AstraZeneca/MedImmune, Cancer Commons, Legend Biotech, Foundation Medicine Research Funding (Inst.): Bristol-Myers Squibb, AstraZeneca/MedImmune, Merck Serono, Five Prime Therapeutics, MedImmune, Genentech, Immunesensor, Tolero Pharmaceuticals Dr. Rachna Shroff: Consulting or Advisory Role: Exelixis, Merck, QED Therapeutics, Incyte, Astra Zeneca, Taiho Pharmaceutical, Boehringer Ingelheim, SERVIER, Genentech, Basilea Research Funding: Pieris Pharmaceuticals, Taiho Pharmaceutical, Merck, Exelixis, QED Therapeutics, Rafael Pharmaceuticals, Bristol-Myers Squibb, Bayer, Immunovaccine, Seagen, Novocure, Nucana, Loxo/Lilly, Faeth Therapeutics        

Dr. Rachna Shroff, of the University of Arizona Cancer Center, tells guest host, Dr. Shaalan Beg, of UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and Science 37, about advances in precision medicine for pancreatic cancer featured at the 2022 ASCO Annual Meeting. She also highlights compelling new data from the FOLFOX, FOENIX-CCA2, and HERB trials in hepatocellular carcinoma, cholangiocarcinoma, and biliary tract cancer.   TRANSCRIPT Dr. Shaalan Beg: Hello and welcome to the ASCO Daily News podcast. I'm Dr. Shaalan Beg, your guest host of the ASCO Daily News podcast today. I'm an adjunct associate professor at UT Southwestern Simmons Comprehensive Cancer Center and vice president of oncology at Science 37. I'm delighted to welcome Dr. Rachna Shroff, the associate dean for clinical and translational research and the chief of gastrointestinal (GI) medical oncology at the University of Arizona Cancer Center where she's also the interim chief of Hematology-Oncology. Dr. Shroff is also the chair-elect for the Gastrointestinal Cancer Symposium. Today we'll be discussing key abstracts in GI cancer that were featured at the 2022 ASCO Annual Meeting. Our full disclosures are available in the show notes and disclosures of all our guests on the podcast can be found on our transcripts at asco.org/podcasts. Dr. Shroff, thank you for being on the podcast today. Dr. Rachna Shroff: Thank you so much for having me. Dr. Shaalan Beg: Let's begin by reviewing what is new in the realm of precision medicine in GI cancers. One of the diseases where precision medicine has not made adequate inroads is pancreatic cancer. One of the most common mutations in pancreas cancer is KRAS, but there haven't been a lot of treatments that can target the most common forms of KRAS. What did we hear at ASCO22 regarding precision medicine and pancreatic cancer? Dr. Rachna Shroff: I agree, I think that the area of precision oncology is, unfortunately, lagging behind a little bit in pancreatic cancer. But I think as we have gotten better and better with our comprehensive genomic profiling, we are identifying subsets of patients within pancreas cancer who are potentially amenable to targeted therapies. You already mentioned KRAS mutations, and we obviously have a number of inhibitors in development in that space, though, we are still missing that key G12D mutation that we see in pancreas cancer. But what I think was really interesting that came out of ASCO22, was a lot of interest and emphasis on better understanding the KRAS wild-type patients in pancreatic cancer. Now, this is obviously a smaller subset of patients, given that the majority of patients have KRAS mutations. But there was a really interesting abstract, LBA4011, that looked at patients with locally advanced or metastatic pancreatic cancer, who were KRAS wild-type. They actually received gemcitabine in combination with a monoclonal antibody targeting EGFR and nimotuzumab. This was a study that was done entirely in Asia. It involved 92 Chinese patients that were randomly assigned to receive the combination of nimotuzumab with gemcitabine. What was interesting in this study is that the patients were found in the full analysis set to have a significantly longer median overall survival of 10.9 months versus 8.5 months with a hazard ratio of 0.5. So, that of course was intriguing and provocative for sure. Similarly, the other endpoints were also somewhat intriguing in terms of improvements in the median progression-free survival (PFS), etc. And specifically, patients without biliary obstruction had a longer PFS, which was an interesting finding as well. The nimotuzumab overall was pretty well tolerated and not any sort of surprising treatment-related adverse events (TRAEs) were noted. And so, this is definitely a drug that, I think, piques our interest in terms of being able to target patients with KRAS wild-type pancreatic cancer. I think that questions, however, that remain, and I think require further study is really understanding what this drug could do in combination with the chemotherapy combinations that we use more frequently in metastatic pancreatic cancers such as gemcitabine and paclitaxel or 5FU-based regimens like FOLFIRINOX. I think given that it is a relatively well-tolerated drug, it would be a very reasonable thing to investigate this drug further in the KRAS wild-type population with the kind of modern-day chemotherapy regimens that we use. And I think, of course, we all know that it is useful to be able to look at these types of drugs in a more global population. And so, a larger patient set I think would be very useful as well, but at least it tells us that there is a way to think about our KRAS wild-type patients with pancreas cancer and that perhaps we really need to understand and identify those patients' potential for precision oncology. Dr. Shaalan Beg: One of the GI cancers that has been a hotbed for precision medicine is cholangiocarcinoma, a disease that's very close to your heart. What updates did we hear at ASCO22 regarding cholangiocarcinoma and precision medicine? Dr. Rachna Shroff: This space of targeted therapy and cholangiocarcinoma has been incredibly exciting for the last few years and I think drug development has been rapid-fire in that space. The oldest, if you will, target that we've been thinking about for some time is the FGFR2 fusion patient population. And in Abstract 4009 by Dr. Goyal and colleagues, we saw the results of the FOENIX-CCA 2 trial which was looking at an oral FGFR inhibitor (futibatinib) in patients with intrahepatic cholangiocarcinoma, who harbor FGFR2 fusions and gene rearrangements. We had initially seen some of this data presented a few years back, but this was the updated data set. It was a single-arm phase 2 study that involved patients with advanced intrahepatic cholangiocarcinoma who had identified FGFR2 gene fusions, and they received futibatinib daily until progression. This was a traditional single-arm phase 2 study with a primary endpoint of overall response rate. At the final data cut, with a median follow-up of 25 months, there's actually a confirmed overall response rate of 41.7%. And I think that what was really exciting about this is this is a refractory patient population. So, in patients who have refractory cholangiocarcinoma, the other drugs, the non-targeted therapy drugs that we think through, really have response rates more in the single-digit to 10% range and so to have a confirmed overall response (OR) over 40% is truly exciting. The duration of the response was also exciting. This is not just a drug that works briefly, it has a duration of response of 9.5 months. And the mature median overall survival was 20 months. And in a disease which we talk about with the ABC-02 data of GemCis, a median OS in advanced disease of 11.7 months. This is really, really exciting for patients who harbor this fusion or gene rearrangement. We know that that's seen in about 10 to 15% of patients. So, again, we're dealing with a smaller subset, but it clearly demonstrates the need to identify FGFR2 gene fusions, so that we can offer these types of targeted therapies. This was not the first FGFR inhibitor that we have seen data on and in fact, we have 2 drugs already U.S. Food and Drug Administration (FDA) approved. And so, when we look at the common treatment-related adverse events that were identified with the futibatinib, there are really class effects related to FGFR inhibition like hyperphosphatemia, alopecia, dry mouth, nothing that really stood out or that was concerning. And so, I think this final analysis for the FOENIX study really just reaffirms the utility of futibatinib in patients with FGFR2 gene fusions, and the mature OS data, the duration of response, all of this really aligns with the need to identify patients with this alteration so that we can, post-gemcitabine based therapies, offer this targeted therapy or an FGFR inhibitor in general to these patients. I think the other really exciting abstract in the glandular carcinoma or biliary tract cancer space was Abstract 4006. This was the updated data from the HERB trial, which was an investigator-initiated multicenter phase 2 trial looking at trastuzumab deruxtecan (T-DXd) in patients who have HER2 expressing unresectable or recurrent biliary tract cancer. Trastuzumab deruxtecan, I'm sure everybody has been hearing about because it has been incredibly effective in HER2 alterations across a myriad of different disease sites. And so, not wanting to be left out, biliary tract cancers were investigated in this study with patients who had HER2 expression, so, that was HER2-positive IHC3+ or IHC2+/ISH+, and they also looked at HER2-low expressing patients, and [whose disease] were refractory or intolerant to gemcitabine-based therapy with the primary endpoint of overall response rate. So, in the HERB trial, a total of 32 patients were enrolled. 24 of them were HER2-positive and 8 were HER2-low and they all received trastuzumab deruxtecan. When you look at the efficacy data, the confirmed overall response rate in the patients with HER2-positive was 36.4%, which again, as I said, in a refractory patient population is certainly very exciting data. And the overall disease control median, PFS, and median OS were all pretty encouraging in terms of efficacy. What was also kind of intriguing was that there was some efficacy seen even in the patients who are HER2-low. Now, this is, in my opinion, a slightly less exciting amount of efficacy, but still important to note that the overall response rate in HER2-low was 12.5% with a median PFS that was also somewhat exciting at 4.2 months. And so, there is a potential clearly for targeting patients with HER2-high or HER2-positive with trastuzumab deruxtecan, and I think in the patients who are HER2-low, we need to better understand the potential utility. The common treatment-related adverse events that we see were the typical things that we've heard about with trastuzumab deruxtecan, but I think the one thing that was really worth noting was 8 patients or 25% of patients had interstitial lung disease (ILD), which we know is an important identified safety concern for patients who receive trastuzumab deruxtecan, and I think that's a pretty sizable number of 25%, so, I think that's going to really require a little bit more fleshing out for us to understand the safety for these patients. One question that a lot of us have had is whether these are patients who have received gemcitabine, which we know can also cause pneumonitis. And so, I don't know if we're seeing a higher percentage of ILD because of, 'priming' with prior gemcitabine. But regardless, I think this is just proof of principle that again, we need to identify patients with biliary tract cancers that have HER2-positivity because we now have a number of drugs including potentially trastuzamab deruxtecan to target [their disease] with after gemcitabine-based treatments Dr. Shaalan Beg: Absolutely. Any new biomarkers to keep on the radar for our listeners? Dr. Rachna Shroff: I think there are a lot of really exciting targets. One that was talked about and that we saw data on at ASCO [Annual Meeting] was from Abstract 4048, which looked at claudin [18]. Claudin is basically a transmembrane protein that kind of helps maintain the tight junctions between cells. In gastric cancer, in particular, we look at claudin 18 isoform 2, and there are 18.1 and 18.2 gene expressions that have been identified in gastric cancer. So, there was a very comprehensive abstract that was presented of over 1,900 samples that underwent comprehensive profiling by next-generation sequencing. And the patients were identified with claudin 18.1, and 18.2, high versus low. Claudin 18.2 expression was actually detected in 97% of the samples. It's slightly lower with claudin 18.1 at 63%. It's important to note that the primary tumors had higher expression levels than the metastatic tumors, so those were really the tumors in which they did a deeper dive. And in the process of doing this deeper dive, they did a really interesting kind of better understanding of the immune microenvironment and the immune profile in the samples that had claudin expression. And what was identified is that there was an inverse relationship basically between claudin 18.1 and 18.2 expression and correlation with PD-L1 positivity, tumor mutational burden (TMB)-high, M1 macrophages expression, NK cell presence, CD4 positive T-cells, myeloid dendritic cells. And so, there's clearly something between the presence of this claudin expression and the effect it has on the immune microenvironment. I think that's very relevant to keep in mind because as we all know, there's a whole space of drug development focused right now on anti-claudin 18.2 monoclonal antibodies, as well as a target for antibody-drug conjugates (ADC) and cellular therapies with CAR T-cell therapies being developed specifically against claudin 18. And so, understanding the immune microenvironment and the interaction between the claudin expression will be really important as we continue to charge forward in that space. Dr. Shaalan Beg: Absolutely. Very, very exciting. Sticking with the liver pancreas theme, what other studies piqued your interest with regards to hepatocellular carcinoma (HCC)? Dr. Rachna Shroff: It's a really exciting time in HCC. I mean, we actually have drugs that are working in the advanced space. And so, now there's a lot of interest in shifting to looking at preoperative neoadjuvant, and adjuvant approaches and what we can do to improve disease-free survival and overall survival in patients who are able to undergo prior resection. So, Abstract 4013 looked specifically at the efficacy and safety of adjuvant hepatic arterial infusion chemotherapy with FOLFOX. And this was a randomized open-label phase 3 trial. It actually included a total of 315 patients between 5 different centers and patients were randomly assigned to receive either 1 to 2 cycles of adjuvant HAIC FOLFOX (Hepatic Arterial Infusion Chemotherapy FOLFOX) versus just follow up, the control group had no adjuvant treatment, and the primary endpoint was disease-free survival here and in the intention to treat population, there was a significantly improved median disease-free survival at 27 months versus 11 months in the patients who were on the control arm. And there was a protocol analysis, there were a number of other efficacy endpoints including disease-free survival rates at 1, 2, and 3 years. And everything kind of leaned towards and or suggested an improvement with the utility of HAI FOLFOX in patients who undergo complete resection. It should be noted that this included patients specifically who had microvascular invasion on their resection. And so, these are patients who are at higher risk for recurrence as we know. This to me suggests that there could be a role for adjuvant treatment in patients who undergo complete resection with microvascular invasion (MVI). HAI is a very specific technique and it requires a highly skilled center in the placement of HAI pumps. And we're seeing more and more trials across the U.S. as well investigating the role of HAI in advanced disease and in perioperative approaches. And so, I think this is an area of much-needed continued research. There are, of course, a number of ongoing adjuvant studies looking at immunotherapy in the adjuvant setting. And so, it'll be really important to see how those read out and then to try to put all of these in context so that we can better understand local therapy like HAI FOLFOX versus more systemic adjuvant approaches like immunotherapy. Dr. Shaalan Beg: Thank you very much, Dr. Shroff for sharing your valuable insights with us. I really appreciate you taking the time to spend with us and our listeners. Dr. Rachna Shroff: Thanks so much. I enjoyed it. Dr. Shaalan Beg: And thank you to our listeners for your time today. You will find links to the abstracts discussed today in the transcript of this episode. Finally, we'd really like to hear your feedback. If you could please take a moment to rate, review, and subscribe wherever you get your podcasts. Thank you very much!   Disclosures: Dr. Shaalan Beg: Employment: Science 37 Consulting or Advisory Role: Ipsen, Array BioPharma, AstraZeneca/MedImmune, Cancer Commons, Legend Biotech, Foundation Medicine Research Funding (Inst.): Bristol-Myers Squibb, AstraZeneca/MedImmune, Merck Serono, Five Prime Therapeutics, MedImmune, Genentech, Immunesensor, Tolero Pharmaceuticals Dr. Rachna Shroff: Consulting or Advisory Role: Exelixis, Merck, QED Therapeutics, Incyte, Astra Zeneca, Taiho Pharmaceutical, Boehringer Ingelheim, SERVIER, Genentech, Basilea Research Funding: Pieris Pharmaceuticals, Taiho Pharmaceutical, Merck, Exelixis, QED Therapeutics, Rafael Pharmaceuticals, Bristol-Myers Squibb, Bayer, Immunovaccine, Seagen, Novocure, Nucana, Loxo/Lilly, Faeth Therapeutics Disclaimer: The purpose of this podcast is to educate and inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.  

Inês' 9-year-old daughter, Clara, is living with achondroplasia. In this episode of On Rare, Inês describes what it was like to learn that her daughter has achondroplasia. She describes the steps she took to get Clara the medical care she needed in the early years of her life and how, in the midst of this stress, she remembered to enjoy being a mother to her newborn daughter. Finally, she tells us how she has watched Clara become a resilient, athletic child who has learned to compete against herself in a world that often caters to taller individuals. Daniela Rogoff, VP of clinical development at BridgeBio's affiliate company QED Therapeutics, joins the conversation to provide an overview of achondroplasia and to explain how it affects bone growth and the body overall.

In her 20s, Chaundra believed she was living the dream with a graduate degree and a new, exciting job. Unfortunately, at the age of 29, results from a routine blood test led to a diagnosis of cholangiocarcinoma. Six years later, Chaundra has endured chemotherapy treatments, surgeries, biopsies, multiple clinical trials and much more. Despite her diagnosis, Chaundra is determined and driven. She has taken on new professional opportunities in different cities, has been promoted in her work, fallen in love, and even, run for political office and won.” She tells David Rintell, head of patient advocacy at BridgeBio, “I am not going to let cancer stop me.”   Dr. Carl Dambkowski, chief medical officer at QED Therapeutics, an affiliate company of BridgeBio, also joins the conversation to describe cholangiocarcinoma, explain why it is difficult to detect and diagnose, and provide updates on how the recent advances in genetic testing has changed the treatment landscape for people with cholangiocarcinoma.

Today, we check in with Dave Fleischer who's just completed his Journey of Hope in memory of his daughter, Sarah, who passed away in 2018 from a horrible cancer, cholangiocarcinoma.In this episode, Dave reports in from Maine after driving more than 15,000 miles as he crisscrossed the country and visited 19 communities called Hope, numerous cholangiocarcinoma caregivers, patients and families. A major goal of the trip, which took Dave to all 48 contiguous states, was to raise money to support research into Cholangiocarcinoma and to spread awareness and bring hope to patients, caregivers, and others along the way. At more than $50,000, exceeded the goal of $45,000 – and more donations are still being accepted.The road trip, in a car with a specially designed wrap promoting cholangiocarcinoma awareness, included stops at hospitals and healthcare institutions that specialize in research and treatment of the disease, plus the get-togethers with patients, caregivers and healthcare providers who were important in Sarah's life. In today's episode, Dave reports on more of these meetings, some that proved to be especially meaningful to him. One such meetup was with Tom Lietzke, a 14-year survivor of Cholangiocarcinoma, and who prepared the image used for this episode.Cholangiocarcinoma starts in the bile duct and is an incredibly deadly cancer, which afflicts about 8,000 people in the United States each year. Most of its victims are 65 or older, but Sarah was only 31 when she was diagnosed. She passed away at age 35.The trip was supported by the Cholangiocarcinoma Foundation, which made the specially designed Honda SUV available for the journey. Sponsors were Incyte, Ken Garff Honda, QED Therapeutics, Servier, Taiho Oncology, Welch's Fruit Snacks and Zymeworks. Tee shirts commemorating the trip are available by clicking on the store at https:cholangiocarcinoma.org.And now, let's talk with Dave Fleischer as he reports in after his sixth and final week on the Journey of Hope.Become a supporter of this podcast: https://www.spreaker.com/podcast/the-lean-to-the-left-podcast--4719048/support.

Today, we check in with Dave Fleischer who's just completed his Journey of Hope in memory of his daughter, Sarah, who passed away in 2018 from a horrible cancer, cholangiocarcinoma.In this episode, Dave reports in from Maine after driving more than 15,000 miles as he crisscrossed the country and visited 19 communities called Hope, numerous cholangiocarcinoma caregivers, patients and families. A major goal of the trip, which took Dave to all 48 contiguous states, was to raise money to support research into Cholangiocarcinoma and to spread awareness and bring hope to patients, caregivers, and others along the way. At more than $50,000, exceeded the goal of $45,000 – and more donations are still being accepted.The road trip, in a car with a specially designed wrap promoting cholangiocarcinoma awareness, included stops at hospitals and healthcare institutions that specialize in research and treatment of the disease, plus the get-togethers with patients, caregivers and healthcare providers who were important in Sarah's life. In today's episode, Dave reports on more of these meetings, some that proved to be especially meaningful to him. One such meetup was with Tom Lietzke, a 14-year survivor of Cholangiocarcinoma, and who prepared the image used for this episode.Cholangiocarcinoma starts in the bile duct and is an incredibly deadly cancer, which afflicts about 8,000 people in the United States each year. Most of its victims are 65 or older, but Sarah was only 31 when she was diagnosed. She passed away at age 35.The trip was supported by the Cholangiocarcinoma Foundation, which made the specially designed Honda SUV available for the journey. Sponsors were Incyte, Ken Garff Honda, QED Therapeutics, Servier, Taiho Oncology, Welch's Fruit Snacks and Zymeworks. Tee shirts commemorating the trip are available by clicking on the store at https:cholangiocarcinoma.org.And now, let's talk with Dave Fleischer as he reports in after his sixth and final week on the Journey of Hope.

Today, we check in with Dave Fleischer who's just completed his fifth week of the Journey of Hope in memory of his daughter, Sarah, who passed away in 2018 from a horrible cancer, cholangiocarcinoma.In this episode, Dave reports in from Colorado Springs, Colorado after driving 13,000 miles as he's crossed the country and visited several towns called Hope, numerous cholangiocarcinoma caregivers, patients and families. Altogether, plans call for the trip to include stops in 19 towns named Hope all across the country.A major goal of the trip, which is taking Dave to all 48 contiguous states, is to raise money to support research into Cholangiocarcinoma and to spread awareness and bring hope to patients, caregivers, and others along the way. He's nearly reached the goal of $45,000 – and with one week to go, is secretly hoping to raise even more. The journey is scheduled to end June 30.The road trip, in a car with a specially designed wrap promoting cholangiocarcinoma awareness, includes stops at hospitals and healthcare institutions that specialize in research and treatment of the disease, plus the get-togethers with patients, caregivers and healthcare providers who were important in Sarah's life. He reports on more of these in this episode.Cholangiocarcinoma starts in the bile duct and is an incredibly deadly cancer, which afflicts about 8,000 people in the United States each year. Most of its victims are 65 or older, but Sarah was only 31 when she was diagnosed. She passed away at age 35.The trip is being supported by the Cholangiocarcinoma Foundation, which has made the specially designed Honda SUV available for the journey. Sponsors are Incyte, Ken Garff Honda, QED Therapeutics, Servier, Taiho Oncology, Welch's Fruit Snacks and Zymeworks. Tee shirts commemorating the trip are available by clicking on the store at https:cholangiocarcinoma.org.And now, let's talk with Dave Fleischer as he reports in after his fifth week on the Journey of Hope.Become a supporter of this podcast: https://www.spreaker.com/podcast/the-lean-to-the-left-podcast--4719048/support.

Today, we check in with Dave Fleischer who's just completed his fifth week of the Journey of Hope in memory of his daughter, Sarah, who passed away in 2018 from a horrible cancer, cholangiocarcinoma.In this episode, Dave reports in from Colorado Springs, Colorado after driving 13,000 miles as he's crossed the country and visited several towns called Hope, numerous cholangiocarcinoma caregivers, patients and families. Altogether, plans call for the trip to include stops in 19 towns named Hope all across the country.A major goal of the trip, which is taking Dave to all 48 contiguous states, is to raise money to support research into Cholangiocarcinoma and to spread awareness and bring hope to patients, caregivers, and others along the way. He's nearly reached the goal of $45,000 – and with one week to go, is secretly hoping to raise even more. The journey is scheduled to end June 30.The road trip, in a car with a specially designed wrap promoting cholangiocarcinoma awareness, includes stops at hospitals and healthcare institutions that specialize in research and treatment of the disease, plus the get-togethers with patients, caregivers and healthcare providers who were important in Sarah's life. He reports on more of these in this episode.Cholangiocarcinoma starts in the bile duct and is an incredibly deadly cancer, which afflicts about 8,000 people in the United States each year. Most of its victims are 65 or older, but Sarah was only 31 when she was diagnosed. She passed away at age 35.The trip is being supported by the Cholangiocarcinoma Foundation, which has made the specially designed Honda SUV available for the journey. Sponsors are Incyte, Ken Garff Honda, QED Therapeutics, Servier, Taiho Oncology, Welch's Fruit Snacks and Zymeworks. Tee shirts commemorating the trip are available by clicking on the store at https:cholangiocarcinoma.org.And now, let's talk with Dave Fleischer as he reports in after his fifth week on the Journey of Hope.

Hey guys, thanks for stopping by the NFN Radio News podcast. Today, we check in with Dave Fleischer who's just completed his fourth week of the Journey of Hope in memory of his daughter, Sarah, who passed away in 2018 from a horrible cancer, cholangiocarcinoma.In this episode, Dave reports in from Hershey, PA after driving 10,000 miles as he's crossed the country and visited several towns called Hope, numerous cholangiocarcinoma caregivers, patients and families. Altogether, plans call for the trip to include stops in 17, maybe 18 towns named Hope all across the country.A major goal of the trip, which will take Dave to all 48 contiguous states, is to help raise money to support research into this disease and during which they hope to spread awareness and bring hope to patients, caregivers, and others along the way. He's closing in on the goal of $45,000 – and the trip has two weeks to go. The journey is scheduled to end June 29 or July 1, depending on circumstances.The road trip, in a car with a specially designed wrap promoting cholangiocarcinoma awareness, includes stops at various hospitals and healthcare institutions that specialize in research and treatment of the disease, in addition to the get-togethers with patients, caregivers and healthcare providers who were important in Sarah's life. He says those visits are remarkable.Cholangiocarcinoma starts in the bile duct and is an incredibly deadly cancer, which afflicts about 8,000 people in the United States each year. Most of its victims are 65 or older, but Sarah was only 31 when she was diagnosed. She passed away at age 35.The trip is being supported by the Cholangiocarcinoma Foundation, which has made the specially designed Honda SUV available for the journey. Sponsors are Incyte, Ken Garff Honda, QED Therapeutics, Servier, Taiho Oncology, Welch's Fruit Snacks and Zymeworks. Tee shirts commemorating the trip are available by clicking on the store at https:cholangiocarcinoma.org.And now, let's talk with Dave Fleischer as he reports in after his fourth week on the Journey of Hope, during which he'll share with us what he's been thinking about while driving all those miles by himself. Some of it's funny. Some pretty meaningful.Become a supporter of this podcast: https://www.spreaker.com/podcast/the-lean-to-the-left-podcast--4719048/support.

Hey guys, thanks for stopping by the NFN Radio News podcast. Today, we check in with Dave Fleischer who's just completed his fourth week of the Journey of Hope in memory of his daughter, Sarah, who passed away in 2018 from a horrible cancer, cholangiocarcinoma.In this episode, Dave reports in from Hershey, PA after driving 10,000 miles as he's crossed the country and visited several towns called Hope, numerous cholangiocarcinoma caregivers, patients and families. Altogether, plans call for the trip to include stops in 17, maybe 18 towns named Hope all across the country.A major goal of the trip, which will take Dave to all 48 contiguous states, is to help raise money to support research into this disease and during which they hope to spread awareness and bring hope to patients, caregivers, and others along the way. He's closing in on the goal of $45,000 – and the trip has two weeks to go. The journey is scheduled to end June 29 or July 1, depending on circumstances.The road trip, in a car with a specially designed wrap promoting cholangiocarcinoma awareness, includes stops at various hospitals and healthcare institutions that specialize in research and treatment of the disease, in addition to the get-togethers with patients, caregivers and healthcare providers who were important in Sarah's life. He says those visits are remarkable.Cholangiocarcinoma starts in the bile duct and is an incredibly deadly cancer, which afflicts about 8,000 people in the United States each year. Most of its victims are 65 or older, but Sarah was only 31 when she was diagnosed. She passed away at age 35.The trip is being supported by the Cholangiocarcinoma Foundation, which has made the specially designed Honda SUV available for the journey. Sponsors are Incyte, Ken Garff Honda, QED Therapeutics, Servier, Taiho Oncology, Welch's Fruit Snacks and Zymeworks. Tee shirts commemorating the trip are available by clicking on the store at https:cholangiocarcinoma.org.And now, let's talk with Dave Fleischer as he reports in after his fourth week on the Journey of Hope, during which he'll share with us what he's been thinking about while driving all those miles by himself. Some of it's funny. Some pretty meaningful.

Hey guys, thanks for stopping by the NFN Radio News podcast. Today, we check in with Dave Fleisher who's just completed his third week of the Journey of Hope in memory of his daughter, Sarah, who passed away in 2018 from a horrible cancer, cholangiocarcinoma.In this episode, Dave reports in from South Carolina, after crossing the country and visiting several towns called Hope, several cholangiocarcinoma caregivers, patients and families. Altogether, plans call for the trip to include stops in 17, maybe 18 towns named Hope all across the country.A major goal of the trip, which will take Dave to all 48 contiguous states, is to help raise money to support research into this disease and during which they hope to spread awareness and bring hope to patients, caregivers, and others along the way. He reports that after three weeks of the Journey, he's closing in on the goal of $45,000 – and the trip is only about half-way completed. The journey is scheduled to end June 29 or July 1, depending on circumstances.“That's pretty cool,” Dave says. The road trip, in a car with a specially designed wrap promoting cholangiocarcinoma awareness, includes stops at various hospitals and healthcare institutions that specialize in research and treatment of the disease, in addition to the get-togethers with patients, caregivers and healthcare providers who were important in Sarah's life. He says those visits are remarkable.Cholangiocarcinoma starts in the bile duct and is an incredibly deadly cancer, which afflicts about 8,000 people in the United States each year. Most of its victims are 65 or older, but Sarah was only 31 when she was diagnosed. She passed away at age 35.The trip is being supported by the Foundation, which has made the specially designed Honda SUV available for the journey. Sponsors are Incyte, Ken Garff Honda, QED Therapeutics, Servier, Taiho Oncology, Welch's Fruit Snacks and Zymeworks.And now, let's talk with Dave Fleisher as he reports in after his third week on the Journey of Hope, during which he'll tell us about conversations with the “unknowings.”Become a supporter of this podcast: https://www.spreaker.com/podcast/the-lean-to-the-left-podcast--4719048/support.

Hey guys, thanks for stopping by the NFN Radio News podcast. Today, we check in with Dave Fleisher who's just completed his third week of the Journey of Hope in memory of his daughter, Sarah, who passed away in 2018 from a horrible cancer, cholangiocarcinoma.In this episode, Dave reports in from South Carolina, after crossing the country and visiting several towns called Hope, several cholangiocarcinoma caregivers, patients and families. Altogether, plans call for the trip to include stops in 17, maybe 18 towns named Hope all across the country.A major goal of the trip, which will take Dave to all 48 contiguous states, is to help raise money to support research into this disease and during which they hope to spread awareness and bring hope to patients, caregivers, and others along the way. He reports that after three weeks of the Journey, he's closing in on the goal of $45,000 – and the trip is only about half-way completed. The journey is scheduled to end June 29 or July 1, depending on circumstances.“That's pretty cool,” Dave says. The road trip, in a car with a specially designed wrap promoting cholangiocarcinoma awareness, includes stops at various hospitals and healthcare institutions that specialize in research and treatment of the disease, in addition to the get-togethers with patients, caregivers and healthcare providers who were important in Sarah's life. He says those visits are remarkable.Cholangiocarcinoma starts in the bile duct and is an incredibly deadly cancer, which afflicts about 8,000 people in the United States each year. Most of its victims are 65 or older, but Sarah was only 31 when she was diagnosed. She passed away at age 35.The trip is being supported by the Foundation, which has made the specially designed Honda SUV available for the journey. Sponsors are Incyte, Ken Garff Honda, QED Therapeutics, Servier, Taiho Oncology, Welch's Fruit Snacks and Zymeworks.And now, let's talk with Dave Fleisher as he reports in after his third week on the Journey of Hope, during which he'll tell us about conversations with the “unknowings.”

Dave Fleischer has now traveled almost 6,000 miles on the Journey of Hope in memory of his daughter, Sarah, who passed away in 2018 from a horrible cancer, cholangiocarcinoma.In this episode, Dave reports in from New England, after crossing the country and visiting several towns called Hope, several cholangiocarcinoma caregivers, patients and families. Altogether, plans call for the trip to include stops in 17 towns named Hope all across the country.A major goal of the trip, which will take Dave to all 48 contiguous states, is to help raise money to support research into this disease and during which they hope to spread awareness and bring hope to patients, caregivers, and others along the way. He reports that two weeks of the Journey, more than $30,000 has been raised – an astonishing amount, as the original goal for the entire trip was $15,000. There is now a new goal of $45,000.“That's pretty cool,” Dave says. The road trip, in a car with a specially designed wrap promoting cholangiocarcinoma awareness, includes stops at various hospitals and healthcare institutions that specialize in research and treatment of the disease, and get-togethers with other patients, caregivers and healthcare providers who were important in Sarah's life. Last week, Dave and his wife, Linda, visited the Mayo Clinic. Cholangiocarcinoma starts in the bile duct and is an incredibly deadly cancer, which afflicts about 8,000 people in the United States each year. Most of its victims are 65 or older, but Sarah was only 31 when she was diagnosed. She passed away at age 35.Linda flew home last Sunday after 10 days on the road with Dave, so he's now on his own – except for the many well-wishers and supporters he is meeting along the way. The journey is scheduled to end June 29 or July 1, depending on circumstances.The trip is being supported by the Foundation, which has made the specially designed Honda SUV available for the journey. Sponsors are Incyte, Ken Garff Honda, QED Therapeutics, Servier, Taiho Oncology, Welch's Fruit Snacks and Zymeworks.And now, let's talk with Dave Fleisher as he reports in after his second week on the Journey of Hope.Become a supporter of this podcast: https://www.spreaker.com/podcast/the-lean-to-the-left-podcast--4719048/support.

Dave Fleischer has now traveled almost 6,000 miles on the Journey of Hope in memory of his daughter, Sarah, who passed away in 2018 from a horrible cancer, cholangiocarcinoma.In this episode, Dave reports in from New England, after crossing the country and visiting several towns called Hope, several cholangiocarcinoma caregivers, patients and families. Altogether, plans call for the trip to include stops in 17 towns named Hope all across the country.A major goal of the trip, which will take Dave to all 48 contiguous states, is to help raise money to support research into this disease and during which they hope to spread awareness and bring hope to patients, caregivers, and others along the way. He reports that two weeks of the Journey, more than $30,000 has been raised – an astonishing amount, as the original goal for the entire trip was $15,000. There is now a new goal of $45,000.“That's pretty cool,” Dave says. The road trip, in a car with a specially designed wrap promoting cholangiocarcinoma awareness, includes stops at various hospitals and healthcare institutions that specialize in research and treatment of the disease, and get-togethers with other patients, caregivers and healthcare providers who were important in Sarah's life. Last week, Dave and his wife, Linda, visited the Mayo Clinic. Cholangiocarcinoma starts in the bile duct and is an incredibly deadly cancer, which afflicts about 8,000 people in the United States each year. Most of its victims are 65 or older, but Sarah was only 31 when she was diagnosed. She passed away at age 35.Linda flew home last Sunday after 10 days on the road with Dave, so he's now on his own – except for the many well-wishers and supporters he is meeting along the way. The journey is scheduled to end June 29 or July 1, depending on circumstances.The trip is being supported by the Foundation, which has made the specially designed Honda SUV available for the journey. Sponsors are Incyte, Ken Garff Honda, QED Therapeutics, Servier, Taiho Oncology, Welch's Fruit Snacks and Zymeworks.And now, let's talk with Dave Fleisher as he reports in after his second week on the Journey of Hope.

Dave and Linda Fleischer are well underway on their Journey of Hope in memory of their daughter, Sarah, who passed away in 2018 from a horrible cancer, cholangiocarcinoma.In this episode, Dave reports in from South Dakota, after visiting several western states, three towns called Hope, and several colangiocarcinoma patients and families. All together, plans call for the trip to include stops in 18 towns named Hope all across the country.A major goal of the trip, which will take Dave to all 48 contiguous states, is to help raise money to support research into this disease and during which they hope to spread awareness and bring hope to patients, caregivers, and others along the way. He reports that in the first week of the Journey, $20,000 has been raised – an astonishing amount, as the original goal for the entire trip was $15,000.“That's pretty cool,” Dave says. The road trip, in a car with a specially designed wrap promoting cholangiocarcinoma awareness, will include stops at various hospitals and healthcare institutions that specialize in research and treatment of the disease, and get-togethers with other patients, caregivers and healthcare providers who were important in Sarah's life. This coming week, Dave and Linda will visit the Mayo Clinic.Cholangiocarcinoma starts in the bile duct and is an incredibly deadly cancer, which afflicts about 8,000 people in the United States each year. Most of its victims are 65 or older, but Sarah was only 31 when she was diagnosed. She passed away at age 35.Linda will be flying home next Sunday after 10 days on the road with Dave, and then he will be on his own – except for the many well-wishers and supporters he is meeting along the way. The journey is scheduled to end June 29 or July 1, depending on circumstances.The trip is being supported by the Foundation, which has made the specially designed Honda SUV available for the journey. Sponsors are Incyte, Ken Garff Honda, QED Therapeutics, Servier, Taiho Oncology, Welch's Fruit Snacks and Zymeworks.And now, let's talk with Dave Fleisher as he reports in after his first week on the Journey of Hope.Become a supporter of this podcast: https://www.spreaker.com/podcast/the-lean-to-the-left-podcast--4719048/support.

Dave and Linda Fleischer are well underway on their Journey of Hope in memory of their daughter, Sarah, who passed away in 2018 from a horrible cancer, cholangiocarcinoma.In this episode, Dave reports in from South Dakota, after visiting several western states, three towns called Hope, and several colangiocarcinoma patients and families. All together, plans call for the trip to include stops in 18 towns named Hope all across the country.A major goal of the trip, which will take Dave to all 48 contiguous states, is to help raise money to support research into this disease and during which they hope to spread awareness and bring hope to patients, caregivers, and others along the way. He reports that in the first week of the Journey, $20,000 has been raised – an astonishing amount, as the original goal for the entire trip was $15,000.“That's pretty cool,” Dave says. The road trip, in a car with a specially designed wrap promoting cholangiocarcinoma awareness, will include stops at various hospitals and healthcare institutions that specialize in research and treatment of the disease, and get-togethers with other patients, caregivers and healthcare providers who were important in Sarah's life. This coming week, Dave and Linda will visit the Mayo Clinic.Cholangiocarcinoma starts in the bile duct and is an incredibly deadly cancer, which afflicts about 8,000 people in the United States each year. Most of its victims are 65 or older, but Sarah was only 31 when she was diagnosed. She passed away at age 35.Linda will be flying home next Sunday after 10 days on the road with Dave, and then he will be on his own – except for the many well-wishers and supporters he is meeting along the way. The journey is scheduled to end June 29 or July 1, depending on circumstances.The trip is being supported by the Foundation, which has made the specially designed Honda SUV available for the journey. Sponsors are Incyte, Ken Garff Honda, QED Therapeutics, Servier, Taiho Oncology, Welch's Fruit Snacks and Zymeworks.And now, let's talk with Dave Fleisher as he reports in after his first week on the Journey of Hope.

Dave and Linda Fleischer are ready to hit the road for a Journey of Hope in memory of their daughter, Sarah, who passed away in 2018 from a horrible cancer, cholangiocarcinoma.Today, they embark on what, for Dave, will be a 15,000 mile road trip across the nation and back to help raise money to support research into this disease and during which they hope to spread awareness and bring hope to patients, caregivers, and others along the way.The road trip, in a car with a specially designed wrap promoting cholangiocarcinoma awareness, will feature visits to 15 towns named Hope, stops at various hospitals and healthcare institutions that specialize in research and treatment of the disease, and get-togethers with other patients, caregivers and healthcare providers who were important in Sarah's life.Cholangiocarcinoma starts in the bile duct and is an incredibly deadly cancer, which afflicts about 8,000 people in the United States each year. Most of its victims are 65 or older, but Sarah was only 30 when she was diagnosed. She passed away at age 35.And so, as they also commemorate the 15th anniversary of the Cholangiocarcinoma Foundation, Fleischer is embarking on a 15,000 mile journey up and down and across the 48 contiguous United States.Linda will be with Dave for the first 10 days of the trip, and then he will be on his own – except for the thousands of well-wishers and supporters he is bound to meet along the way.“I intend to honor the memory of my daughter, Sarah,” says Dave. “Sarah would have loved to do this trip with me.” The journey is scheduled to end June 29 or July 1, depending on circumstances.The trip is being supported by the Foundation, which has made the specially designed Honda SUV available for the journey. Sponsors are Incyte, Ken Garff Honda, QED Therapeutics, Servier, Taiho Oncology, Welch's Fruit Snacks and Zymeworks.And now, let's talk with Dave Fleisher as he gets set for the Journey of Hope.Become a supporter of this podcast: https://www.spreaker.com/podcast/the-lean-to-the-left-podcast--4719048/support.

Dave and Linda Fleischer are ready to hit the road for a Journey of Hope in memory of their daughter, Sarah, who passed away in 2018 from a horrible cancer, cholangiocarcinoma.Today, they embark on what, for Dave, will be a 15,000 mile road trip across the nation and back to help raise money to support research into this disease and during which they hope to spread awareness and bring hope to patients, caregivers, and others along the way.The road trip, in a car with a specially designed wrap promoting cholangiocarcinoma awareness, will feature visits to 15 towns named Hope, stops at various hospitals and healthcare institutions that specialize in research and treatment of the disease, and get-togethers with other patients, caregivers and healthcare providers who were important in Sarah's life.Cholangiocarcinoma starts in the bile duct and is an incredibly deadly cancer, which afflicts about 8,000 people in the United States each year. Most of its victims are 65 or older, but Sarah was only 30 when she was diagnosed. She passed away at age 35.And so, as they also commemorate the 15th anniversary of the Cholangiocarcinoma Foundation, Fleischer is embarking on a 15,000 mile journey up and down and across the 48 contiguous United States.Linda will be with Dave for the first 10 days of the trip, and then he will be on his own – except for the thousands of well-wishers and supporters he is bound to meet along the way.“I intend to honor the memory of my daughter, Sarah,” says Dave. “Sarah would have loved to do this trip with me.” The journey is scheduled to end June 29 or July 1, depending on circumstances.The trip is being supported by the Foundation, which has made the specially designed Honda SUV available for the journey. Sponsors are Incyte, Ken Garff Honda, QED Therapeutics, Servier, Taiho Oncology, Welch's Fruit Snacks and Zymeworks.And now, let's talk with Dave Fleisher as he gets set for the Journey of Hope.