Podcast appearances and mentions of Bristol Myers Squibb

In this JCO Article Insights episode, Dr. Ece Cal interviews Dr. Martin Wermke, author of the JCO article, "Phase I Dose-Escalation Results for the Delta-Like Ligand 3/CD3 IgG-Like T-Cell Engager Obrixtamig (BI 764532) in Patients With Delta-Like Ligand 3+ Small Cell Lung Cancer or Neuroendocrine Carcinomas." TRANSCRIPT The disclosures for guests on this podcast can be found in the transcript. Dr. Ece Cali: Welcome to this episode of JCO Article Insights. This is Dr. Ece Cali, JCO editorial fellow, and today I am joined by Dr. Martin Wermke, Professor for Experimental Cancer Therapy at Dresden University of Technology, to discuss the manuscript “Phase 1 Dose-Escalation Results for the Delta-Like Ligand 3/CD3 IgG-like T-Cell Engager Obrixtamig in Patients with DLL3+ Small Cell Lung Cancer or Neuroendocrine Carcinomas.” Obrixtamig is a bispecific T-cell engager that binds to DLL3 on tumor cells and CD3 on T-cells. This manuscript presents the phase 1A dose escalation results of Obrixtamig in patients with DLL3+ small cell lung cancer and neuroendocrine carcinomas. In this study, 168 patients were treated with Obrixtamig across four different dosing regimens. 49% of the patients had small cell lung cancer, 42% had extrapulmonary neuroendocrine carcinoma, and 8% had large cell neuroendocrine carcinoma of the lung. Patients received a median of two prior lines of therapy. 33% of the patients had brain metastases at baseline. Of note, this trial did not mandate baseline brain imaging. Maximum tolerated dose was not reached. 88% of the patients experienced a treatment-related adverse event, however, only 3.6% of the patients had to discontinue treatment due to treatment-related AEs, and dose reduction due to treatment-related AEs was documented in 2.4% of the patient population. Similar to the other DLL3-targeted bi-therapies, the most common adverse events included CRS in 57%, dysgeusia in 23%, and pyrexia in 21% of the patients. CRS events were mostly mild. They occurred more frequently in the first two to three doses. 9% of the patients experienced ICANS, of which 3% were graded as Grade 3 or higher. And let's review the efficacy results. Responses were only seen in patients who received 90 microgram per kg or more once weekly or once every three weeks dosing. The objective response rate in patients who received an effective dose was 28%. If we review by tumor type, 21% of the small cell lung cancer patients, 27% of the extrapulmonary neuroendocrine carcinoma patients, and 70% of the large cell neuroendocrine carcinoma patients had objective response. Median duration of response was 8.5 months, though this data is immature due to short follow-up. Dr. Wermke, DLL3-targeted bispecific T-cell engagers are reshaping the treatment landscape of small cell lung cancer. This trial investigates Obrixtamig in other high-grade neuroendocrine tumors as well. Can you put this trial into context for us and explain why it may represent an important step forward? Dr. Martin Wermke: Yeah, thank you for providing me with the opportunity to discuss our data today. I think the data with Obrixtamig in small cell lung cancer are largely similar to what has been observed with other bispecific T-cell engagers such as tarlatamab with respect to the response rate and duration. It has, however, been to be mentioned that BI 1438001 had a bit more liberal inclusion criteria than other trials around. You already mentioned the fact that we allowed the inclusion of patients without mandatory brain imaging, which led to some patients having their brain mets been diagnosed during the treatment with obrixtamig and then adding to the progressive disease patients. That is something which was not the case with the tarlatamab trials where you really had to have a brain imaging before, and in the Phase 1 trial you were even required to treat the brain mets before you included the patient. So it is a bit different, more poorest patient population. I think the trial adds on existing data by being the first trial to also include non-SCLC neuroendocrine carcinoma of other origin, for example from the gastrointestinal tract, and also by including large cell neuroendocrine carcinoma of the lung, which is a really hard to treat pulmonary neoplasm which currently lacks any standardized treatment. So that is really a step forward which we will build on in the future. Dr. Ece Cali: And one thing I would note in this trial, only patients with tumor expressing DLL3 were enrolled. Can you tell us a little bit more about this target, DLL3 in the context of neuroendocrine tumors, and does DLL3 expression predict clinical outcomes after treatment with DLL3 BiTEs, or do we actually need other predictive biomarkers for these novel agents? Dr. Martin Wermke: Yeah, thank you. That's a pretty interesting question. First of all, DLL3 is an atypical notch ligand, which is expressed by the majority of neuroendocrine carcinomas, virtually absent on healthy adult tissues. Therefore, turning it really into a bona fide target for T-cell engaging therapies, pretty low risk for on-target off-tumor side effects. We found that in all the patients we screened, we had an expression rate of about 94% in small cell lung cancer, 80% of large cell neuroendocrine carcinoma of the lung were positive, and also about 80% of the extrapulmonary neuroendocrine carcinoma. So it's really a high prevalence. So the fact that we only included DLL3+ tumors still means we included most of the patients that presented with these diseases. I think at the moment there are no data suggesting a clear-cut association between DLL3 expression levels and outcome on DLL3 CD3 T-cell engagers. There's also not a lot published. If you want to find this out for tarlatamab, you have to look into their patent to really see the data, but it's not clear-cut and I'm sure we need other markers to complement that. And I think what probably plays a major role is intrinsic T-cell fitness. So the question how really diseased your T-cells are, how old you are, because age also correlates with the fitness of the immune system, and other patient characteristics such as tumor burden, we've seen all across the board that the higher the tumor burden, the lower the rate of prolonged response is in such trials. And I also think we need to focus on other components of the tumor microenvironment. So see how high the T-cell infiltration with obrixtamig is and how abundant suppressive elements like regulatory T-cells or myeloid-derived suppressive cells are. That is work which is currently being done. Data are emerging, but I don't think that at the moment we have any clear biomarker helping us to select who should not receive DLL3 T-cell engagers. Dr. Ece Cali: Those are great points and there is a lot we need to learn about how to use these novel agents in the future. I'd like to highlight the results in large cell neuroendocrine carcinoma of the lung. The response rate in this group was remarkably high at 70%. Though we should note the small sample size of only 14 patients in this trial. After first line chemoimmunotherapy, current approved options for this population have very modest clinical activity. Given these trial results, how do you envision the field moving forward for patients with large cell neuroendocrine carcinoma? Dr. Martin Wermke: Yeah, I think LCNEC is really an area which urgently needs further improvement of therapeutic standards. At the moment, as I said, there is no real standard. We are usually extrapolating from results we have in small cell lung cancer or non-small cell lung cancer, but I don't think we have too many prospective trials really informing this. Of course, 14 patients is a small sample size, but I think it's still fair to say that we can claim that DLL3 T-cell engagers are not doing worse in LCNEC than they do in SCLC. And that's why I think we really need to move forward clinical trials that are specifically targeting this population. Although I fear a bit that, given the rareness of this disease and the aggressiveness of its phenotype, that this is probably not the main focus of the pharmaceutical industry. So I think it's up to us academic investigators to really come up with investigator-initiated trials trying to fill the knowledge gaps we have here. Dr. Ece Cali: And one more thing that I want to talk about is the accessibility for these drugs. These novel agents are showing real promise in improving outcomes for patients with high-grade neuroendocrine tumors, an area where progress has been limited until very recently. However, as DLL3 BiTEs become more widely used, issues of logistics and access come into sharper focus. With unique toxicities and the specialized monitoring, their use is restricted to certain centers. Looking ahead, what kinds of strategies could help mitigate some of these adverse events or make these treatments more broadly available? Dr. Martin Wermke: Yeah, I think if you look at countries like the United States where tarlatamab has already been approved, we can see how the management strategies are evolving. I've heard about a colleague equipping their patients with thermometers and a pill of Dexamethasone, alongside with a temperature control protocol and clearly instructing them, "If you measure a temperature above a certain level then start taking the Dexamethasone and come back to our office and we're going to take care of you." I think that's one way to move forward. I think we are lucky in a way that CRS usually manifests within the first 24 hours. This was the same in our study, like in the tarlatamab studies. So we really know when the time of trouble is for our patients. And in this time, I think we need to instruct the patients to stay close to the hospital. I don't think we need to hospitalize all of them, but we probably need them to stay in a nearby hotel to be able to reach the emergency room if needed in a short period of time. And I think we can also learn in this strategy how to manage bispecific antibodies from the experience our colleagues in hematology had because they have been using bispecific T-cell engagers for quite some years right now and they developed strategies and networks that were able to successfully treat these patients also on an outpatient basis. And I think that is clearly an experience we need to follow, acknowledging that we are talking about diseases which are much more frequent than the standard hematology indications. Dr. Ece Cali: Thank you so much, Dr. Wermke, for this informative discussion and for sharing your perspective on this evolving field. Dr. Martin Wermke: Yeah, thank you for providing me with the opportunity to talk about data. It was really great being able to share that, and I really think that we are just at the beginning of a new exciting area for the treatment of neuroendocrine carcinomas, and I think much improvement is yet to come for our patients. Dr. Ece Cali: Yes, that's really exciting. And thank you everyone for listening to JCO Article Insights. Please come back for more interviews and article summaries and be sure to leave us a rating and review so others can find our show. For more podcasts and episodes from ASCO, please visit 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, experience, and conclusions. Guest statements on this 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. Dr. Martin Wermke's Disclosures Honoraria: Lilly, Boehringer Ingelheim, SYNLAB, Janssen, Merck Serono, GWT, Amgen, Novartis, Pfizer,  BMS GmbH & Co. KG, Regeneron, MJH/PER, Takeda Consulting or Advisory Role: Bristol-Myers Squib, Novartis, Lilly, Boehringer Ingelheim, ISA Pharmaceuticals, Amgen, immatics, Bayer, ImCheck therapeutics, AstraZeneca, Tacalyx, Regeneron, Daiichi Sankyo Europe GmbH, Zymeworks, PharmaMar, Iovance Biotherapeutics, T-Knife, Genentech Research Funding: Roche Patents, Royalties, Other Intellectual Property Travel, Accommodations, Expenses: Pfizer, Bristol-Myers Squibb, AstraZeneca,  Amgen,  GEMoaB, Sanofi/Aventis, immatics,  Merck Serono, Janssen Oncology, Iovance Biotherapeutics, Daiichi Sankyo Europe GmbH"

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/NCPD/CPE/AAPA information, and to apply for credit, please visit us at PeerView.com/XBK865. CME/MOC/NCPD/CPE/AAPA credit will be available until September 18, 2026.Moving HCM Excellence Into the Fast Lane: Harnessing Technology to Reconfigure Clinical Workflows in an Academic Medical CenterThe University of Florida College of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.This activity is developed in collaboration with our educational partner, PVI, PeerView Institute for Medical Education. 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 through an educational grant from Bristol Myers Squibb.Disclosure information is available at the beginning of the video presentation.

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/NCPD/CPE/AAPA information, and to apply for credit, please visit us at PeerView.com/XBK865. CME/MOC/NCPD/CPE/AAPA credit will be available until September 18, 2026.Moving HCM Excellence Into the Fast Lane: Harnessing Technology to Reconfigure Clinical Workflows in an Academic Medical CenterThe University of Florida College of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.This activity is developed in collaboration with our educational partner, PVI, PeerView Institute for Medical Education. 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 through an educational grant from Bristol Myers Squibb.Disclosure information is available at the beginning of the video presentation.

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/NCPD/CPE/AAPA information, and to apply for credit, please visit us at PeerView.com/XBK865. CME/MOC/NCPD/CPE/AAPA credit will be available until September 18, 2026.Moving HCM Excellence Into the Fast Lane: Harnessing Technology to Reconfigure Clinical Workflows in an Academic Medical CenterThe University of Florida College of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.This activity is developed in collaboration with our educational partner, PVI, PeerView Institute for Medical Education. 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 through an educational grant from Bristol Myers Squibb.Disclosure information is available at the beginning of the video presentation.

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/NCPD/CPE/AAPA information, and to apply for credit, please visit us at PeerView.com/XBK865. CME/MOC/NCPD/CPE/AAPA credit will be available until September 18, 2026.Moving HCM Excellence Into the Fast Lane: Harnessing Technology to Reconfigure Clinical Workflows in an Academic Medical CenterThe University of Florida College of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.This activity is developed in collaboration with our educational partner, PVI, PeerView Institute for Medical Education. 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 through an educational grant from Bristol Myers Squibb.Disclosure information is available at the beginning of the video presentation.

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/NCPD/CPE/AAPA information, and to apply for credit, please visit us at PeerView.com/XBK865. CME/MOC/NCPD/CPE/AAPA credit will be available until September 18, 2026.Moving HCM Excellence Into the Fast Lane: Harnessing Technology to Reconfigure Clinical Workflows in an Academic Medical CenterThe University of Florida College of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.This activity is developed in collaboration with our educational partner, PVI, PeerView Institute for Medical Education. 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 through an educational grant from Bristol Myers Squibb.Disclosure information is available at the beginning of the video presentation.

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/NCPD/CPE/AAPA information, and to apply for credit, please visit us at PeerView.com/XBK865. CME/MOC/NCPD/CPE/AAPA credit will be available until September 18, 2026.Moving HCM Excellence Into the Fast Lane: Harnessing Technology to Reconfigure Clinical Workflows in an Academic Medical CenterThe University of Florida College of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.This activity is developed in collaboration with our educational partner, PVI, PeerView Institute for Medical Education. 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 through an educational grant from Bristol Myers Squibb.Disclosure information is available at the beginning of the video presentation.

Co-hosts Ryan Piansky, a graduate student and patient advocate living with eosinophilic esophagitis (EoE) and eosinophilic asthma, and Holly Knotowicz, a speech-language pathologist living with EoE who serves on APFED's Health Sciences Advisory Council, interview three high school students who made less invasive EoE diagnostics the focus of a science fair project. Disclaimer: The information provided in this podcast is designed to support, not replace, the relationship that exists between listeners and their healthcare providers. Opinions, information, and recommendations shared in this podcast are not a substitute for medical advice. Decisions related to medical care should be made with your healthcare provider. Opinions and views of guests and co-hosts are their own.   Key Takeaways: [:51] Co-host Ryan Piansky introduces the episode, brought to you thanks to the support of Education Partners Bristol Myers Squibb, GSK, Sanofi, Regeneron, and Takeda. Ryan introduces co-host Holly Knotowicz.   [1:08] Holly introduces today's guests, three high school students from Texas who made EoE diagnostics the focus of a science fair project: Leyna, Nhu, and Jaden.   [1:47] Leyna, Nhu, and Jaden are best friends. Nhu was diagnosed with EoE last summer. Leyna said Nhu told them it took a long time for the doctors to diagnose her because they thought it could be different conditions.   [2:07] Nhu told them about her appointments and her endoscopy procedures. She had to miss school sometimes. Leyna and Jaden were concerned for her.   [2:22] Leyna took AP Bio. Her teacher was a sponsor for the science fair. Leyna thought this would be a meaningful project for the three friends to learn more about Nhu's condition.    [2:45] Holly shares that she wasn't diagnosed until her 20s, but she was sick for much of her childhood.   [3:13] Ryan shares that he was diagnosed when he was two, after two years of his parents taking him to different doctors and undergoing different tests.   [3:31] Nhu says it was hard to find a specialist. They found one and had to wait six months for an appointment. It was a long time, suffering from the effects of EoE with constant symptoms, a lot of heartburn, and painful vomiting.   [4:00] Nhu was diagnosed with EoE in her sophomore year of high school. Her friends have seen her endure a lot, but she's strong. Nhu had to miss an orchestra concert where she had a big solo, because of her EoE.   [4:32] Doctors thought Nhu could have something different, like H. Pylori or cyclic vomiting syndrome. They didn't have clear answers, which was confusing and frustrating for her family.   [4:50] Holly talks about how difficult it was for her to get a diagnosis, and how she was told she was vomiting to get attention. She shared her reaction when diagnosed. She would like someone to do a research study about the pain tolerance of people with EoE.   [5:41] Leyna says junior year is the hardest year of high school. She doesn't know how Nhu survived physics and AP classes with EoE on top of it, and making up late work.   [6:14] Nhu takes a weekly injection. Her symptoms happen almost monthly. Sometimes she misses school for two weeks and has to catch up on work. Leyna and Jaden help her with her schoolwork.   [6:47] Ryan shared how he missed a third of his senior year in high school. He's now on an injectable biologic that has helped him a lot. That treatment option wasn't available when he was in high school. Having supportive friends to send him his schoolwork and keep him up-to-date was very helpful.   [7:11] Ryan explains the esophageal string test (EST). This is a tool that was developed to help monitor eosinophilic esophagitis (EoE). The test works by having the patient swallow a capsule about the size of a Tic Tac that has a string attached.   [7:25] The capsule dissolves in the stomach while the string stays in place in the esophagus. After about an hour, it's gently removed. Along the way, the string collects samples from the lining of the esophagus, which are reviewed, similarly to a biopsy.   [7:37] Holly adds that what makes the string test unique is that it doesn't require an endoscope, anesthesia, or recovery time, things that usually come with a traditional endoscopy and biopsy.   [7:46] It's now being used with patients as young as four years old. While some people might feel some minor discomfort, it's generally much easier for regular monitoring than an endoscopy.   [7:57] Holly explains that she was involved in testing the device and developing a swallowing protocol for it at Children's Hospital of Colorado. We will talk more about this later in the episode.   [8:06] Ryan adds, to learn more about the development of the string test, listen to episode 26 of this podcast.   [8:10] The string test is one of multiple, less-invasive monitoring tools for eosinophilic esophagitis. Others include the sponge test and unsedated trans-nasal endoscopy.   [8:19] To learn more about unsedated transnasal endoscopy, listen to episodes 19 and 20, where we talk to clinicians and patients about this method.   [8:27] During that episode, we talked to the developers of the EST.   [8:38] Jaden tells how he, Leyna, and Nhu brainstormed ideas and decided to base their project specifically on how to diagnose EoE in a less invasive way than endoscopies.   [9:12] Before this project, they were not familiar with the EST. Nhu says her only option for diagnosis was an endoscopy.   [9:21] Holly says it's still like that in Maine. She came from an area of the country where the EST was researched, and it's interesting to her that she doesn't have access to it now.   [9:37] What appealed to the group about the EST as an alternative to endoscopies is that it was so different. There are so many advanced technologies, and the EST is just a capsule taped to a string. It is simple but innovative.   [10:13] Real Talk: Eosinophilic Diseases had Drs. Robin Shandas and Steven Ackerman, who were instrumental in the development of the esophageal string test, as guests on episode 26 of this podcast. Ryan encourages listeners to check out that episode at apfed.org/podcasts.   [10:42] They searched for keywords and analyzed a variety of scholarly literature. They collected a lot of data from Dr. Ackerman's papers.   [11:10] They also reached out to gastroenterologists on social media. A hard thing about science fair projects is coming up with an experiment. They didn't know what they could do just with compiled research, but they had a great sponsor who helped along the way.   [11:56] Leyna says they trusted that the doctors they reached out to on social media were competent in their understanding of different diagnostic methods. She notes that different locations may have different resources and different biases.   [12:14] Leyna says they talked to doctors in the U.S. and from different countries, including India and Mexico. She commented that communities in Mexico might not have the same resources as communities in the U.S. or India. That might change their understanding of the EST.   [12:33] We might have different biases because we don't have the same technology to research and find the same things about the EST.   [13:12] Leyna says they reached out to doctors on social media, but didn't get responses from that many doctors. Reaching out to patients would be a good thing if they want to continue the project.   [14:00] Jaden says most of the data they found was from Dr. Ackerman, including a survey he did comparing the data of the EST and the biopsies.   [14:10] They found that the EST and the biopsies were relatively similar in terms of discovering the eosinophilic count and determining whether the EoE is active or inactive.   [15:30] They found differences between ESTs and biopsies in finding how much of a certain chemical is in the patient's cells.   [14:43] Leyna comments that one of the doctors they reached out to told them about the sponge test, another less invasive method. They didn't research the sponge test, but it sounded interesting.   [15:00] Ryan says there are a lot of cool new techniques that are being researched, like the transnasal endoscopy that goes in through the nose, the string test, and the sponge test.   [15:13] Leyna says the cool thing was hearing about all these methods. They had hypothesized that there are less invasive methods that may be better than endoscopies.   [15:27] They were not able to prove their hypothesis yet. They learned a lot of different things that could be beneficial.   [15:42] Holly points out that the transnasal endoscopy is not scary. It's also known as the unsedated endoscopy. Holly has done both the EST and the unsedated endoscopy,  and they each have pluses and minuses.   [16:15] Nhu explains how the team would meet at one of their houses, usually Leyna's house. One day, they watched Interstellar together, and the “Eureka moment” scene motivated them.   [16:41] They helped each other whenever necessary. When the project board was due, they all went to Leyna's house to work on the project board. They worked together as a team.   [16:51] Jaden analyzed a lot of the data. Leyna reached out to professors. Nhu helped Jaden understand some terms. On the day they presented the project, Nhu was sick in the hospital, which made them sad. They included a photo of her on the project board.   [17:28] Holly says that although Nhu wasn't there, it may have helped people know how sick EoE can make you feel.   [18:28] Leyna says one of the doctors they reached through social media told them that endoscopies have lots of benefits. The biopsy samples give healthcare professionals a clear idea of how many eosinophils per high-powered field, a key indicator in diagnosing EoE.   [18:57] The diagnosis gives a baseline for starting treatment for the patient, monitoring how effective the treatment is. You can't count the number of eosinophils per high-powered field using the string test.   [19:11] The EST is a gelatin capsule attached to a long string that you swallow. It dissolves in the stomach. It's less expensive than an endoscopy.   [19:33] Holly says one of the big differences is that you can't diagnose EoE on a string test. It has to be diagnosed with an endoscopy.   [19:40] Leyna says they learned that from the doctors and medical students who reviewed their project board. You can't diagnose EoE with the EST, but you can monitor it.   [19:52] The string test doesn't provide a direct eosinophil count, but it reflects the level of inflammation in your esophagus, and it can measure the protein biomarkers. That correlates with the eosinophil count from a biopsy. It is good for monitoring EoE.   [20:12] Ryan says that's a great idea. In the show notes, there is a link to the diagnostic consensus guidelines. They specify that you need an endoscopy and 15 eosinophils per high-powered field to be diagnosed with EoE.   [20:28] The EST can monitor the progression of the disorder as you're trying new medicines or an elimination diet. If you need an endoscopy every three to six months, it can be taxing.    [20:49] Ryan comments on the cost. Going through anesthesia for an endoscopy is very expensive, and not everyone has the insurance to cover these diagnostic procedures. The EST is an option you can do in a doctor's office in just over an hour.   [21:16] Holly asks if Nhu has participated in a string test. Nhu has not, but she would love to do a string test if she had the chance. Whenever she sees her doctor, she brings up her condition, and what could be better for her, such as the string test.   [22:06] The science fair is a huge regional fair in Houston, called the Science and Engineering Fair of Houston (SEFH). This was their first year participating. They were regional qualifiers from their district. When they got there, everyone else had six-foot-tall printed boards. It was a shock to them.   [22:56] They hope to level up their board for next year's fair. It was cool and eye-opening to see all these student researchers and get feedback from the people who walked by their booth. They heard some interesting things to use in their next project.   [23:15] One medical student in attendance came by their project board and suggested that while the EST may not diagnose EoE, maybe it could be used as a screening tool [to help identify people who should follow up with a gastroenterologist for a diagnostic work-up]. Interestingly, this was a medical student, and she had recently scheduled an appointment with a gastroenterologist for an endoscopy to see if she has EoE.   [24:04] This student didn't seem to know much about EoE, but felt she was experiencing symptoms that might indicate EoE. She told them she had learned so much from their board. Ryan says it's great that the project was able to help this person.   [24:44] Jaden says that the students at their school didn't know much about EoE, but when they looked at the project board, they were shocked by how incredibly difficult it is to diagnose EoE and how the EST could change a lot of things as a screening method.   [25:11] Jaden says their science teacher came by to see their board and how they were doing. He liked how they included not only the research information but also the stories of why they chose their project and why they were passionate about it.   [25:34] The day of the project, Leyna and Jaden were sad that Nhu couldn't be there with them. Their sponsor, Leyna's biology teacher, was sick, but showed up at the fair to view their presentation. They raised awareness about EoE. People learned about it.   [25:54] When Nhu told Leyna about her EoE, Leyna had no idea what it was. She's glad their project brought the issue to the table. They emphasized that more research needs to be done. There is much we don't know about less invasive methods.   [26:23] Nhu has considered a career in medicine since she has been in many hospitals and talked to a lot of doctors. Jaden sees himself in the engineering field, but he enjoys researching like this and seeing things through a different perspective.   [27:05] Nhu learned a lot about herself with EoE. Leyna loves how much they learned from this project. She is interested in pursuing scientific research. She thinks it's cool that Ryan is a graduate student.   [27:24] Leyna just got back from a five-week summer research program. It was insightful. She doesn't see herself becoming a doctor, but possibly doing research and advocating for different conditions.   [27:43] When Ryan was in high school, with all his hospital time, he had an interest in medicine, then he took a turn into engineering. He enjoys research. He's passionate about engaging in patient advocacy work through APFED.   [28:10] Ryan is glad for Leyna, Nhu, and Jaden that they were able to engage with this research and do it as a group and as friends. He says it's fantastic to hear from the group about the whole process they went through.   [28:23] Holly asks, looking back on everything you guys learned and experienced in this project, what's one question or idea you would still like to explore if you had more time and resources?   [28:38] Nhu wants to research finding more ways to diagnose EoE. Testing for EoE and finding EoE are very interesting for her.   [28:53] Jaden thinks that if they had more time, they would try to create a model of the EST to show how it works. He would possibly try to improve upon the model or develop something new. Instead of just relying on the data we have, he would try to collect data.   [29:26] Leyna agrees. She would like to build a prototype, understand how the capsule works, and find out whether the string down the esophagus is uncomfortable.   [33:41] Ryan suggests there is a doctor who would let them try the string test so they could see how it feels. Holly tried the string test at a major children's hospital while it was being researched. She doesn't want to ask her patients to do something she hasn't done, since she has the diagnosis too.   [30:37] Ryan comments that he enjoyed hearing about the process of the project.   [30:51] Ryan gives a quick recap: The esophageal string test is a tool to help monitor EoE. It is not a tool to diagnose EoE. If you or a loved one has EoE or suspect that you might, ask your clinician about the string test to see if it's an option for you.   [31:03] Holly adds: School science fairs are one way to bring education about eosinophilic disorders to schools. We love hearing about community science fairs and school projects that teach others about these conditions.   [31:13] For those of you looking to learn more about eosinophilic esophagitis, we encourage you to visit apfed.org/EoE.   [31:23] For those looking to find specialists who treat EoE, we encourage you to use APFED's Specialist Finder at apfed.org/specialist.   [31:30] Ryan thanks Leyna, Nhu, and Jaden for joining us today. Holly also thanks APFED's Education Partners Bristol Myers Squibb, GSK, Sanofi, Regeneron, and Takeda for supporting this episode.   Mentioned in This Episode: Dr. Robin Shandas Dr. Steven Ackerman “Updated international consensus diagnostic criteria for eosinophilic esophagitis: Proceedings of the AGREE conference”   APFED on YouTube, Twitter, Facebook, Pinterest, Instagram Real Talk: Eosinophilic Diseases Podcast apfed.org/specialist apfed.org/connections   Education Partners: This episode of APFED's podcast is brought to you thanks to the support of Bristol Myers Squibb, GSK, Sanofi, Regeneron, and Takeda.   Tweetables:   “Nhu and Jaden are my best friends. Recently, Nhu was diagnosed with EoE. I remember her telling us about the long diagnosis process. It took the doctors quite a long time to diagnose her because they thought it could be different conditions.” — Leyna   “I thought that this would be a meaningful project for us to learn more about Nhu's condition [of EoE].” — Leyna   “The students at our school didn't know much about EoE, but when they looked at the project board, they were shocked by how incredibly difficult it is to diagnose EoE.” — Jaden   “One of the main benefits of the string test is that endoscopies can be quite expensive, especially the anesthesia. It could be beneficial for people who don't have the money for an endoscopy.” — Nhu

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/NCPD/CPE/AAPA information, and to apply for credit, please visit us at PeerView.com/XBK865. CME/MOC/NCPD/CPE/AAPA credit will be available until September 18, 2026.Moving HCM Excellence Into the Fast Lane: Harnessing Technology to Reconfigure Clinical Workflows in an Academic Medical CenterThe University of Florida College of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.This activity is developed in collaboration with our educational partner, PVI, PeerView Institute for Medical Education. 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 through an educational grant from Bristol Myers Squibb.Disclosure information is available at the beginning of the video presentation.

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/NCPD/CPE/AAPA information, and to apply for credit, please visit us at PeerView.com/XBK865. CME/MOC/NCPD/CPE/AAPA credit will be available until September 18, 2026.Moving HCM Excellence Into the Fast Lane: Harnessing Technology to Reconfigure Clinical Workflows in an Academic Medical CenterThe University of Florida College of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.This activity is developed in collaboration with our educational partner, PVI, PeerView Institute for Medical Education. 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 through an educational grant from Bristol Myers Squibb.Disclosure information is available at the beginning of the video presentation.

Host: Susanna Price Guest: Robert Storey Want to watch that extended interview? Go to: https://esc365.escardio.org/event/2092?resource=interview Disclaimer: ESC TV Today is supported by Bristol Myers Squibb and Novartis. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsors. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. The ESC is not liable for any translated content of this video. The English-language always prevails. Declarations of interests: Stephan Achenbach, Yasmina Bououdina, Nicolle Kraenkel and Susanna Price have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. John-Paul Carpenter has declared to have potential conflicts of interest to report: stockholder Mycardium AI. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Konstantinos Koskinas has declared to have potential conflicts of interest to report: honoraria from MSD, Daiichi Sankyo, Sanofi.  Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Robert Storey has declared to have potential conflicts of interest to report: research grants and personal fees from AstraZeneca and Cytosorbents, and personal fees from Abbott, Afortiori Development/Thrombolytic Science, Boehringer Ingelheim/Lilly, Bristol Myers Squibb/Johnson & Johnson, Chiesi, Idorsia/Viatris, Novo Nordisk, PhaseBio and Tabuk. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

This episode covers: Cardiology This Week: A concise summary of recent studies Strategic decisions in valvular heart disease Optimising drug therapy in chronic coronary syndromes Mythbusters: Does wearing a white coat make you smarter? Host: Susanna Price Guests: John-Paul Carpenter, Fabien Praz, Robert Storey Want to watch that episode? Go to: https://esc365.escardio.org/event/2092 Want to watch that extended interview on Optimising drug therapy in chronic coronary syndromes ? Go to: https://esc365.escardio.org/event/2092?resource=interview Disclaimer: ESC TV Today is supported by Bristol Myers Squibb and Novartis. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsors. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. The ESC is not liable for any translated content of this video. The English-language always prevails. Declarations of interests: Stephan Achenbach, Yasmina Bououdina, Nicolle Kraenkel, Fabien Praz and Susanna Price have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. John-Paul Carpenter has declared to have potential conflicts of interest to report: stockholder Mycardium AI. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Konstantinos Koskinas has declared to have potential conflicts of interest to report: honoraria from MSD, Daiichi Sankyo, Sanofi. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Robert Storey has declared to have potential conflicts of interest to report: research grants and personal fees from AstraZeneca and Cytosorbents, and personal fees from Abbott, Afortiori Development/Thrombolytic Science, Boehringer Ingelheim/Lilly, Bristol Myers Squibb/Johnson & Johnson, Chiesi, Idorsia/Viatris, Novo Nordisk, PhaseBio and Tabuk. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

The FDA is working to reapprove GSK's long-dormant drug Wellcovorin (leucovorin) for cerebral folate deficiency, which the agency linked to “developmental delays with autistic features.” This immediately followed a much-anticipated press conference in which President Donald Trump, flanked by Health Secretary Robert F. Kennedy Jr and other healthcare administrators, linked the use of Tylenol during pregnancy to rising rates of autism.  Meanwhile, Pfizer woke us all up Monday with the news that it had acquired breakout obesity rockstar Metsera for $4.9B. The deal should pump new life into Pfizer's portfolio, which over the last two years has suffered three discontinued assets. Bite-sized deals—or those at or below the $5 billion mark—have defined biopharma recently, with Roche picking up metabolic dysfunction-associated steatohepatitis biotech 89bio for a potential $3.5 billion last week and Novartis putting another $5.7 billion on the line with partner Monte Rosa Therapeutics in a second molecular glue agreement.  Another therapeutic space primed for M&A action is psychedelics. After AbbVie bought Gilgamesh Pharmaceuticals' lead depression asset for $1.2B last month, BioSpace spoke sought opinions from experts on who might be next to take the plunge. A few potential names included Eli Lilly, Bristol Myers Squibb and Merck.  On the policy front, the CDC's revamped vaccine advisory committee convened for their first meeting to discuss COVID-19, MMRV and hepatitis B vaccine schedules. Industry watchers who spoke to BioSpace commented on the “lack of knowledge” and dearth of previous experience on the committee. And while the advisors ultimately voted to change the schedule for the MMRV vaccine, it appears unlikely to significantly affect manufacturers' bottom lines. Finally, in rare disease, Stealth BioTherapeutics secured its long-sought approval for elamipretide—now Forzinity—in Barth syndrome—a disorder that would fall under the purview of the FDA's new Rare Disease Evidence Principles framework for ultra rare diseases affecting less than 1,000 people in the U.S. And we said “Bye Bye Bluebird,” as the famed gene therapy biotech—which was recently bought out by two private equity firms—returned to its original moniker, Genetix Biotherapeutics.  Lastly, make sure to sign up for Biopharm Executive here for access to a special deep dive into China biopharma.  

By Adam Turteltaub Being a leader is hard.  Being a compliance leader is harder.  Being a compliance leader in fast-changing times takes it up yet another level, but it's not impossible. Kim Jablonski, Chief Compliance & Ethics Officer at Bristol Myers Squibb shares that with these challenges it's important for leaders not to think in static terms but to recognize that the landscape is constantly changing.  The transformations include not just new laws and regulations but also new expectations for compliance programs, such as when it comes to taking a more data-driven approach. At the same time, though, some things don't change.  For example, you need to communicate with the workforce the importance of acting with integrity, even when there is business pressure to deliver.  That same message should come from leadership as well so that employees see integrity as a part of the culture and behavioral expectations. For their part, compliance leaders, and their teams, need to have a deep understanding of the business and how it works.  They must also be flexible with more than one solution to a problem. She also advocates for a collaborative approach.  Working together with a wide range of internal teams leads to better outcomes, both from a compliance and business perspective. Most notably of all, she shares an insight that is relatable and very eye opening:  We all have obstructed view seats.  As she explains, we all only see a part of the picture and need to be mindful that we benefit from the views of others and that bad decisions are often the product of not being able to see the whole panorama before us. Listen in for more eye-opening insights.

New survival data from the FLAURA2 and MARIPOSA trials represent “a massive advance for our patients” in terms of frontline treatment for EGFR-mutated non-small cell lung cancer says Sandip P. Patel, MD, professor of medicine at the University of California San Diego. However, the findings have led to new questions about sequencing. “Just like in chess, when you make a move, you're restricted in the moves that you can make afterward,” he explains to Robert A. Figlin, MD, the interim director of Cedars-Sinai Cancer in Los Angeles and Steven Spielberg Family Chair. Discussions have become “much more nuanced,” and “thinking about the patient holistically becomes even more important in the setting of all these excellent treatment options for our patients,” Dr. Patel shares. Dr. Patel reported scientific advisory income from Amgen, AstraZeneca, BeiGene, Bristol Myers Squibb, Certis, Eli Lilly, Jazz, Genentech, Illumina, Merck, Pfizer, Natera, and Tempus. Dr. Figlin reported various financial relationships.

Dr. Pedro Barata and Dr. Rana McKay discuss the integration of innovative advances in molecular imaging and therapeutics to personalize treatment for patients with renal cell and urothelial carcinomas. TRANSCRIPT Dr. Pedro Barata: Hello, I'm Dr. Pedro Barata, your guest host of By the Book, a podcast series featuring insightful conversations between authors and editors of the ASCO Educational Book. I'm a medical oncologist at University Hospitals Seidman Cancer Center and an associate professor of medicine at Case Western Reserve University in Cleveland, Ohio. I'm also an associate editor of the ASCO Educational Book. Now, we all know the field of genitourinary cancers (GU) is evolving quite rapidly, and we have new innovations in molecular imaging as well as targeted therapeutics. Today's episode will be exploring novel approaches that are transforming the management of renal cell and urothelial carcinomas and also their potential to offer a more personalized treatment to patients. For that, joining for today's discussion is Dr. Rana McKay, a GU medical oncologist and professor at University of California San Diego. Dr. McKay will discuss her recently published article titled, “Emerging Paradigms in Genitourinary Cancers: Integrating Molecular Imaging, Hypoxia-Inducible Factor-Targeted Therapies, and Antibody-Drug Conjugates in Renal Cell and Urothelial Carcinomas.”  Our full disclosures are available in the transcript of this episode.  And with that, Rana McKay, great to have you on the podcast today. Dr. Rana McKay: Oh, thank you so much, Dr. Barata. It's really wonderful to be here with you. So, thanks for hosting. Dr. Pedro Barata: No, thanks for taking the time, and I'm looking forward to this conversation. And by the way, let me start by saying congrats on a great article in the Educational Book. Really super helpful paper. I'm recommending it to a lot of the residents and fellows at my own institution. I would like to first ask you to kind of give our listeners some context of how novel approaches in the molecular imaging as well as targeted therapeutics are actually changing the way we're managing patients with GU, but specifically with renal cell carcinoma and urothelial carcinoma. So, what are the areas you would call out as like being big areas for innovation in this context, and why are they important? Dr. Rana McKay: Very good question. And I think this is really what this article highlights. It highlights where are we going from an imaging diagnostics standpoint? Where are we going from a therapeutic standpoint? And I think if we have to step back, from the standpoint of diagnostics, we've seen PET imaging really transform diagnostics in prostate cancer with the advent of PSMA PET imaging, and now PSMA PET imaging is used as a biomarker for selection for theranostics therapy. And so, we're starting to see that enter into the RCC landscape, enter into the urothelial cancer landscape to a lesser extent. And I think it's going to potentially be transformative as these tools get more refined. I think when we think about therapeutics, what's been transformative most recently in the renal cell carcinoma landscape has been the advent of HIF2α inhibition to improve outcomes for patients. And we have seen the approval of belzutifan most recently that has reshaped the landscape. And now there's other HIF2α inhibitors that are being developed that are going to be further important as they get refined. And lastly, I think when we think about urothelial carcinoma, the greatest transformation to treatment in that context has been the displacement of cisplatin and platinum-based chemotherapy as a frontline standard with the combination of enfortumab vedotin plus pembrolizumab. And we've seen antibody-drug conjugates really reshape treatment and tremendously improve outcomes for patients. So, I think those are the three key areas of interest. Dr. Pedro Barata: So with that, let's focus first on the imaging and then we'll get to the therapeutic area. So, we know there's been a paradigm shift, really, when prostate-specific targets emerged as tracers for PET scanning. And so, we now commonly use prostate-specific membrane antigen, or PSMA-based PET scanning, and really transform how we manage prostate cancer. Now, it appears that we're kind of seeing a similar wave in renal cell carcinoma with the new radiotracer against the target carbonic anhydrase IX. What can you tell us about this? And is this going to be available to us anytime soon? And how do you think that might potentially change the way we're managing patients with RCC today? Dr. Rana McKay: First, I'll step back and say that in the context of PSMA PET imaging, we have actually been able to better understand RCC as well. So, we know that PSMA is expressed in the neovasculature of tumors, and it can actually be used to detect renal cell carcinoma tumors. It has a detection rate of about 84% when used for detection. And so, you know, I don't think it's just restricted to carbonic anhydrase IX, but we will talk about that. So, PSMA expressed in the neovasculature has a detection rate of around 84%, particularly if we're looking at clear cell RCC. CAlX is overexpressed in clear cell RCC, and it's actually used in diagnosing renal cell carcinoma when we think of CAlX IHC for diagnosing clear cell RCC. And now there are CAlX PET tracers. The first foray was with the ZIRCON study that was actually an interestingly designed study because it was designed to detect the likelihood of PET imaging to identify clear cell RCC. So, it was actually used in the early diagnostics setting when somebody presents with a renal mass to discriminate that renal mass from a clear cell versus a non-clear cell, and it was a positive study. But when I think about the potential application for these agents, you know, I think about the entire landscape of renal cell carcinoma. This is a disease that we do treat with metastasis-directed therapy. We have certainly seen patients who've undergone metastasectomy have long, durable remissions from such an approach. And I think if we can detect very early onset oligometastatic disease where a metastasis-directed therapy or SABR could be introduced - obviously tested in a trial to demonstrate its efficacy - I think it could potentially be transformative. Dr. Pedro Barata: Wonderful. It's a great summary, and I should highlight you are involved in some of those ongoing studies testing the performance of this specific PET scanning for RCC against conventional imaging, right? And to remind the listeners, thus far, for the most part, we don't really do FDG-PET for RCC. There are some specific cases we do, but in general, they're not a standard scanning. But maybe that will change in the future. Maybe RCC will have their own PSMA-PET. And to your point, there's also emerging data about the role of PSMA-PET scanning in RCC as well, as you very elegantly summarized. Wonderful. So, let me shift gears a little bit because you did, in your introduction, you did highlight a novel MOA that we have in renal cell carcinoma, approved for use, initially for VHL disease, and after that for sporadic clear cell renal cell carcinoma. We're talking about hypoxia-inducible factor 2-alpha inhibitors, or HIF2α inhibitors, such as belzutifan. But there's also others coming up. So, as a way to kind of summarize that, what can you tell us about this breakthrough in terms of therapeutic class, this MOA that got to our toolbox of options for patients with advanced RCC? Tell us a little bit what is being utilized currently in the management of advanced RCC. And where do you see the future going, as far as, is it moving early on? Is it getting monotherapy versus combinations? Maybe other therapies? What are your thoughts about that? What can you tell us about it? Dr. Rana McKay: Belzutifan is a first-in-class HIF2α inhibitor that really established clinical validation for HIF2α as a therapeutic target. When we think about the activity of this agent, the pivotal LITESPARK-005 trial really led to the approval of belzutifan in patients who were really heavily pretreated. It was patients who had received prior IO therapy, patients who had received prior VEGF-targeted therapy. And in the context of this study, we saw a median PFS of 5.6 months, and there did seem to be a tail on the curve when you looked at the 12-month PFS rate with belzutifan. It was 33.7% compared to 17.6% with everolimus. And then when we look at the response rate, it was higher with belzutifan on the order of 22-23%, and very low with everolimus, as we've previously seen. I think one of the Achilles heels of this regimen is the primary PD rate, which was 34% when used in later line. There are multiple studies that are testing belzutifan in combination across the treatment landscape. So, we have LITESPARK-011, which is looking at the combination of belzutifan plus lenvatinib in the second-line setting. We've got the MK-012 [LITESPARK-012] study, which is looking at belzutifan in various combinations in the frontline setting. So there is a combination with IO plus belzutifan. And so this is also being looked at in that context. And then we also have the LITESPARK-022 study, which is looking at pembrolizumab with belzutifan in the adjuvant setting. So there's a series of studies that will be exploring belzutifan really across the treatment landscape. Many of these studies in combination. Additionally, there are other HIF2α inhibitors that are being developed. We have casdatifan, which is another very potent HIF2α inhibitor. You know, I think pharmacologically, these are different agents. There's a different half-life, different dosing. What is going to be the recommended phase 3 dose for both agents, the EPO suppression levels, the degree of EPO suppression, and sustainability of EPO suppression is very different. So, I think we've seen data from casdatifan from the ARC-20 trial from monotherapy with a respectable response rate, over 30%, primary PD rate hovering just around 10%.  And then we've also seen data of the combination of casdatifan with cabozantinib as well that were recently presented this year. And that agent is also being tested across the spectrum of RCC. It's being looked at in combination with cabozantinib in the PEAK-1 study, and actually just at the KCRS (Kidney Cancer Research Summit), we saw the unveiling of the eVOLVE-RCC trial, which is going to be looking at a volrustomig, which is a PD-1/CTLA-4 inhibitor plus casdatifan compared to nivo-ipi in the frontline setting.  So, we're going to see some competition in this space of the HIF2α inhibitors. I think when we think of mechanism of action in that these are very potent, not a lot of off-target activity, and they target a driver mutation in the disease. And that driver mutation happens very early in the pathogenesis. These are going to be positioned much earlier in the treatment landscape. Dr. Pedro Barata: All these studies, as you're saying, look really promising. And when we talk about them, you mentioned a lot of combinations. And to me, when I think of these agents, it makes a lot of sense to combine because there's not a lot of overlapping toxicities, if you will. But perhaps for some of our listeners, who have not used HIF2α inhibitors in practice yet, and they might be thinking about that, what can you tell us about the safety profile? How do you present it to your patients, and how do you handle things like hypoxia or anemia? How do you walk through the safety profile and tolerability profile of those agents like belzutifan? Dr. Rana McKay: I think these drugs are very different than your traditional TKIs, and they don't cause the classic symptoms that are associated with traditional TKIs that many of us are very familiar with like the rash, hand-foot syndrome, hypertension, diarrhea. And honestly, these are very nuanced symptoms that patients really struggle with the chronicity of being on a chronic daily TKI. The three key side effects that I warn patients about with HIF2α inhibitors are: (1) fatigue; (2) anemia; and (3) hypoxia and dysregulation in the ability to sense oxygen levels. And so, many of these side effects - actually, all of them - are very dose-dependent. They can be very well-managed. So, we can start off with the anemia. I think it's critically important before you even start somebody on belzutifan that you are optimizing their hemoglobin and bone marrow function. Make sure they don't have an underlying iron deficiency anemia. Make sure they don't have B12 or folate deficiency. Check for these parameters. Many patients who have kidney cancer may have some hematuria, other things where there could be some low-level blood loss. So, make sure that those are resolved or you're at least addressing them and supplementing people appropriately. I monitor anemia very closely every 3 to 4 weeks, at least, when people start on these medications. And I do initiate EPO, erythropoietin, should the anemia start to worsen. And I typically use a threshold of around 10g/dL  for implementing utilization of an EPO agent, and that's been done very safely in the context of the early studies and phase 3 studies as well. Now, with regards to the hypoxia, I think it's also important to make sure that you're selecting the appropriate individual for this treatment. People who have underlying COPD, or even those individuals who have just a very high burden of disease in their lung, lymphangitic spread, pleural effusions, maybe they're already on oxygen - that's not an ideal candidate for belzutifan. Something that very easily can be done in the clinic before you think about initiating somebody on this treatment, and has certainly been integrated into some of the trials, is just a 6-minute walk test. You know, have the patient walk around the clinic with one of the MAs, one of the nurses, put the O2 sat on [measuring oxygen saturation], make sure they're doing okay. But these side effects, like I said, are very dose-dependent. Typically, if a patient requires, if the symptoms are severe, the therapy can be discontinued and dose reduced. The standing dose is 120 mg daily, and there's two dose reductions to 80 mg and 40 mg should somebody warrant that dose modification. Dr. Pedro Barata: This is relatively new, right? Like, it was not that we're used to checking oxygen levels, right? In general, we're treating these patients, so I certainly think there's a learning curve there, and some of the points that you highlight are truly critical. And I do share many of those as well in our practice. Since I have you, I want to make sure we touch base on antibody-drug conjugates as well. It's also been a hot area, a lot of developments there. When I think of urothelial carcinoma and renal cell carcinoma, I see it a little bit different. I think perhaps in urothelial carcinoma, antibody-drug conjugates, or ADCs, are somewhat established already. You already mentioned enfortumab vedotin. I might ask you to expand a little bit on that. And then in renal cell carcinoma, we have some ADCs as well that you include in your chapter, and that I would like you to tell us what's coming from that perspective. So, tell us a little bit about how do you see ADCs in general for GU tumors, particularly UC and RCC? Tell us a little bit about the complexity or perhaps the challenges you still see. At the same time, tell us about the successes. Dr. Rana McKay: Stepping back, let's just talk about like the principles and design of ADCs. So, most ADCs have three components. There's a monoclonal antibody that typically targets a cell surface antigen, which is conjugated by a linker, which is the second component, to a payload drug. And typically, that payload drug has been chemotherapy, whether it be topoisomerase or whether it be MMAE or other chemotherapeutic. We can start in the RCC space. There's been multiple antibody-drug conjugates that have been tested. There's antibody-drug conjugates to CD70, which is expressed on clear cell RCC. There's been antibody-drug conjugates to ENPP3, which is also expressed on RCC. There's antibody-drug conjugates to CDH6. And they have different payloads, like I said, whether it be topoisomerase I or other microtubule inhibitors. Now, when we think about kidney cancer, we don't treat this disease with chemotherapy. This disease is treated with immunotherapy. It is treated with treatments that target the VEGF pathway and historically has not been sensitive to chemo. So, I think even though the targets have been very exciting, we've seen very underwhelming data regarding activity, and in some context, seen increased toxicity with the ADCs. So, I think we need to tread lightly in the context of the integration and the testing of ADCs in RCC. We just came back from the KCRS meeting, and there was some very intriguing data about a c-Kit ADC that's being developed for chromophobe RCC, which is, you know, a huge unmet need, these variant tumors that really lack appropriate therapeutics. But I just caution us to tread lightly around how can we optimize the payload to make sure that the tumor that we're treating is actually sensitive to the agent that's targeting the cell kill. So, that's a little bit on the ADCs in RCC. I still think we have a long way to go and still in early testing. Now, ADCs for UC are now the standard of care. I think the prototypical agent, enfortumab vedotin, is a nectin-4-directed ADC that's conjugated to an MMAE payload and was the first ADC approved for advanced urothelial, received accelerated approval following the EV-201 trial, which was basically a multicenter, single-arm study that was investigating EV in cisplatin-ineligible patients with advanced urothelial carcinoma, and then ultimately confirmed in the EV-301 study as well. And so, that study ended up demonstrating the support superiority of EV from an overall survival standpoint, even PFS standpoint. Building on that backbone is the EV-302 study, which tested EV in combination with pembrolizumab versus platinum-based chemotherapy in the frontline setting. And that was a pivotal, landmark study that, like I said, has displaced platinum therapy as a frontline treatment for people with advanced urothelial carcinoma. And when we think about that study and the median overall survival and just how far we've come in urothelial cancer, the median OS with EV-pembro from that trial was 31 and a half months. I mean, that's just incredible. The control arm survival was 16 and a half months. The hazard ratio for OS, 0.47. I mean this is why when this data was presented, it was literally a standing ovation that lasted for several minutes because we just haven't seen data that have looked that good. And there are other antibody-drug conjugates that are being tested. We've all been involved in the saga with sacituzumab govitecan, which is a trophoblast cell surface antigen 2 (Trop-2) targeted ADC with a topoisomerase I payload. It was the second ADC to receive approval, but then that approval was subsequently withdrawn when the confirmatory phase 3 was negative, the TROPiCS-04 trial. So, approval was granted based off of the TROPHY-U-01, single-arm, phase 2 study, demonstrating a response rate of around 28% and a PFS of, you know, about 5 and a half months. But then failure to show any benefit from an OS standpoint. And I think there's a lot of controversy in the field around whether this agent still has a role in advanced urothelial carcinoma. And I think particularly for individuals who do not have molecular targets, like they're not HER2-amplified or have HER2-positivity or FGFR or other things like that. Dr. Pedro Barata: Fantastic summary, Rana. You were talking about the EV, and it came to mind that it might not be over, right, for the number of ADCs we use in clinical practice in the near future. I mean, we've seen very promising data for ADC against the HER2, right, and over-expression. It also can create some challenges, right, in the clinics because we're asking to test for HER2 expression. It's almost like, it's not exactly the same to do it in breast cancer, but it looks one more time that we're a little bit behind the breast cancer field in a lot of angles. And also has vedotin as a payload. Of course, I'm referring to disitamab vedotin, and there's very elegant data described by you in your review chapter as well. And it's going to be very interesting to see how we sequence the different ADCs, to your point as well. So, before we wrap it up, I just want to give you the opportunity to tell us if there's any area that we have not touched, any take-home points you'd like to bring up for our listeners before we call it a day. Dr. Rana McKay: Thank you so much. I have to say, you know, I was so excited at ASCO this year looking at the GU program. It was fantastic to see the progress being made, novel therapeutics that really there's a tremendous excitement about, not just in RCC and in UC, but also in prostate cancer, thinking about the integration of therapies, not just for people with refractory disease that, even though our goal is to improve survival, our likelihood of cure is low, but also thinking about how do we integrate these therapies early in the treatment landscape to enhance cure rates for patients, which is just really spectacular. We're seeing many of these agents move into the perioperative setting or in combination with radiation for localized disease. And then the special symposium on biomarkers, I mean, we've really come a long, long way. And I think that we're going to continue to evolve over the next several years. I'm super excited about where the field is going in the treatment of genitourinary malignancies. Dr. Pedro Barata: Oh, absolutely true. And I would say within the Annual Meeting, we have outstanding Educational Sessions. And just a reminder to the listeners that actually that's where the different teams or topics for the Educational Book chapters come from, from actually the educational sessions from ASCO. And your fantastic chapter is an example of that, right, focusing on advanced GU tumors. So, thank you so much, Rana, for taking the time, sharing your insights with us today on the podcast. It was a fantastic conversation as always. Dr. Rana McKay: My pleasure. Thanks so much for having me, Dr. Barata. Dr. Pedro Barata: Of course.  And thank you to our listeners for your time today. You will find the link to the article discussed today in the transcript of this episode. I also encourage you to check out the 2025 ASCO Educational Book. You'll find an incredible wealth of information there. It's free, available online, and you'll find, hopefully, super, super important information on the key science and issues that are shaping modern oncology, as we've heard from Dr. McKay and many other outstanding authors. So, thank you, everyone, and I hope to see you soon. 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. Follow today's speakers:        Dr. Pedro Barata @PBarataMD Dr. Rana McKay @DrRanaMcKay Follow ASCO on social media:        @ASCO on X (formerly Twitter)        ASCO on Bluesky       ASCO on Facebook        ASCO on LinkedIn        Disclosures:     Dr. Pedro Barata: Stock and Other Ownership Interests: Luminate Medical Honoraria: UroToday Consulting or Advisory Role: Bayer, BMS, Pfizer, EMD Serono, Eisai, Caris Life Sciences, AstraZeneca, Exelixis, AVEO, Merck, Ipson, Astellas Medivation, Novartis, Dendreon Speakers' Bureau: AstraZeneca, Merck, Caris Life Sciences, Bayer, Pfizer/Astellas Research Funding (Inst.): Exelixis, Blue Earth, AVEO, Pfizer, Merck  Dr. Rana McKay: Consulting or Advisory Role: Janssen, Novartis, Tempus, Pfizer, Astellas Medivation, Dendreon, Bayer, Sanofi, Vividion, Calithera, Caris Life Sciences, Sorrento Therapeutics, AVEO, Seattle Genetics, Telix, Eli Lilly, Blue Earth Diagnostics, Ambrx, Sumitomo Pharma Oncology, Esiai, NeoMorph, Arcus Biosciences, Daiichi Sankyo, Exelixis, Bristol Myers Squibb, Merck, Astrazeneca, Myovant Research Funding (Inst.): Bayer, Tempus, AstraZeneca, Exelixis, Bristol Myers Squibb, Oncternal Therapeutics, Artera    

Dr. Sumanta (Monty) Pal and Dr. Petros Grivas discuss innovative new intravesical therapies and other recent advances in the treatment of non-muscle invasive bladder cancer. TRANSCRIPT Dr. Sumanta (Monty) Pal: Hello and welcome. I'm Dr. Monty Pal here at the ASCO Daily News Podcast. I'm a medical oncologist and professor and vice chair of academic affairs at the City of Hope Comprehensive Cancer Center in Los Angeles. And I'm really delighted to be your new host here. Today's episode is going to really sort of focus on an area near and dear to my heart, something I actually see in the clinics, and that's bladder cancer. We're specifically going to be discussing non-muscle invasive bladder cancer, which actually comprises about 75% of new cases. Now, in recent years, there's been a huge shift towards personalized bladder-preserving strategies, including innovative therapies and new agents that really are reducing reliance on more primitive techniques like radical cystectomy and radiation therapy. And I'm really excited about this new trend. And really at the forefront of this is one of my dear friends and colleagues, Dr. Petros Grivas. He's a professor in the Department of Medicine and Division of Hematology Oncology at the University of Washington. It's going to take a while to get through all these titles. He's taken on a bunch of new roles. He is medical director of the International Program, medical director of the Local and Regional Outreach Program, and also professor in the Clinical Research Division at the Fred Hutch Cancer Center. Petros, welcome to the program. Dr. Petros Grivas: Thank you so much, Monty. It's exciting for me to be here. Dr. Sumanta (Monty) Pal: Just FYI for our audience, our disclosures are available in the transcript of this episode.  We're going to get right into it, Petros. Non-muscle invasive bladder cancer, this is a really, really challenging space. We see a lot of recurrence and progression of the disease over time, about 50% to 70% of patients do have some recurrence after initial treatment, and about 30% are ultimately going to progress on to muscle-invasive or metastatic disease. Now, I will say that when you and I were in training, non-muscle invasive bladder cancer was something that was almost relegated to the domain of the urologist, right? They would use treatments such as BCG (Bacillus Calmette-Guérin) in a serial fashion. It was rare, I think, for you and I to really enter into this clinical space, but that's all changing, isn't it? I mean, can you maybe tell us about some of the new therapies, two or three that you're really excited about in this space? Dr. Petros Grivas: Monty, you're correct. Traditionally and conventionally, our dear friends and colleagues in urology have been managing patients with non-muscle invasive bladder cancer. The previous term was superficial bladder cancer. Now, it has changed, to your point, to non-muscle invasive bladder cancer. And this has to do with the staging of this entity. These tumors in superficial layers of bladder cancer, not invading the muscularis propria, the muscle layer, which makes the bladder contract for urine to be expelled. As you said, these patients have been treated traditionally with intravesical BCG, one of the oldest forms of immunotherapy that was developed back in the 1970s, and this is a big milestone of immunotherapy development. However, over the years, in the last 50 years, there were not many options for patients in whom the cancers had progression or recurrence, came back after this intravesical BCG. Many of those patients were undergoing, and many of them still may be undergoing, what we call radical cystectomy, meaning removal of the bladder and the lymph nodes around the bladder. The development of newer agents over the last several years has given the patients the option of having other intravesical therapies, intravesical meaning the delivery of drugs, medications inside the bladder, aiming to preserve the bladder, keep the bladder in place. And there are many examples of those agents. Just to give you some examples, intravesical chemotherapy, chemotherapy drugs that you and me may be giving intravenously, some of them can be given inside the bladder, intravesical installation. One example of that is a combination of gemcitabine and docetaxel. These drugs are given in sequence one after the other inside the bladder, and they have seen significant efficacy, good results, again, helping patients keeping the bladder when they can for patients with what we call BCG unresponsive non-muscle invasive bladder cancer. And again, there's criteria that the International Bladder Cancer Group and the FDA developed, how to define when BCG fails, when we have BCG unresponsive non-muscle invasive bladder cancer. Dr. Sumanta (Monty) Pal: And we're actually going to get into some of the FDA requirements and development pathways and so forth. What I'm really interested in hearing, and I'm sure our audience is too, are maybe some of the new intravesical treatments that are coming around. I do think it's exciting that the gemcitabine and docetaxel go into the bladder indeed, but what are some of the top new therapies? Pick two or three that you're excited about that people should be looking out for in this intravesical space. Dr. Petros Grivas: For sure, for sure. In terms of the new up-and-coming therapies, there are a couple that come to mind. One of them is called TAR-200, T-A-R 200. This agent is actually a very interesting system. It's an intravesical delivery of a chemotherapy called gemcitabine, the one that I just mentioned a few minutes ago, that is actually being delivered through what we call a pretzel, which is like a rounded [pretzel-shaped] structure working like an osmotic pump, and that is being delivered inside the bladder intravesically by urologists. And this drug is releasing, through the osmotic release mechanism, this chemotherapeutic drug, gemcitabine, inside the bladder. And this can be replaced once every 3 weeks in the beginning. And the data so far from early-phase trials are really, really promising, showing that this agent may be potentially regulatory approved down the road. So TAR-200 is something to keep in mind. And similarly, in the same context, there is a different drug that also uses the same mechanism, and this osmotic release, this pretzel, it's just encoded with a different agent. The different agent is an FGFR inhibitor, a target therapy called erdafitinib, a drug that you and me may give in patients with metastatic urothelial carcinoma if they have an FGFR3 mutation or fusion. And that drug is called TAR-210. Dr. Sumanta (Monty) Pal: And can I ask you, in that setting, do you have to have an FGFR3 mutation to receive it? Or what is the context there? Dr. Petros Grivas: So for TAR-210, TAR-2-1-0, usually there is a checking to see if there is an FGFR3 mutation or fusion. And the big question, Monty, is do we have adequate tissue, right? From a limited tissue on what we call the TURBT, right, that urologists do. And now there is a lot of development in technology, for example, urine circulating tumor DNA to try to detect these mutations in the urine to see whether the patient may be eligible for this TAR-210. Both of those agents are not FDA approved, but there are significant promising clinical trials. Dr. Sumanta (Monty) Pal: So now let's go to a rapid-fire round. Give us two more agents that you're excited about in this intravesical space. What do you think? Dr. Petros Grivas: There is another one called cretostimogene. It's a long name. Dr. Sumanta (Monty) Pal: They really make these names very easy for us, don't they? Dr. Petros Grivas: They are not Greek names, Monty, I can tell you, you know. Even my Greek language is having trouble pronouncing them. The cretostimogene, it's actually almost what we call a growth factor, a GM-CSF. The actual name of this agent is CG0070. This is a replicating mechanism where GM-CSF is replicating in cells. And this agent has shown significant results again, like the TAR-200, in BCG unresponsive non-muscle invasive bladder cancer. I would say very quickly, two agents that actually were recently approved and they're already available in clinical practice, is nadofaragene firadenovec, another long name. That's a non-replicating vector that has the gene of interferon alfa-2b that stimulates the immune system in the bladder. It's given once every 3 months. And the last one that was, as I mentioned, already FDA approved, it's an interleukin-15 superagonist. It's another long name, which is hard to pronounce, but I will give it a try. It's a drug that was recently actually approved also in the UK. The previous name was N-803. It's given together with BCG as a combination for BCG unresponsive non-muscle invasive bladder cancer. Dr. Sumanta (Monty) Pal: This is a huge dilemma, I think, right? Because if you're a practicing, I'm going to say urologist for the moment, I guess the challenge is how do you decide between an IL-15 superagonist? How do you decide between a pretzel-eluting agent? How do you decide between that and maybe something that's ostensibly, I'm going to guess, cheaper, like gemcitabine and docetaxel? What's sort of the current thinking amongst urologists? Dr. Petros Grivas: Multiple factors play into our account when the decision is being made. I discuss with urologists all the time. It's not an easy decision because we do not have head-to-head comparisons between those agents. As you mentioned, intravesical chemotherapy with gemcitabine and docetaxel has been used over the years and this is the lowest cost, I would say, the cheapest option with good efficacy results. Obviously, the nadofaragene firadenovec every 3 months and the interleukin-15 superagonist, N-803, plus BCG have also been approved. The question is availability of those agents, are they available? Are they reimbursed? Cost of those agents can come into play. Frequency of administration, you know, once every 3 months versus more frequent. And of course, the individual efficacy and toxicity data, preference of the patients; sometimes the provider, the urologist, may have something that they may be more familiar with. But we lack this head-to-head comparison. Of course, I want to make sure I mention that radical cystectomy may still be the option for appropriate patients. So that complicates also the decision making and has to be individualized, customized, and personalized, taking into account all those factors. And there is not one size fitting all. Dr. Sumanta (Monty) Pal: So I think we discussed five intravesical therapies. As you point out, and you know, I'm going to get some calls about this: I think I referred to radical cystectomy as being a more primitive procedure. Not true at all. I think it's something that still is, you know, a mainstay of management in this disease space. But I guess it gets even more complicated, am I right, Petros? Because now we have systemic therapies that we can actually apply in this non-muscle invasive setting for at this point, refractory disease. Can you maybe just give us a quick two-minute primer on that? Dr. Petros Grivas: Absolutely, and systemic therapies now come into play, as you said. And a classical example of that, Monty, came from the KEYNOTE-057 trial that we published about 6 years ago. This is intravenous pembrolizumab, given intravascularly, intravenously, as opposed to the previously discussed intravesical administration of agents. Pembrolizumab was tested in that KEYNOTE-057 trial and showed efficacy about, I would say, one out of five patients, about 20%, had a complete response of the tumor in the bladder in a year after starting the treatment. Again, it's hard to compare across different agents, but obviously when we give something intravenously, there is a risk of toxicity, side effects systemically, what we call immune-related adverse events. And this can also play in the decision making, right? When you have intravesical agents versus intravascular agents, there is different toxicity profiles in terms of systemic toxicity. But intravenous pembrolizumab has been an option, FDA approved, since, if I remember, it was early 2020 when this became FDA approved. There are other agents being tested in this disease, but like atezolizumab through the SWOG study that Dr. Black and Dr. Singh led, but atezolizumab is not FDA approved for this indication. Again, this is for BCG unresponsive, high-risk, non-muscle invasive bladder cancer. Dr. Sumanta (Monty) Pal: So maybe teach us how it works, for instance, at an expert center like the Fred Hutch. When you see a patient with non-muscle invasive bladder cancer, there's obviously the option of surgery, there's the intravesical therapies, which I imagine the urology team is still really at the helm of. But then, I guess there has to be consideration of all options. So you've got to bring up systemic therapy with agents like pembrolizumab. In that context, are you involved that early on in the conversation? Dr. Petros Grivas: That's a great discussion, Monty. Paradigm is shifting as we mentioned together. The urologists have been treating these patients and still they are the mainstay of the treaters, the managers in this disease. But medical oncologists come to play more and more, especially with the FDA approval of intravenous pembrolizumab about 5 years ago [GC1]  [KM2] . We have the concept of multidisciplinary bladder cancer clinic here at Fred Hutch and University of Washington. This happens every Tuesday morning, and we're very excited because it's a one-stop shop for the patients. We have the urologist, a medical oncologist, radiation oncologist, and experts from radiology and pathology, and we all review cases specifically with muscle-invasive bladder cancer. But every now and then, we see patients with BCG unresponsive non-muscle invasive bladder cancer. And this is where we discuss and we talk to the patient about pros and cons of all those options. And that's a classic example where medical oncologists may start to see those patients and offer their input and expertise. In addition to that, sometimes we have clinical trials, we may see these patients because there are systemic agents that may be administered in this setting. We have the SunRISe trial program that includes also a systemically administered checkpoint inhibitor. So that's another example where we see patients either in the context of multi-clinic or in individual solo clinics to counsel the patients about the pros and cons of the systemically administered agents in the context of clinical trials. Usually checkpoint inhibitors are the class of agents that are being tested in this particular scenario. Dr. Sumanta (Monty) Pal: I can see a scenario where it's really going to require this sort of deep dive, much in the way that we do for prostate cancer, for instance, where the medical oncologist is involved very early on and planning out any sort of systemic therapy component of treatment or at the very least, at least spelling out those options. I think it's going to be really interesting to see what this space looks like 5 or 10 years down the road. In closing, I wanted to go through something that I think is so different in this space, at least for the time being, and that is the paradigm for FDA approval. When you and I have our fellows in the clinics, we always say, “Look, you know, the paradigm in this disease and that disease and the other disease needs to be phase 3 randomized trials, right? Big thousand patient experiences where you're testing clinical endpoints.” That's tough in non-muscle invasive bladder cancer, right? Because thankfully, outcomes can actually be quite good, you know, in this setting, right? It's tough to actually estimate overall survival in some of these early-stage populations. Tell me what the current regulatory bar is, and this is a tough thing to do in 2 minutes or less but tell me where you see it headed. Dr. Petros Grivas: You alluded to that before, Monty, when I was giving the background and we talked about the regulatory approval. And I have to very quickly go back in time about 10 years ago because it's important for context that can help us in other disease types too. We had workshops with the FDA and the NCI with the help of the International Bladder Cancer Group and other colleagues. And we try to define a framework, what endpoints are meaningful for those patients in this disease. It was a multidisciplinary, multiple stakeholders meeting, where we tried to define what is important for patients. What are the available agents? What are the trial designs we can accept? And what are the meaningful endpoints that the regulatory agencies can accept for regulatory approval? And that was critical in that mission because it allowed us to design clinical trials, for example, single-arm trials in a disease where there was no standard of care. There was intravesical valrubicin and chemotherapy anthracycline that was approved for many years, but was not practically used in clinical practice, despite being approved, the valrubicin. And because of that, the FDA allowed these single-arm trials to happen. And obviously the endpoint was also discussed in that meeting. For example, for carcinoma in situ, complete response, clinical complete response, because the bladder remains intact in many patients, clinical complete response was a meaningful primary endpoint, also duration of response is also very important. So what is the durable clinical complete response in 1 year or 18 months is relevant. And when you have papillary tumors like Ta or T1 with CIS, for papillary tumors, event-free survival becomes one of the key endpoints and you look at it over time, for example, at 12 or 18 months, what is the event-free survival? So clinical complete response, duration of response, event-free survival, depending on the CIS presence or papillary tumors, I think these are endpoints that have allowed us to design those trials, get those agents approved.  Now, the question going forward, Monty, and we can close with that is, since now we have the embarrassment of riches, many more options available compared to where we were 6 and 7 years ago, is now the time to do randomized trials? And if we do randomized trials, which can be the control group? Which of those agents should be allowed to be part of the control group? These are ongoing discussions right now with the NCI, with other agencies, cooperative groups, trying to design those trials and move forward from here.[GC3]  Dr. Sumanta (Monty) Pal: Well, it's awesome to have you here on the program so we can get some early looks into some of these conversations. I mean, clearly, you're at the table at a lot of these discussions, Petros. So I want to thank you for sharing your insights with us today. This was just tremendous. Dr. Petros Grivas: Thank you, Monty. You know, patients in the center, I just came back from the Bladder Cancer Advocacy Network meeting in Washington, D.C., and we discussed all those questions, the topics you very eloquently mentioned and asked me today, and patients gave us great feedback and patients guide us in that effort. Thank you so, so much for having me and congratulations for the amazing podcast you're doing. Dr. Sumanta (Monty) Pal: Oh, cheers, Petros, thanks so much.  And thank you to the listeners who joined us today. If you really like the insights that you heard on this ASCO Daily News Podcast, please rate, review, and subscribe wherever you get your podcasts. Thanks, everyone. 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. Sumanta (Monty) Pal  @montypal  Dr. Petros Grivas @PGrivasMDPhD   Follow ASCO on social media:     @ASCO on Twitter    ASCO on Bluesky   ASCO on Facebook     ASCO on LinkedIn     Disclosures:    Dr. Sumanta (Monty) Pal:   Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview  Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical  Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis  Dr. Petros Grivas: Consulting or Advisory Role: Merck, Bristol-Myers Squibb, AstraZeneca, EMD Serono, Pfizer, Janssen, Roche, Astellas Pharma, Gilead Sciences, Strata Oncology, Abbvie, Bicycle Therapeutics Replimune, Daiichi Sankyo, Foundation Medicine, Bicycle Therapeutics, Eli Lilly, Urogen Pharma, Tyra Biosciences Research Funding (Inst.): Bristol-Myers Squibb, Merck, EMD Serono, Gilead Sciences, Acrivon Therapeutics, ALX Oncology, ALX Oncology, Genentech Travel, Accommodations, Expenses: Gilead Sciences

In this episode, Dr Brad Kahl and Dr Noopur Raje discuss the recent advances and emerging data for CAR T-cell therapy in lymphomas and multiple myeloma including the latest evidence from long-term clinical trial follow-up and real-world data, plus new data with CAR T-cell therapies in new lymphoma settings and novel CAR T-cell therapies currently under development for multiple myeloma.LymphomasDLBCL: Real-world outcomes post axi-cel, CAR T vs autologous HSCTFL: Tisa-cel (ELARA), axi-cel (ZUMA-5)MZL: Liso-cel (TRANSCEND FL)MCL: Real-world outcomes post brexu-celCLL: Liso-cel (TRANSCEND CLL 004)Multiple MyelomaCilta-cel (CARTITUDE-1)Anito-cel (iMMagine-1)GC012FArlo-celBMS-986453TriPRIL Presenters:Brad Kahl, MDProfessor of MedicineWashington University St Louis, MissouriNoopur Raje, MD Director, Center for Multiple MyelomaMassachusetts General Hospital Cancer CenterProfessor of MedicineHarvard Medical SchoolBoston, Massachusetts Content based on an online CME program supported by an independent educational grant from Bristol Myers Squibb.Link to full program: https://bit.ly/3ViR62V

Join panelists as they discuss rheumatologist impressions, knowledge and practices over the last 20 years when treating rheumatoid arthritis. Experts will unpack the results of a nationwide, three-part survey — covering treatment milestones, changing practices, and what the future holds for RA therapy. Don't miss this opportunity to hear what your peers are saying — and where the field is headed. Panelists: Katherine Liao, MD, MPH Stanley B. Cohen, MD Jeff Curtis, MD, MS, MPH Jack Cush, MD - moderator Sponsored by: Bristol Myers Squibb

In der heutigen Folge sprechen die Finanzjournalisten Anja Ettel und Philipp Vetter über KI-Optimismus bei Dell, eine neue Toniebox-Euphorie in Kinderzimmern und einen Analysten-Push für Siemens. Außerdem geht es um Ulta Beauty, Marvell, Gap, Amazon, Microsoft, Meta, Spotify, IBM, Alphabet, Bristol Myers Squibb, Argenx, Legend Biotech, Summit Therapeutics, Denali Therapeutics, Intellia, Regeneron, Immunocore, Viking Therapeutics, Novo Nordisk und Eli Lilly. Die Tickets zum Finance Summit am 17. September bekommt ihr 40 Euro günstiger – aber nur mit dem exklusiven Code AAA2025, der ihr unter dem folgenden Link eingeben müsst: https://veranstaltung.businessinsider.de/BN5aLV Außerdem könnt ihr unter diesem Link euer Depot hochladen – und mit etwas Glück wird kein Geringerer als Christian W. Röhl euer Depot beim Summit checken und optimieren. https://form.jotform.com/Product_Unit/formular-finance-summit-depot-check Wir freuen uns an Feedback über aaa@welt.de. Noch mehr "Alles auf Aktien" findet Ihr bei WELTplus und Apple Podcasts – inklusive aller Artikel der Hosts und AAA-Newsletter. Hier bei WELT: https://www.welt.de/podcasts/alles-auf-aktien/plus247399208/Boersen-Podcast-AAA-Bonus-Folgen-Jede-Woche-noch-mehr-Antworten-auf-Eure-Boersen-Fragen.html. Der Börsen-Podcast Disclaimer: Die im Podcast besprochenen Aktien und Fonds stellen keine spezifischen Kauf- oder Anlage-Empfehlungen dar. Die Moderatoren und der Verlag haften nicht für etwaige Verluste, die aufgrund der Umsetzung der Gedanken oder Ideen entstehen. Hörtipps: Für alle, die noch mehr wissen wollen: Holger Zschäpitz können Sie jede Woche im Finanz- und Wirtschaftspodcast "Deffner&Zschäpitz" hören. +++ Werbung +++ Du möchtest mehr über unsere Werbepartner erfahren? Hier findest du alle Infos & Rabatte! https://linktr.ee/alles_auf_aktien Impressum: https://www.welt.de/services/article7893735/Impressum.html Datenschutz: https://www.welt.de/services/article157550705/Datenschutzerklaerung-WELT-DIGITAL.html

In this special edition episode, recorded live at the ASCO Annual Meeting, hosts Shikha Jain, MD, and Edward Kim, MD, honor Healio's 2025 Disruptive Innovators for their positive disruption in the field of hematology/oncology, and for pushing the status quo to improve clinical practice.  •    Welcome to the fourth annual Healio Disruptive Innovator Awards in hematology/oncology. 1:00 •    VK Gadi, MD PhD, presents the Health Equity Award. 3:56 •    The Health Equity Award winner, Ana Velázquez Mañana, MD, makes a speech. 6:00 •    Morgan Collier presents the Woman Disruptor of the Year Award. 7:38 •    Betty S. Pace, MD, accepts the Woman Disruptor of the Year Award. 9:19 •    The Social Media Influencer Award, presented by Eleonora Teplinsky, MD. 11:53 •    Amani Jambhekar, MD, also known as @ajvictorymd on Instagram and TikTok, accepts the Social Media Influencer Award. 13:13 •    Brenda M. Nevidjon, MSN, RN, FAAN, presents the Advanced Practice Trailblazer Award. 14:40 •    Ashley Leak Bryant, PhD, RN, OCN, FAAN, delivers her acceptance speech for the Advanced Practice Trailblazer Award. 16:19 •    Kamal Jethwani, MD, MPH, presents the Patient Voice Award. 18:44 •    Founder Kimberly Richardson, MA, accepts the Patient Voice Award for the Black Cancer Collaborative. 20:44 •    Healio's chief content officer, Joan-Marie Stiglich, ELS, presents the NextGen Disruptor Award to Nazli Dizman, MD. 22:22 •    The Clinical Innovation Award goes to UNC Lineberger Comprehensive Cancer Center for their at-home symptom reporting, led by Ethan Basch, MD, MSc. 24:18 •    Hope S. Rugo, MD, wins the Lifetime Disruptor Award. 26:48 •    The Industry Breakthrough Award goes to Breyanzi (lisocabtagene maraleucel, or liso-cel) from Bristol Myers Squibb. 30:57 •    On behalf of Bristol Myers Squibb, Amy Corrao, MSN, NP-C, accepts the Industry Breakthrough Award. 32:33 •    Thanks to all of the winners, nominees and sponsors! 35:39 •    Thanks for listening. 36:21 We'd love to hear from you! Send your comments/questions to Dr. Jain at oncologyoverdrive@healio.com. Follow Healio on X and LinkedIn: @HemOncToday and https://www.linkedin.com/company/hemonctoday/. Follow Dr. Jain on X: @ShikhaJainMD. Read the full coverage from Healio's Disruptive Innovators here.

In this episode of The Daily Mastermind, host George Wright III welcomes an inspiring guest, the founder and CEO of Florida's Cotton Clouds, Onahira Rivas. She talks about her entrepreneurial journey from starting a business as a child to scaling multiple multimillion-dollar ventures. They share insightful lessons on leveraging corporate experience, implementing systems and SOPs, and the importance of sales and marketing as a foundation. The episode introduces the Bold Business Framework designed to help six and seven-figure business owners transform their businesses into legacy enterprises through sales and marketing, operational systems, investor readiness, and growth strategies. Real-world examples, including a car dealership's success story, illustrate the practical application of the framework. 02:05 Corporate Experience and Transition to Entrepreneurship04:07 Building and Scaling a Business06:22 Creating a Legacy and Manufacturing in America10:55 The Bold Business Framework17:57 Case Study: Transforming a Car Dealership23:27 Mindset Shifts for EntrepreneursYou have GREATNESS inside you. I BELIEVE in You. Let's Make Today the Day You Unleash Your Potential!George Wright IIICEO, The Daily Mastermind | Evolution X_________________________________________________________P.S. Whenever you're ready, here are ways I can help you…Get to know me:1. Subscribe to The Daily Mastermind Podcast- daily inspiration, motivation, education2. Follow me on social media Facebook | Instagram | Linkedin | TikTok | Youtube3. Get the Prosperity Pillars Poster I Developed over 20 years from my Mentors.Work with me:My mission is to help you Master Your Mind, Money, & Business, and I firmly believe:It's Never Too Late to Create the Life You Were Meant to Live…a LIFESTYLE of Health, Wealth, and Happiness. Here are ways I've been able to help thousands of people over the past 20 years…About the Guest: Onahira RivasOnahira Rivas is the founder and CEO of Florida's Cotton Clouds, the first woman-led cotton manufacturing facility in the U.S. With over two decades of global leadership experience at companies like Novo Nordisk and Bristol Myers Squibb, she has launched and scaled multimillion dollar brands across pharma, retail, and consumer goods. Onahira has introduced hundreds of products to major retailers and now focuses on purpose-driven business. Her work is rooted in values like resilience, transparency, and faith. She's a member of the Forbes Business Council, a winner of The Blox TV competition, and a passionate advocate for U.S.-based manufacturing and female leadership in business.Guest ResourcesValiant CEO Article: https://valiantceo.com/onahira-rivas-of-floridas-cotton-clouds-resilient-leadership-amidst-business-challenges/Website: https://onahirarivas.com/Florida Cotton Clouds Website: https://floridascottonclouds.com/ Meet with Onahira: https://intro.co/ONAHIRARIVAS?source=introFacebook & Instagram: @onahirarivasTikTok: Tiktok@onahirarivasLinkedIn: https://www.linkedin.com/in/onahirarivas

After many U.S. biopharma companies posted sales declines in the first quarter, the domestic pharma industry largely bounced back to growth in the second quarter. In this episode of "The Top Line," Fierce Pharma's Eric Sagonowsky and Kevin Dunleavy break down the numbers behind the industry’s second-quarter performance. Among U.S. pharma heavyweights, J&J, AbbVie, Pfizer, Regeneron, Bristol Myers Squibb and Biogen each eked out gains this past quarter. Their results varied, with individual stories worth highlighting at each of these major companies. Beyond earnings, Sagonowsky and Dunleavy also discuss the growing competition in diabetes and obesity treatments between Eli Lilly and Novo Nordisk, as well as Merck’s rising financial reliance on its blockbuster cancer drug Keytruda, among other topics. To learn more about the topics in this episode: Several US pharma giants stage Q2 sales turnaround after subpar results earlier in year The battle of the obesity drug heavyweights 7 top pharmas posted revenue declines in Q1. The common thread? All are US firms Biopharma briefing: Q1 trends, gene therapy updates and ASCO preview See omnystudio.com/listener for privacy information.

Dr. Sumanta (Monty) Pal and Dr. Arielle Elkrief discuss the clinical relevance of the gut microbiome in cancer immunotherapy and the importance of antibiotic stewardship, as well as interventions currently being explored to treat gut dysbiosis and optimize immunotherapy response. TRANSCRIPT Dr. Sumanta (Monty) Pal: Hi everyone, I'm Dr. Monty Pal, welcoming you to the ASCO Daily News Podcast. I'm a medical oncologist. I'm a professor and vice chair of academic affairs at the City of Hope Comprehensive Cancer Center in Los Angeles.  Today we're here to discuss one of my favorite topics, which is the gut microbiome. It's almost hard to avoid the gut microbiome nowadays if you look at medical literature within oncology. It's an emerging phenomenon, but there are a couple of individuals that I would really define as pioneers in the field. And one of them is actually with me today, Dr. Arielle Elkrief, to discuss the clinical relevance of the gut microbiome, particularly amongst patients receiving immunotherapy, although I imagine our conversation today will take many twists and turns. Arielle is an assistant professor and clinician scientist in the Department of Oncology at the University of Montreal, and she is co-director of the CHUM Microbiome Center there.  FYI for the listeners, we have our full disclosures in the transcript of this episode.  Arielle, thank you so much for joining us today. Dr. Arielle Elkrief: Thanks so much, Monty. This is going to be amazing. Dr. Sumanta (Monty) Pal: Well, I have to tell you what sort of inspired me to bring you on as a guest. It was one of many things, but it was this really terrific ASCO Educational [Book] article that you wrote. Now, I have to tell you, I've read all the articles sort of cover to cover in the book, and they're always a wonderful primer, so if our audience is studying for board research or something of that sort, it's a terrific resource to go through. I have to tell you, this piece on the gut microbiome that you wrote is nothing short of a masterpiece. If you read this cover to cover, it's actually going to give you, I think, a sense of the current state and future state of the field. I wanted to start by just sort of beginning with sort of the origin story for a lot of this, which is this association between the gut microbiome and immunotherapy response. This takes us back several years to this pivotal series of papers in Science. Maybe you could walk our audience through that. Dr. Arielle Elkrief: Absolutely. Well, thank you so much for your kind words about the ASCO [Educational] Book. It was a team effort with a lot of key opinion leaders in the field, so I'm really glad to learn that you've liked it.  Moving backwards in terms of how we came to understand that the gut microbiome is essential to priming a response to cancer immunotherapy actually goes back to 2015 and seminal papers that looked at what happens when we take mice that are germ-free mice that have never been exposed to a microbiome. These are mice that are born by cesarean section and essentially live in a bubble. And when we give those mice tumors and treat them, in the first papers with anti-CTLA-4 treatment, we realized that these antibodies don't work at all. And that was the first observation that the presence of a gut microbiome was essential to mounting an anti-cancer immune response. When we supplemented those same mice with beneficial bacteria or feces from responder patients, we were able to restore the response to immunotherapy. And so those were really the first preclinical observations that made us understand the critical role of the microbiome in immunotherapy response. Moving a little bit in the future, we examined the fecal microbiome composition using shotgun metagenomic sequencing in different cohorts of patients with solid tumors, namely lung cancers, kidney cancers, and also skin tumors like melanoma, and found that patients who responded to immunotherapy had a distinct microbiome that was characterized by beneficial bacteria compared to patients who experienced resistance to immunotherapy that had a dysbiotic or diseased microbiome. Dr. Sumanta (Monty) Pal: So, you know, it's interesting, these techniques that we're using to sequence the gut, they're a little bit different. So I wonder if you can give the audience a quick primer on these techniques that you're so well versed in, shotgun metagenomic sequencing, 16S rRNA sequencing. If you had to describe this in 30 seconds, which is a tall task, how would you do that? Dr. Arielle Elkrief: That's a tall task. Much of what we know about the microbiome initially came from a technique called 16S rRNA sequencing. This is a technique that amplifies the 16S region and basically tells you at the genus level what's going on at the level of bacterial composition. This technique is fast, relatively cheap, and can be performed on a laptop computer, which is excellent. The problem is that it's prone to a lot of technical variations. Different primers might give you different results, and you're really limited at the genus resolution. You can't get a good resolution in terms of species, and we're learning that different species from the same genus might have different physiological properties, and the same thing goes at the strain level. So when we really zone in and look at inter-species changes, we're seeing that these actually have specific functions in the host. So that brings us to metagenomic sequencing, which is a whole genome sequencing, next-generation sequencing based method that looks at the whole composition and gives you information not only on bacteria, but you might also get fungal and viral properties. You can zoom in on the strain level. You can also get functional output, so we can examine what the metabolic properties of specific species or strains might look like. The negative aspects of shotgun metagenomic sequencing is that it takes a lot of computational power in order to analyze the results and it might take a little bit longer. And certainly, within the clinical setting, not something that's feasible yet.  And that brings us to more novel point-of-care biomarker tools that we've collaborated in developing along with Dr. Laurence Zitvogel and Dr. Lisa Derosa at Gustave Roussy, that learning from the shotgun metagenomics results designed a probe using quantitative PCR which looks for this specific bacteria we know to be important and developed a ratio of harmful bacteria to beneficial bacteria. This is called the TOPOSCORE, and it actually is able to predict quite nicely the response to immunotherapy using a stool sample and a really good turnaround time of almost 72 hours. Dr. Sumanta (Monty) Pal: That was a perfect overview and a lot of information in a short amount of time. It also makes you take out your high school biology textbooks, doesn't it, to understand that the bacterial ribosome, right, is a different size and shape, and that's what we're sequencing here. But these techniques I think are incredibly important, and I'm glad you actually discussed this, this RT-PCR based strategy of calculating the TOPOSCORE. It lends itself to this phenomenon of dysbiosis, and I think for our audience, that's going to be an important term to understand as time goes on. There's the normal healthy gut and then there's this phenomenon of dysbiosis, which is, I guess, simply put, an unhealthy gut. But tell us about, you know, how often you see dysbiosis in a cancer patient, maybe versus a normal healthy adult. Dr. Arielle Elkrief: So, I think we can split up your question into two parts. One is we know from cohort studies and population level-based studies that the microbiome of patients with cancer is distinct from healthy patients or healthy people. And we know that because of the global composition. We also think that there are diversity metrics that lend themselves to being described as dysbiotic. But we do know that the microbiome of people with cancer is distinct from healthy volunteers. That's the first point.  In terms of how frequently dysbiosis occurs in patients with cancer, it's not very well defined. We know that even among healthy people, there is a certain level of dysbiosis. Laurence in her talk mentioned that to be about 10% to 20%. And the other fascinating component is that when we're thinking about dysbiosis and the cancer associated microbiome, in terms of the species that are enriched, it's quite striking that a lot of these dysbiotic or negative bacteria are also found to be enriched in patients with metabolic disease, like cardiovascular disease, for example. And so it's unclear if dysbiosis is the cause or consequence, but there definitely seems to be a general pattern of disease when looking at the microbiome compared to healthy people. Dr. Sumanta (Monty) Pal: That's interesting. So, I'll tell you, my second favorite portion of your article, and I'll tell you my favorite portion as well in the context of this podcast, but my second favorite part was the section around antibiotic stewardship. You know, the utilization of antibiotics in a very pragmatic fashion amongst our patients. Can you describe why that's so critical in the context of the microbiome? Dr. Arielle Elkrief: Antibiotics can disrupt the gut microbiome composition. We know this from mouse studies, but also cohort studies of patients that are exposed to antibiotics. And most importantly, we know that patients who are exposed to antibiotics, either before or during the immunotherapy period, have significantly worse progression-free survival and overall survival to immunotherapy. And this is true for immunotherapy in the monotherapy setting, but also when combined with chemotherapy. What's striking is that when we look at patients who are just treated with chemotherapy, we don't see the negative outcome of antibiotics on outcome and progression-free survival and overall survival, suggesting that the negative impact of antibiotics on outcomes is really specific to immunotherapy backbones. The other important point is that this negative signal is maintained even after adjusting for standard prognostic variables in the specific malignancies that we're looking at. And then most importantly, at the mechanistic level, we were able to actually pinpoint the mechanism behind this antibiotic related dysbiosis. And we see this with a bloom of negative bacteria which induces a loss of MAd-CAM, which is an endothelial gut checkpoint immune marker, and that causes an efflux of immunosuppressive T cells, which are usually in the gut, to go straight into the tumor where they make the tumor unamenable to an immunotherapy response. And so now we finally have the mechanism as to why antibiotics are harmful and why we need to practice antibiotic stewardship. Dr. Sumanta (Monty) Pal: And just to be clear for the audience, I mean, if a patient needs antibiotics, they need antibiotics. But perhaps it just suggests that, and we have, I suppose, this predilection as oncologists, just for the minor cold or cough or what have you, we maybe should be a little bit more cognizant of whether or not antibiotics are truly necessary. Is that fair? Dr. Arielle Elkrief: Absolutely. So what we're advocating for is antibiotic stewardship, and this is the clear recommendation that we can make. So that means confirming a bacterial infection. If it's there and antibiotics are indicated, to choose the most narrow spectrum for the shortest course and constantly re-evaluate the indication of antibiotics. And of course, we need to work with our colleagues in infectious diseases who've done incredible work in antibiotic stewardship. And all along this process we also need to be mindful of other medications and polypharmacy, such as proton pump inhibitors or narcotics, for example, we think that these other medications which are frequently prescribed in our cancer population can also potentially have negative impacts on the microbiome and immunotherapy response. Dr. Sumanta (Monty) Pal: I think that's a terrific summary and big guidance for the audience.  I promised you I'd tell you my favorite part of your article, and this is this huge table. I think the table is two and a half pages long, if I remember correctly, but it's an awesome table, and I highly recommend our audience to check this out. It lists literally every therapeutic trial for the microbiome under the sun. And so it begins with the approach of fecal microbiota transplant, which I'm going to ask you to tell us about in a second, but it also hinges on a lot of really cool sort of novel therapies, live bacterial products, mixes of different microbial products. Maybe take us through this whole approach of FMT (fecal microbiota transplantation). I actually wasn't aware of the dozens of trials that you listed there in this space. It seems like it's a very active area of research. Dr. Arielle Elkrief: Definitely. So, as you alluded to, FMT or fecal microbiota transplantation is the most well studied and direct way to modify the patient's microbiome. This technique aims to replace the patient's dysbiotic microbiome with that of a healthy microbiome, either from a healthy donor volunteer that's been heavily screened, or from a patient who experienced response to immunotherapy. And, as three landmark studies so far that have been published demonstrated the potential of FMT to reduce primary resistance or secondary resistance to immunotherapy, and this has been in melanoma.  We also recently reported on the results of our FMT-LUMINate trial, which looked at patients with lung cancer and melanoma. Once again, FMT, when combined with immunotherapy was safe and led to a higher proportion of responses than we would normally expect.  We're now also looking at randomized trials that have come out. So the first being the TACITO trial in kidney cancer, which compared FMT plus pembrolizumab and axitinib to placebo in patients with RCC, and again, FMT was safe and feasible and also led to an increased progression-free survival at one year, meeting the study's primary endpoint.  And so, so far, there's a wealth of data really showing the promise of FMT when combined with immunotherapy, and we're now in the process of conducting larger randomized trials, including in melanoma with the CCTG (Canada Cancer Trials Group) in our ME17 or Canbiome2 trial, where we're going to be enrolling 128 patients with metastatic melanoma to receive FMT and standard of care immunotherapy compared to standard of care immunotherapy alone. Dr. Sumanta (Monty) Pal: You're very humble, so I've got to highlight for our audience. This was a mega grant that Arielle received to fund really the largest prospective exploration of FMT that will exist to date. So I'm really excited about that. I wish this was something we could participate in stateside.  Before we jump into the other approach, which is live bacterial products and mixes thereof, where do you see FMT going? I think that one of the perceived challenges with FMT is that it's hard to implement, right? You need to have a really robust framework when it comes to gastroenterology, the preparation's challenging. Is there a way to envision FMT use being more generalized? Dr. Arielle Elkrief: Those are great questions. So we're lucky in Canada to work with pioneers in FMT, Michael Silverman, Saman Maleki, and John Lenehan in London, Ontario, who had this really robust FMT healthy donor screening program, which literally screens for every pathogen under the sun, and we haven't had any problems with feasibility or implementing FMT in Canada. But I think that once we're going to hopefully start doing larger scale, randomized phase three studies, that we might run into problems with scalability. And I think also with regards to reproducibility, and that's the feedback that we're getting from some regulatory authorities, especially at the level of the FDA, where there are some concerns around inter- and intra-donor variability because, of course, we can't guarantee that every fecal sample is going to be the same. So that has really pushed the field to think about other strategies, such as live biotherapeutic products which take modified FMT or bacteria from stools from either healthy donors or from responder patients and basically turn them into drugs that are regulated as drugs and can then be studied in the context of investigational new drugs or products. Dr. Sumanta (Monty) Pal: I like this and, you know, I do think that there's a future for it. We just have to kind of put our heads together and figure out how to get over all of these logistical hurdles, but, you know, I agree, I think your group and others have demonstrated, especially with this trial that you're fanning out all throughout Canada, that it can potentially be done.  This is a topic that could probably go on for another couple of hours, right, especially based on the size of the table that you put together in this brilliant article, but tell us about live bacterial products or LBPs, as we call them these days. What's the current status, what's the future there? And maybe I'll give you less than two minutes here, although again, I realize it's a two-hour topic. Dr. Arielle Elkrief: You're probably better suited to speak about that because you've been one of the pioneers in terms of this. So we can think about LBPs in terms of single strain organisms, like CBM588 for an example, which your group did some amazing work in showing that, in a randomized setting, that this led to better responses than we would expect compared to just work with controls. We also know that LBPs can have multiple strains, up to 30. We're collaborating with a company called Cannabis Bioscience that is actually working on much larger communities of consortia. And so we're really excited about the direction that that's taking in terms of taking these LBPs and developing them from the drug perspective. In addition to LBPs, we know that there are other ways that we can change the microbiome, notably prebiotics, which are compounds which can have a beneficial impact on the microbiome. And one of these is camu camu, which I know your group is leading a clinical trial looking at camu camu and kidney cancer, and we're excited to see how that compares to FMT or LBPs, because that might be a potentially scalable alternative. Dr. Sumanta (Monty) Pal: That's awesome. What a terrific overview, and that was less than two minutes. I don't know how you did it. That's terrific.  Arielle, this has been such an insightful conversation. I just want to thank you for, again, a terrific article in the ASCO Educational Book. I highly recommend all of our listeners to go there and check it out, and also for sharing all these terrific insights on the podcast today. Dr. Arielle Elkrief: Thank you so much, Monty. Dr. Sumanta (Monty) Pal: And thanks to our listeners, too. If you value the insights that you heard today on the ASCO Daily News Podcast, please rate, review, and subscribe wherever you get your podcasts. Thanks, everyone. 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. Sumanta (Monty) Pal  @montypal Dr. Arielle Elkrief Follow ASCO on social media:     @ASCO on Twitter    ASCO on Bluesky   ASCO on Facebook     ASCO on LinkedIn     Disclosures:    Dr. Sumanta (Monty) Pal:   Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview  Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical  Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis  Dr. Arielle Elkrief: Honoraria: AstraZenica, Bristol-Myers Squibb, Merck, EMD Serono Consulting or Advisory Role: Bristol-Myers Squibb Research Funding (Inst.): Kanvas Bioscience, AstraZeneca, Merck Other Relationship: Royal College of Surgeons and Physicians of Canada, Cedar's Cancer Center (Henry R. Shibata Fellowship), Canadian Institutes of Health Research (CIHR)

This episode covers: Cardiology This Week: A concise summary of recent studies Oral anticoagulation in atrial fibrillation: answers to frequent questions Smartwatch, heart rate and ECG Milestones: Lyon Diet Heart study Host: Emer Joyce Guests: Carlos Aguiar, Tim Chico, Paulus Kirchhof Want to watch that episode? Go to: https://esc365.escardio.org/event/1811 Want to watch that extended interview on smartwatch, heart rate and ECG? Go to: https://esc365.escardio.org/event/1811?resource=interview   Disclaimer ESC TV Today is supported by Bristol Myers Squibb and Novartis. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsors.  This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. The ESC is not liable for any translated content of this video. The English-language always prevails.   Declarations of interests Stephan Achenbach, Emer Joyce and Nicolle Kraenkel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Tim Chico has declared to have potential conflicts of interest to report: research funding from Google. Paulus Kirchhof has declared to have potential conflicts of interest to report: partially supported by European Union MAESTRIA (grant agreement 965286), British Heart Foundation (AA/18/2/34218), German Center for Cardiovascular Research supported by the German Ministry of Education and Research (DZHK, grant numbers DZHK FKZ 81X2800182, 81Z0710116, and 81Z0710110), German Research Foundation (Ki 509167694), Dutch Heart Foundation (DHF), the Accelerating Clinical Trials funding stream in Canada, and the Else-Kröner-Fresenius Foundation. Research support for basic, translational, and clinical research projects from German Research Foundation (DFG), European Union, British Heart Foundation, Leducq Foundation, Else-Kröner-Fresenius Foundation, Dutch Heart Foundation (DHF), the Accelerating Clinical Trials funding stream in Canada, Medical Research Council (UK), and German Center for Cardiovascular Research, from several drug and device companies active in atrial fibrillation, and has received honoraria from several such companies in the past, but not in the last five years. Listed as inventor on two issued patents held by University of Hamburg (Atrial Fibrillation Therapy WO 2015140571, Markers for Atrial Fibrillation WO 2016012783). Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada.  Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

Host: Emer Joyce Guest: Tim Chico Want to watch that extended interview on smartwatch, heart rate and ECG? Go to: https://esc365.escardio.org/event/1811?resource=interview Want to watch that episode? Go to: https://esc365.escardio.org/event/1811   Disclaimer  ESC TV Today is supported by Bristol Myers Squibb and Novartis. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsors.  This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. The ESC is not liable for any translated content of this video. The English-language always prevails.   Declarations of interests Stephan Achenbach, Emer Joyce and Nicolle Kraenkel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Tim Chico has declared to have potential conflicts of interest to report: research funding from Google. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada.  Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

Sergey Jakimov is the Managing Partner and co-founder of LongeVC, one of Europe's most active longevity-focused venture capital firms, currently raising its second fund targeting $250 million.In this episode, Chris and Sergey explore the investment landscape shaping longevity biotechnology today. They discuss LongeVC's pragmatic approach to longevity investing—focusing on disease-modifying therapies rather than targeting aging itself—and why this strategy has been successful across their portfolio. Sergey shares insights from major successes including Rubedo's $500M+ partnership with Bristol Myers Squibb and Turn Bio's $300M deal with Hansol, explaining what these deals signal about pharma's evolving interest in longevity approaches. The conversation covers critical topics for researchers and entrepreneurs: common pitfalls in academic spin-offs, the importance of clear regulatory pathways, and how the upcoming patent cliff is creating new opportunities for early-stage biotechs in the longevity space.Listeners will gain valuable insights into what makes a longevity company investable, how to navigate the transition from academic research to commercial venture, and why solving age-related diseases one by one may ultimately lead to a holistic understanding of aging itself.The Finer Details:Sergey's journey from aspiring neurosurgeon to deep tech entrepreneur to longevity investorLongeVC's pragmatic philosophy: targeting specific diseases rather than aging as a wholeThe convergence of biotech, regenerative medicine, and AI in the longevity spaceKey criteria for early-stage investment: disease indication, balanced teams, clean IP transferWhy "five scientists in a room" and "great mouse data" don't make an investable companyThe importance of platforms having their own pipelines, not just service modelsHow LongeVC's scientific advisory board (including Alex Zhavoronkov, Vadim Gladyshev, Thomas Rando) evaluates investmentsSuccess stories: Rubedo's senolytic partnership and Turn Bio's epigenetic reprogramming dealThe changing dynamics between pharma and biotech driven by patent cliffs and urgency to find the "next GLP-1"Regulatory strategies: focusing on specific endpoints rather than aging broadlyMaking longevity medicine accessible through disease-focused approaches and data-driven validationPersonal motivation: Sergey's experience as a rare disease patient and the urgency of advancing treatmentsQuotes:"Longevity as an industry is by far the industry with the biggest added value out there, because that is the issue that we all share. Without solving these things, none of the other stuff really matters—not FinTech, not blockchain, not sustainability.""Five scientists in a room generally don't make a company. Prolonging rodent lives does not make a company either.""The ultimate longevity drug version 1.0 would be a therapeutic which has an original disease indication, which also has somehow cracked the mechanism of action that would be translatable across several age-related disease domains.""It is extremely arrogant for the space to say that we're not interested in age-related diseases, like we're not interested in curing the diseases. That's traditional biotech. We're not that. We are the longevity space.""Pharma is still thinking in terms of assets rather than processes. It is almost impossible to sell a process to them... What pharma still wants is the result of that capacity actually coming to life.""At the point when something has happened to you and a rare disease has happened to you... you're only equipped with that standard of treatment that is currently available and that has made it to the clinic.""I think the presence of the FDA as this kind of gatekeeper-type agency saying, 'No, you...

Episode 129! Robert and Kay Lee Fukui are joining us in the studio today!Robert grew up in California and learned the power of teamwork and fighting through improbable victories as a three-sport athlete.  He went on to use those experiences as the foundation for a successful sales and marketing career, where he was directly responsible for leading global launches and generating over $150 million in sales for brands like Coca-Cola, Novartis Pharmaceutical and Bristol-Myers Squibb where he won multiple sales and leadership awards.Kay Lee grew up around the family feed store as the child of a business owner and entrepreneur.  Working in the family business through college, she watched her dad make his business the #1 priority while letting the family take a back seat.  After earning her Bachelors in business Kay Lee went to work for a bank and became the Ambassador President for the Alhambra Chamber of Commerce outside of Los Angeles. When Robert and Kay Lee married, they started a marketing consulting business that soared as they helped entrepreneurs create long-term profitability and sustainability for their companies. They lived the life that said it was impossible not to bring home your work or allow home life to creep in the office.  This understanding and empathy for the lack of balance small business owners experience led Robert and Kay Lee to create their Power Couples by Design program which helps married entrepreneurs and "couplepreneurs" harmonize work and home life.Tune in to hear Robert and Kay Lee share how their focus on faith in God and mission to help and serve others first has helped them build a better future for their clients and themselves in the process. Enjoy!========================================================================Connect with Robert and Kay Lee here: Website: https://marriedentrepreneur.co/authenticityInstagram: @thrivingintandemhttps://www.instagram.com/thrivingintandem/Facebook: Thriving In Tandemhttps://www.facebook.com/thrivingintandemPodcast: Thriving in Tandemhttps://open.spotify.com/show/4dIPkM0adCoCPQ72ZjwHEL?si=11e841ba17c14478Thanks for listening! Eric Sardina Executive Life Coaching As a business and life coach, I help individuals work towards authentic lives of meaning and purpose. I also work with organizations to optimize their teams and individual contributors. Interested in working with me or learning more? Connect with me below: Website: https://www.ericsardina.com - book a free, 15-minute strategy session. https://calendly.com/ericsardina/8-session-authentically-you-discovery-call-website-linkFollow me on: Instagram: @theericsardina Facebook: Eric SardinaLinkedIn: https://www.linkedin.com/in/ericsardina/ YouTube: https://www.youtube.com/@EricSardina Affiliate: LMNT hydration drink mix: get a free sample pack with your first order by using this link: http://elementallabs.refr.cc/ericsardina

This episode covers:  Cardiology this Week: A concise summary of recent studies Atrial fibrillation in heart failure Temperature management following cardiac arrest Statistics Made Easy: Collider bias Host: Emer Joyce Guests: Carlos Aguiar, Christian Hassager, Theresa McDonagh Want to watch that episode? Go to: https://esc365.escardio.org/event/1812 Want to watch that extended interview on temperature management following cardiac arrest? Go to: https://esc365.escardio.org/event/1812?resource=interview   Disclaimer ESC TV Today is supported by Bristol Myers Squibb and Novartis. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsors. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. The ESC is not liable for any translated content of this video. The English-language always prevails.   Declarations of interests Stephan Achenbach, Emer Joyce, Christian Hassager, Nicolle Kraenkel and Theresa McDonagh have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

Host: Emer Joyce Guest: Christian Hassager Want to watch that extended interview? Go to: https://esc365.escardio.org/event/1812?resource=interview  Want to watch the full episode? Go to: https://esc365.escardio.org/event/1812   Disclaimer ESC TV Today is supported by Bristol Myers Squibb and Novartis. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsors. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. The ESC is not liable for any translated content of this video. The English-language always prevails.   Declarations of interests Stephan Achenbach, Emer Joyce, Christian Hassager, Nicolle Kraenkel and Theresa McDonagh have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

The Sarepta saga continued into another week as the FDA recommended that the voluntary hold on the company's Duchenne muscular dystrophy gene therapy be lifted for ambulatory patients, after determining that the death of an 8-year-old Brazilian Duchenne patient who had received Elevidys' was not caused by the drug.  Sarepta's stock has swung wildly and its transparency questioned after it elected not to reveal the death of a third patient—a participant in a trial of a gene therapy for limb girdle muscular dystrophy—during a business update last week.    Speaking of entities—or individuals—who have trouble staying out of the news, Health Secretary Robert F. Kennedy Jr. plans to dissolve the U.S. Preventive Services Task Force because it is “too woke.” Also on Monday, Kennedy addressed what he called the “broken” vaccine injury compensation program. Without offering details, he vowed to “fix” the U.S.'s VICP and return it to its “original Congressional intent.”   On the business side of the biopharma house, Q2 earnings are in full swing, with AstraZeneca announcing estimate-beating numbers and CEO Pascal Soriot saying the world “needs to share” in global pharma R&D, while Merck cut $3 billion to support an aggressive launch schedule. Meanwhile, a week ahead of its own earnings report, Novo Nordisk named a new CEO and lowered its 2025 sales guidance for the second time this year.   In clinical development, the Alzheimer's Association Annual Conference is underway in Toronto, with Roche's trontinemab the standout so far. In a Phase Ib/IIa trial, the next-gen anti-amyloid antibody rapidly cleared amyloid from the brains of patients with Alzheimer's disease after just seven months—besting the 18-month timeframe for Biogen and Eisai's Leqembi and Eli Lilly's Kisunla. While Leqembi and Kisunla have shown some progress is slowing down the progression of Alzheimer's, their effect size is modest and they don't work for all patients—leaving plenty of room for symptomatic treatments, such as those being developed by Bristol Myers Squibb and Acadia Pharmaceuticals. The space is gearing up for several readouts, for both symptomatic and disease-modifying therapies alike.   And in BioPharm Executive this week, we dig into the top VC rounds so far this year and highlight a few scrappy biotechs walking the solo road.  

Hear Christopher McKim's journey with moderate to severe plaque psoriasis and the latest clinical trial results from dermatologist, Dr. Christine Cornejo. Join this discussion with moderator Archie Franklin as Christopher McKim, a BMS employee living with moderate to severe plaque psoriasis, and Dr. Christine Cornejo, Director and US Medical Engagement Lead for Dermatology and Rheumatology at BMS, offer a patient and physician's perspective on treating plaque psoriasis from the inside. Listen as Chris presents his journey along with Dr. Cornejo addressing effectiveness and safety information with clinical trial results for a prescription oral treatment option. The intent of this episode is to encourage those who have moderate to severe plaque psoriasis to work with their health care provider to find a treatment option that is right for them. This episode is sponsored by Bristol Myers Squibb. For more information view Full Prescribing Information and Medication Guide . ·       (0:00)   Intro to Psoriasis Uncovered and guest welcome to Bristol Myers Squibb employee and patient Christopher McKim and Dr. Christine Cornejo, Director and US Medical Engagement Lead for Dermatology and Rheumatology at Bristol Myers Squibb. ·       (2:15)  Where the journey to finding the right treatment option for Chris and his moderate to severe plaque psoriasis began.  ·       (3:09)   The decision by Chris and his provider to try an oral systemic medication. ·       (3:28)  The effects and impact of an oral systemic treatment for Chris and his plaque psoriasis. ·       (4:09)   Dr. Cornejo addresses efficacy and clinical trials results. ·       (5:58)   Common side effects and safety concerns for the treatment Chris and his health care provider decided to try.   ·       (6:28)   Health considerations patients and providers should discuss prior to using a systemic treatment.    ·       (6:54)   What to do should side effects occur. ·       (7:10)   How Chris feels with clearer skin after making a change in treatment. ·       (8:14)   Indication and Important Safety Information. Key Takeaways: ·       Moderate to severe plaque psoriasis is a systemic disease.    ·       If you're ready to treat from the inside there is a treatment option that may help.   ·       Work with a health care provider to find the right treatment for moderate to severe plaque psoriasis.   ·       Be proactive by taking steps to learn about treatment options including effectiveness, side effects, safety concerns, and what should be discussed with a health care provider before beginning a new treatment for plaque psoriasis.  Guest Bios:   Christopher (Chris) McKim joined BMS in June of 2022. In his current role he is a Regional Marketer for the dermatology division, prior to that he provided support for 9 Therapeutic Area Specialists for the Pacific South District in the GI division.  Prior to joining BMS, Chris worked at Sanofi, J&J, Leo Pharma, and Sun Pharma in various field and home office roles. Chris resides in beautiful San Diego with his family Susan (wife), Morgan 18, Maddy 16, Mason 14 and two Golden Retrievers and enjoys traveling, cooking and anything associated with the ocean (Deep Sea Fishing, S.C.U.B.A. diving, snorkeling, and boogie boarding). Dr. Christine Cornejo joined Bristol Myers Squibb in 2024 as Director, Medical Engagement Lead for Dermatology and Rheumatology. Prior to joining BMS, she practiced dermatology at Brigham and Women's Hospital and Dana-Farber Cancer Institute in Boston, MA, where she specialized in melanoma and high-risk skin cancer management and served as the Director of Confocal Microscopy. She also served as an Instructor at Harvard Medical School and led the Immunology and Infectious Diseases course for 1st year medical students. Resources: Current Oral Systemic Treatments For additional questions about treatment options contact the NPF Patient Navigation Center

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma e Biotech world. GSK has entered a partnership with Hengrui worth up to $12 billion, focusing on the COPD candidate HRS-9821. The FDA's new voucher policy has caused confusion among experts, as it lacks clear definition and was announced without public input. The American Medical Association urges RFK Jr. to maintain the preventive task force, and Sarepta denies a patient death is linked to Elevidys as the FDA launches a probe. Biopharma companies are leaning towards holistic treatments for Alzheimer's, while Atai-partnered schizophrenia drug fails in a mid-stage trial. Boehringer partners with Irish startup Re-Vana in a $1 billion+ eye deal.As the Alzheimer's space becomes more competitive, biopharma companies are focusing on holistic treatments beyond disease-modifying drugs like Leqembi and Kisunla. Companies such as Bristol Myers Squibb, Acadia, Otsuka, and Lundbeck are renewing their search for symptomatic treatments. Five upcoming data drops could potentially lead to more effective therapies for Alzheimer's. Sarepta Therapeutics is facing challenges due to safety concerns surrounding its gene therapies, leading to a drop in stock value. The FDA's new voucher program aims to offer accelerated pathways for drugs meeting certain criteria, but experts criticize the lack of transparency and public input in the policy's announcement. Sarepta's future is uncertain as the FDA considers a new study for Elevidys, and the EU issues a negative opinion on the drug. Other news includes delays in the FDA decision on GSK's Blenrep, AstraZeneca's PIII win with nanobody treatment for myasthenia gravis, and the removal of thimerosal from influenza vaccines. George Tidmarsh has been appointed as the new chief of FDA's CDER.

Nidhi Oberoi is a dedicated medtech executive with over 17 years of experience and currently serves as Business Leader, Imaging Franchise at Terumo Medical Corporation. She discusses her journey from India to the heart of the medtech industry, her impactful work on innovative heart valve treatments while at Medtronic, and her advocacy for women's health. Nidhi shares her leadership philosophy centered on empowerment, the importance of mindfulness in business, and her vision for a future in cardiology and women's health.   Guest links: https://www.linkedin.com/in/nidhi-oberoi-278a111/ Charity supported: Save the Children Interested in being a guest on the show or have feedback to share? Email us at theleadingdifference@velentium.com.  PRODUCTION CREDITS Host: Lindsey Dinneen Editing: Marketing Wise Producer: Velentium   EPISODE TRANSCRIPT Episode 060 - Nidhi Oberoi [00:00:00] Lindsey Dinneen: Hi, I'm Lindsey and I'm talking with MedTech industry leaders on how they change lives for a better world. [00:00:09] Diane Bouis: The inventions and technologies are fascinating and so are the people who work with them. [00:00:15] Frank Jaskulke: There was a period of time where I realized, fundamentally, my job was to go hang out with really smart people that are saving lives and then do work that would help them save more lives. [00:00:28] Diane Bouis: I got into the business to save lives and it is incredibly motivating to work with people who are in that same business, saving or improving lives. [00:00:38] Duane Mancini: What better industry than where I get to wake up every day and just save people's lives. [00:00:42] Lindsey Dinneen: These are extraordinary people doing extraordinary work, and this is The Leading Difference. Hello, and welcome back to another episode of The Leading Difference podcast. I'm your host, Lindsey, and today I'm excited to introduce you to my guest, Nidhi Oberoi. Nidhi is a seasoned MedTech executive dedicated to the mission of serving clinicians and patients. With over 17 years of experience working on commercialization of innovative technologies, She has led various strategic and operational initiatives that have transformed standard of care. Her bold, collaborative, and empathetic leadership style allows her to push boundaries and inspire teams to create durable value. She currently leads business initiatives for the structural heart business in Medtronic, which serves patients with heart valve disease. She's also an advocate for evidence based care for women's health. Nidhi has an undergraduate degree in economics from India and an MBA in marketing and entrepreneurship from Syracuse University. Thank you so much for being here, Nidhi, I'm so excited to speak with you. [00:01:44] Nidhi Oberoi: Yeah, thanks for having me. [00:01:46] Lindsey Dinneen: Of course. Well, I would love, if you don't mind just starting off by sharing a little bit about yourself and your background and what led you to MedTech. [00:01:56] Nidhi Oberoi: Yeah, absolutely. I was born and raised in India, and just like any typical Asian Indian household in those days, if you were a bright student, you were generally expected to pursue a track in sciences, medicine or engineering, or maybe a second option in accounting and finance. Predictably, after I completed my high school, I was on my path to pursue a career in sciences. But then I changed courses and ended up pursuing an undergraduate degree in economics, and eventually an MBA in marketing and entrepreneurship from upstate New York. Now, as I reflect back and realize that what attracted me to business eventually, it was this realization that it's both in art and a science. The science aspect helps to ensure that the business can financially run smoothly with a strong P&L, while the art side of the business is the ability to set the vision, the direction, inspiring people, innovating, connecting with people. So what I really was interested was in a career in marketing and general management. You asked me what led me to medtech, I'd say my entry into the healthcare industry was by chance. I got recruited into this industry through a summer internship when I was doing my MBA with a company called Conva Tech, which was part of Bristol Myers Squibb then. And by the time I had completed my internship, I already knew I wanted to be in the healthcare industry given the impact you have on the patient's lives. I did have opportunities to interview with other companies like Philip Morris and others, and I just decided that this is what I wanted to do. And after I graduated, I started working for a company called Covidian, which was then a spinoff from TCO International. And Covidian was eventually acquired by Medtronic. It's been 16, 17 years since I've been working for this company and it has a really strong mission of elevating pain, restoring health, and extending life of patients around the world. So that's that's my story there. [00:04:07] Lindsey Dinneen: Excellent. Thank you so much for sharing that. I'm curious. Of course your career trajectory has been really interesting and you've had a lot of different experiences along the way. So what are some of the key things that say maybe your schooling or your early career really set you up for success for what you're doing now? [00:04:29] Nidhi Oberoi: Yeah, so there's just so many different experiences that either have shaped my interest, where I wanna go, or has shaped my leadership style. Now, as I mentioned, I decided to move away from sciences to a more kind of social sciences field, economics and then business, and that was due to the fact that I was not the person who could just crunch numbers sitting on the table. I liked connecting with people. So I think some of those personality traits helped me decide what I wanted to do. And I would say one of my core value is impact, purpose. And so healthcare, it was just natural for me to gravitate towards healthcare because you are truly impacting people with different technologies. And I'd also say, as I grew further along in my career, early on when I joined Covidian, I had some great leaders who gave me a lot of ownership, and that shaped my leadership style as well. And that's how I operate. I empower my teams. I coach them along, but give them a lot of accountability. So there's so many different experiences, but these are some of the experiences that come to mind as. As as I reflect back now what that has shaped my career and also my leadership style. [00:05:55] Lindsey Dinneen: Yeah, absolutely. And speaking maybe more into your leadership style, I'm really curious if you could tell us a little bit more about that philosophy of yours. I love that ownership mentality. It sounds very counter to what a lot of folks don't appreciate, and that's micromanagement. And so I'm curious, how do you bridge the gap yourself as a leader between making sure that, your team stays on track and the goals and really key, important performance indicators are met, while also giving them that ownership and that empowerment to make decisions and do things in a way that best aligns. [00:06:35] Nidhi Oberoi: Yeah. So I think there's so many different facets of leadership, and let me highlight some of the others that feeds into the third aspect, which is the empowering team. So I think as a leader, first thing first, you need to provide clarity, direction, focus. I've been part of so many different teams where if people can relate to what they're doing, why they're doing, they can get lost, right? So I think that's the first thing. You need to have the ability to cut through the noise, provide direction to the team, organization you're leading. And then the second part is inspiring and bringing people together to execute on that vision. So this is the culture piece. You are listening to others, you're hearing others' perspectives and being inclusive. And the last thing, which I mentioned early on, is empowering your teams and making them accountable. So to your question of how you bridge the gap, I think you have to give clear direction. And when you empower teams doesn't mean that you don't coach them, right? You are just telling them that you trust them to do the job and you are here to help them. And one of the technique that I use is I ask questions, so I don't give answers. When you ask someone in your team to lead the project, they come to you. Then you ask questions. And I've seen, based on my experiences, that gives them a sense of ownership that this is something they're thought through. And oftentimes I've heard from people that they feel like they become a better version of themselves because I ask a lot of questions. I make them think. So that's my approach on how I kind of bridge the gap, but also make sure along the way that you're supporting them in the right direction. [00:08:24] Lindsey Dinneen: Absolutely. Yeah, and you mentioned as you were speaking a little bit towards how your past experiences shape who you are and how you kind of relate to the world now, you mentioned core values, and I would love, if you don't mind, if you would share a little bit more about your core values. I noticed that on your LinkedIn profile, that was something that was very highlighted as being extremely important to you, which I love. I'd love if you would share a little bit about maybe how you developed your core values and how those play out for you. [00:08:57] Nidhi Oberoi: Yeah, absolutely. I think core values is something that you always have, but you just sometimes need a little bit of handholding to unfold those, right? And so in my case, a few years back, I had an opportunity to work with a coach, and she really helped me understanding what I'm good at. These are things that you already have, but you may not realize or you may not know how to articulate. So for me, the number one thing that came out was purpose. And I'm like, "No wonder I'm in the healthcare industry. I'm big on impact. I like building things." And so that's where it's coming from. The other core value of mine is excellence. I like to do things with excellence. I put my heart and soul into things. I'm a very passionate person. But also you gotta have an eye on quality versus decision making, right? Over time, I've learned excellence is my core value, but it's a journey, it's a process. It's not a destination. So you don't have to dwell on things. Sometimes things go wrong and you just have to keep moving on and have a growth mindset. So there's a good aspect of the value, but there could be a blind spot, like in this case for excellence and I've learned to manage that as well. And yeah, so I think these are some of the core values, which is, I think, also part of being a leader. You have to have self-reflection. You need to dig deeper and understand what you stand for. And, this has just guided me along the way. And yeah, so those are some of the things that I'd say has really helped me all along in my career. [00:10:41] Lindsey Dinneen: Yeah, of course. So, tell me a little bit more about your current position and what are you looking forward to as you move forward in your own career as well? [00:10:53] Nidhi Oberoi: Yeah, currently I'm in the structural heart space, and these are really old and sick patients. And it's just amazing to see these patients getting impacted by our technology, getting back to their day-to-day life. And as part of structural heart, also, most recently I've been able to work on therapies. I've been focusing on the congenital portfolio, which is, these are devices that are used to treat patients that have congenital disease, and it's very impact driven because you're dealing with children here who tend to get multiple surgeries throughout their lifetime. So my role right now is to focus on business initiatives. Some of it is expansion across geographies. Some of it is increasing supply for these products. I mean, there's not a big business case for these kind of products, but the impact is huge. So that's my current focus. And, moving forward, in my career, I'm looking to grow into a general management track, and that's what attracted me to marketing because I consider marketing as running a business within the organization. So for me, running a business would be something that I would be looking forward to. And that's why I have spent time in so many different kind of roles, whether it's marketing, it's commercial transformation, whether it's global roles. So that's how I've been building my skillset so that I can one day lead a business. [00:12:25] Lindsey Dinneen: Yeah, that's very exciting. Okay, so you're building all of these skill sets. You're working towards this incredible goal. Do you have an idea of what kind of business you would want to get into? Or is this, " We'll see," and I'll interview you again when that happens? [00:12:38] Nidhi Oberoi: Yeah, I think cardiology, there's so much opportunity in cardiology. There are so many people getting impacted by cardiovascular disease around the world, and there's so much innovation too happening, not just on the treatment side, but also on the diagnostic side. So I would say either something in the cardiology space would be very attractive because it's innovative. There's such a huge population that gets impacted by it. Or the other area of interest for me is women's health, and I think it just makes me smile how there's progress being made. I know there's so much work that needs to be done. We know there's not enough evidence, it's underfunded, but I think the work is starting there, and better evidence generation will lead to better decision making, which will lead to better outcomes. So I would say either in the cardiology space or the women's health space, these are the two areas of interest to me. [00:13:38] Lindsey Dinneen: Yeah. And I noticed again, with LinkedIn, you are very passionate about women's health and I love that. And I am wondering if you could speak a little bit towards some of themes that I kind of picked up on, things like stigma with women's health, medical gaslighting and self-diagnosis. And I know there's a lot to that and it's probably too much for one conversation today, but can you highlight a couple of the areas that you particularly find concerning, that are things that we can all do better? [00:14:11] Nidhi Oberoi: Yeah. Yeah. I think first of all there's such lack of education and awareness. As women transition through different stages of life, I feel like a lot of it is taken for granted. We don't question it. And as someone who's been following this for a little bit of a time, I almost feel like it's my duty and being in the healthcare industry, to raise awareness about this or encourage them to be more educated patients. When they go to a doctor, if they don't get answers, they should ask more questions. So I think, so that's that lack of education and awareness piece. There's a lot of work happening. There's so many advocacy groups. Women are coming together, supporting each other, so I think that's happening as well. The other thing that really bothers me is on the diagnostic side. I wrote an article around women get mammograms. Just because there's not enough evidence out there, sometimes you just have to go through a number of tests to have a diagnosis, either a positive or a negative. So I also feel like maybe the advent of technologies like AI in the diagnostic field can help improve that, because it starts with the diagnostic side, and we just don't have enough right now. And like I said, it can either be a good thing or bad thing. I've also heard of women going through a number of tests to find out that they don't have anything, which is fine, but it's just a lot of money along the way getting to the diagnosis. And then, the third thing I'd say is as we get more intelligent with evidence, it will lead to better awareness among the physician community too. And that's what gaslighting comes because there's not a lot of evidence, there's not a lot of awareness. Even physicians sometimes can't guide you in the right direction. But if you have more studies coming out, it will make them more aware and guide their patients in the right direction. So there's just so many different things, but I feel like you could start being a self-aware patient and not just assume as you go through different stages of your life that this is what it comes being with a woman. Be more proactive, ask questions, research, talk to other people and get help. [00:16:32] Lindsey Dinneen: Yeah. Yeah, that's really great advice, and I appreciate your perspective in sharing with us a little bit about maybe even some of the things that we all can do as we're trying to hopefully push the quality of women's healthcare forward and make it more widely available and whatnot. So thank you for sharing. As you have been going throughout your career-- and you obviously care so much about purpose and you have a lot of passion for helping people and for the healthcare industry in general-- are there any moments that really stand out to you as affirming, "Hey, I am in the right industry at the right time?" [00:17:11] Nidhi Oberoi: Yeah, there's been so many moments and I would say most of these moments are when I've interacted with patients. When I started with Covidian, I was leading an initiative which would help a lot of women who were having open hysterectomies-- this is like 10, 15 years back-- to have a minimally invasive hysterectomy through a new procedure technique. So it was called single incision surgery. And I happened to talk to some patients, and it was just amazing to hear those stories where they were telling me how they could get back on their feet, travel, within just a week after the procedure. So that's the defining moment. And then, when I was working on one of the businesses where patients have very varicose veins, I met a patient who was a mom of four. So she had four kids within a span of six, seven years, and she had very visible varicose veins on her legs. And that impacted her quality of life. And when she got the procedure done with our technology, she was just so happy. It was not just cosmetic, but also less painful, and being more present with her kids because of that. And then I'd say most recently in the cardiology space, these are really sick patients, older patients with multiple conditions, and just hearing their stories of getting a new heart valve, it's amazing to see how, again it's getting back to life. So it's always, when you meet these patients, those are the defining moments, and it just reaffirms why you're in healthcare and why you need to continue to work in the healthcare space. [00:18:58] Lindsey Dinneen: Yes. I love that so much. Yeah, so pivoting the conversation a little bit just for fun. Imagine that you were to be offered a million dollars to teach a masterclass on anything you want. It can be within your industry. It could be related to anything your background, your experience, but it doesn't have to be. What would you choose to teach? [00:19:19] Nidhi Oberoi: Yeah, that's a great question. I don't think I have an expertise right now, but maybe something on mindfulness and yoga. One of my goals is to do a yoga teacher training, but the importance of mindfulness in business. There's so many things you can do: power walks, taking a break, journaling. These are so underrated, but I think these things are necessary. It's more important than ever now, given the fast change. There's so much, so many changes happening at such a fast pace. So I would say that would be my topic, but I don't think I'm ready yet to have that masterclass. [00:20:03] Lindsey Dinneen: Fair enough. Fair enough. So I'm curious, how long have you been incorporating these kinds of really important mindfulness practices into your own life and your own routine. Is this something that you've had for years and years or is it a more recent development? [00:20:19] Nidhi Oberoi: Yeah, I think it's more recent. I would say three to four years, although I wonder why I did not do that. I think within the organization, as you are managing multiple things, it just forced me at that point of time when I was juggling a lot of things in my life and I wanted some pause and clarity. And I actually, years back, I had take a yoga class and then I started doing core barre yoga as well. So I realized that it really has a big impact on me. And then I just try to be more disciplined and try to take out time, if not every day, maybe every two days, but I would say it's more of a recent phenomena. It does require a lot of discipline. Earlier you start, the better it is because you're not going to get it right away. It takes a lot of discipline and commitment to incorporate these. And you won't be able to do it all the time, but at least starting that and trying to incorporate day to day life is a good start. [00:21:26] Lindsey Dinneen: Yeah, absolutely. I found personally that starting my day with a much more intentional routine that includes things like meditation and those kinds of mindfulness practices makes a huge difference in how I feel throughout the whole day and the week in general. So, and that's a more recent development for me too. So it's one of those interesting things about how that evolves over time. So I love that. Thank you for sharing about your own journey. All right, and then how do you wish to be remembered after you leave this world? [00:21:59] Nidhi Oberoi: As I said purpose is my core value, big on impact. So I just want to leave the world a little bit better and do my bit. And whether it's working on things, like working on technologies and providing access to health care to patients, probably globally. So it's just continuing to make an impact in the healthcare space and leaving the world a little bit better than I inherited it. [00:22:27] Lindsey Dinneen: Yes. Excellent. And final question, what is one thing that makes you smile every time you see or think about it? [00:22:37] Nidhi Oberoi: Yeah. There are so many different things. As you start meditating or focusing on mindfulness, it's the small things in life that you start enjoying. Being in Minnesota, the good weather is difficult to come by. So sunshine really makes me happy. But yeah, I think being present makes you more joyful. You just start enjoying everything in life. The other thing I would say is just simple acts of kindness. People helping other people is also something that just moves me and touches me. [00:23:11] Lindsey Dinneen: Yeah, of course. I'm really curious. Okay, so I said final question, but then I have a follow up. So when you said being present helps bring you joy, could you share a little bit more about what you mean by that? [00:23:24] Nidhi Oberoi: Yeah. So I think being present means that you are not thinking about your past and you're not thinking about your future. And so what that means is all you're focusing is what's in the now, and I'm going to start speaking the language of someone who teaches yoga or meditation, but being present really is you're not in the past. You're not in the future. You're just enjoying your day, the moment, as it comes by, it's as simple as that. You're centered. You're aligned with yourself and you just focus on what's in your control. You don't dwell on things either of the past or in the future. So I think that's a very, that's a beautiful moment to be in. [00:24:11] Lindsey Dinneen: Yes, I couldn't agree more. Well, thank you for sharing a little bit more about that. I really appreciate it. And thank you so much for your time today. This has been such a great conversation. I've loved learning about you, and I'm so excited about your career future, especially with your goal of starting your own company at some point. So I will be cheering you on for that whole process. I know that's no small undertaking. But in the meantime, I just want to say thanks again for your time, and thank you so much for working hard to change lives for a better world. [00:24:45] Nidhi Oberoi: Well, thank you so much. Thank you for the opportunity. It's been so fun chatting with you. You're joyful. [00:24:52] Lindsey Dinneen: Thank you. Well, excellent. We are so honored to be making a donation on your behalf as a thank you for your time today to Save the Children, which works to end the cycle of poverty by ensuring communities have the resources to provide children with a healthy, educational, and safe environment. So thank you so much for choosing that charity to support. Thank you also so much to our listeners for tuning in. And if you're feeling as inspired as I am right now, I'd love it if you'd share this episode with a colleague or two. And we'll catch you next time. [00:25:30] Ben Trombold: The Leading Difference is brought to you by Velentium. Velentium is a full-service CDMO with 100% in-house capability to design, develop, and manufacture medical devices from class two wearables to class three active implantable medical devices. Velentium specializes in active implantables, leads, programmers, and accessories across a wide range of indications, such as neuromodulation, deep brain stimulation, cardiac management, and diabetes management. Velentium's core competencies include electrical, firmware, and mechanical design, mobile apps, embedded cybersecurity, human factors and usability, automated test systems engineering, and contract manufacturing. Velentium works with clients worldwide, from startups seeking funding to established Fortune 100 companies. Visit velentium.com to explore your next step in medical device development.

What if the smartest career move you could make looked like a step backwards? In this episode, Keith Gaub, Vice President and Assistant Treasurer at Bristol-Myers Squibb, shares how taking a pay and title cut led him to one of the most rewarding chapters of his treasury career -and why playing the long game is the ultimate career strategy.Keith Gaub is the Vice President and Assistant Treasurer at Bristol-Myers Squibb, a global biopharmaceutical company. With prior roles at Lehman Brothers, Barclays, and Zoetis, Keith brings deep experience across banking, corporate treasury, and investor relations. His journey reflects the power of strategic career transitions, calculated risk-taking, and building treasury operations from the ground up.Main topics discussed:Why Keith left a leadership role in banking to join a fledgling corporate treasury teamThe sacrifices (and eventual payoffs) of stepping “back” in title and compensationHow Keith helped build a treasury department from scratch at ZoetisNavigating the 2008 financial crisis from inside Lehman BrothersTransitioning from technical finance to people management and leadershipThe mindset of deliberate, long-term career planningThe evolving role of treasury in M&A, forecasting, and risk managementThe importance of mentorship, team culture, and maintaining strong professional networksYou can connect with Keith Gaub on LinkedIn. ---

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/FVK865. CME/MOC/AAPA/IPCE credit will be available until June 30, 2026.4x4 in Multiple Myeloma: Maintaining Momentum for Delivering Innovative Care in Newly Diagnosed and Relapsed Disease In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and HealthTree Foundation for Multiple Myeloma. 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 independent medical education grants from Bristol Myers Squibb, GSK, Johnson & Johnson, and Regeneron Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

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/FVK865. CME/MOC/AAPA/IPCE credit will be available until June 30, 2026.4x4 in Multiple Myeloma: Maintaining Momentum for Delivering Innovative Care in Newly Diagnosed and Relapsed Disease In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and HealthTree Foundation for Multiple Myeloma. 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 independent medical education grants from Bristol Myers Squibb, GSK, Johnson & Johnson, and Regeneron Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

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/FVK865. CME/MOC/AAPA/IPCE credit will be available until June 30, 2026.4x4 in Multiple Myeloma: Maintaining Momentum for Delivering Innovative Care in Newly Diagnosed and Relapsed Disease In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and HealthTree Foundation for Multiple Myeloma. 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 independent medical education grants from Bristol Myers Squibb, GSK, Johnson & Johnson, and Regeneron Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

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/FVK865. CME/MOC/AAPA/IPCE credit will be available until June 30, 2026.4x4 in Multiple Myeloma: Maintaining Momentum for Delivering Innovative Care in Newly Diagnosed and Relapsed Disease In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and HealthTree Foundation for Multiple Myeloma. 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 independent medical education grants from Bristol Myers Squibb, GSK, Johnson & Johnson, and Regeneron Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

In this episode, Jonathan W. Friedberg, MD; Alex F. Herrera, MD; and Kara Kelly, MD, discuss the latest frontline treatment options for advanced Hodgkin lymphoma (HL) and approaches to personalizing treatment for the general patient population, older patients, and pediatric patients. This podcast was adapted from a live presentation held in May 2025.The Landscape of Frontline Options in HLSpecial Considerations for Older PatientsSpecial Considerations for Pediatric PatientsFuture Directions in HLPresenters:Jonathan W. Friedberg, MDDirector, Wilmot Cancer InstituteSamuel Durand Professor of Medicine and OncologyUniversity of RochesterRochester, New YorkAlex F. Herrera, MDChief, Division of LymphomaProfessor, Department of Hematology and Hematopoietic Cell TransplantationMedical Director of the City of Hope Clinical Trials OfficeAssociate Medical Director of the Briskin Center for Clinical ResearchCity of Hope Medical CenterDuarte, CaliforniaKara M. Kelly, MDWaldemar J. Kaminski Endowed Chair of PediatricsRoswell Park Comprehensive Cancer CenterDivision Chief and Professor of PediatricsUniversity at Buffalo Jacobs School of Medicine and Biomedical SciencesBuffalo, New YorkContent based on an online CME program supported by an independent educational grant from Bristol Myers Squibb.Link to CME: Claim Credithttps://bit.ly/3TQ0M45Link to full program: https://bit.ly/4eV8AuW

This episode covers: Cardiology This Week: A concise summary of recent studies ICD Indications in primary prevention Drug treatment of cardiac amyloidosis Mythbusters Host: Rick Grobbee Guests: Carlos Aguiar, Gerhard Hindricks, Marianna Fontana Want to watch that episode? Go to: https://esc365.escardio.org/event/1810   Disclaimer: ESC TV Today is supported by Bristol Myers Squibb and Novartis. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsors.  This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. The ESC is not liable for any translated content of this video. The English-language always prevails. Declarations of interests: Stephan Achenbach, Rick Grobbee, Gerhard Hindricks and Nicolle Kraenkel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Marianna Fontana has declared to have potential conflicts of interest to report: consultancy for Alnylam, Alexion/Caelum Biosciences, Astrazeneca, Bridgbio/Eidos, Prothena, Attralus, Intellia Therapeutics, Ionis Pharmaceuticals, Cardior, Lexeo Therapeutics, Janssen Pharmaceuticals, Prothena, Pfizer, Novonordisk, Bayer, Mycardium. Research grants from: Alnylam, Bridgbio, Astrazeneca, Pfizer. Share options in LexeoTherapeutics and shares in Mycardium. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

Host: Rick Grobbee Guest: Gerhard Hindricks Want to watch that extended interview? Go to: https://esc365.escardio.org/event/1810?r Disclaimer: ESC TV Today is supported by Bristol Myers Squibb and Novartis. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsors. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. The ESC is not liable for any translated content of this video. The English-language always prevails. Declarations of interests: Stephan Achenbach, Rick Grobbee, Gerhard Hindricks and Nicolle Kraenkel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

In this episode, Jesus Berdeja, MD; Amrita Krishnan, MD, FACP; and Sagar Lonial, MD, FACP, discuss key topics with CELMoD therapy for multiple myeloma, including: Mechanistic differences between CELMoDs and IMiDsEmerging data with CELMoDs and their potential therapeutic roles across the disease continuum of multiple myelomaThe clinical implications of MRD negativity as a surrogate marker of long-term outcomes in clinical trials in multiple myelomaPresenters:Jesus Berdeja, MDDirector of Myeloma ResearchGreco-Hainsworth Centers for ResearchTennessee OncologyNashville, TennesseeAmrita Krishnan, MD, FACPDirector, Judy and Bernard Briskin Center for MyelomaExecutive Director of HematologyCity of Hope Orange CountyProfessor of Hematology/HCTCity of Hope Cancer CenterIrvine, CaliforniaSagar Lonial, MD, FACPChair and ProfessorDepartment of Hematology and Medical OncologyAnne and Bernard Gray Family Chair in CancerChief Medical OfficerWinship Cancer InstituteEmory UniversityAtlanta, GeorgiaContent based on an online CME program supported by an independent educational grant from Bristol Myers Squibb.Link to full program: https://bit.ly/3IwbslQ

ROBERT KAY Lee  | Co-founders of i61, inc.,INTRODUCTION :they assist married entrepreneurs  create better work/life balance by structuring the business to scale while giving precious time back to the owner to invest into their marriage and family.Robert received his marketing degree from San Jose State University and experienced 25 successful years in sales/marketing with companies such as Coca-Cola, Novartis Pharmaceutical and Bristol-Myers Squibb. He played instrumental roles in the launch of six major brands and a recipient of national sales and leadership awards. His business acumen allows him to help family businesses build a more profitable, efficient and sustainable company.Kay Lee Fukui earned her business degree from the University of La Verne. She worked in the banking industry for many years and in her family business as operations manager for over 10 years before meeting the love of her life, Robert. She understands the highs and lows of running a family business and the sacrifices the owners make; often at the expense of marriage and family. Her passion is to see marriages flourish in the midst of building a profitable business and to help the entrepreneur couple understand that you don't have to sacrifice the marriage and family for the business.Together, they have developed an innovative consulting program, Power Couples by DesignTM, which equips the married entrepreneur to build a Thriving Marriage AND Prosperous Business. They have also authored the book, Tandem: The married entrepreneurs' guide for greater work-life balance.

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 information, and to apply for credit, please visit us at PeerView.com/DTG865. CME/MOC/AAPA credit will be available until June 30, 2026.Purpose in Practice for HCC: Delivering Effective Care With Modern Systemic Platforms Across Disease Settings 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 activity is supported through independent educational grants from AstraZeneca, Bristol Myers Squibb, and Merck & Co., Inc., Rahway, NJ, USA.Disclosure information is available at the beginning of the video presentation.

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/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/NZA865. CME/MOC/NCPD/AAPA/IPCE credit will be available until June 30, 2026.Catalysts for Redefined Care in Colorectal Cancer: Adapting Systemic Therapy Regimens Across Disease Settings In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Colorectal Cancer Alliance. 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 medical education grants from Bristol Myers Squibb and GSK.Disclosure information is available at the beginning of the video presentation.

Dr. Diwakar Davar and Dr. Jason Luke discuss novel agents in melanoma and other promising new data in the field of immunotherapy that were presented at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Diwakar Davar: Hello. My name is Diwakar Davar, and I am welcoming you to the ASCO Daily News Podcast. I'm an associate professor of medicine and the clinical director of the Melanoma and Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center. Today, I'm joined by my colleague and good friend, Dr. Jason Luke. Dr. Luke is a professor of medicine. He is also the associate director of clinical research and the director of the Phase 1 IDDC Program at the University of Pittsburgh's Hillman Cancer Center. He and I are going to be discussing some key advancements in melanoma and skin cancers that were presented at the 2025 ASCO Annual Meeting. Our full disclosures are available in the transcript of this episode.  Jason, it is great to have you back on the podcast. Dr. Jason Luke: Thanks again so much for the opportunity, and I'm really looking forward to it. Dr. Diwakar Davar: Perfect. So we will go ahead and start talking a little bit about a couple of key abstracts in both the drug development immunotherapy space and the melanoma space. The first couple of abstracts, the first two, will cover melanoma. So, the first is LBA9500, which was essentially the primary results of RELATIVITY-098. RELATIVITY-098 was a phase 3 trial that compared nivolumab plus relatlimab in a fixed-dose combination against nivolumab alone for the adjuvant treatment of resected high-risk disease. Jason, do you want to maybe give us a brief context of what this is? Dr. Jason Luke: Yeah, it's great, thanks. So as almost all listeners, of course, will be aware, the use of anti–PD-1 immunotherapies really revolutionized melanoma oncology over the last 10 to 15 years. And it has become a standard of care in the adjuvant setting as well. But to review, in patients with stage III melanoma, treatment can be targeted towards BRAF with BRAF and MEK combination therapy, where that's relevant, or anti–PD-1 with nivolumab or pembrolizumab are a standard of care. And more recently, we've had the development of neoadjuvant approaches for palpable stage III disease. And in that space, if patients present, based on two different studies, either pembrolizumab or nivolumab plus ipilimumab can be given prior to surgery for somewhere in the 6- to 9-week range. And so all of these therapies have improved time-to-event endpoints, such as relapse-free or event-free survival. It's worth noting, however, that despite those advances, we've had a couple different trials now that have actually failed in this adjuvant setting, most high profile being the CheckMate-915 study, which looked at nivolumab plus ipilimumab and unfortunately was a negative study. So, with RELATIVITY-047, which was the trial of nivolumab plus relatlimab that showed an improvement in progression-free survival for metastatic disease, there's a lot of interest, and we've been awaiting these data for a long time for RELATIVITY-098, which, of course, is this adjuvant trial of LAG-3 blockade with relatlimab plus nivolumab. Dr. Diwakar Davar: Great. So with that, let's briefly discuss the trial design and the results. So this was a randomized, phase 3, blinded study, so double-blinded, so neither the investigators knew what the patients were getting, nor did the patients know what they were getting. The treatment investigational arm was nivolumab plus relatlimab in the fixed-dose combination. So that's the nivolumab standard fixed dose with relatlimab that was FDA approved in RELATIVITY-047. And the control arm was nivolumab by itself. The duration of treatment was 1 year. The patient population consisted of resected high-risk stage III or IV patients. The primary endpoint was investigator-assessed RFS. Stage and geography were the standard stratifying factors, and they were included, and most of the criteria were balanced across both arms. What we know at this point is that the 2-year RFS rate was 64% and 62% in the nivolumab and nivolumab-combination arms, respectively. The 2-year DMFS rate was similarly equivalent: 76% with nivolumab monotherapy, 73% with the combination. And similar to what you had talked about with CheckMate 915, unfortunately, the addition of LAG-3 did not appear to improve the RFS or DMFS compared to control in this patient population. So, tell us a little bit about your take on this and what do you think might be the reasons why this trial was negative? Dr. Jason Luke: It's really unfortunate that we have this negative phase 3 trial. There had been a lot of hope that the combination of nivolumab with relatlimab would be a better tolerated combination that increased the efficacy. So in the metastatic setting, we do have 047, the study that demonstrated nivolumab plus relatlimab, but now we have this negative trial in the adjuvant setting. And so as to why exactly, I think is a complicated scenario. You know, when we look at the hazard ratios for relapse-free survival, the primary endpoint, as well as the secondary endpoints for distant metastasis-free survival, we see that the hazard ratio is approximately 1. So there's basically no difference. And that really suggests that relatlimab in this setting had no impact whatsoever on therapeutic outcomes in terms of efficacy. Now, it's worth noting that there was a biomarker subanalysis that was presented in conjunction with these data that looked at some immunophenotyping, both from circulating T cells, CD8 T cells, as well as from the tumor microenvironment from patients who were treated, both in the previous metastatic trial, the RELATIVITY-047 study, and now in this adjuvant study in the RELATIVITY-098 study. And to briefly summarize those, what was identified was that T cells in advanced melanoma seemed to have higher expression levels of LAG-3 relative to T cells that are circulating in patients that are in the adjuvant setting. In addition to that, there was a suggestion that the magnitude of increase is greater in the advanced setting versus adjuvant. And the overall summary of this is that the suggested rationale for why this was a negative trial may have been that the target of LAG-3 is not expressed as highly in the adjuvant setting as it is in the metastatic setting. And so while the data that were presented, I think, support this kind of an idea, I am a little bit cautious that this is actually the reason for why the trial was negative, however. I would say we're not really sure yet as to why the trial was negative, but the fact that the hazard ratios for the major endpoints were essentially 1 suggests that there was no impact whatsoever from relatlimab. And this really makes one wonder whether or not building on anti–PD-1 in the adjuvant setting is feasible because anti–PD-1 works so well. You would think that even if the levels of LAG-3 expression were slightly different, you would have seen a trend in one direction or another by adding a second drug, relatlimab, in this scenario. So overall, I think it's an unfortunate circumstance that the trial is negative. Clearly there's going to be no role for relatlimab in the adjuvant setting. I think this really makes one wonder about the utility of LAG-3 blockade and how powerful it really can be. I think it's probably worth pointing out there's another adjuvant trial ongoing now of a different PD-1 and LAG-3 combination, and that's cemiplimab plus fianlimab, a LAG-3 antibody that's being dosed from another trial sponsor at a much higher dose, and perhaps that may make some level of difference. But certainly, these are unfortunate results that will not advance the field beyond where we were at already. Dr. Diwakar Davar: And to your point about third-generation checkpoint factors that were negative, I guess it's probably worth noting that a trial that you were involved with, KeyVibe-010, that evaluated the PD-1 TIGIT co-formulation of vibostolimab, MK-4280A, was also, unfortunately, similarly negative. So, to your point, it's not clear that all these third-generation receptors are necessarily going to have the same impact in the adjuvant setting, even if they, you know, for example, like TIGIT, and they sometimes may not even have an effect at all in the advanced cancer setting. So, we'll see what the HARMONY phase 3 trial, that's the Regeneron cemiplimab/fianlimab versus pembrolizumab control with cemiplimab with fianlimab at two different doses, we'll see how that reads out. But certainly, as you've said, LAG-3 does not, unfortunately, appear to have an impact in the adjuvant setting. So let's move on to LBA9501. This is the primary analysis of EORTC-2139-MG or the Columbus-AD trial. This was a randomized trial of encorafenib and binimetinib, which we will abbreviate as enco-bini going forward, compared to placebo in high-risk stage II setting in melanoma in patients with BRAF V600E or K mutant disease. So Jason, you know, you happen to know one or two things about the resected stage II setting, so maybe contextualize the stage II setting for us based on the trials that you've led, KEYNOTE-716, as well as CheckMate-76K, set us up to talk about Columbus-AD. Dr. Jason Luke: Thanks for that introduction, and certainly stage II disease has been something I've worked a lot on. The rationale for that has been that building off of the activity of anti–PD-1 in metastatic melanoma and then seeing the activity in stage III, like we just talked about, it was a curious circumstance that dating back about 7 to 8 years ago, there was no availability to use anti–PD-1 for high-risk stage II patients, even though the risk of recurrence and death from melanoma in the context of stage IIB and IIC melanoma is in fact similar or actually higher than in stage IIIA or IIIB, where anti–PD-1 was approved. And in that context, a couple of different trials that you alluded to, the Keynote-716 study that I led, as well as the CheckMate 76K trial, evaluated pembrolizumab and nivolumab, respectively, showing an improvement in relapse-free and distant metastasis-free survival, and both of those agents have subsequently been approved for use in the adjuvant setting by the US FDA as well as the European Medicines Agency.  So bringing then to this abstract, throughout melanoma oncology, we've seen that the impact of anti–PD-1 immunotherapy versus BRAF and MEK-targeted therapy have had very similar outcomes on a sort of comparison basis, both in frontline metastatic and then in adjuvant setting. So it was a totally reasonable question to ask: Could we use adjuvant BRAF and MEK inhibitor therapy? And I think all of us expected the answer would be yes. As we get into the discussion of the trial, I think the unfortunate circumstance was that the timing of this clinical trial being delayed somewhat, unfortunately, made it very difficult to accrue the trial, and so we're going to have to try to read through the tea leaves sort of, based on only a partially complete data set. Dr. Diwakar Davar: So, in terms of the results, they wanted to enroll 815 patients, they only enrolled 110. The RFS and DMFS were marginally improved in the treatment arm but certainly not significantly, which is not surprising because the trial had only accrued 16% to 18% of its complete accrual. As such, we really can't abstract from the stage III COMBI-AD data to stage II patients. And certainly in this setting, one would argue that the primary treatment options certainly remain either anti–PD-1 monotherapy, either with pembrolizumab or nivolumab, based on 716 or 76K, or potentially active surveillance for the patients who are not inclined to get treated.  Can you tell us a little bit about how you foresee drug development going forward in this space because, you know, for example, with HARMONY, certainly IIC disease is a part of HARMONY. We will know at least a little bit about that in this space. So what do you think about the stage IIB/C patient population? Is this a patient population in which future combinations are going to be helpful, and how would you think about where we can go forward from here? Dr. Jason Luke: It is an unfortunate circumstance that this trial could not be accrued at the pace that was necessary. I think all of us believe that the results would have been positive if they'd been able to accrue the trial. In the preliminary data set that they did disclose of that 110 patients, you know, it's clear there is a difference at a, you know, a landmark at a year. They showed a 16% difference, and that would be in line with what has been seen in stage III. And so, you know, I think it's really kind of too bad. There's really going to be no regulatory approach for this consideration. So using BRAF and MEK inhibition in stage II is not going to be part of standard practice moving into the future. To your point, though, about where will the field go? I think what we're already realizing is that in the adjuvant setting, we're really overtreating the total population. And so beyond merely staging by AJCC criteria, we need to move to biomarker selection to help inform which patients truly need the treatment. And in that regard, I don't think we've crystallized together as a field as yet, but the kinds of things that people are thinking about are the integration of molecular biomarkers like ctDNA. When it's positive, it can be very helpful, but in melanoma, we found that, unfortunately, the rates are quite low, you know, in the 10% to 15% range in the adjuvant setting. So then another consideration would be factors in the primary tumor, such as gene expression profiling or other considerations.  And so I think the future of adjuvant clinical trials will be an integration of both the standard AJCC staging system as well as some kind of overlaid molecular biomarker that helps to enrich for a higher-risk population of patients because on a high level, when you abstract out, it's just clearly the case that we're rather substantially overtreating the totality of the population, especially given that in all of our adjuvant studies to date for anti–PD-1, we have not yet shown that there's an overall survival advantage. And so some are even arguing perhaps we should even reserve treatment until patients progress. I think that's a complicated subject, and standard of care at this point is to offer adjuvant therapy, but certainly a lot more to do because many patients, you know, unfortunately, still do progress and move on to metastatic disease. Dr. Diwakar Davar: Let's transition to Abstract 2508. So we're moving on from the melanoma to the novel immunotherapy abstracts. And this is a very, very, very fascinating drug. It's IMA203. So Abstract 2508 is a phase 1 clinical update of IMA203. IMA203 is an autologous TCR-T construct targeting PRAME in patients with heavily pretreated PD-1-refractory metastatic melanoma. So Jason, in the PD-1 and CTLA-4-refractory settings, treatment options are either autologous TIL, response rate, you know, ballpark 29% to 31%, oncolytic viral therapy, RP1 with nivolumab, ORR about 30-ish percent. So new options are needed. Can you tell us a little bit about IMA203? Perhaps tell us for the audience, what is the difference between a TCR-T and traditional autologous TIL? And a little bit about this drug, IMA203, and how it distinguishes itself from the competing TIL products in the landscape. Dr. Jason Luke: I'm extremely enthusiastic about IMA203. I think that it really has transformative potential based on these results and hopefully from the phase 3 trial that's open to accrual now. So, what is IMA203? We said it's a TCR-T cell product. So what that means is that T cells are removed from a patient, and then they can be transduced through various technologies, but inserted into those T cells, we can then add a T-cell receptor that's very specific to a single antigen, and in this case, it's PRAME. So that then is contrasted quite a bit from the TIL process, which includes a surgical resection of a tumor where T cells are removed, but they're not specific necessarily to the cancer, and they're grown up in the lab and then given to the patient. They're both adoptive cell transfer products, but they're very different. One is genetically modified, and the other one is not. And so the process for generating a TCR-T cell is that patients are required to have a new biomarker that some may not be familiar with, which is HLA profiling. So the T-cell receptor requires matching to the concomitant HLA for which the peptide is bound in. And so the classic one that is used in most oncology practices is A*02:01 because approximately 48% of Caucasians have A*02:01, and the frequency of HLA in other ethnicities starts to become highly variable. But in patients who are identified to have A*02:01 genotype, we can then remove blood via leukapheresis or an apheresis product, and then insert via lentiviral transduction this T-cell receptor targeting PRAME. Patients are then brought back to the hospital where they can receive lymphodepleting chemotherapy and then receive the reinfusion of the TCR-T cells. Again, in contrast with the TIL process, however, these T cells are extremely potent, and we do not need to give high-dose interleukin-2, which is administered in the context of TIL. Given that process, we have this clinical trial in front of us now, and at ASCO, the update was from the phase 1 study, which was looking at IMA203 in an efficacy population of melanoma patients who were refractory at checkpoint blockade and actually multiple lines of therapy. So here, there were 33 patients and a response rate of approximately 50% was observed in this population of patients, notably with a duration of response approximately a year in that treatment group. And I realize that these were heavily pretreated patients who had a range of very high-risk features. And approximately half the population had uveal melanoma, which people may be aware is a generally speaking more difficult-to-treat subtype of melanoma that metastasizes to the liver, which again has been a site of resistance to cancer immunotherapy. So these results are extremely promising. To summarize them from what I said, it's easier to make TCR-T cells because we can remove blood from the patient to transduce the T cells, and we don't have to put them through surgery. We can then infuse them, and based on these results, it looks like the response rate to IMA203 is a little bit more than double what we expect from lifileucel. And then, whereas with lifileucel or TILs, we have to give high-dose IL-2, here we do not have to give high-dose IL-2. And so that's pretty promising. And a clinical trial is ongoing now called the SUPREME phase 3 clinical trial, which is hoping to validate these results in a randomized global study. Dr. Diwakar Davar: Now, one thing that I wanted to go over with you, because you know this trial particularly well, is what you think of the likelihood of success, and then we'll talk a little bit about the trial design. But in your mind, do you think that this is a trial that has got a reasonable likelihood of success, maybe even a high likelihood of success? And maybe let's contextualize that to say an alternative trial, such as, for example, the TebeAM trial, which is essentially a T-cell bispecific targeting GP100. It's being compared against SOC, investigator's choice control, also in a similarly heavily pretreated patient population. Dr. Jason Luke: So both trials, I think, have a strong chance of success. They are very different kinds of agents. And so the CD3 bispecific that you referred to, tebentafusp, likely has an effect of delaying progression, which in patients with advanced disease could have a value that might manifest as overall survival. With TCR-T cells, by contrast, we see a very high response rate with some of the patients going into very durable long-term benefit. And so I do think that the SUPREME clinical trial has a very high chance of success. It will be the first clinical trial in solid tumor oncology randomizing patients to receive a cell therapy as compared with a standard of care. And within that standard of care control arm, TILs are allowed as a treatment. And so it will also be the first study that will compare TCR-T cells against TILs in a randomized phase 3. But going back to the data that we've seen in the phase 1 trial, what we observe is that the duration of response is really connected to the quality of the response, meaning if you have more than a 50% tumor shrinkage, those patients do very, very well. But even in patients who have less than 50% tumor shrinkage, the median progression-free survival right now is about 4.5 months. And again, as we think about trial design, standard of care options for patients who are in this situation are unfortunately very bad. And the progression-free survival in that population is probably more like 2 months. So this is a trial that has a very high likelihood of being positive because the possibility of long-term response is there, but even for patients who don't get a durable response, they're likely going to benefit more than they would have based on standard chemotherapy or retreatment with an anti–PD-1 agent. Dr. Diwakar Davar: Really, a very important trial to enroll, a trial that is first in many ways. First of a new generation of TCR-T agents, first trial to look at cell therapy in the control arm, a new standard of efficacy, but potentially also if this trial is successful, it will also be a new standard of trial conduct, a new kind of trial, of a set of trials that will be done in the second-line immunotherapy-refractory space. So let's pivot to the last trial that we were going to discuss, which was Abstract 2501. Abstract 2501 is a first-in-human phase 1/2 trial evaluating BNT142, which is the first-in-class mRNA-encoded bispecific targeting Claudin-6 and CD3 in patients with Claudin-positive tumors. We'll talk a little bit about this, but maybe let's start by talking a little bit about Claudin-6. So Claudin-6 is a very interesting new target. It's a target that's highly expressed in GI and ovarian tumors. There are a whole plethora of Claudin-6-targeting agents, including T-cell bispecifics and Claudin-6-directed CAR-Ts that are being developed. But BNT142 is novel. It's a novel lipid nanoparticle LNP-encapsulated mRNA. The mRNA encodes an anti–Claudin-6 CD3 bispecific termed RiboMAB-021. And it then is administered to the patient. The BNT142-encoding mRNA LNPs are taken up by the liver and translated into the active drug. So Jason, tell us a little bit about this agent. Why you think it's novel, if you think it's novel, and let's talk a little bit then about the results. Dr. Jason Luke: So I certainly think this is a novel agent, and I think this is just the first of what will probably become a new paradigm in oncology drug development. And so you alluded to this, but just to rehash it quickly, the drug is encoded as genetic information that's placed in the lipid nanoparticle and then is infused into the patient. And after the lipid nanoparticles are taken up by the liver, which is the most common place that LNPs are usually taken up, that genetic material in the mRNA starts to be translated into the actual protein, and that protein is the drug. So this is in vivo generation, so the patient is making their own drug inside their body. I think it's a really, really interesting approach. So for any drug that could be encoded as a genetic sequence, and in this case, it's a bispecific, as you mentioned, CD3-Claudin-6 engager, this could have a tremendous impact on how we think about pharmacology and novel drug development moving into the future in oncology. So I think it's an extremely interesting drug, the like of which we'll probably see only more moving forward. Dr. Diwakar Davar: Let's maybe briefly talk about the results. You know, the patient population was heavily pretreated, 65 or so patients, mostly ovarian cancer. Two-thirds of the patients were ovarian cancer, the rest were germ cell and lung cancer patients. But let's talk a little bit about the efficacy. The disease control rate was about 58% in the phase 1 population as a whole, but 75% in the ovarian patient population. Now tell us a little bit about the interesting things about the drug in terms of the pharmacokinetics, and also then maybe we can pivot to the clinical activity by dose level. Dr. Jason Luke: Well, so they did present in their presentation at ASCO a proportionality showing that as higher doses were administered, that greater amounts of the drug were being made inside the patient. And so that's an interesting observation, and it's an important one, right? Suggesting that the pharmacology that we classically think of by administering drugs by IV, for example, would still be in play. And that did translate into some level of efficacy, particularly at the higher dose levels. Now, the caveat that I'll make a note of is that disease control rate is an endpoint that I think we have to be careful about because what that really means is sometimes a little bit unclear. Sometimes patients have slowly growing tumors and so on and so forth. And the clinical relevance of disease control, if it doesn't last at least 6 months, I think is probably pretty questionable. So I think these are extremely interesting data, and there's some preliminary sense that getting the dose up is going to matter because the treatment responses were mostly observed at the highest dose levels. There's also a caveat, however, that across the field of CD3 bispecific molecules like this, there's been quite a bit of heterogeneity in terms of the response rate, with some of them only really generating stable disease responses and other ones having more robust responses. And so I think this is a really interesting initial foray into this space. My best understanding is this molecule is not moving forward further after this, but I think that this really does set it up to be able to chase after multiple different drug targets on a CD3 bispecific backbone, both in ovarian cancer, but then basically across all of oncology. Dr. Diwakar Davar: Perfect. This is a very new sort of exciting arena where we're going to be looking at, in many ways, these programmable constructs, whether we're looking at in vivo-generated, in this case, a T-cell bispecific, but we've also got newer drugs where we are essentially giving drugs where people are generating in vivo CAR T, and also potentially even in vivo TCR-T. But certainly lots of new excitement around this entire class of drugs. And so, what we'd like to do at this point in time is switch to essentially the fact that we've got a very, very exciting set of data at ASCO 2025. You've heard from Dr. Luke regarding the advances in both early drug development but also in advanced cutaneous melanoma. And Jason, as always, thank you so much for sharing your very valuable and great, fantastic insights with us on the ASCO Daily News Podcast. Dr. Jason Luke: Well, thanks again for the opportunity. Dr. Diwakar Davar: And thank you to our listeners for taking your time to listen today. You will find the links to the abstracts that we discussed today in the transcript of this episode. And 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 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. Follow today's speakers:    Dr. Diwakar Davar    @diwakardavar    Dr. Jason Luke @jasonlukemd Follow ASCO on social media:     @ASCO on Twitter       ASCO on Bluesky   ASCO on Facebook       ASCO on LinkedIn   Disclosures:     Dr. Diwakar Davar:      Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences     Consulting or Advisory Role: Instil Bio, Vedanta Biosciences     Consulting or Advisory Role (Immediate family member): Shionogi     Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences     Research Funding (Inst.): Zucero Therapeutics     Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy     Dr. Jason Luke:     Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX     Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine     Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure     Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)     Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio

Dr. Neeraj Agarwal and Dr. Jeanny Aragon-Ching discuss important advances in the treatment of prostate, bladder, and kidney cancers that were presented at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Neeraj Agarwal: Hello, and welcome to the ASCO Daily News Podcast. I am Dr. Neeraj Agarwal, your guest host of the ASCO Daily News Podcast today. I am the director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah Huntsman Cancer Institute and editor-in-chief of the ASCO Daily News.  I am delighted to be joined by Dr. Jeanny Aragon-Ching, a GU medical oncologist and the clinical program director of the GU Center at the Inova Schar Cancer Institute in Virginia. Today, we will be discussing some key abstracts in GU oncology that were presented at the 2025 ASCO Annual Meeting.  Our full disclosures are available in the transcript of this episode.  Jeanny, it is great to have you on the podcast. Dr. Jeanny Aragon-Ching: Oh, thank you so much, Neeraj. Dr. Neeraj Agarwal: Jeanny, let's begin with some prostate cancer abstracts. Let's begin with Abstract 5017 titled, “Phase 1 study results of JNJ-78278343 (pasritamig) in metastatic castration-resistant prostate cancer.” Can you walk us through the design and the key findings of this first-in-human trial? Dr. Jeanny Aragon-Ching: Yeah, absolutely, Neeraj. So this study, presented by Dr. Capucine Baldini, introduces pasritamig, a first-in-class T-cell redirecting bispecific antibody that simultaneously binds KLK2 on prostate cancer cells and CD3 receptor complexes on T cells. KLK2 is also known as human kallikrein 2, which is selectively expressed in prostate tissue. And for reference, KLK3 is what we now know as the PSA, prostate-specific antigen, therefore making it an attractive and specific target for therapeutic engagement. Now, while this was an early, first-in-human, phase 1 study, it enrolled 174 heavily pretreated metastatic CRPC patients. So many were previously treated with ARPIs, taxanes, and radioligand therapy. So given the phase 1 nature of this study, the primary objective was to determine the safety and the RP2D, which is the recommended phase 2 dose. Secondary objectives included preliminary assessment of antitumor activity. So, pasritamig was generally well tolerated. There were no treatment-related deaths. Serious adverse events were rare. And in the RP2D safety cohort, where patients received the step-up dosing up to 300 mg of IV every 6 weeks, the most common treatment-related adverse events were low-grade infusion reactions. There was fatigue and grade 1 cytokine release syndrome, what we call CRS. And no cases of neurotoxicity, or what we call ICANS, the immune effector cell-associated neurotoxicity syndrome, reported. Importantly, the CRS occurred in just about 8.9% of patients. All were grade 1. No patients required tocilizumab or discontinued treatment due to adverse events. So, this suggests a favorable safety profile, allowing hopefully for outpatient administration without hospitalization, which will be very important when we're thinking about bispecifics moving forward. In terms of efficacy, pasritamig showed promising activity. About 42.4% of evaluable patients achieved a PSA50 response. Radiographic PFS was about 6.8 months. And among patients with measurable disease, the objective response rate was about 16.1% in those with lymph node or bone metastases, and about 3.7% in those with visceral disease, with a median duration of response of about 11.3 months. So, altogether, this data suggests that pasritamig may offer a well-tolerated and active new potential option for patients with metastatic CRPC.   Again, as a reminder, with the caveat that this is still an early phase 1 study. Dr. Neeraj Agarwal: Thank you, Jeanny. These are promising results for a bispecific T-cell engager, pasritamig, in prostate cancer. I agree, the safety and durability observed here stand out, and this opens the door for further development, possibly even in earlier disease settings.  So, shifting now from immunotherapy to the evolving role of genomics in prostate cancer. So let's discuss Abstract 5094, a real-world, retrospective analysis exploring the prognostic impact of homologous recombination repair gene mutations, especially BRCA1 and BRCA2 mutations, in metastatic hormone-sensitive prostate cancer. Can you tell us more about this abstract, Jeanny? Dr. Jeanny Aragon-Ching: Sure, Neeraj. So this study was presented by Dr. David Olmos, represents one of the largest real-world analyses we have evaluating the impact of homologous recombination repair, or what we would call HRR, alterations in metastatic hormone-sensitive prostate cancer. So, this cohort included 556 men who underwent paired germline and somatic testing. Now, about 30% of patients had HRR alterations, with about 12% harboring BRCA1 or BRCA2 mutations and 16% having alterations in other HRR genes. Importantly, patients were stratified via CHAARTED disease volume, and outcomes were examined across treatment approaches, including ADT alone, doublet therapy, and triplet therapy. The prevalence of BRCA and HRR alterations were about similar between the metastatic hormone-sensitive prostate cancer and the metastatic castrate-resistant prostate cancer, with no differences observed, actually, between the patients with high volume versus low volume disease.  So, the key finding was that BRCA and HRR alterations were associated with poor clinical outcomes in metastatic hormone-sensitive prostate cancer. And notably, the impact of these alterations may actually be even greater in metastatic hormone-sensitive prostate cancer than previously reported in metastatic CRPC. So, the data showed that when BRCA mutations are present, the impact of the volume of disease is actually limited. So, poor outcomes were observed across the board for both high-volume and low-volume groups. So, the analysis showed that patients with HRR alterations had significantly worse outcomes compared to patients without HRR alterations. Median radiographic progression-free survival was about 20.5 months for the HRR-altered patients versus 30.6 months for the non-HRR patients, with a hazard ratio of 1.6. Median overall survival was 39 months for HRR-altered patients compared to 55.7 months for the non-HRR patients, with a hazard ratio of 1.5. Similar significant differences were observed when BRCA-mutant patients were compared with patients harboring non-BRCA HRR mutations. Overall, poor outcomes were independent of treatment of ARPI or taxanes. Dr. Neeraj Agarwal: Thank you, Jeanny. So, these data reinforce homologous recombination repair mutations as both a predictive and prognostic biomarker, not only in the mCRPC, but also in the metastatic hormone-sensitive setting as well. It also makes a strong case for incorporating genomic testing early in the disease course and not waiting until our patients have castration-resistant disease. Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. And I think this really brings home the point and the lead up to the AMPLITUDE trial, which is LBA5006, a phase 3 trial that builds on this very concept of testing with a PARP inhibitor, niraparib, in the hormone-sensitive space. Can you tell us a little bit more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure. So, the AMPLITUDE trial, a phase 3 trial presented by Dr. Gerhardt Attard, enrolled 696 patients with metastatic hormone-sensitive prostate cancer and HRR gene alterations. 56% of these patients had BRCA1 and BRCA2 mutations. Patients were randomized to receive abiraterone with or without niraparib, a PARP inhibitor. The majority of patients, 78% of these patients, had high-volume metastatic hormone-sensitive prostate cancer, and 87% of these patients had de novo metastatic HSPC. And 16% of these patients received prior docetaxel, which was allowed in the clinical trial. So, with a median follow-up of nearly 31 months, radiographic progression-free survival was significantly prolonged with the niraparib plus abiraterone combination, and median was not reached in this arm, compared to abiraterone alone, which was 29.5 months, with a hazard ratio of 0.63, translating to a 37% reduction in risk of progression or death. This benefit was even more pronounced in the BRCA1 and BRCA2 subgroup, with a 48% reduction in risk of progression, with a hazard ratio of 0.52. Time to symptomatic progression also improved significantly across all patients, including patients with BRCA1, BRCA2, and HRR mutations. Although overall survival data remain immature, early trends favored the niraparib plus abiraterone combination. The safety profile was consistent with prior PARP inhibitor studies, with grade 3 or higher anemia and hypertension were more common but manageable. Treatment discontinuation due to adverse events remained low at 11%, suggesting that timely dose modifications when our patients experience grade 3 side effects may allow our patients to continue treatment without discontinuation. These findings support niraparib plus abiraterone as a potential new standard of care in our patients with metastatic hormone-sensitive prostate cancer with HRR alterations, and especially in those who had BRCA1 and BRCA2 mutations. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. This trial is especially exciting because it brings PARP inhibitors earlier into the treatment paradigm. Dr. Neeraj Agarwal: Exactly. And it is exciting to see the effect of PARP inhibitors in the earlier setting.  So Jeanny, now let's switch gears a bit to bladder cancer, which also saw several impactful studies. Could you tell us about Abstract 4502, an exploratory analysis from the EV-302 trial, which led to approval of enfortumab vedotin plus pembrolizumab for our patients with newly diagnosed metastatic bladder cancer? So here, the authors looked at the outcomes in patients who achieved a confirmed complete response with EV plus pembrolizumab. Dr. Jeanny Aragon-Ching: Sure, Neeraj. So, EV-302 demonstrated significant improvements in progression-free and overall survival for patients previously treated locally advanced or metastatic urothelial cancer, I'll just call it metastatic UC, as a frontline strategy, establishing EV, which is enfortumab vedotin, plus pembro, with pembrolizumab as standard of care in this setting.  So, this year at ASCO, Dr Shilpa Gupta presented this exploratory responder analysis from the phase 3 EV-302 trial. Among 886 randomized patients, about 30.4% of patients, this is about 133, in the EV+P arm, and 14.5% of the patients in the chemotherapy arm, achieved a confirmed complete response. They call it the CCR rates. So for patients who achieved this, median PFS was not reached with EV+P compared to 26.9 months with chemotherapy, with a hazard ratio of 0.36, translating to a 64% reduction in the risk of progression. Overall survival was also improved. So the median OS was not reached in either arm, but the hazard ratio favored the EV+P at 0.37, translating to a 63% reduction in the risk of death. The median duration of complete response was not reached with EV+P compared to 15.2 months with chemotherapy. And among those patients who had confirmed CRs at 24 months, 78% of patients with the EV+P arm remained progression-free, and around 95% of the patients were alive, compared to 54% of patients who were progression-free and 86% alive of the patients in the chemotherapy arm. Safety among responders were also consistent with prior reports. Grade 3 or higher treatment-related adverse events occurred in 62% of EV+P responders and 72% of chemotherapy responders. Most adverse events were managed with dose modifications, and importantly, no treatment-related deaths were reported among those who were able to achieve complete response.  So these findings further reinforce EV and pembro as the preferred first-line therapy for metastatic urothelial carcinoma, offering a higher likelihood of deep, durable responses with a fairly manageable safety profile. Dr. Neeraj Agarwal: Thank you for the great summary, Jeanny. These findings underscore the depth and durability of responses achievable with this combination and also suggest that achieving a response may be a surrogate for long-term benefit in patients with metastatic urothelial carcinoma.  So now, let's move to Abstract 4503, an exploratory ctDNA analysis from the NIAGARA trial, which evaluated perioperative durvalumab, an immune checkpoint inhibitor, in muscle-invasive bladder cancer. So what can you tell us about this abstract? Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. So, in NIAGARA, presented by Dr. Tom Powles, the addition of perioperative durvalumab to neoadjuvant chemotherapy, gem/cis, significantly improved event-free survival, overall survival, and pathologic complete response in patients with cisplatin-eligible muscle-invasive bladder cancer. Recall that this led to the U.S. FDA approval of this treatment regimen on March 28, 2025.  So, a planned exploratory analysis evaluated the ctDNA dynamics and their association with clinical outcomes, which was the one presented recently at ASCO. So, the study found that the incidence of finding ctDNA positivity in these patients was about 57%. Following neoadjuvant treatment, this dropped to about 22%, with ctDNA clearance being more common in the durvalumab arm, about 41%, compared to the chemotherapy control arm of 31%. Notably, 97% of patients who remained ctDNA positive prior to surgery failed to achieve a pathologic CR. So, this indicates a strong association between ctDNA persistence and lack of tumor eradication. So, postoperatively, only about 9% of patients were ctDNA positive. So, importantly, durvalumab conferred an event-free survival benefit regardless of ctDNA status at both baseline and post-surgery. Among patients who were ctDNA positive at baseline, durvalumab led to a hazard ratio of 0.73 for EFS. So, this translates to a 27% reduction in the risk of disease recurrence, progression, or death compared to the control arm. In the post-surgical ctDNA-positive group, the disease-free survival was also improved with a hazard ratio of 0.49, translating to a 51% reduction in the risk of recurrence.  So, these findings underscore the prognostic value of ctDNA and suggest that durvalumab provides clinical benefit irrespective of molecular residual disease status. So, the data also supports that ctDNA is a promising biomarker for future personalized strategies in the perioperative treatment of muscle-invasive bladder cancer. Dr. Neeraj Agarwal: Thank you, Jeanny. It is great to see that durvalumab is improving outcomes in these patients regardless of ctDNA status. However, based on these data, presence of ctDNA in our patients warrants a closer follow-up with imaging studies, because these patients with positive ctDNA seem to have a higher risk of recurrence. Dr. Jeanny Aragon-Ching: I agree, Neeraj.  Let's round out the bladder cancer discussion with Abstract 4518, which reported the interim results of SURE-02, which is a phase 2 study evaluating neoadjuvant sacituzumab govitecan plus pembrolizumab in cisplatin-ineligible muscle-invasive bladder cancer. Can you tell us more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure, Jeanny. So, Dr Andrea Necchi presented interim results from the SURE-02 trial. This is a phase 2 study evaluating neoadjuvant sacituzumab govitecan plus pembrolizumab, followed by a response-adapted bladder-sparing treatment and adjuvant pembrolizumab in patients with muscle-invasive bladder cancer.  So, in this interim analysis, 40 patients were treated and 31 patients were evaluable for efficacy. So, the clinical complete response rate was 38.7%. All patients achieving clinical complete response underwent bladder-sparing approach with a repeat TURBT instead of radical cystectomy. Additionally, 51.6% of patients achieved excellent pathologic response with a T stage of 1 or less after neoadjuvant therapy. The treatment was well tolerated, with only 12.9% of patients experiencing grade 3 or higher adverse events without needing dose reduction of sacituzumab. Molecular profiling, interestingly, showed that clinical complete response correlated with luminal and genomically unstable subtypes, while high stromal gene expression was associated with lack of response.  These results suggest that sacituzumab plus pembrolizumab combination has promising activity in this setting, and tolerability, and along with other factors may potentially allow a bladder preservation approach in a substantial number of patients down the line. Dr. Jeanny Aragon-Ching: Yeah, agree with you, Neeraj. And the findings are very provocative and support completing the full trial enrollment and further exploration of this strategy in muscle-invasive bladder cancer in order to improve and provide further bladder-sparing strategies. Dr. Neeraj Agarwal: Agree. So, let's now turn to the kidney cancer, starting with Abstract 4505, the final overall analysis from CheckMate-214 trial, which evaluated nivolumab plus ipilimumab, so dual checkpoint inhibition strategy, versus sunitinib in our patients with metastatic clear cell renal cell carcinoma. Dr. Jeanny Aragon-Ching: Yeah, absolutely, Neeraj. So, the final 9-year analysis of the phase 3 CheckMate-214 trial confirms the long-term superiority of nivolumab and ipilimumab over sunitinib for first-line treatment of advanced metastatic renal cell carcinoma. So, this has a median follow-up of 9 years. Overall survival remains significantly improved with the combination. So, in the ITT patient population, the intention-to-treat, the hazard ratio for overall survival was 0.71. So, this translates to a 29% reduction in the risk of death. 31% of patients were alive at this 108-month follow-up compared to 20% only in those who got sunitinib. So, similar benefits were observed in the intermediate- and poor-risk groups with a hazard ratio of 0.69, and 30% versus 19% survival at 108 months.  Importantly, a delayed benefit was also seen in those favorable-risk patients. So, the hazard ratio for overall survival improved from 1.45 in the initial report and now at 0.8 at 9 years follow-up, with 35% of patients alive at 108 months compared to 22% in those who got sunitinib. Progression-free survival also favored the nivo-ipi arm across all risk groups. At 96 months, the probability of remaining progression-free was about 23% compared to 9% in the sunitinib arm in the ITT patient population, 25% versus 9% in the intermediate- and poor-risk patients, and 13% compared to 11% in the favorable-risk patients. Importantly, at 96 months, 48% of patients in the nivo-ipi responders remained in response compared to just 19% in those who got sunitinib. And in the favorable-risk group, 36% of patients who responded remained in response, although data were not available for sunitinib in this subgroup.  So, this data reinforces the use of nivolumab and ipilimumab as a durable and effective first-line effective strategy for standard of care across all risk groups for advanced renal cell carcinoma. Dr. Neeraj Agarwal: Thank you, Jeanny. And of course, since ipi-nivo data were presented, several other novel ICI-TKI combinations have emerged. And I'm really hoping to see very similar data with TKI-ICI combinations down the line. It is really important to note that we are not seeing any new safety signals with the ICI combinations or ICI-based therapies, which is very reassuring given the extended exposure. Dr. Jeanny Aragon-Ching: Absolutely agree with you there, Neeraj.  Now, going on and moving on to Abstract 4514, which is the KEYNOTE-564 trial, and they reported on the 5-year outcomes of adjuvant pembrolizumab in clear cell RCC in patients who are at high risk for recurrence. Can you tell us a little bit more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure. So, the KEYNOTE-564 trial established pembrolizumab monotherapy as the first adjuvant regimen to significantly improve both disease-free survival and overall survival compared to placebo after surgery for patients with clear cell renal cell carcinoma. So, Dr Naomi Haas presented the 5-year update from this landmark trial.  A total of 994 patients were randomized to receive either pembrolizumab or placebo. The median follow-up at the time of this analysis was approximately 70 months. Disease-free survival remained significantly improved with pembrolizumab. The median DFS was not reached with pembrolizumab compared to 68.3 months with placebo, with a hazard ratio of 0.71, translating to a 29% reduction in risk of recurrence. At 5 years, 60.9% of patients receiving pembrolizumab remained disease-free compared to 52.2% with placebo. Overall survival also favored pembrolizumab. The hazard ratio for OS was 0.66, translating to a 34% reduction in risk of death, with an estimated 5-year overall survival rate of 87.7% with pembrolizumab compared to 82.3% for placebo. Importantly, these benefits were consistent across all key subgroups, including patients with sarcomatoid features. In addition, no new serious treatment-related adverse events have been reported in the 3 years since treatment completion.  So, these long-term data confirm pembrolizumab as a durable and effective standard adjuvant therapy for patients with resected, high-risk clear cell renal cell carcinoma. Dr. Jeanny Aragon-Ching: Thank you for that wonderful summary, Neeraj. Dr. Neeraj Agarwal: That wraps up our kidney cancer highlights. Any closing thoughts, Jeanny, before we conclude? Dr. Jeanny Aragon-Ching: It's been so wonderful reviewing these abstracts with you, Neeraj. So, the 2025 ASCO Annual Meeting showcased a lot of transformative data across GU cancers, from first-in-class bispecifics to long-term survival in RCC. And these findings are already shaping our clinical practices. Dr. Neeraj Agarwal: I agree. And we have covered a broad spectrum of innovations in GU cancers with strong clinical relevance.  So, thank you, Jeanny, for joining me today and sharing your insights.  And thank you to our listeners for joining us. You will find links to the abstracts discussed today in the transcript of this episode. If you find these conversations valuable, please take a moment to rate, review, and subscribe to the ASCO Daily News Podcast wherever you listen. Thank you so 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. Neeraj Agarwal     @neerajaiims     Dr. Jeanny Aragon-Ching   Follow ASCO on social media:       @ASCO on Twitter       ASCO on Bluesky   ASCO on Facebook       ASCO on LinkedIn       Disclosures:   Dr. Neeraj Agarwal:   Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences  Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas  Dr. Jeanny Aragon-Ching:   Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc., Pfizer/EMD Serono   Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis,    Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb, Astellas/Seattle Genetics

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