Podcasts about cd3

Featuring an interview with Dr Jennifer Crombie, including the following topics: Overview of similarities and differences among CD20 x CD3 targeted bispecific antibodies for the treatment of lymphomas (0:00) Optimal integration of CD20 x CD3 bispecific antibodies into treatment algorithms for lymphomas (9:40) Case: A man in his late 60s with relapsed follicular lymphoma (FL) who received mosunetuzumab (23:52) Case: A man in his late 80s with transformed, double-hit diffuse large B-cell lymphoma (DLBCL) who received epcoritamab (28:46) Case: A woman in her early 70s with recurrent FL who received odronextamab on the ELM-1 trial (34:06) Case: A man in his early 80s with multiregimen-relapsed DLBCL who receives glofitamab (43:19) CME information and select publications

Dr Jennifer Crombie from the Dana-Farber Cancer Institute in Boston, Massachusetts, reviews available and investigational CD20 x CD3 targeted bispecific antibodies for the treatment of follicular and diffuse large B-cell lymphomas. CME information and select publications here.

Tiziana Life Sciences CEO Ivor Elrifi joined Steve Darling from Proactive to share news the company has announced promising PET scan results from a patient with moderate Alzheimer's disease treated for three months with intranasal foralumab under an expanded access program. The scan revealed a significant reduction in microglial activation, a key marker of neuroinflammation linked to Alzheimer's progression. This outcome represents a major milestone for the company's intranasal foralumab program. With no approved therapies for moderate Alzheimer's disease, Tiziana sees foralumab—a fully human anti-CD3 monoclonal antibody—as a potential treatment option, both as a monotherapy and in combination with amyloid-targeting therapies. Foralumab has shown the ability to induce regulatory T cells (Tregs) that migrate to the brain and suppress neuroinflammation. These effects have been validated in preclinical models and in patients with secondary progressive multiple sclerosis, supporting further clinical development in neurodegenerative conditions. The company is set to begin a Phase 2 randomized, placebo-controlled trial in June 2025 involving mild Alzheimer's patients. Data from this trial are expected by the end of 2025. The aim is to determine if reducing neuroinflammation translates into improved quality of life. #proactiveinvestors #tizianalifescienceslts #nasdaq #tlsa #newceo #ivorelrifi #Foralumab #AlzheimersResearch #Neuroinflammation #BiotechNews #PETscan #ClinicalTrials #AlzheimersTreatment #PharmaUpdates #HealthcareInnovation

CD3: Peak-Time Anthems & Enduring Club ClassicsLaTour – Blue (Harmes Trance Mix) – 3:46Underground Sound Of Lisbon – Dance With Me (Original Mix) – 3:33Opus III – Hand In Hand (Looking For Sweet Inspiration) (Perfecto Mix) – 3:50Tony Moran – Same Sun, Same Sky (Red Sun Mix) – 4:01Quiver – Twist And Shout – 6:58Clino – Horizon (Spectralized) – 3:51Moby – Move (DJ Kid Paul Mix) – 6:01Judy Cheeks – Reach (Quivver's Amytiville Dub) – 3:42Zee – Dreamtime (Vocal Mix) – 7:28Angel Moraes feat. Basil Roderick – Heaven Knows (I Can't Understand) (Galvatron Dub) – 4:34Blue Amazon – No Other Love – 12:34Robert Miles – Children (Remix) – 7:37L'Homme Van Renn – The (Real) Love Thang (Northern Frontier Mix) – 5:25

March 28, 2025#WhatILearnedTodayDownload The Daily MoJo App: HERE"Ep 032825: Freedom Friday: You Do You, Boo - The Daily MoJo"Women don't take bathroom pix of men! The NPR CEO is kinda hot, but still a phoney mcphonerson. The Gene Hackman mystery deepens. Phil Bell - TDM's DC Correspondent  - Joins the program  LIVE to discuss the judicial coup against Trump, the failure of Republicans to do better in elections around the coutry, and the effect tariffs will have on the auto industry.All American Talk ShowAllThingsTrainsPhil's YouTube Channel: HEREMarisa Simonetti - Republican Candidate for CD3 in Minnesota - joins the program to discuss the challenges of running a campaign, and what it means to be an authentic person in the lublic eye.Marisa's Linktree: HEREMarisa on X: HEREOur affiliate partners:Pantell Less Lethal Protection - an official dealer of Byrna Technologies - has your alternative to deadly force. It's the Byrna Launcher, and it's legal in all 50 states! Check your state's laws for any special restrictions that may exist. Find the Byrna Launcher that's perfect for you: ProtectMyMojo.comPromo Code: dailymojoRoss's Cell: 908.642.2636Romika Designs is an awesome American small business that specializes in creating laser-engraved gifts and awards for you, your family, and your employees. Want something special for someone special? Find exactly what you want at MoJoLaserPros.com  There have been a lot of imitators, but there's only OG – American Pride Roasters Coffee. It was first and remains the best roaster of fine coffee beans from around the world. You like coffee? You'll love American Pride – from the heart of the heartland – Des Moines, Iowa. AmericanPrideRoasters.com   Find great deals on American-made products at MoJoMyPillow.com. Mike Lindell – a true patriot in our eyes – puts his money where his mouth (and products) is/are. Find tremendous deals at MoJoMyPillow.com – Promo Code: MoJo50  Life gets messy – sometimes really messy. Be ready for the next mess with survival food and tools from My Patriot Supply. A 25 year shelf life and fantastic variety are just the beginning of the long list of reasons to get your emergency rations at PrepareWithMoJo50.comStay ConnectedWATCH The Daily Mojo LIVE 7-9a CT: www.TheDailyMojo.com (RECOMMEDED)Watch:Rumble: HEREFacebook: HEREFreedomsquare: HEREYouTube: HEREListen:LISTEN: HEREBecome a supporter of this podcast: https://www.spreaker.com/podcast/the-daily-mojo-with-brad-staggs--3085897/support

Featuring an interview with Ms Robin Klebig, including the following topics: Overview of the natural history and treatment landscapes of lymphoma subtypes (0:00) Structure and mechanisms of action of bispecific antibodies (23:41) Similarities and differences among the various approved and investigational CD20 x CD3 bispecific antibodies for non-Hodgkin lymphoma (28:14) Case: A man in his early 50s with multiagent/multiregimen-refractory follicular lymphoma who experienced disease progression with chimeric antigen receptor T-cell therapy now receives mosunetuzumab (39:14) Case: A woman in her mid 60s with relapsed/refractory (R/R) diffuse large B-cell lymphoma receives glofitamab (49:08) Case: A man in his mid 60s with R/R high-grade B-cell lymphoma with MYC and Bcl-2 rearrangements receives epcoritamab (52:57) Case: A man in his early 60s with composite lymphoma receives epcoritamab (56:55) NCPD information and select publications

In this week's episode we'll find out about longer term results from a pivotal trial of mosunetuzumab in relapsed/refractory follicular lymphoma, potential use of CD70 CAR T-cells that secrete an anti-CD33/anti-CD3 bispecific antibody as a therapy for acute myeloid leukemia, and how ferroptosis regulates hemolysis in stored red blood cells.Featured Articles:Long-term 3-year follow-up of mosunetuzumab in relapsed or refractory follicular lymphoma after ≥2 prior therapiesCD70 CAR T cells secreting an anti-CD33/anti-CD3 dual-targeting antibody overcome antigen heterogeneity in AMLFerroptosis regulates hemolysis in stored murine and human red blood cells

Gloria Yiu, M.D., Ph.D., delves into the transformative potential of genetic editing technologies in addressing rare immune disorders, with a focus on CD3δ severe combined immunodeficiency (SCID)—a condition characterized by impaired T-cell development and severely compromised immune function. Leveraging her expertise as a physician-scientist, Yiu explores how CRISPR and other precision gene-editing tools can correct genetic mutations at the cellular level, potentially restoring T-cell production and immune resilience in patients with CD3δ SCID. Her presentation underscores the challenges and breakthroughs in treating such life-threatening conditions, emphasizing the role of interdisciplinary research, clinical innovation, and ethical considerations in advancing the frontiers of personalized medicine. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 40245]

Gloria Yiu, M.D., Ph.D., delves into the transformative potential of genetic editing technologies in addressing rare immune disorders, with a focus on CD3δ severe combined immunodeficiency (SCID)—a condition characterized by impaired T-cell development and severely compromised immune function. Leveraging her expertise as a physician-scientist, Yiu explores how CRISPR and other precision gene-editing tools can correct genetic mutations at the cellular level, potentially restoring T-cell production and immune resilience in patients with CD3δ SCID. Her presentation underscores the challenges and breakthroughs in treating such life-threatening conditions, emphasizing the role of interdisciplinary research, clinical innovation, and ethical considerations in advancing the frontiers of personalized medicine. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 40245]

Gloria Yiu, M.D., Ph.D., delves into the transformative potential of genetic editing technologies in addressing rare immune disorders, with a focus on CD3δ severe combined immunodeficiency (SCID)—a condition characterized by impaired T-cell development and severely compromised immune function. Leveraging her expertise as a physician-scientist, Yiu explores how CRISPR and other precision gene-editing tools can correct genetic mutations at the cellular level, potentially restoring T-cell production and immune resilience in patients with CD3δ SCID. Her presentation underscores the challenges and breakthroughs in treating such life-threatening conditions, emphasizing the role of interdisciplinary research, clinical innovation, and ethical considerations in advancing the frontiers of personalized medicine. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 40245]

Gloria Yiu, M.D., Ph.D., delves into the transformative potential of genetic editing technologies in addressing rare immune disorders, with a focus on CD3δ severe combined immunodeficiency (SCID)—a condition characterized by impaired T-cell development and severely compromised immune function. Leveraging her expertise as a physician-scientist, Yiu explores how CRISPR and other precision gene-editing tools can correct genetic mutations at the cellular level, potentially restoring T-cell production and immune resilience in patients with CD3δ SCID. Her presentation underscores the challenges and breakthroughs in treating such life-threatening conditions, emphasizing the role of interdisciplinary research, clinical innovation, and ethical considerations in advancing the frontiers of personalized medicine. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 40245]

Gloria Yiu, M.D., Ph.D., delves into the transformative potential of genetic editing technologies in addressing rare immune disorders, with a focus on CD3δ severe combined immunodeficiency (SCID)—a condition characterized by impaired T-cell development and severely compromised immune function. Leveraging her expertise as a physician-scientist, Yiu explores how CRISPR and other precision gene-editing tools can correct genetic mutations at the cellular level, potentially restoring T-cell production and immune resilience in patients with CD3δ SCID. Her presentation underscores the challenges and breakthroughs in treating such life-threatening conditions, emphasizing the role of interdisciplinary research, clinical innovation, and ethical considerations in advancing the frontiers of personalized medicine. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 40245]

Gloria Yiu, M.D., Ph.D., delves into the transformative potential of genetic editing technologies in addressing rare immune disorders, with a focus on CD3δ severe combined immunodeficiency (SCID)—a condition characterized by impaired T-cell development and severely compromised immune function. Leveraging her expertise as a physician-scientist, Yiu explores how CRISPR and other precision gene-editing tools can correct genetic mutations at the cellular level, potentially restoring T-cell production and immune resilience in patients with CD3δ SCID. Her presentation underscores the challenges and breakthroughs in treating such life-threatening conditions, emphasizing the role of interdisciplinary research, clinical innovation, and ethical considerations in advancing the frontiers of personalized medicine. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 40245]

Guests: Raj Doraisamy - Defend Florida and Defend U.S. talks about the importance of embracing States Rights and our responsibilities to ensure a successful transfer from Federal oversight to States domain.  States Rights Resources: www.StatesRights.US www.PatriotDigest.US/Resources  Jeff Hoffman - National Operations Director & VA State Chapter President, VFAF. A war college veteran with over 20 years in national security, who served on the 58th Trump Presidential Inauguration Committee along with private-sector work on the National Intelligence Council during the Trump Administration. He is a two-time General Assembly level candidate and has over 20 years of political experience, including graduate of The Leadership Institute Campaign Leadership College. Alongside VA VFAF, Jeff is a father, college instructor in New York City, President and CEO of Cyber Intelligent Partners, a Virginia-based LLC, and founder/Chair of the Virginia Freedom Leader Coalition PAC. Veterans For America First: www.VFAF.US  Berney Flowers - Lieutenant Colonel, USAF (Ret), Former GOP Candidate for US Congress (MD's CD3), National Director of Political Affairs & MD State Chapter President, VFAF.  Berney's Podcast:  The Loyal Opposition Podcast Social Media & Online Platforms: Website: https://berneyflowers.com/ Facebook: https://www.facebook.com/BerneyFlowers/ Twitter: https://twitter.com/Berney_Flowers Buy his book “Black Values Matter” See omnystudio.com/listener for privacy information.

Dr. Greg Kalemkerian reviews the latest evidence-based rapid update from the Expert Panel on systemic therapy for small cell lung cancer. He discusses the updated recommendations for patients with limited-stage SCLC based on the ADRIATIC trial, and for patients with relapsed SCLC based on the DeLLphi-301 trial. Dr. Kalemkerian shares insights on what these changes mean for clinicians and patients, and highlights new trials in progress to provide more options for patients diagnosed with SCLC. Read the full rapid update, “Systemic Therapy for Small Cell Lung Cancer: ASCO Guideline Rapid Recommendation Update” at www.asco.org/thoracic-cancer-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/thoracic-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-24-02245   Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges and advances in oncology. You can find all the shows, including this one at asco.org/podcasts. My name is Brittany Harvey and today I'm interviewing Dr. Greg Kalemkerian from the University of Michigan, lead author on, “Systemic Therapy for Small Cell Lung Cancer: ASCO Guideline Rapid Recommendation Update”. Thank you for being here today, Dr. Kalemkerian. Dr. Greg Kalemkerian: Thank you. Thank you for the invitation. Brittany Harvey: Great. Then, before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Kalemkerian, who has joined us here today, are available online with the publication of the update in the Journal of Clinical Oncology, which is linked in the show notes. So then, to dive into the content of this rapid update, Dr. Kalemkerian, what prompted this update to the Systemic Therapy for Small Cell Lung Cancer Guideline, which was previously published in 2023? Dr. Greg Kalemkerian: So even though the original guideline only came out a year ago, the past year we've seen two significant advances in small cell lung cancer with two reports, one in limited stage with the addition of immunotherapy, the other in the addition of a new immunotherapeutic agent in relapsed small cell lung cancer. Brittany Harvey: It's great to have this new data in the small cell lung cancer space. So based on these new changes, what are the updated recommendations from the expert panel? Dr. Greg Kalemkerian: So the first recommendations have to do with patients with limited-stage small cell lung cancer based on the ADRIATIC trial which added consolidation durvalumab for patients who had not had progression after standard chemotherapy and radiotherapy. And this study demonstrated a significant improvement in overall survival with about a 10% improvement in both 2- and 3-year overall survival, up to a 57% overall survival at 3 years for the patients receiving consolidation durvalumab. And based on those findings, we updated the recommendation for the standard treatment for limited-stage small cell lung cancer such that it included the use of consolidation immunotherapy with durvalumab for up to two years in patients who had had no disease progression, and completion of concurrent chemoradiotherapy for limited-stage small cell lung cancer. Of course, those patients would be those who do not have contraindications to the use of immunotherapy. As a corollary to that recommendation, for patients who have poorer performance status, so performance status of 3 or 4, who had had initial treatment perhaps with sequential chemotherapy and radiotherapy, if their performance status improves with their initial treatment, then it would also be reasonable to add consolidation immunotherapy for those patients as long as their performance status maintains improvement and they have no evidence of progression. The other update of the guidelines had to do with patients with relapsed small cell lung cancer and that was based on the DeLLphi-301 trial which was a phase II study looking at the use of tarlatamab, a bispecific T cell engager, binds to both DLL3 and CD3 in order to increase the immune killing of small cell lung cancer cells. So what this study did was it treated patients who had had at least two prior regimens. So this is third-line or beyond was what the population that this study looked at. And the majority of these patients had already had some immune checkpoint therapy. They all had good performance status and it did allow patients with brain metastases to be included in the study. When we look at the patients who received the approved 10 milligram dose of the drug, the response rate was about 40%. Responses were seen in both patients with sensitive and refractory based on the time since their prior treatment and the median duration of response was 10 months, which is much better than anything we've seen before with relapsed small cell lung cancer patients, remembering that all these patients were also third-line or beyond. So based on the results of the DeLLphi-301 trial, we updated two of the recommendations regarding relapsed small cell lung cancer. In the first one, we stated that in patients with relapsed small cell lung cancer with a chemotherapy free interval of less than 90 days, single agent systemic therapy would be considered standard of care, and that the preferred agents would include topotecan, lurbinectedin, or, now, tarlatamab. We did mention as a qualifying statement that single-agent chemotherapy is preferred over multi-agent chemotherapy. And the second recommendation was that, in patients with relapsed small cell lung cancer with a chemotherapy interval longer than 90 days, the rechallenge with a platinum-based regimen or single-agent chemotherapy was considered standard and the preferred agents for single agent therapy would be topotecan, lurbinectedin, or tarlatamab being added in the recent study. Tarlatamab was approved by the FDA for use in patients with relapsed small cell lung cancer with no stipulations with regard to the treatment. Brittany Harvey: Understood. I appreciate you describing those updated recommendations along with the supporting data for both limited stage small cell lung cancer and relapsed small cell lung cancer. So then, what should clinicians know as they implement these new and updated recommendations into practice? Dr. Greg Kalemkerian: So with regard to the ADRIATIC trial or the consolidation durvalumab being added for limite- stage small cell lung cancer patients, I think the important considerations are that this was done after patients had demonstrated no progression of disease after chemotherapy and radiotherapy, so the initial treatment does not change with platinum-etoposide plus definitive radiotherapy being recommended. The addition of durvalumab is going to be potentially useful in patients generally with good performance status, so performance statuses 0 to 1, and we still have to pay attention to the patients who may have contraindications to immunotherapy, things like interstitial lung disease, autoimmune problems that do occur in patients with small cell lung cancer where they develop paraneoplastic autoimmune syndromes such as Lambert-Eaton myasthenic syndrome. Those patients with those types of preexisting conditions would not be good candidates for immunotherapy use. So still having the tailored treatment to the individual patient is what's most important. The duration of the durvalumab was up to two years and not beyond that, so following those specific guidelines for the use of durvalumab in patients with limited-stage small cell lung cancer. With regard to tarlatamab, tarlatamab is an immunotherapy treatment. So we still do have the exclusions of people who have had prior severe immune-related adverse events, people who have pneumonitis, people who have interstitial lung disease, people with autoimmune neurologic problems we can see with small cell lung cancer, these patients should not be considered good candidates for the use of tarlatamab. The study did include patients who had had treated and asymptomatic brain metastases and there is some evidence that tarlatamab can have some control of brain metastases. So that's not necessarily an exclusion. Tarlatamab does have some other specific considerations to it in that 51% of patients had some evidence of cytokine release syndrome (CRS). Only 1% of those patients had grade 3 CRS. So even though they had frequent fevers and hypotension and hypoxia, it was generally not severe. But this concern for CRS and also for neurologic complications after treatment does require that patients be admitted to the hospital for a 24-hour observation period during the first and second doses. Subsequent to that, patients can be observed for some time after the infusion in the outpatient setting. But they also need to have very clear and strict guidance for when they go home about what things to look for. Looking for fevers, looking for shortness of breath, looking for any neurologic changes. It's a good idea for them to have a caregiver with them in order to observe them during that time. Most of these complications occur during the first or second cycles, but it is a drug that is going to require significant education not only of our staff, but also of the patients in order to ensure that the drug's used safely. Brittany Harvey: Absolutely. For these new options, it's important to tailor cancer treatment to the individual patient and the factors that you mentioned and be mindful of these potential toxicities. So, it's always great to learn of new options for patients. But in your view, how will this update impact patients with small cell lung cancer? Dr. Greg Kalemkerian: Well, clearly we need longer term follow up. So, with regard to the limited-stage small cell lung cancer situation, that's a curative situation. We have been curing patients with limited-stage disease with chemotherapy and radiotherapy for several decades now, but the cure rates were relatively low with about 25%, 30% of people becoming long term survivors. Now the hope is with the durvalumab being added on, that we can increase that number. Thus far, we have three-year survival data with a three-year survival of 57% overall survival and we're hoping that that is maintained over time and that we're not just delaying recurrences, but that we're actually preventing recurrences and helping people live longer, as has been seen with non-small cell lung cancer in stage III disease with the addition of durvalumab to chemoradiotherapy. So hopefully, we will be improving the cure rate of people with limited-stage small cell lung cancer. There are several other trials with immunotherapy in this space coming down the line and we're anxiously awaiting not only long term follow up from ADRIATIC, but also initial data from studies such as KEYLYNK and ACHILLES and NRG-LU005. So all of these studies in the next few years are hopefully going to guide treatment for limited-stage small cell lung cancer and hopefully improve the long term survival outcomes. With regard to tarlatamab, unclear at this point what the long term outcomes are going to be. Is a 40% response rate substantially better than what we've seen before? Well, lurbinectedin also had about a 40% response rate in patients who had sensitive disease, but the duration of response does look longer. And there are some patients now who have been on this study that are doing very well for quite long periods of time with the drug. So, the hope here also is that we will have some small subset of patients who continue to do better for long periods of time. Whether that'll translate into a cure or not, way too early to know, clearly hoping to add another brick in the wall so that we can keep the disease at bay, at least for a longer period of time for these patients. How we will integrate tarlatamab into the regimens is a bit unclear. Whether most of us will start using it as second-line therapy or whether we will use perhaps lurbinectedin or topotecan as second-line and tarlatamab as third-line, we're all going to have to work that out based on the potential toxicities, the logistical complications of using the drug at this point in time. But I do think that it's nice to have more options to add to our armamentarium to treat this very, very challenging and difficult disease. Brittany Harvey: Definitely. So, you've just discussed the need for both longer term follow up here along with some important ongoing trials in this space. So we'll look forward to future readouts of those trials to learn more about caring for patients in small cell lung cancer. So, I want to thank you so much for your work to rapidly update this guideline and thank you for your time today, Dr. Kalemkerian. Dr. Greg Kalemkerian: Okay. Again, thank you for the invitation, Brittany, and thanks to ASCO for developing the whole guideline structure to help all of us take better care of our patients. Brittany Harvey: Absolutely. And also thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full update, go to www.asco.org/thoracic-cancer-guidelines.  You can also find many of our guidelines and interactive resources in the free ASCO Guidelines App available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.   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.

Dr. Jeng Her, Founder and CEO of AP Biosciences, is developing T-Cube bispecific antibodies that can target cancer cells and engage T-cells to kill them more effectively and safely than existing treatments. The company is focused on treating hard-to-treat cancers such as HER2-positive breast cancer, lung cancer, head and neck cancer, and pancreatic cancer. The T-Cube bispecific antibodies use CD137 instead of CD3 to activate T-cells, which can lead to better efficacy and safety compared to other T-cell engager antibodies. Jeng explains, "So why not just take two, let's say, monospecific antibodies and then put them together and give them to the patient in the combination therapy? Instead, we wanted to develop bispecific antibodies by fusing two antibodies together into one single molecule. So what's the advantage? Eventually, what it comes down to is the therapeutic window of bispecific antibodies. This means you want your antibodies, your bispecific, to have better efficacy, better safety, and sometimes lower cost of goods since you are only expressing or producing one single drug molecule. So, the way we look at bispecific and the real advantage is not just the additive effect. It's not even the synergistic effect, which means we would like our bispecific antibodies to do something combination therapy cannot do. And that's the value of our bispecific antibodies." "Basically, we have two technology platforms. The first one is an antibody phage display library. We call it Omni-mAb. This library is a live library, which means it has more than 100 billion antibody sequences. That's a collection of the 100 billion sequences. And whatever antigen, whatever conformation of the structure of antigens you have, you could isolate a very high-affinity antibody from the library in probably 4-6 weeks."  #APBiosciences #Antibody #Biotech #Bispecific #ImmunoOncology #Cancer #SolidTumors APBioInc.com Download the transcript here

Dr. Jeng Her, Founder and CEO of AP Biosciences, is developing T-Cube bispecific antibodies that can target cancer cells and engage T-cells to kill them more effectively and safely than existing treatments. The company is focused on treating hard-to-treat cancers such as HER2-positive breast cancer, lung cancer, head and neck cancer, and pancreatic cancer. The T-Cube bispecific antibodies use CD137 instead of CD3 to activate T-cells, which can lead to better efficacy and safety compared to other T-cell engager antibodies. Jeng explains, "So why not just take two, let's say, monospecific antibodies and then put them together and give them to the patient in the combination therapy? Instead, we wanted to develop bispecific antibodies by fusing two antibodies together into one single molecule. So what's the advantage? Eventually, what it comes down to is the therapeutic window of bispecific antibodies. This means you want your antibodies, your bispecific, to have better efficacy, better safety, and sometimes lower cost of goods since you are only expressing or producing one single drug molecule. So, the way we look at bispecific and the real advantage is not just the additive effect. It's not even the synergistic effect, which means we would like our bispecific antibodies to do something combination therapy cannot do. And that's the value of our bispecific antibodies." "Basically, we have two technology platforms. The first one is an antibody phage display library. We call it Omni-mAb. This library is a live library, which means it has more than 100 billion antibody sequences. That's a collection of the 100 billion sequences. And whatever antigen, whatever conformation of the structure of antigens you have, you could isolate a very high-affinity antibody from the library in probably 4-6 weeks."  #APBiosciences #Antibody #Biotech #Bispecific #ImmunoOncology #Cancer #SolidTumors APBioInc.com Listen to the podcast here

Dr. Ryan Augustin and Dr. Jason Luke discuss neoadjuvant immunotherapy and the importance of multidisciplinary team coordination, promising new TIL therapy for advanced melanoma, and the emerging role of CD3 engagers in treatment strategies. TRANSCRIPT Dr. Ryan Augustin: Hello, I'm Dr. Ryan Augustin, your guest host of the ASCO Daily News Podcast today. I'm a medical oncology fellow at Mayo Clinic in Rochester, Minnesota. Joining me today is Dr. Jason Luke, an associate professor of medicine and the director of the Cancer Immunotherapeutic Center at the University of Pittsburgh Hillman Cancer Center. I had the privilege of working as a postdoc in Jason's translational bioinformatics lab, where we investigated mechanisms of resistance to immunotherapy in melanoma and other cancers.  Today, we'll be discussing 3 important topics, including neoadjuvant immunotherapy and the importance of multidisciplinary team coordination, the impact and practical considerations for incorporating TIL therapy into melanoma, and the current and future use of CD3 engagers in both uveal and cutaneous melanoma.  You'll find our full disclosures in the transcript of this episode.  Jason, it's great to have this opportunity to speak with you today. Dr. Jason Luke: Absolutely. Thanks, Ryan. It's great to see you. Dr. Ryan Augustin: So, to kick things off, Jason, we, of course, have seen tremendous advances in cancer immunotherapy, not only in metastatic disease but also the perioperative setting. Recent data have shown that the use of neoadjuvant therapy can provide not only critical prognostic information but can also help individualize post-resection treatment strategies and potentially even eliminate adjuvant therapy altogether in patients who achieve a pathologic, complete response. This signifies a conceptual shift in oncology with the goal of curing patients with immunotherapy. In triple-negative breast cancer, the KEYNOTE-522 regimen with pembrolizumab is standard of care. In non-small cell lung cancer, there are now four FDA approved chemo-IO regimens in both the neoadjuvant and perioperative settings. And, of course, in melanoma, starting with SWOG S1801 utilizing pembro mono therapy, and now with combined CTLA-4 PD-1 blockade based on results from the NADINA trial, neoadjuvant IO is the new standard of care in high-risk, resectable melanoma. It's important to highlight this because whereas other tumor types have more mature multidisciplinary care, for example, patients with breast cancer are reviewed by the whole team in every center, and every patient with lung cancer certainly benefits from multidisciplinary care conferences, that's not always the case with melanoma, given the relative frequency of cases compared to other tumor types.  Jason, would you say that we have now moved into an era where the integration of a multidisciplinary team and melanoma needs to be prioritized. And why is it important to have multidisciplinary team coordination from the onset of a patient's diagnosis? Dr. Jason Luke: Well, I think those are great questions, Ryan, and I think they really speak to the movement in our field and the great success that we've had integrating systemic therapy, particularly immunotherapy, into our treatment paradigms. And so, before answering your question directly, I would add even a little bit more color, which is to note that over the last few years, we've additionally seen the development of adjuvant therapy into stages of melanoma that, historically speaking, were considered low-risk, and medical oncologists might not even see the patient. To that, I'm speaking specifically about the stage 2B and 2C approvals for adjuvant anti-PD-1 with pembrolizumab or nivolumab. So this has been an emerging complication.  Classically, patients are diagnosed with melanoma by either their primary care doctor or a dermatologist. Again, classically, the next step was referral to a surgeon who had removed the primary lesion, with discussion around nodal evaluation as well. And that paradigm has really changed now, where I think integration of medical oncology input early on in the evaluation of the appropriate treatment plan for patients with melanoma is quite a pressing issue now, both because we have FDA approvals for therapeutics that can reduce risk of recurrence, and whether or not to pursue those makes a big difference to the patient for discussion early on.  And, moreover, the use of systemic therapies now, prior to surgery, of course, then, of course, requires the involvement of medical oncology. And just for an emphasis point on this, it's classically the case, for good reason, that surgeons complete their surgery and then feel confident to tell the patient, “Well, we got it all, and you're just in really good shape.” And while I understand where that's coming from, that often leaves aside the risk of recurrence. So you can have the most perfect surgery in the world and yet still be at very high risk of recurrence. And so it's commonly the case that we get patients referred to us after surgery who think they're just in totally good shape, quite surprised to find out that, in fact, they might have a 20% to 50% risk of recurrence. And so that's where this multidisciplinary integration for patient management really does make a big difference.  And so I would really emphasize the point you were making before, which is that we need multidisciplinary teams of med onc with derm, with surgery early on, to discuss “What are the treatment plans going to be for patients?” And that's true for neoadjuvant therapy, so, for palpable stage 3, where we might give checkpoint inhibitors or combinations before surgery. But it's true even in any reasonably high-risk melanoma, and I would argue in that state, anything more than stage 1 should be discussed as a group, because that communication strategy with the patient is so important from first principles, so that they have an expectation of what it's going to look like as they are followed out over time. And so we're emphasizing this point because I think it's mostly the case at most hospitals that there isn't a cutaneous oncology disease management meeting, and I think there needs to be.  It's important to point out that usually the surgeons that do this kind of surgery are actually either the GI surgeons who do colon cancer or the breast surgeons. And so, given that melanoma, it's not the most common kind of cancer, it could easily be integrated into the existing disease review groups to review these cases. And I think that's the point we really want to emphasize now. I think we're not going to belabor the data so much, but there are enormous advantages to either perioperative or adjuvant systemic therapy in melanoma. We're talking about risk reduction of more than 50%, 50-75% risk reduction. It's essential that we make sure we optimally offer that to patients. And, of course, patients will choose what they think is best for their care. But we need to message to them in a way that they can understand what the risks and benefits of those treatments are and then are well set up to understand what that treatment might look like and what their expectations would be out over time.  So I think this is a great art of medicine place to start. Instead of belaboring just the details of the trial to say, let's think about how we take care of our patients and how we communicate with them on first principles so that we can make the most out of the treatments that we do have available. Dr. Ryan Augustin: That's great, Jason. Very insightful points. Thank you.  So, shifting gears now, I'd also like to ask you a little bit about TIL therapy in melanoma. So our listeners will be aware that TIL is a promising new approach for treating advanced melanoma and leverages the power of a patient's cytotoxic T cells to attack cancer cells. While we've known about the potential of this therapy for some time, based on pioneering work at the NCI, this therapy is now FDA approved under the brand AMTAGVI (Lifileucel) from Iovance Biotherapeutics, making it the first cellular therapy to be approved for a solid tumor. Now, I know TIL therapy has been administered at your institution, Jason, for several years now, under trial status primarily for uveal melanoma using an in-house processing. But for many cancer centers, the only experience with cellular therapy has come under the domain of malignant hematology with CAR T administration. At our institution, for example, we have only recently started administering TIL therapy for melanoma, which has required a tremendous multidisciplinary effort among outpatient oncology, critical care, and an inpatient hematology service that has expertise in cytokine release syndrome.  Jason, where do you see TIL therapy fitting into the metastatic space? Which patients do you think are truly candidates for this intensive therapy? And what other practical or logistical considerations do you think we should keep in mind moving forward? Dr. Jason Luke: Well, thanks for raising this. I think the approval of lifileucel, which is the scientific name for the TIL product that's on the market now. It really is a shift, a landscape shift in oncology, and we're starting in melanoma again, as seems to be commonly the case in drug development. But it's really important to understand that this is a conceptually different kind of treatment, and therefore, it does require different considerations. Starting first with data and then actualization, maybe secondarily, when we see across the accelerated approval package that led to this being available, we quote patients that the response rate is likely in the range of 30%, maybe slightly lower than that, but a meaningful 25% to 30% response rate, and that most of those patients that do have response, it seems to be quite durable, meaning patients have been followed up to four years, and almost all the responders are still in response. And that's a really powerful thing to be able to tell a patient, particularly if the patient has already proceeded through multiple lines of prior standard therapy. So this is a very, very promising therapy.  Now, it is a complicated therapy as well. And so you highlighted that to do this, you have to have a tumor that's amenable for resection, a multidisciplinary team that has done a surgery to remove the tumor, sent it off to the company. They then need to process the TIL out of the tumor and then build them up into a personalized cell product, bring it back, you have to lympho-deplete the patient, re-introduce this TIL. So this is a process that, in the standard of care setting under best circumstances, takes roughly six weeks. So how to get that done in a timely fashion, I think, is evolving within our paradigms. But I think it is very important for people who practice in settings where this isn't already available to realize that referring patients for this should be a strong consideration. And thinking about how you could build your multidisciplinary team in a way to be able to facilitate this process, I think is going to be important, because this concept of TIL is relevant to other solid tumors as well. It's not approved yet in others, but we kind of assume eventually it probably will be. And so I think, thinking through this, how could it work, how do you refer patients is very important.  Now, coming back to the science, who should we treat with this? Well, of course, it's now an air quotes “standard of care option”, so really it ought to be available to anybody. I will note that currently, the capacity across the country to make these products is not really adequate to treat all the patients that we'd want. But who would we optimally want to treat, of course, would be people who have retained a good performance status after first line therapy, people who have tumors that are easily removable and who have not manifested a really rapid disease progression course, because then, of course, that six-week timeline probably doesn't make sense. The other really interesting data point out of the clinical trials so far is it has looked like the patients who got the least amount of benefit from anti-PD-1 immunotherapy, in other words, who progressed immediately without any kind of sustained response, those patients seem to have the best response to TILs, and that's actually sort of a great biomarker. So, this drug works the best for the population of patients where checkpoint inhibitors were not effective. And so as you think about who those patients might be in your practice, as you're listening, I think prioritizing it for primary progression on anti PD-1, again and giving it ahead thought about how would you get the patient through this process or referred to this process very quickly is really important because that lag time is a problem. Patients who have melanoma tend to progress reasonably quickly, and six weeks can be a long time in melanoma land. So, thinking ahead and building those processes is going to be important moving into the future Dr. Ryan Augustin: Definitely appreciate those practical considerations. Jason, thank you.  Moving on to our final topic, I was hoping to discuss the use of immune cell engagers in melanoma. So, similar to CAR T therapy, bispecific T-cell engagers, or BiTEs, as they're commonly known, are standard of care in refractory myeloma and lymphoma. But these antibodies engaging CD-3 on T cells and a tumor specific antigen on cancer cells are relatively new in the solid tumor space. Tarlatamab, which is a DLL-3 and CD-3 bispecific antibody, was recently approved in refractory small cell lung cancer, and, of course, tebentafusp, an HLA-directed CD-3 T cell engager was approved in uveal melanoma in 2022. Both T and NK cell engaging therapies are now offering hope in cancers where there has historically been little to offer. However, similar to our discussion with TIL therapy, bispecifics can lead to CRS and neurotoxicity, which require considerable logistical support and care coordination.  Jason, I was wondering if you could briefly discuss the current landscape of immune cell engagers in melanoma and how soon we may see these therapies enter the treatment paradigm for cutaneous disease. Dr. Jason Luke: I think it is an exciting, novel treatment strategy that I think we will only see emerge more and more. You alluded to the approval of tebentafusp in uveal melanoma, and those trials were, over the course of a decade, where those of us in solid tumor land learned how to manage cytokine release syndrome or the impact of these C3 bispecifics, in a way that we weren't used to. And what I'll caution people is that CRS, as this term, it sounds very scary because people have heard of patients that, of course, had difficult outcomes and hematological malignancies, but it's a spectrum of side effects. And so, when we think about tebentafusp, which is the approved molecule, really what we see is a lot of rash because GP100, the other tumor antigen target, is in the skin. So, patients get a rash, and then people do get fevers, but it's pretty rare to get more than that. So really what you have to have is the capacity to monitor patients for 12 hours, but it's really not more scary than that. So it really just requires treating a few people to kind of get used to these kinds of symptoms, because they're not the full-on ICU level CRS that we see with, say, CAR T-cells.  But where is the field going? Well, there's a second CD3 bispecific called brenetafusp that targets the molecule PRAME, that's in a phase 3 clinical trial now for frontline cutaneous melanoma. And tebentafusp is also being evaluated in cutaneous melanoma for refractory disease. So, it's very possible that these could be very commonly used for cutaneous melanoma, moving into, say, a two-to-four-year time horizon. And so therefore, getting used to what are these side effects, how do you manage them in an ambulatory practice for solid tumor, etc., is going to be something everyone's going to have to learn how to deal with, but I don't think it should be something that people should be afraid of.  One thing that we've seen with these molecules so far is that their kinetics of treatment effect do look slightly different than what we see with more classic oncology therapies. These drugs have a long-term benefit but doesn't always manifest as disease regression. So, we commonly see patients will have stable disease, meaning their tumor stops growing, but we don't see that it shrank a lot, but that can turn into a very meaningful long-term benefit. So that's something that we're also, as a community, going to have to get used to. It may not be the case we see tumors shrink dramatically upfront, but rather we can actually follow people with good quality- of-life over a longer period of time.  Where is the field going? You mentioned tarlatamab in small cell lung cancer, and I think we're only going to see more of these as appropriate tumor antigens are identified in different tumors. And then the other piece is these CD3 engagers generally rely upon some kind of engagement with a T cell, whether CD3 engagers, and so they can be TCR or T-cell receptor-based therapies, although they can be also SCFV-based. But that then requires new biomarkers, because TCR therapy requires HLA restriction. So, understanding that now we're going to need to profile patients based on their germline in addition to the genomics of the tumor. And those two things are separate. But I would argue at this point, basically everybody with cutaneous melanoma should be being profiled for HLA-A(*)0201, which is the major T-cell receptor HLA haplotype that we would be looking for, because whether or not you can get access immediately to tebentafusp, but therefore clinical trials will become more and more important.  Finally, in that T-cell receptor vein, there are also T cell receptor-transduced T cells, which are also becoming of relevance in the oncology community and people listening will be aware in synovial sarcoma of the first approval for a TCR-transduced T cell with afamitresgene autoleucel. And in melanoma, we similarly have TCR-transduced T cells that are coming forward in clinical trials into phase 3, the IMA203 PRAME-directed molecule particularly. And leveraging our prior conversation about TILs, we're going to have more and more cellular based therapies coming forward, which is going to make it important to understand what are the biomarkers that go with those, what are the side effect profiles of these, and how do you build your practice in a way that you can optimally get your patients access to all of these different treatments, because it will become more logistically complicated, kind of as more of these therapies come online over the next, like we said, two to four years kind of time horizon. So, it's very exciting, but there is more to do, both logistically and scientifically. Dr. Ryan Augustin: That's excellent. Thanks, Jason, and thank you so much for sharing your great insight with us today on the ASCO Daily News Podcast. Dr. Jason Luke: Thanks so much for the opportunity. Dr. Ryan Augustin: And thank you to our listeners for your time today. You will find links to the abstracts discussed today in the transcript of this episode, and you can follow Dr. Luke on X, formerly known as Twitter, @jasonlukemd. And you can find me, @RyanAugustinMD. 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: @ryanaugustinmd Dr. Jason Luke @jasonlukemd   Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn   Disclosures: Dr. Ryan Augustin: No relationships to disclose 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

RINO GOP Mayor Heather Graham endorses the Democrat in tight CD3 race.... aided and abetted by CO's RNC Committee woman fellow traitor RINO Christy Fidura.  

Guest, Donna Walter VIDEO: 1. Carville This is why we can never trust a RINO - Pueblo Republican Mayor Heather Graham endorses the Democrat candidate in CD3. Talk about a traitor! Plus Donna Walter, a great GOP candidate in Colorado's House District 52 joins the show.

UTAH US SENATE RACE Congressman John Curtis currently representing Utah's CD3 is the Republican Candidate for US Senate. Curtis serves on the Energy and Commerce Committee including as Vice-Chair of the Energy, Climate and Grid Security Subcommittee and a member of the Communications & Technology Subcommittee. Heidi Hatch interviewed the candidate on October 22, 2024, two weeks before the Election EconomyClean energyDebt: $35 trillionUkraine/Israel FundingImmigration and Border Issues Continuing Resolution VoteSocial Security solvencyHome Ownership, Mortgage, and Equity Savings (HOMES) Utah U.S. Senate Candidates Caroline Gleich Democrat https://www.carolineforutah.com/aboutJohn Curtis Republican https://www.johncurtis.org/Carlton Bowen Independent https://www.carlton4ussenate.com/Utah voter information https://vote.utah.gov/See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Kamala dances and sings to her favorite song and things get a little wild when discussing whether or not the government should pay for contraceptives. We also visit with CD3 candidate, Dr. Bob Onder, during his visit to the southern border.

We announce the sequel to our original Presidential Debate watch party at Lakeside Ashland. Stephanie and Randy discuss whether or not a candidate's residence within a district matters to voters, especially in CD3.

Send us a Text Message.In this episode of DigiPath Digest, broadcasting from Poland,  we delve into advances in digital pathology, including AI applications in bone marrow evaluation, classification of hematology cells, and the use of synthetic images for data augmentation. Additionally, we review a survey on pathologists' perceptions of ChatGPT and consider the feasibility of GANs for enhancing medical image analysis.00:00 Welcome and Troubleshooting from Poland00:21 Live Stream Challenges and Conference Details02:21 Digital Pathology Podcast Introduction02:51 Technical Difficulties and Audience Interaction06:18 Exploring Digital Pathology Papers06:43 Advances in Bone Marrow Evaluation09:03 AI in Hematology and Pathology12:28 Colorectal Cancer Prognostication19:34 Pan-Cancer Xenograft Repository25:16 ChatGPT and Pathology Survey30:55 Synthetic Image Generation in Pathology36:35 Upcoming Conferences and Courses42:27 Closing Remarks and Future PlansTHE ABSTRACTS WE COVERED TODAY

We're joined by David Wasinger and Dr. Bob Onder, the winners of the Lieutenant Governor and CD3 primaries.

Bob Thorpe joins me for the first part of the show and we hit on the DOW getting destroyed today, the economic uncertainty, who will be Harris VP pick, I guess the Shapiro from PA (she needs those electoral votes). We also hit on a crazy 9th Circuit ruling that disallows use of ID to vote in AZ. CD3 in souther AZ is too close to call and AZ could get a REALY left member of Congress. Plus Curtis Moore of Energy Fuels talks about a controversy that's developed over transport of uranium ore through the Navajo Nation.    Previous interview with Curtis Moore HERE.  https://youtu.be/5wQ_OhRK7xU?si=bdwFrEJxxZAbvQBh   —————————————— Please FOLLOW or SUBSCRIBE to the Jeff Oravits Show! RUMBLE   YouTube   ApplePodCasts   AmazonMusic   Spotify        Also on Twitter and www.TalkWithJeff.com   Disclaimer: The information provided on the Jeff Oravits Show does not constitute legal, medical, financial or tax advice.  All information is the opinions of the host's and his guests.  You should always seek the advice of a professional regarding any of these complex issues to make sure all circumstances of your situation are properly considered.   ——————————————

Outside money is pouring into one Democratic primary race, and it's not from the usual suspects. We'll hear how a pro-cryptocurrency PAC is ramping up the pressure in CD3. Plus, a Deep Dive conversation with an advocate whose history of drug use led her to work to prevent overdoses. That and more on The Show.

We catch up with CD3 candidate, Kurt Schaefer and his progress on the campaign trail. Jacob Schelp, who would have been on the list of delegates for the RNC had the convention not overturned their decision on the delegates, joins us.

Missouri Politico Chris Arps discusses the big Trump endorsement received by one of the candidates in the CD3 race. Looking at Hurricane Beryl's impacts on Mid-Missouri.

Former military special operations officer Jeff Niklaus joins the program to discuss his experiences in Afghanistan and Iraq. He shares his experience which inspired the Black Hawk Down movie and the real life scenario they found themselves part of. He also explains his time as a special operations officer working to end the poppy production in Afghanistan. What really happened behind the scenes. Finally we discuss current operations and how you can identify them, develop situational awareness and be more able to protect you and your family.You can learn more about his products at https://www.complianttechnologies.net/

The Chuck & Julie Show with Chuck Bonniwell and Julie Hayden With Guest, Lori Saine Establishment Republicans launch attack ads full of lies against grassroots candidates Ron Hanks in CD3 and Lori Saine in Weld County. Lori joins the show to set the record straight. Plus will the media's ridiculous attempts to call the Biden gaffe tapes “cheap fakes” backfire?

  An unexpected rallying point during the Cd3 debate was unanimous nuclear power support from all of the candidates. Dave and Debbie get into the bigger discussion of nuclear power and if there is concern with moving in that direction, followed by listener calls.  

Mike Ferguson in the Morning 06-04-24 Former Missouri Congressional candidate Brandon Wilkinson talks about his exit from the CD3 race and his endorsement of Dr. Bob Onder. (@brawil86) NewsTalkSTL website: https://newstalkstl.com/ Rumble: https://rumble.com/c/NewsTalkSTL Twitter/X: https://twitter.com/NewstalkSTL Livestream 24/7: http://bit.ly/newstalkstlstreamSee omnystudio.com/listener for privacy information.

https://youtube.com/live/YyKsnl_D6Ps?feature=share The Police are set to release a 6CD super deluxe edition of their acclaimed 1983 album, Synchronicity. This extensive reissue includes a wealth of previously unheard alternate takes, outtakes, and demos. As their fifth and final studio album, Synchronicity features hit singles such as "Every Breath You Take," "Wrapped Around Your Finger," "King of Pain," and "Synchronicity II." The album has sold 15 million copies globally, with 8.5 million in the USA alone. This reissue project, which took three years to complete, was created with the band's involvement and endorsement. It includes a 60-page hardcover book with comprehensive new sleeve notes by music journalist Jason Draper, detailing the album's creation and history. The box set contains: CD1: The original album, including "Murder By Numbers," remastered from the original tapes. CD2: 18 tracks featuring all original 7" / 12" B-sides plus 11 exclusive non-album bonus tracks, available on CD for the first time. CD3 and CD4: Previously unreleased alternate takes of all the Synchronicity songs. CD4 also includes unreleased Police tracks, such as an early version of Andy Summers' "Goodbye Tomorrow" (later renamed "Someone To Talk To"), a demo of Stewart Copeland's "I'm Blind" (later "Brothers on Wheels" for the Rumble Fish soundtrack), a first take of "Truth Hits Everybody," and rare covers of Eddie Cochran's "Three Steps To Heaven" and Chuck Berry's "Rock and Roll Music." CD5 and CD6: 19 previously unreleased live recordings from the September 10, 1983, concert at the Oakland-Alameda Coliseum, USA. The 6CD box also includes four art prints. Additional formats include a 2CD set (repeating the first two discs of the super deluxe edition), a 4LP vinyl edition (42 tracks), and a vinyl picture disc with a revised track order. #thepolice #Synchronicity #sting #stewartcopeland #andysummers #johnnybeaneTV

The jury is deliberating in the Trump New York trial.  We do our best to read the jury tea leaves.  Plus who is behind the bizarre attack ad against CD3 candidate Ron Hanks?

Dr. Diwakar Davar and Dr. Jason Luke discuss key abstracts from the 2024 ASCO Annual Meeting that explore triplet therapy in advanced melanoma, TIL cell therapy in immune checkpoint inhibitor–naive patients, and other novel approaches that could shape the future of immunotherapy in melanoma and beyond.  TRANSCRIPT Dr. Diwakar Davar: Hello and welcome to the ASCO Daily News Podcast. I am your guest host, Dr. Diwakar Davar. 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. I'm delighted to have my friend and colleague, Dr. Jason Luke, on the podcast today to discuss key abstracts in melanoma and immunotherapy that will be featured and highlighted at the 2024 ASCO Annual Meeting. Dr. Luke is an associate professor of medicine, the director of the Cancer Immunotherapeutic Center, as well as the associate director for clinical research at the University of Pittsburgh's Hillman Cancer Center.  You will find our full disclosures in the transcript of this episode.  Jason, as always, it's a pleasure to have you on this podcast to hear your key insights on trials in the immunotherapy space and melanoma development paradigm, and to have you back on this podcast to highlight some of this work.  Dr. Jason Luke: Thanks so much for the opportunity to participate. I always enjoy this heading into ASCO.  Dr. Diwakar Davar: We're going to go ahead and talk about three abstracts in the melanoma space, and we will be starting with Abstract 9504. Abstract 9504 essentially is the RELATIVITY-048 study. It describes the efficacy and safety of the triplet nivolumab, relatlimab, and ipilimumab regimen in advanced PD-1 naive melanoma. So in this abstract highlighted by Dr. Ascierto and colleagues, they report on the results of this phase 2 trial in this setting. By way of background, PD-1 inhibitors and immune checkpoint inhibitors starting in PD-1 and CTLA-4, as well as PD-1 and LAG-3, are all FDA-approved on the basis of several pivotal phase 3 trials, including KEYNOTE-006, CheckMate-066, CheckMate-067, and most recently, RELATIVITY-047. Jason, can you briefly summarize for this audience what we know about each of these drugs, at least the two combinations that we have at this time?  Dr. Jason Luke: For sure. And of course, these anti PD-1 agents, became a backbone in oncology and in melanoma dating back to more than 10 years ago now, that response rates in the treatment-naive setting to anti PD-1 with either pembrolizumab or nivolumab are roughly in the range of mid-30s to high-40s. And we've seen clinical trials adding on second agents. You alluded to them with the seminal study being CheckMate-067, where we combined a PD-1 antibody and CTLA-4 antibody or nivo + ipi. And there the response rate was increased to approximately 56%. And more recently, we have data combining PD-1 inhibitors with anti-LAG-3. So that's nivolumab and relatlimab. Now, in that trial, RELATIVITY-047, the overall response rate was described as 43%. And so that sounds, on a first pass, like a lower number, of course, than what we heard for nivolumab and ipilimumab. We have to be cautious, however, that the cross-trial comparison between those studies is somewhat fraught due to different patient populations and different study design. So I think most of us think that the response rate or the long-term outcomes between PD-1, CTLA-4, and PD-1 LAG-3 are probably roughly similar, albeit that, of course, we have much better or much longer follow up for the nivo + ipi combo.  The one other caveat to this, of course then, is that the side effect profile of these two combinations is distinct, where the incidence of high-grade immune-related adverse events is going to be roughly half with nivolumab and relatlimab, a combination of what you would see with the nivolumab and ipilimumab. So that has caused a lot of us to try to think about where we would use these different combinations. But we do see that all of these treatments can land a durable long-term response in the subset of patients that do have an initial treatment benefit. The landmark, I think, for the field has been the 7-and-a-half-year median overall survival that we've seen with PD-1 plus CTLA-4, nivo + ipi; of course, we don't have such long-term follow up for PD-1 and LAG-3. But I think that's the setting for thinking about the rationale for combining a triplet regimen of PD-1, CTLA-4, and LAG-3. Dr. Diwakar Davar: So, Jason, in your mind, given the difference in the disparity and durability of the responses for the 067 regimen of nivo-ipi, and the RELATIVITY-047 regiment of nivo-rela, what is the standard of care in the U.S., and how does it change in the rest of the world, knowing that nivo-rela is not necessarily approved in all jurisdictions? Dr. Jason Luke: So this is a major complication in our field, is that there is perhaps not complete agreement across the world in terms of what the frontline standard of care should be. I think most United States investigators, or those of us that really treat melanoma most of the time, would suggest that a combination regimen, given the enhanced response rate and longer-term outcomes, should be the consideration for the majority of patients. In fact, in my practice, it's hard to think of who I would treat with a monotherapy PD-1 approach in the PD-1 naive setting. So either nivo + ipi or nivo + rela. As you alluded to however, in other regulatory settings throughout the world, combinations might not actually even be approved at this point. So PD-1 monotherapy would be the backbone of that setting. It does set up some complications when you think about a comparator arm; say you were going to look at various combinations, probably PD-1 monotherapy would be the worldwide comparator. You have to understand though, in the United States, I think that that's a less attractive option. Dr. Diwakar Davar: So in RELATIVITY-047, Dr. Ascierto and his colleagues are looking at generating a triplet. And in this case, they looked at this in the context of frontline metastatic melanoma, 46 patients. Very interestingly, the dose of ipilimumab studied here was 1 mg/kg through 8 weeks, not the 3 mg/kg every three weeks times four doses using 067, or even the low dose ipilimumab regimen that you studied in the second line setting, which was 1 mg/kg every 3 weeks for 4 doses. So let's talk about the results and specifically the implications of potentially studying lower doses of ipi. Dr. Jason Luke: I appreciate you raising that point. I think it's really important as we think about this dataset because this triplet regimen is not by any means the only version of a triplet that could be developed using these agents. So just to give the high-level numbers from the abstract, we see from these data that the overall response rate is described as 59% and 78%, a disease control rate with patients having an unreached link. So duration of response of unreached, and then the progression-free survival at about 5 months. So those are really interesting data. But as was alluded to, it's not totally clear to me that that's the best that we could do with this regimen.   Now, you alluded to this low-dose ipilimumab schedule at 1 mg/kg every 8 weeks, and it's really important to note that we have no benchmark for that regimen in melanoma oncology. And in fact, the one study that used that regimen, which was the adjuvant study of nivolumab and ipilimumab, known as CheckMate915, is in fact the only immune checkpoint inhibitor study in melanoma oncology that was actually negative. That study noted no benefit to adding ipilimumab at 1 mg/kg every 8 weeks on top of nivolumab, again, the adjuvant setting. So it's a little bit curious to then understand what it means in this study to have that amount of ipilimumab added to the rela-nivo backbone. And that manifests in a few different ways. We see the response rate here at 59%. Again, if you compare that just against the standard nivo + ipi dosing schedule, it's about the same. So is that really an advantage to having the triplet as compared to just doing standard nivo + ipi?   We do see that it manifests in a slightly lower rate of grade 3/4 immune-related adverse events, at 39%. That's a little bit lower than what we'd expect for standard nivo + ipi. But again, I think that that emphasizes to me the possibility that some efficacy was left on the table by using this very low dose ipilimumab regimen. I think that's really a concern. It's not clear to me that these triplet data really differentiate from what we'd expect with the already approved regimen of nivo + ipi. Therefore, it makes it difficult to think about how would we really want to move this regimen forward, or should there be more work done about dose and schedule to optimize how we might want to do this?  Dr. Diwakar Davar: As far as triplet therapy in the context of frontline metastatic melanoma, meaning triplet immune therapy, because there are at least several targeted therapy triplets that are FDA-approved, [but] not necessarily widely utilized. How would you summarize the future for triplet therapy? Do you think it's potentially attractive? Do you think it's very attractive with some caveats? Dr. Jason Luke: Well, I think it's attractive, and we have 3 independently active agents. And so I do think it's a priority for the field to try to figure out how we could optimize the therapy. We've had such a revolution in melanoma oncology, talking about 7.5-year median survival from CheckMate-067, but that still implies that 7.5 years, half the patients have passed away. There's more to do here. And so I do think it should be a priority to sort this out. I guess I would be cautious, though, about advancing this regimen directly to a phase 3 trial because it doesn't seem clear to me that this is optimized in terms of what the outcome could be. If we're willing to tolerate higher rates of toxicity from other dose schedules of nivo-ipi alone, then I think we should do a little bit more here to potentially explore the space that might be possible to increase that overall response rate a little more without getting into a completely exaggerated toxicity profile that would be unacceptable. So, I do think it's exciting, but there's possibly more to do before really think about going big time with this. Dr. Diwakar Davar: Great. So now we'll switch gears and move from frontline metastatic melanoma to the second line and beyond looking at a new agent and contextualizing the effects of that actually in the frontline settings. So Abstract 9505 describes the efficacy and safety of lifileucel, which is essentially autologous tumor-infiltrating lymphocyte cell therapies, also known as TIL, in combination with pembrolizumab in patients with ICI naive, so not necessarily pretreated, but ICI naive metastatic or unresectable melanoma. This is data from the IOV-COM-202 Cohort 1A oral abstract presented by Dr. Thomas and colleagues. In this abstract, Dr. Thomas and colleagues are presenting data from the 1A cohort, which is the phase 2 portion of the frontline trial that is evaluating autologous TIL with pembro in checkpoint inhibited naive metastatic melanoma.  By way of background, TIL is FDA approved on the basis of several cohorts from a phase 2 trial. The data has been presented multiple times now by Drs. Sarli, Chesney, and multiple colleagues of ours. And essentially autologous TIL, which is generated from a surgical procedure in which a patient undergoes a surgery to extract a tumor from which T cells are then grown after ex vivo expansion and rapid expansion protocol. The entire procedure was essentially pioneered by several colleagues at the NCI, primarily Dr. Steve Rosenberg, and this approach produces objective response rates of approximately 31% to 36%. And the most recent publication demonstrated that at median follow up of approximately 2 years, the median duration of response was not reached. The median OS was about 14 months and PFS was about 4 months or so. So, can you contextualize the results of the abstract in the frontline setting? And then we'll talk a little bit about where we think this is going to go. Dr. Jason Luke: So I think this is a timely study given the recent approval. And in the abstract presented here, we see an early data cut from the PD-1 naive study, as you alluded to. So here we had 22 patients and distributed across various states of advanced melanoma. Ten out of the 22 had M1C, but there also were smatterings of earlier M1A and M1B at 18.2% and 9.1%. So this is important, as we think who the treatment population is that's going to be optimized with a TIL procedure. The median sum of diameters, meaning how much tumor burden the patients have, was about 5.5cm, and I'll note that that's a relatively modest amount of tumor burden, albeit not that unusual for an early-stage trial. So of the patients that participated, 8 had BRAF mutations so that's 36%. That's not that high, but it's reasonable. And I think the important overlying number, the response rate so far in the study, with about 17 months of follow up, was 63.6%, and that includes 22% or 23% having complete response. So those are interesting data.  And another point that was made in the abstract, which we've all seen, is that responses to TIL, all of immunotherapy but especially TIL, do seem to mature over time, meaning they deepen over time. So it's possible the response rate could go up some extent as we watch this study advance. So I think these are exciting data on some level. Also, a 63.6% response rate sounds pretty impressive, but we do have to put that in the context of a double checkpoint blockade, which we just got done discussing, gives you almost a 60% response rate, 59% response rate. So then the question really is: Is it worth the amount of effort that we could go into generating a TIL product in a treatment naive patient, and put them through the lymphodepletion that is associated with TIL and the high dose interleukin 2 treatment that accompanies the reinfusion of the TIL, if you're going to get a response rate that's roughly the same as what you would get if you gave them off the shelf nivo plus ipilimumab?  At this point it's a little bit hard to know the answer to that question. I think it could be possible that the answer is yes, because we don't know exactly which populations or patients are most likely to benefit from each of these therapies. And if it could be teased out who's not going to benefit to nivo + ipi from the get-go, then of course, we would want to offer them a therapy that has that frontline potential, durable, long-term response. But I have to say, on a one-to-one with TIL therapy, you get a lot of toxicity initially with the treatment; with nivo + ipi on the back end, you get a fair amount of toxicity with the treatment. How are we going to judge those two things? And I think we probably need a larger dataset to really have a good handle on that.  So these are interesting early data, but it's not totally clear to me that even if this holds up all the way through the trial, and we're going to talk about the design of the registration trial here in a second, a 60% response rate on its own without further biomarker stratification is a little bit hard for me to see in clinical practice why we would want to do that, given we can already just go off the shelf and give checkpoint inhibitors. Dr. Diwakar Davar: So that brings us to TILVANCE-301. So TILVANCE is a phase 3 trial. It's a registration intent trial by our Iovance colleagues evaluating the pembro-TIL regimen versus pembrolizumab alone. So in this phase 3 trial, approximately 670 patients will be randomized to either arm A, which is lifileucel + pembro. And in this arm A, patients are going to be getting lifileucel with the tumor resection, non-myeloablative lymphoid depletion, the lifileucel and abbreviated course of high-dose IL-2, and thereafter, continued pembro for the study mandated duration versus arm B, where patients will be getting just pembrolizumab monotherapy per label. Arm B patients, per the design, may cross over to receive TIL monotherapy at the time of central-blinded, radiology-confirmed disease progression.   The study design otherwise is fairly routine and, per most of our registration trials these days, patients have actually been permitted to receive neoadjuvant and adjuvant therapy, including checkpoint inhibitors, as long as the receipt of the therapy was more than 6 months prior to the inclusion of the patient in that registration trial. The dual primary efficacy endpoints as stated are BICR-assessed objective response rate as well as PFS, and the key secondary endpoint is overall survival.   So Jason, what are your thoughts on the study design and potentially the regulatory implications, particularly given, one, the control arm of pembro monotherapy, and two, the role of TIL crossover to receive TIL monotherapy at the time of BICR mandated progression for arm B? Dr. Jason Luke: So this goes to a few points that we've touched on already in the discussion here. When we think about the primary endpoints for this study, with one of them being overall response rate, one has to assume that that's a given that they would get that. I feel like that's a low bar. And we go back to that cross-trial comparison. If their results end up being that the response rates are about 60%, I don't know that that differentiates necessarily from what's already available in the field with combination immune checkpoint blockade. For the purposes of the study that would mean it's a positive study, so I think that would probably be good. But again, the comparator to pembrolizumab monotherapy, I think some of us would argue, isn't really consistent with what we would do with a patient in our clinic. So it's not that it's bad per se, but I think there's going to be a whole lot of cross-trial comparison. So if the study is positive, that would be good for getting the drug available. It's still a bit hard though, based on the preliminary data that I've seen, to imagine how this would have uptake in terms of utilization as a frontline therapy.  You alluded to the crossover, and I think there, the assumption is that patients who get TIL therapy as a second line perhaps would have an attenuated benefit. But I'm not sure that's really true. It certainly looks from the data that we have, like the patients who benefit most from TIL are going to be those who didn't respond to anti PD-1 in the front line. So I'm not sure how much difference there's going to be between first- and second-line TIL therapy, but those data will kind of wait to be seen. So I think it's an important study. Of course, the accelerated approval of TIL as a later line therapy is dependent on this trial being positive. So there is some risk that if this trial ended up not being positive, that that could have regulatory implications on the utility or availability of TILs, a subsequent line therapy. But all of these, I guess we'll have to wait to see the results. We do hope for a positive trial here, although I think it'll be nuanced to sort of interpret those data given that pembrolizumab monotherapy control arm.  Dr. Diwakar Davar: Fantastic. So we've learned a lot about TIL, both its use in the second-line setting and this very exciting but potentially risky frontline trial that is ongoing at some centers in the United States and certainly a lot of ex-U.S. enrollment.   So we'll now pivot to a related product which actually belongs to a much larger class of agents that are antigen specific T-cell therapies in a variety of different formats. And that is Abstract 9507, which is the “Phase 1 safety and efficacy of IMC-F106C, a PRAME × CD3 ImmTAC bispecific, in post-checkpoint cutaneous melanoma (CM).” Now, in this abstract, Dr. Omid Hamid and colleagues reported the results of this phase 1 trial. As a disclosure, I'm an investigator and the last author on this manuscript. Jason, it would be important for our audience, for us to maybe firstly, outline the PRAME as a target, and then the ImmTAC as a platform prior to discussing these results. So let's start with the target PRAME, which I think is a target that you know well. So why don't you start with the target and we'll talk a little bit about that and then the platform? Dr. Jason Luke: Yeah, so I think for the audience, being aware of PRAME, or the Preferentially Expressed Antigen in Melanoma, is going to be quite important moving into the future. So PRAME as a therapeutic target is a cancer testis antigen that's overexpressed in tumor tissues. And of course the name has melanoma in it, but it's not uniquely present in melanoma. So the expression patterns of PRAME as a target are very high in melanoma. So in cutaneous disease, this is upwards of almost 100%, somewhere between 95% and 100%, in metastatic melanoma tissues. And PRAME has several different roles on a molecular level, although I don't think for our purposes here, it's so much important to be aware of them, but rather that this is a very highly expressed target, which then can make it attractive for using T cell receptor-based therapies. And so in the case we're talking about here on the ImmTAC platform, that's a CD3 PRAME×CD3 bispecific approach. But of course there are other approaches that can also be taken, such as TCR T cells that directly go after PRAME itself. Dr. Diwakar Davar: Let's now talk about the platform and how it differs from some of the other antigen targeting platforms that you have just alluded to. I think the Immtac platform is basically a fusion protein comprising engineered TCRs with a CD3 specific short chain variable fragment. And then the engineered TCR therefore binds antigens in an HLA dependent fashion. But you know quite a lot about some of these alternative platforms, and I think it'll be important to contextualize for the audience the difference between ImmTAC, which is a prototype drug that is already approved in the context of tebentafusp. But how does this differ from some of the other more nuanced platforms, such as the Immatics TCR or TCR platform and TScan TCRT nanoplasmonic platform.  Dr. Jason Luke: Right. So the ImmTAC platform as alluded to is already approved on the market with tebentafusp, which is the gp100-CD3 bispecific molecule. And the advantage of that approach is infusion off the shelf of a drug. The downside of it is that it is a weekly dosing strategy as it stands now. And there are some complicated disease kinetics associated with treatment response, which we'll come back to in the context of the PRAME bispecific. Those are, in contrast with T-cell receptor-transduced T cells, as an alternative strategy, which is a form of adopted cell transfer. So we just got done talking about TIL therapy, which of course, is trying to take lymphocytes out of the tumor and grow them up and then give them back. Here with TCR-transduced T cells, we're talking about taking leukopak from the blood and then using different transfection approaches to try to insert into the lymphocytes of the patient a T cell receptor that recognizes to a certain cancer antigen, in this case, PRAME.  So you alluded to a couple of different companies that have different platforms to do this. Immatics has a molecule called IMA 203, for which there have been data disclosed in the past year, again showing some very interesting responses in patients who have highly refractory melanoma. That process, though, again, does require lymphodepletion before you reinfuse the cells. Again, in contrast, the ImmTAC, which is an off the shelf revenue administer, there you have to make the product and then bring the patient back, lymphodeplete, and give the cells back. Immatics platform uses a viral transfection vector. The T scan approach that you alluded to before uses an approach of a mixed system on multiple HLA backgrounds to try to get past HLA-A*02:01 only, and in this case, uses a plasmid-based transfection syndrome that perhaps can be more broadly utilized given the lack of a lentiviral vector.   So this is a complicated area of technology that starts to get into immune engineering, and I think for the purposes of this discussion, we don't want to belabor it. But both of these technologies, talking about the CD3 bispecific with the off the shelf aspect of it and the adoptive cell transfer, each of these using a T cell receptor-based therapy to try to go after PRAME, I think have very high upsides, and I think we'll initially see it in melanoma over the next year or so. But this is likely to be relevant to multiple tumor types beyond melanoma.  Dr. Diwakar Davar: So let's discuss the results of this phase 1 trial. IMC-F106C, like all other ImmTAC, is administered intravenously and does require step-up dosing. You alluded to the fact that the tebentafusp was approved, and it's one of those drugs that is fortunately otherwise administered weekly, which can be difficult for the patient and requires at least the patient spend the first 3 doses overnight under some kind of monitoring, whether it's in the hospital or extended outpatient monitoring, for at least 23 hours. The efficacy of this agent and this platform appears to be surprising in that you tend to see a relatively low RECIST response rate. We'll have you comment a little bit on why that is the case and what may be the role of ctDNA, as opposed to conventional RECIST in assessing response.   At least in this trial, they mandated pre-testing, but did not require it for study enrollment. And pre-positivity was defined using immunohistochemistry with a relatively low H-score of 1%. And the molecular response definition was a 0.5 log or a 68% ctDNA reduction just prior to the first imaging assessment. So how do you contextualize the results? But maybe before you talk a little bit about the results, the ctDNA aspect, that was a recent publication by Drs. Rich Carvajal, Alex Shoushtari, and I think you are also involved in that.  Dr. Jason Luke: So, I think an interesting observation around tebentafusp has been that ctDNA may be a better predictor of long-term outcomes. And how you define ctDNA response is still something that the field is grappling with, albeit that I think is going to be an important consideration as we think about these novel therapies, these ImmTACs and other CD3 engagers moving into the future. But for the purposes of the abstract here, we see that in the population of patients treated, there were 46 patients with cutaneous melanoma. The majority got monotherapy with IMC-F106C, and that's the PRAME bispecific. So 40 patients that got monotherapy and six who got a combination with checkpoint inhibitor. All these patients had prior treatment with immunotherapy, and most of them had PD-1 and CTLA-4 antibody with a small spanner that also had BRAF inhibitors.  In terms of that PRAME testing that you alluded to, based on the immunohistochemistry H-score greater than 1%, 35 out of 40 patients were positive, so they defined 5 as negative. And we could come back if we have time, but there are other ways to do PRAME testing as well that I think may become unique for different agents, maybe an important biomarker. In the data, 31 out of the 46 patients were RECIST evaluable. The outcomes of those patients were to note that the response rate was 13%, which was four partial responses. But 35% of patients had tumor regression with a disease control rate at 65%. It was clear that there was an enrichment by PRAME positivity for both progression free and overall survival. So those patients who had obvious positivity essentially had a doubling of the PFS and more than the doubling of the OS, 2.1 to 4.1 months for TFS and landmark OS, 40% to 94%. So I think these are quite intriguing data.  It does suggest that for the vast majority of patients, we do see some induction of the antitumor effect, albeit that RECIST might undercall the effect. And so this may become another area where the ctDNA monitoring might be able to help us to understand who is likely to have really long-term benefit from this therapy. And given the number of emerging treatments that we have for melanoma, we might be able to really focus in on that group of patients in terms of optimizing how we would use this drug moving into the future. Dr. Diwakar Davar: So you talked about a response rate, and at first glance, this response rate is a little underwhelming. We're talking about 4 out of 31 RECIST evaluable patients, 13%. So it's in the double digits, but barely. So how enthusiastic are you about the results? How does it contrast with at least the publicly known data from other brain targeting approaches, such as the IMA203 agent, understanding that while they may be all targeting somewhat the same target, they are actually extraordinarily different platforms. One's off the shelf, one's highly customized. How do you contextualize the results? How would it contrast with other cellular approaches?  Dr. Jason Luke: I think it's important, again, to emphasize the point you made, which is that they're very different kinds of treatments. So even though they both target PRAME, they're going to be differently useful, and they could be quite useful for different groups of patients. And so here we see that there is a subfraction of patients who are deriving long-term benefit. And we commonly have an argument in our field about, is overall response rate really a useful monitor that describes a patient-centric outcome? While, of course, patients like to know their tumors are shrinking, what they want the most is for the tumors not to get worse and for them not to pass away from cancer. So I think I'm enthusiastic about these results, but emphasizing the point that we need to better understand who is going to benefit the most from this CD3 bispecific PRAME approach and how we're going to be able to harness that into long term benefit for patients because there's no doubt that an off the shelf therapy has a high degree of value relative to adoptive cell transfer, which sort of requires a big wind up.   So when you say, what does it contrast with? Well, the data for IMA203 has shown more than a 50% response rate in patients with more than 5 lines of therapy for metastatic disease. That really looks quite exciting. And several of those patients are now out for quite an extended period, meaning 2 years or more given only a single dose of IMA203. But again, the caveat being, you have to make the cell product for the patient, and that takes time. You lymphodeplete the patient, not all patients can tolerate that in the refractory disease setting, and then they have to be able to tolerate the reinfusion of the cells. And so this drug, IMC-F106C, looks very promising. Moving into the earlier phase trial that we'll talk about, I think the TCR T cell program has a lot of upsides for patients, especially with refractory disease. And so I think these two different approaches are really on parallel tracks. They both target PRAME, but I don't think they necessarily need to be compared one to one, as if they're going to go head-to-head with each other. Dr. Diwakar Davar: So now we'll talk a little bit about the frontline setting, because on the basis of some of these results, Immunocore is now exploring IMC-F106C frontline melanoma. This trial is actually being presented as a trial in progress at this meeting by Georgina Long and colleagues. Some of us are co-authors in that abstract. And in this study, HLA-A*02:01 positive patients with advanced unresectable melanoma will be randomized one to one to the combination of IMC-F106C, which actually, I think after this meeting will be known as bre-ni in combination with nivolumab versus nivolumab regimens, which will either be nivo or nivo-rela, investigators choice and likely dependent on region. So what do you think of the challenge of this trial? We talked about some of the challenges of the TILVANCE trial earlier. But what is going to be the challenge of this trial and in this setting, particularly given the response rates that we've seen so far? Dr. Jason Luke: Yeah, so, similar to comments we had before, thinking about what the optimal control arm is for a study like this is difficult, and so that'll be important as we think about interpreting the results. One has to assume for the purpose of this conversation that it is a positive trial, and that adding the PRAME bispecific theory does lead to an improvement in progression free survival relative to those in checkpoint alone approaches. And I think the magnitude of that difference is going to be of some relevance. And then I think importantly, also figure out who needs this treatment and who's going to benefit long term are going to be really important considerations.  We alluded to how this drug requires an intensive dosing period at the get go, and so telling patients that they need to come in weekly or bi-weekly initially for some number of weeks before they switch to a longer-term intermittent regimen, that comes with real world considerations for patients, their families, their finances, etc. So the benefit has to be clearly obvious that makes it worthwhile doing that, again, because a default could be giving drugs that we've had for 10 years with the nivolumab and ipilimumab. So there's going to be a lot of cross-trial comparison that is going to necessarily have to take place here to think about what these results really mean in the context of other available therapies.  I think the study is reasonable to do. I think this is a very active agent. There's no doubt there's a subset of patients who seem to benefit a lot from it. And I would just emphasize the point that that's probably going to be the most important thing to really drill down on is under the assumption there's a positive trial, we need to know who those people are so we could optimize giving this kind of a treatment to them. Dr. Diwakar Davar: I guess one important point to underscore what Jason said about potential predictive biomarkers, I think as part of the presentation, Dr. Hamid and colleagues will be talking about a candidate predictive biomarker of this agent, which is potentially class specific and not necessarily agent specific of a T cell signature that potentially could define patients who are more likely to benefit from this agent.  So, Jason, as always, thank you for sharing your expertise and insights with the team today. We certainly look forward to catching up again for our wrap up episode after the annual meeting where we'll talk about some of the data that we could not talk about, particularly the late breaking abstracts and other key advances that will shape the future of, certainly the field of immunotherapy and melanoma, potentially the field of cancer immunotherapy at large. Dr. Jason Luke: Oh, thanks very much for the opportunity. Dr. Diwakar Davar: And thank you to our listeners today. You'll find the links to the abstracts discussed today in the transcript of this episode. And finally, if you value the insights that you hear on this podcast, please take a moment to rate, review, and subscribe wherever you get your podcast. So thank you, and we'll 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. Diwakar Davar   @diwakardavar   Dr. Jason Luke   @jasonlukemd      Follow ASCO on social media:    @ASCO on Twitter   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      

A new drug for small-cell lung cancer, a bispecific, targeting DLL3 on small-cell lung cancer and CD3 on T-cells is FDA approved. But, infigratinib's FDA approval for cholangiocarcinoma is withdrawn.

Oregon voters have now cast their ballots for the primary election. May primary elections tend to draw low turnouts, despite some big items on the ballot, including an open race for the Congressional seat held for nearly 30 years by Rep. Earl Blumenauer (D-Portland), who announced his retirement last October. We hear from some of the winners of key Congressional, county and mayoral contests that were on the ballot. OPB political reporter Dirk VanderHart also joins us for analysis of the primary, from the massive amounts of outside money flowing into the CD3 race, to contests to decide who will be Oregon’s next state treasurer and attorney general. 

In this interview from the American Association for Cancer Research (AACR) 2024 Annual Meeting, Dr. Alankrita Taneja, third-year Hematology/Oncology Fellow at Roswell Park Cancer Institute and Oncology Data Fellows Forum Member, speaks with Dr. Sundar Jagannath, Professor of Medicine (Hematology and Medical Oncology) and Director of the Center of Excellence for Multiple Myeloma at the Mount Sinai Icahn School of Medicine and Tisch Cancer Institute. At the meeting, Dr. Jagannath presented results of the phase 1/2 LINKER-MM1 trial of linvoseltamab, a CD3-directed B-cell maturation antigen (BCMA) antibody under investigation for relapsed/refractory multiple myeloma. In this follow-up conversation, Dr. Jagannath shares further insights into the trial, including: • The study design, which includes triple-class–refractory patients • The unique dosing schedule of linvoseltamab, which reduces the frequency of administration to improve patient convenience • The response, survival, and measurable residual disease (MRD) negativity outcomes demonstrated in the trial, including among high-risk patients • Management of side effects, including cytokine release syndrome (CRS), neutropenia, anemia, and infections • The future role of linvoseltamab in the treatment landscape for relapsed/refractory multiple myeloma as it advances through investigation • And more!

Another candidate from the St. Louis area officially enters the race for the US Congressional seat for district 3. Missouri Politico weighs in on the CD3 race and the viral video of a Hazelwood teen being beaten that has gone viral online.

Some funny reasons members of Gen Z use as excuses for calling in sick. Congressman Blaine Luetkemeyer on the House's budget, and his opinions on the CD3 race locally.

Visit nascentmc.com/podcast for full show notes Visit learnamastyle.com for the free course on ChatGPT4 for medical writers and editors.  - The FDA has approved amivantamab (Rybrevant) in combination with chemotherapy (carboplatin-pemetrexed) for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test. This approval converts the May 2021 accelerated approval of amivantamab to full approval. - The FDA approved the AGENT Drug-Coated Balloon (DCB) for treating in-stent restenosis in coronary artery disease patients, introducing the first drug-coated coronary balloon in the US. It uses a paclitaxel-coated catheter to deliver medication directly to the vessel wall, offering an alternative to traditional treatments and aiming to reduce recurrence risks. The approval was based on the AGENT IDE trial, demonstrating its effectiveness over uncoated balloon angioplasty in reducing lesion failure, with no significant adverse events reported. - The FDA approved an oral suspension form of ibrutinib (Imbruvica) for several conditions, including chronic lymphocytic leukemia and chronic graft versus host disease, addressing the needs of patients who have difficulty swallowing pills. This is the first oral suspension formulation of a Bruton's tyrosine kinase inhibitor, originally approved in 2013 for mantle cell lymphoma. The approval, granted to Johnson & Johnson and Pharmacyclics, aims to simplify treatment for patients challenged with pill-swallowing. - Epcoritamab-bysp (Epkinly) received FDA approval for treating adult patients with relapsed or refractory follicular lymphoma after at least two prior therapies, marking it as the first subcutaneously administered bispecific antibody for this condition. It works by targeting both CD3 on T cells and CD20 on B cells to induce cell death. Based on the EPCORE NHL-1 trial results, this approval extends its use beyond diffuse large B-cell lymphoma, with AbbVie and Genmab sharing commercial responsibilities.  - The FDA granted priority review to the New Drug Application for govorestat (AT-007), a treatment for classic galactosemia, potentially the first of its kind if approved. Govorestat, an aldose reductase inhibitor, aims to reduce harmful galactitol levels, based on phase 3 study results among pediatric patients. Applied Therapeutics announced a PDUFA target action date of August 28, 2024, highlighting the urgent need for treatments in this area. - Obeticholic acid (Ocaliva) received FDA consideration for an expanded application to treat primary biliary cholangitis, building on its 2016 accelerated approval. It's designed for patients with or without cirrhosis, showing promise in post-marketing studies to confirm its clinical benefits. The review includes data from various studies and real-world evidence, with a PDUFA target date of October 15, 2024, aiming to address the needs of this autoimmune liver disease population.  - The FDA approved Biktarvy for HIV patients with suppressed viral loads who exhibit M184V/I resistance, offering a new treatment option for those with specific resistance mutations. Biktarvy combines three therapies in a single tablet, based on successful 48-week study data. Manufactured by Gilead Sciences, this approval expands treatment possibilities for patients facing resistance challenges. - The FDA rejected Minerva Neurosciences' New Drug Application for roluperidone as a treatment for schizophrenia's negative symptoms, citing insufficient evidence from a single study and lack of comprehensive data. Despite showing promise in targeting specific brain receptors, the FDA's concerns highlight the need for more extensive research and data to confirm its effectiveness and safety. Minerva plans to engage with the FDA to address these issues.

Please visit answersincme.com/XHR860 to participate, download slides and supporting materials, complete the post test, and obtain credit. In this activity, experts in follicular lymphoma discuss the integration of bispecific antibodies into the treatment of relapsing/refractory follicular lymphoma. Upon completion of this activity, participants should be better able to: Review the clinical profiles of novel CD20 x CD3 bispecific antibodies (BsAbs) for relapsing/refractory follicular lymphoma (R/R FL); Describe patient-centered strategies to manage BsAb-associated adverse events in R/R FL; and Outline evidence-based multidisciplinary strategies for optimal integration of BsAbs in the treatment plans of patients with R/R FL.

輕食新時尚 我的新感覺 無論是濃情蜜意的甜美滋味-草莓夾心、可可夾心、花生夾心- 還是清爽不膩、經典鹹口味的雞蛋沙拉、鮪魚沙拉 新感覺隨時都能滿足味蕾，給你全新輕食選項 每一天都散發優雅時尚、自信向前 https://bit.ly/49es7mF -- 【00941】全台首檔鎖定半導體上游設備與材料廠的ETF，2/26稱王募集！ 半導體不是只有護國神山，想投資真正的隱形英雄，力爭「上游」就對了！中信上游半導體(00941)，帶你與科技王者中的王者同行：https://bit.ly/3Umqe2r －－－－以上訊息由 SoundOn 動態廣告贊助商提供－－－－ 飛碟聯播網《飛碟早餐 唐湘龍時間》2024.02.20 週二醫療保健單元 潘懷宗的醫學新知時間 《令人興奮！比化療友善的兒童抗血癌新藥出現》 英國倫敦「奧蒙德街醫院」 (Great Ormond Street Hospital；GOSH) 的醫生們領導完成一項在英國和愛爾蘭20多個中心的臨床試驗，近期公布了令人振奮與滿意的結果。此試驗是針對患有B急性淋巴細胞白血病(B-Acute Lymphoblastic Leukaemia；B-ALL)的兒童，在接受「引導性化學治療」後，若產生嚴重的副作用，就可以改用免疫治療新藥---百利妥注射劑(Blincyto；有效成分blinatumomab)，後期再合併其他治療，讓整個療程更加溫和友善。目前，此治療新藥在台灣，健保給付「治療無效」和「已復發」的B-ALL兒童病患，但從這次英國的試驗結果，等於是證明此藥的使用時機，可以考慮再往前擴大到第一階段就能使用。 這款免疫藥物，其副作用遠遠低於現階段所使用的化療藥物，因為此藥只針對癌細胞進行死亡狩獵，一般健康的細胞則不受影響。百利妥注射劑的藥物作用原理如圖1所示，它有兩隻手，第一隻手可以抓住血癌細胞的特異部分CD19，讓癌細胞無法逃走，另一隻手則是抓住殺手T細胞上面的特異部位CD3，亦即是把血癌細胞抓住後，同時吸引殺手T細胞過來將其殺死。英國病童家長稱這種療法為“一束溫暖的陽光”照進了難過黑暗的心靈，此藥除了有效，能讓病情緩解外，更重要的是，這款藥物的治療，不需要在醫院裡面進行，可以在任何場合，像是在家裡、在學校或者是在公園。 ▶ 《飛碟早餐》FB粉絲團 https://www.facebook.com/ufobreakfast/ ▶ 飛碟聯播網FB粉絲團 https://www.facebook.com/ufonetwork921/ ▶ 網路線上收聽 http://www.uforadio.com.tw ▶ 飛碟APP，讓你收聽零距離 IOS：https://reurl.cc/3jYQMV Android：https://reurl.cc/5GpNbR ▶ 飛碟Podcast SoundOn : https://bit.ly/30Ia8Ti Apple Podcasts : https://apple.co/3jFpP6x Spotify : https://spoti.fi/2CPzneD Google 播客：https://bit.ly/3gCTb3G KKBOX：https://reurl.cc/MZR0K4

In the 2nd hour of the Marc Cox Morning Show: Trump to have a town hall on the Laura Ingram show Truck drivers are boycotting New York  Former MO Senator John Lamping joins the Marc Cox Morning  Show to talk about the filibuster that is happening by the Dems in Jeff City to stop Initiative Petition.  They talk the CD3 race which is getting more crowded In Other News with Ethan:  Paul McCartney is reunited with his bass, An amputee plays baseball, and maggots rain down on Delta passengers. Coming Up:  Todd Piro and Mark Walters

Former MO Senator John Lamping joins the Marc Cox Morning  Show to talk about the filibuster that is happening by the Dems in Jeff City to stop Initiative Petition and they talk the CD3 race which is getting more crowded

Randy dives into the latest Lauren Boebert controversy with her announcement that she will no longer be running in her home district, CD3, but instead will join the crowded primary field to fill the seat being vacated by Ken Buck in CD4.  One of her opponents, lifetime movement Conservative and former state senator, Ted Harvey, may have something to say about that.  He joins the show.  Plus, he joins Randy in predicting that Donald Trump will be the Republican nominee and Creepy, Sleepy Joe Biden will not be the Democrat nominee.  Who will?See omnystudio.com/listener for privacy information.

The Chuck & Julie Show with Chuck Bonniwell and Julie Hayden With Guest, Ashe Epp Rep. Lauren Boebert abandons her constituents in CD3 and announces she will run in CD4 because she has a better chance of winning. But maybe not as CD4 voter Ashe in America calls out the carpetbagger move. Plus Maine's SoS takes Trump off the ballot in a shocking move of election interference.

Original text by David Pogue, Macworld December 1994. Watch the CD3 compact disc storage and retrieval box in action. Photos of the salami-like CD3: 1, 2, 3, 4, 5. The product lasted into the 2000s and the companion DiscGear website is still up, featuring no less than three CD3-like units on its front page. Decorate your classic Mac desktop: Holiday Lights, Xmas Lights, Snow. YesterYear's Mac Games review of “After Dark: The Simpsons Collection”. LabelOnce is still around, having wisely chosen not to focus exclusively on floppy disk labels.

We’re back after Thanksgiving weekend; Matt spends the first hour covering various topics related to artificial intelligence; sports roundup; Derek Chauvin stabbed in prison; Dean Phillips will not run again for CD3; Elon Musk and Twitter; CWD.