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

El Dr. Jorge A. Alatorre, oncólogo médico de México y el Dr. Santiago Viteri, oncólogo médico de España, comparten su análisis de los estudios más relevantes en cáncer de pulmón presentados durante la Reunión Anual 2025 de la Sociedad Americana de Oncología Clínica, celebrada en Chicago. Su revisión se enfoca en los avances más destacados en enfermedad resecable, enfermedad avanzada, mutaciones, entre otros con base en la información disponible al momento de esta grabación.CheckMate 816 (abstract#LBA8000)NeoADAURA (abstract #8001)KRYSTAL-7 (abstract #8500)LOXO-RAS-20001 (abstract #8519)OptiTROP-Lung03 (abstract #8507)REZILIENT1 (abstract #8503)TROPION LUNG 2 (abstract #8501)IMforte (abstract #8006)DeLLphi-304 (abstract # LBA8008)Material exclusivo para profesionales de la salud. Este material ha sido desarrollado únicamente con fines educativos e informativos y no tiene la intención de sustituir el juicio clínico de los profesionales de la salud.Las opiniones y declaraciones presentadas en este contenido son responsabilidad exclusiva de los ponentes y no reflejan necesariamente la postura institucional de ScienceLink ni de terceros mencionados. La información presentada se basa en el conocimiento y la experiencia profesional de los ponentes. La veracidad, exactitud y actualidad científica de los datos son de su exclusiva responsabilidad. Así mismo garantizan que el contenido utilizado no infringe derechos de autor de terceros y asumen toda responsabilidad por su uso.Se deberán de revisar las indicaciones aprobadas en el país con estricto apego al marco regulatorio aplicable para cada uno de los tratamientos y medicamentos comentados. ASCO® es una marca registrada de la American Society of Clinical Oncology. Este material ha sido producido de manera independiente y no está autorizado, patrocinado ni avalado por dicha organización.

MeidasTouch host Ben Meiselas reports on how world leaders at NATO perfectly isolated Trump by forming security pacts and deals that do not include the United States like the new European Union and Canada security deal. Zbiotics: Head to https://zbiotics.com/MEIDAS to get 15% off your first order when you use MEIDAS at checkout. Visit https://meidasplus.com for more! Remember to subscribe to ALL the MeidasTouch Network Podcasts: MeidasTouch: https://www.meidastouch.com/tag/meidastouch-podcast Legal AF: https://www.meidastouch.com/tag/legal-af MissTrial: https://meidasnews.com/tag/miss-trial The PoliticsGirl Podcast: https://www.meidastouch.com/tag/the-politicsgirl-podcast The Influence Continuum: https://www.meidastouch.com/tag/the-influence-continuum-with-dr-steven-hassan Mea Culpa with Michael Cohen: https://www.meidastouch.com/tag/mea-culpa-with-michael-cohen The Weekend Show: https://www.meidastouch.com/tag/the-weekend-show Burn the Boats: https://www.meidastouch.com/tag/burn-the-boats Majority 54: https://www.meidastouch.com/tag/majority-54 Political Beatdown: https://www.meidastouch.com/tag/political-beatdown On Democracy with FP Wellman: https://www.meidastouch.com/tag/on-democracy-with-fpwellman Uncovered: https://www.meidastouch.com/tag/maga-uncovered Coalition of the Sane: https://meidasnews.com/tag/coalition-of-the-sane Learn more about your ad choices. Visit megaphone.fm/adchoices

Music for Breakfast: Grammy 2025 Highlights and Hot Takes!In this episode of Music for Breakfast, hosts Octavia March and Rell Roulette break down the most memorable moments from the 2025 Grammy Awards. They discuss Kendrick Lamar's big wins, Beyonce's historic night, Chris Brown's controversial absence, and the impact of DEI initiatives on the event. The hosts also touch on some of the more petty moments, like JLo and Shakira's Super Bowl spat, and Janelle Monáe's performance in the Michael Jackson tribute. They wrap up with shout-outs to standout performances and urge listeners to share their thoughts in the comments.00:00 Introduction and Apologies00:15 Chris Brown and the Michael Jackson Tribute00:45 Kendrick Lamar's Grammy Sweep01:07 Music for Breakfast Hosts Introduction02:55 Grammy Highlights and Petty Moments08:17 Diversity and Inclusion at the Grammys11:57 Beyoncé's Big Win21:19 AI and the Beatles25:57 Final Thoughts and Wrap-Up #musicivbreakfast  #hiphop #youtube #fyp #trendingCopyright Disclaimer Under Section 107 of the Copyright Act 1976, allowance is made for "fair use" for purposes such as criticism, comment, news reporting, teaching, scholarship, and research. Fair use is a use permitted by copyright statute that might otherwise be infringing. Non-profit, educational or personal use tips the balance in favor of fair use. No copyright infringement intended. ALL RIGHTS BELONG TO THEIR RESPECTIVE OWNERS

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

It's part 2 of our wild, unfiltered, and unexpectedly emotional episode when Carolyn Wiger returns to break down her time on The Traitors, share behind-the-scenes drama, and reflect on life, loyalty, and lips. Carolyn explains why she refused to eliminate Dorinda Medley early in the game—despite strategy and pressure—calling her a “badass bitch” and recognizing how much fans adore her. She also unleashes her honest take on Boston Rob Mariano, criticizing his overexposure and dominance, saying it made others feel like “pawns.” She calls out Bob the Drag Queen and Danielle Reyes for backstabbing her mid-game, which left her feeling betrayed and emotional. There's still no real resolution, and Carolyn opens up about how much it hurt—especially from people she expected more compassion from.

Dr. Vamsi Velcheti and Dr. Nate Pennell discuss novel treatment approaches in small cell and non-small cell lung cancer that were featured at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Vamsi Velcheti: Hello, I'm Dr. Vamsi Velcheti, your guest host of the ASCO Daily News Podcast. I'm a professor of medicine and chief of hematology and oncology at the Mayo Clinic in Jacksonville, Florida. The 2025 ASCO Annual Meeting featured some exciting advancements in small cell lung cancer, targeted therapies for non-small cell lung cancer, and other novel [treatment] approaches. Today, I'm delighted to be joined by Dr. Nate Pennell to discuss some of the key abstracts that are advancing the lung cancer field. Dr. Pennell is the co-director of the Cleveland Clinic Lung Cancer Program and also the vice chair of clinical research at the Taussig Cancer Institute. Our full disclosures are available in the transcript of this episode. Nate, it's great to have you back on the podcast. Thanks so much for being here. Dr. Nate Pennell: Thanks, Vamsi. Always a pleasure. Dr. Vamsi Velcheti: Let's get started, and I think the first abstract that really caught my attention was Abstract 8516, “The Randomized Trial of Relevance of Time of Day of Immunotherapy for Progression-Free and Overall Survival in Patients With Non-Small Cell Lung Cancer.” What are your thoughts about this, Nate? Dr. Nate Pennell: I agree. I thought this was one of the most discussed abstracts, certainly in the lung cancer session, but I think even outside of lung cancer, it got some discussion. So, just to put this in perspective, there have been a number of publications that have all been remarkably consistent, and not just in lung cancer but across multiple cancer types, that immunotherapy, immune checkpoint inhibitors, are commonly used. And all of them have suggested, when looking at retrospective cohorts, that patients who receive immune checkpoint inhibitors earlier in the day – so in the morning or before the early afternoon – for whatever reason, appear to have better outcomes than those who get it later in the day, and this has been repeated. And I think many people just sort of assumed that this was some sort of strange association and that there was something fundamentally different from a prognostic standpoint in people who came in in the morning to get their treatment versus those who came later in the afternoon, and that was probably the explanation. The authors of this randomized trial actually decided to test this concept. And so, about 210 patients with previously untreated advanced non-small cell lung cancer were randomly assigned to get chemo and immune checkpoint inhibitor – either pembrolizumab or sintilimab – and half of them were randomly assigned to get the treatment before 3 PM in the afternoon, and half of them were assigned to get it after 3 PM in the afternoon. And it almost completely recapitulated what was seen in the retrospective cohorts. So, the median progression-free survival in those who got earlier treatment was 13.2 months versus only 6.5 months in those who got it later in the day. So, really enormous difference with a hazard ratio of 0.43, which was statistically significant. And perhaps even more striking, the median overall survival was not reached in the early group versus 17.8 months in the late group with a hazard ratio of 0.43, also highly statistically significant. Even the response rate was 20% higher in the early patients; 75% response rate compared to 56% in the late-time-of-day patients. So very consistent across all measures of efficacy with pretty good matched characteristics across the different groups. And so, I have to tell you, I don't know what to make of this. I certainly was a skeptic about the retrospective series, but now we have a prospective randomized trial that shows essentially the same thing. So, maybe there is a difference between getting treated in the morning, although I have yet to hear someone give a very good mechanistic explanation as to why this would be. What were your thoughts on this? Dr. Vamsi Velcheti: It's indeed fascinating, Nate, and I actually think this was a very interesting abstract. Really, I was caught off guard looking at the data. I mean, if it were a drug, we would be so excited, right? I mean, with those kind of survival benefits. I don't know. I think circadian rhythm probably has something to do with it, like different cytokine profiles at the time of administration. I mean, who knows? But I think it's a randomized trial, and I think I would expect to see a mad rush for treatment appointments early in the morning given this, and at least I want my patients to come in first thing in the morning. It'll be interesting to see. Dr. Nate Pennell: It's important to point out that in this study, everyone got chemo and immunotherapy. And, at least in our cancer center, most patients who are getting platinum-doublet chemotherapy and immunotherapy actually do get treated earlier in the day already, just because of the length of the infusion appointment that's needed. So it really is oftentimes people getting single-agent immunotherapy who are often getting the later, shorter visits. But if you have a choice, I think it would be very reasonable to have people treated earlier in the day. And I do think most of the impressions that I got from people about this is that they would like to see it reproduced but certainly well worth further investigation. And I personally would like to see more investigation into what the rationale would be for this because I still can't quite figure out, yes, if you got it at, say, you know, 5 PM, that's later in the day and I can understand that maybe your immune system is somewhat less receptive at that point than it would be in the morning. But because these checkpoint inhibitors have such long half-lives, it's still in your system the next morning when your immune system is supposedly more receptive. So I don't quite understand why that would be the case. Well, let's move on to the next study. I would like to hear your thoughts on Abstract 8515, “Plasma-Guided, Adaptive First-Line Chemoimmunotherapy for Non-Small Cell Lung Cancer.” Dr. Vamsi Velcheti: Yeah, this was another abstract that seems to be really interesting in my opinion. I think there's kind of a lot of emphasis lately on ctDNA and MRD-based assays to monitor disease. In the lung cancer space, we haven't had a lot of clinical trials looking at this prospectively, and this was one of those pilot studies where they looked at circulating free DNA (cfDNA)-based response-adaptive strategy for frontline patients who are PD-L1 positive. So, patients started with pembrolizumab monotherapy, and based on plasma molecular response after 2 cycles, those patients without response received early treatment intensification with a platinum doublet. So the approach essentially was to reduce the chemotherapy exposure in patients who respond to immunotherapy. And only about 17.5% of the patients on the trial received chemotherapy based on lack of molecular response. So, in this trial, what they found was patients with the cfDNA response had a markedly improved PFS of 16.4 months versus 4.8 months. So essentially, like, this is a really nice study to set a foundation on which we have to do larger studies to incorporate molecular markers trying to look at cfDNA response to inform treatment strategy, either escalation or de-escalation strategies. So, I thought it was a very interesting study. Dr. Nate Pennell: Yeah. I mean, we always have this question for patients, “Should they get immunotherapy alone or combined with chemo?” and I think this certainly is intriguing, suggesting that there may be ways you can monitor people and perhaps rescue those that aren't going to respond to single agent. I'd like to see a randomized trial against, you know, this strategy, perhaps against everyone getting, say, chemoimmunotherapy or make sure that you're not potentially harming people by doing this strategy. But I agree, it's time to move beyond just observing that cell-free DNA is prognostic and important and start using it to actually guide treatment. Dr. Vamsi Velcheti: Yeah, and I would just caution though, like, you know, I think we need more data, but, however, it's certainly a very interesting piece of data to kind of help inform future trials. So, there was another abstract that caught my attention, and I think this would be a very interesting abstract in the EGFR space. Abstract 8506, "Patritumab Deruxtecan (HER3-DXd) in Resistant EGFR-Mutant Advanced Non-Small Cell Lung Cancer Patients After Third-Generation EGFR TKI," it's the HERTHENA-Lung02 study. What do you think about the results of this study? Dr. Nate Pennell: Yeah, this was, I would say, very widely anticipated and ultimately a little disappointing, despite being a positive trial. So, these are patients with EGFR-mutant non-small cell lung cancer who have progressed after a third-generation EGFR TKI like osimertinib. This is really an area of major unmet need. We do have drugs like amivantamab in this space, but still definitely an area where essentially patients move from having a highly effective oral therapy to being in the realm of chemotherapy as their best option. So, this HER3 antibody-drug conjugate, patritumab deruxtecan, had some good single-arm data for this. And we're sort of hoping this would become an available option for patients. This trial was designed against platinum-doublet chemotherapy in this setting and with a primary endpoint of progression-free survival. And it actually was positive for improved progression-free survival compared to chemo with a hazard ratio of 0.77. But when you look at the medians, you can see that the median PFS was only 5.8 versus 5.4 months. It was really a modest difference between the two arms. And on the interim analysis, it appeared that there will not be a difference in overall survival between the two arms. In fact, the hazard ratio at the interim analysis was 0.98 for the two arms. So based on this, unfortunately, the company that developed the HER3-DXd has withdrawn their application to the FDA for approval of the drug, anticipating that they probably wouldn't get past approval without that overall survival endpoint. So, unfortunately, probably not, at least for the near future, going to be a new option for these patients. Dr. Vamsi Velcheti: Yeah, I think this is a space that's clearly an unmet need, and this was a big disappointment, I should say. I think all of us were going into the meeting anticipating some change in the standard of care here. Dr. Nate Pennell: Yeah, I agree. It was something that I was telling patients, honestly, that I was expecting this to be coming, and so now, definitely a bit of a disappointment. But it happens and, hopefully, it will still find perhaps a role or other drugs with a similar target. Certainly an active area. Well, let's leave the EGFR-mutant space and move into small cell. There were a couple of very impactful studies. And one of them was Abstract 8006, “Lurbinectedin Plus Atezolizumab as First-Line Maintenance Treatment in Patients With Extensive-Stage Small Cell Lung Cancer, Primary Results from the Phase III IMforte Trial.” So, what was your impression of this? Dr. Vamsi Velcheti: Yeah, I think this is definitely an interesting study, and small cell, I remember those days when we had barely any studies of small cell at ASCO, and now we have a lot of exciting developments in the small cell space. It's really good to see. The IMforte trial is essentially like a maintenance lurbinectedin trial with atezolizumab maintenance. And the study was a positive trial. The primary endpoint was a PFS, and the study showed improvement in both PFS and OS with the addition of lurbinectedin to atezolizumab maintenance. And definitely, it's a positive trial, met its primary endpoint, but I always am a little skeptical of adding maintenance cytotoxic therapies here in this setting. In my practice, and I'd like to hear your opinion, Nate, most patients with small cell after 4 cycles of a platinum doublet, they're kind of really beaten up. Adding more cytotoxic therapy in the maintenance space is going to be tough, I think, for a lot of patients. But also, most importantly, I think this rapidly evolving landscape for patients with small cell lung cancer with multiple new, exciting agents, actually like some FDA-approved like tarlatamab, also like a lot of these emerging therapeutics like I-DXd and other ADCs in this space. You kind of wonder, is it really optimal strategy to bring on like another cytotoxic agent right after induction chemotherapy, or do you kind of delay that? Or maybe have like a different strategy in terms of maintenance. I know that the tarlatamab maintenance trial is probably going to read out at some point too. I think it's a little challenging. The hazard ratio is also 0.73. As I said, it's a positive trial, but it's just incremental benefit of adding lurbi. And also on the trial, we need to also pay attention to the post-progression second-line treatments, number of patients who received tarlatamab or any other investigational agents.  So I think it's a lot of questions still. I'm not quite sure I'd be able to embrace this completely. I think a vast majority of my patients might not be eligible anyway for cytotoxic chemotherapy maintenance right away, but yeah, it's tough. Dr. Nate Pennell: Yeah. I would call this a single and not a home run. It definitely is real. It was a real overall survival benefit. Certainly not surprising that a maintenance therapy would improve progression-free survival. We've known that for a long time in small cell, but first to really show an overall survival benefit. But I completely agree with you. I mean, many people are not going to want to continue further cytotoxics after 4 cycles of platinum-doublet chemo. So I would say, for those that are young and healthy and fly through chemo without a lot of toxicity, I think certainly something worth mentioning. The problem with small cell, of course, is that so many people get sick so quickly while on that observation period after first-line chemo that they don't make it to second-line treatment. And so, giving everyone maintenance therapy essentially ensures everyone gets that second-line treatment. But they also lose that potentially precious few months where they feel good and normal and are able to be off of treatment. So, I would say this is something where we're really going to have to kind of sit and have that shared decision-making visit with patients and decide what's meaningful to them. Dr. Vamsi Velcheti: Yeah, I agree. The next abstract that was a Late-Breaking Abstract, 8000, “Overall Survival of Neoadjuvant Nivolumab Plus Chemotherapy in Patients With Resectable Non-Small Cell Lung Cancer in CheckMate-816.” This was a highly anticipated read-out of the OS data from 816. What did you make of this abstract? Dr. Nate Pennell: Yeah, I thought this was great. Of course, CheckMate-816 changed practice a number of years ago when it first reported out. So, this was the first of the neoadjuvant or perioperative chemoimmunotherapy studies in resectable non-small cell lung cancer. So, just to review, this was a phase 3 study for patients with what we would now consider stage II or stage IIIA resectable non-small cell lung cancer. And they received three cycles of either chemotherapy or chemotherapy plus nivolumab, and that was it. That was the whole treatment. No adjuvant treatment was given afterwards. They went to resection. And patients who received the chemoimmunotherapy had a much higher pathologic complete response rate and a much better event-free survival. And based on this, this regimen was approved and, I think, at least in the United States, widely adopted.  Now, since the first presentation of CheckMate 816, there have been a number of perioperative studies that have included an adjuvant component of immunotherapy – KEYNOTE-671, the AEGEAN study – and these also have shown improved outcomes. The KEYNOTE study with pembrolizumab also with an overall survival benefit. And I think people forgot a little bit about CheckMate-816. So, this was the 5-year overall survival final analysis. And it did show a statistically and, I think, clinically meaningful difference in overall survival with the 3 cycles of neoadjuvant chemo-nivo compared to chemo with a hazard ratio of 0.72. The 5-year overall survival of 65% in the chemo-IO group versus 55% with the chemo alone. So a meaningful improvement. And interestingly, that hazard ratio of 0.72 is very similar to what was seen in the peri-operative pembro study that included the adjuvant component. So, very much still relevant for people who think that perhaps the value of those neoadjuvant treatments might be really where most of the impact comes from this type of approach. They also gave us an update on those with pathologic complete response, showing really astronomically good outcomes. If you have a pathologic complete response, which was more than a quarter of patients, the long-term survival was just phenomenal. I mean, 95% alive at 5 years if they were in that group and suggesting that in those patients at least, the adjuvant treatment may not be all that important.  So, I think this was an exciting update and still leaves very much the open question about the importance of continuing immunotherapy after surgery after the neoadjuvant component. Dr. Vamsi Velcheti: Yeah, I completely agree, Nate. I think the million-dollar question is: “Is there like a population of patients who don't have complete response but like maybe close to complete response?” So, would you like still consider stopping adjuvant IO? I probably would not be comfortable, but I think sometimes, you know, we all have patients who are like very apprehensive of continuing treatments. So, I think that we really need more studies, especially for those patients who don't achieve a complete CR. I think trying to find strategies for like de-escalation based on MRD or other risk factors. But we need more trials in that space to inform not just de-escalation, but there are some patients who don't respond at all to a neoadjuvant IO. So, there may be an opportunity for escalating adjuvant therapies. So, it is an interesting space to watch out for. Dr. Nate Pennell: No, absolutely. Moving to KRAS-mutant space, so our very common situation in patients with non-small cell lung cancer, we had the results of Abstract 8500, “First-Line Adagrasib With Pembrolizumab in Patients With Advanced or Metastatic KRASG12C-Mutated Non-Small Cell Lung Cancer” from the phase 2 portion of the KRYSTAL-7 study. Why was this an interesting and important study? Dr. Vamsi Velcheti: First of all, there were attempts to kind of combine KRASG12C inhibitors in the past with immune checkpoint inhibitors, notably sotorasib with pembrolizumab. Unfortunately, those trials have led to like a lot of toxicity, with increased especially liver toxicity, which was a major issue. This is a phase 2 study of adagrasib in combination with pembrolizumab, and this is a study in the frontline setting in patients with the G12C-mutant metastatic non-small cell lung cancer. And across all the PD-L1 groups, the ORR was 44%, and the median PFS was 11 months, comparable to the previous data that we have seen with adagrasib in this setting. So it's not like a major improvement in clinical efficacy. However, I think the toxicity profile that we were seeing was slightly better than the previous trials in combination with sotorasib, but you still have a fair amount of transaminitis even in the study. At this point, this is not ready for clinical primetime. I don't think we should be using sotorasib or adagrasib in the frontline or even in the second line in combination with checkpoint inhibitors. Combining these drugs with checkpoint inhibitors in the clinical practice might lead to adverse outcomes. So, we need to wait for more data like newer-generation G12C inhibitors which are also being studied in combination, so we'll have to kind of wait for more data to emerge in this space. Dr. Nate Pennell: I agree, this is not immediately practice changing. This is really an attempt to try to combine targeted treatment with immune checkpoint inhibitor. And I agree with you that, you know, it does appear to be perhaps a little bit better tolerated than some of the prior combinations that have tried in this space. The outcomes overall were not that impressive, although in the PD-L1 greater than 50%, it did have a better response rate perhaps than you would expect with either drug alone. And I do think that the company is focusing on that population for a future randomized trial, which certainly would inform this question better. But in the meantime, I agree with you, there's a lot of newer drugs that are coming along that potentially may be more active and better tolerated. And so, I'd say for now, interesting but we'll wait and see. Dr. Vamsi Velcheti: Yeah, so now moving back again to small cell. So, there was a Late-Breaking Abstract, 8008. This is a study of tarlatamab versus chemotherapy as second-line treatment for small cell lung cancer. They presented the primary analysis of the phase III DeLLphi-304 study. What do you think about this? Dr. Nate Pennell: Yeah, I thought this was really exciting. This was, I would say, perhaps the most important lung study that was presented. Tarlatamab is, of course, the anti-DLL3 bispecific T-cell engager compound, which is already FDA approved based on a prior single-arm phase II study, which showed a very nice response rate as a single agent in previously treated small cell lung cancer and relatively manageable side effects, although somewhat unique to solid tumor docs in the use of these bispecific drugs in things like cytokine release syndrome and ICANS, the neurologic toxicities. So, this trial was important because tarlatamab was approved, but there were also other chemotherapy drugs approved in the previously treated space. And so, this was a head-to-head second-line competition comparison between tarlatamab and either topotecan, lurbinectedin, or amrubicin in previously treated small cell patients with a primary endpoint of overall survival. So, a very well-designed trial. And it did show, I think, a very impressive improvement in overall survival with a median overall survival in the tarlatamab group of 13.6 months compared to 8.3 months with chemotherapy, hazard ratio of 0.6. And progression-free survival was also longer at 4.2 months versus 3.2 months, hazard ratio of 0.72. In addition to showing improvements in cancer-related symptoms that were improved in tarlatamab compared to chemotherapy, there was actually also significantly lower rates of serious treatment-related adverse events with tarlatamab compared to chemotherapy. So, you do still see the cytokine release syndrome, which is seen in most people but is manageable because these patients are admitted to the hospital for the first two cycles, as well as a significant number of patients with neurologic side effects, the so-called ICANS, which also can be treated with steroids. And so, I think based upon the very significant improvement in outcomes, I would expect that this should become our kind of standard second-line treatment since it seems to be much better than chemo. However, tarlatamab is definitely a new drug that a lot of places are not used to using, and I think a lot of cancer centers, especially ones that aren't tied to a hospital, may have questions about how to deal with the CRS. So, I'm curious your thoughts on that. Dr. Vamsi Velcheti: Yeah, thank you, Nate. And I completely agree. I think the data looked really promising, and I've already been using tarlatamab in the second-line space. The durability of response and overall, having used tarlatamab quite a bit - like, I participated in some of the early trials and also used it as standard of care - tarlatamab has unique challenges in terms of like need for hospitalization for monitoring for the first few treatments and make sure, you know, we monitor those patients for CRS and ICANS. But once you get past that initial administration and monitoring of CRS, these patients have a much better quality of life, they're off chemotherapy, and I think it's really about the logistics of actually administering tarlatamab and coordination with the hospital and administration in the outpatient setting. It's definitely challenging, but I think it definitely can be done and should be done given what we are seeing in terms of clinical efficacy here. Dr. Nate Pennell: I agree. I think hospital systems now are just going to have to find a way to be able to get this on formulary and use it because it clearly seems to be more effective and generally better tolerated by patients. So, should move forward, I think. Finally, there's an abstract I wanted to ask you about, Abstract 8001, which is the “Neoadjuvant osimertinib with or without chemotherapy versus chemotherapy alone in resectable epidermal growth factor receptor-mutated non-small cell lung cancer: The NeoADAURA Study”. And this is one that I think was also fairly highly anticipated. So, what are your thoughts? Dr. Vamsi Velcheti: You know, I wasn't probably surprised with the results, and I believe we were all expecting a positive trial, and we certainly were handed a positive trial here. It's a phase III trial of osimertinib and chemotherapy or osimertinib in the neoadjuvant space followed by surgery, followed by osimertinib. It's a global phase 3 trial and very well conducted, and patients with stage II to stage IIIB were enrolled in the study. And in the trial, patients who had a neoadjuvant osimertinib with or without chemotherapy showed a significant improvement in major pathologic response rates over chemotherapy alone. And the EFS was also positive for osimertinib and chemotherapy, osimertinib monotherapy as well compared to chemotherapy alone. So overall, the study met its primary endpoint, and I think it sheds light on how we manage our patients with early-stage lung cancer. I think osimertinib, we know that osimertinib is already FDA approved in the adjuvant space, but what we didn't really know is how was osimertinib going to work in the neoadjuvant space. And there are always situations, especially for stage III patients, where we are on the fence about, are these patients already close to being metastatic? They have, like, almost all these patients have micrometastatic disease, even if they have stage III. As we saw in the LAURA data, when you look at the control arm, it was like a very short PFS. Chemoradiation does nothing for those patients, and I think these patients have systemic mets, either gross or micrometastatic disease at onset. So, it's really important to incorporate osimertinib early in the treatment course. And I think, especially for the locally advanced patients, I think it's even more important to kind of incorporate osimertinib in the neoadjuvant space and get effective local control with surgery and treat them with adjuvant. I'm curious to hear your thoughts, Nate. Dr. Nate Pennell: I am a believer and have long been a believer in targeted adjuvant treatments, and, you know, it has always bothered me somewhat that we're using our far and away most effective systemic therapy; we wait until after they go through all their pre-op treatments, they go through surgery, then they go through chemotherapy, and then finally months later, they get their osimertinib, and it still clearly improves survival in the adjuvant setting. Why not just start the osimertinib as soon as you know that the patient has EGFR-mutant non-small cell lung cancer, and then you can move on to surgery and adjuvant treatment afterwards? And I think what was remarkable about this study is that all of these patients almost - 90% in each arm - went to surgery. So, you weren't harming them with the neoadjuvant treatment. And clearly better major pathologic response, nodal downstaging, event-free survival was better. But I don't know that this trial is ever going to show an overall survival difference between neoadjuvant versus just surgery and adjuvant treatment, given how effective the drug is in the adjuvant setting. Nonetheless, I think the data is compelling enough to consider this, certainly for our N2-positive, stage IIIA patients or a IIIB who might be otherwise surgical candidates. I think based on this, I would certainly consider that. Dr. Vamsi Velcheti: Yeah, and especially for EGFR, like even for stage IIIB patients, in the light of the LAURA study, those patients who do not do too well with chemoradiation. So you're kind of delaying effective systemic therapy, as you said, waiting for the chemoradiation to finish. So I think probably time to revisit how we kind of manage these locally advanced EGFR patients. Dr. Nate Pennell: Yep, I agree. Dr. Vamsi Velcheti: Nate, thank you so much for sharing your fantastic insights today on the ASCO Daily News Podcast. It's been an exciting ASCO again. You know, we've seen a lot of positive trials impacting our care of non-small cell lung cancer and small cell lung cancer patients. Dr. Nate Pennell: Thanks for inviting me, Vamsi. Always a pleasure to discuss these with you. Dr. Vamsi Velcheti: And thanks to our listeners for your time today. You will find links to all of the abstracts discussed today in the transcript of the episode. Finally, if you value the insights that you hear from the ASCO Daily News Podcast, please take a moment to rate, review, subscribe wherever you get your podcast. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. 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. More on today's speakers:    Dr. Vamsi Velcheti   @VamsiVelcheti    Dr. Nathan Pennell   @n8pennell   Follow ASCO on social media:     @ASCO on Twitter     ASCO on Facebook     ASCO on LinkedIn   ASCO on BlueSky   Disclosures:   Dr. Vamsi Velcheti:   Honoraria: ITeos Therapeutics   Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus   Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline   Dr. Nathan Pennell:     Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron    Research Funding (Inst): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi 

In the wake of the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, CancerNetwork® put together an X Spaces discussion hosted by Stephen Liu, MD, and Joshua Sabari, MD, to highlight the most intriguing and practice-changing lung cancer abstracts. Discussed topics ranged from long-term follow-up with commonplace therapies to an analysis of what time of day is the best to administer immunochemotherapy.  Liu, an associate professor of Medicine at Georgetown University, and the director of Thoracic Oncology and head of Developmental Therapeutics at the Georgetown Lombardi Comprehensive Cancer Center, and Sabari, an assistant professor in the Department of Medicine at the NYU Grossman School of Medicine, and the director of High Reliability Organization Initiatives at the Perlmutter Cancer Center, shared expert insights on the latest non–small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) breakthroughs. Trials of note that they discussed included: The phase 3 DeLLphi-304 trial (NCT05740566) - Tarlatamab (Imdelltra) versus chemotherapy (CTx) as second-line (2L) treatment for small cell lung cancer (SCLC): primary analysis of Ph3 DeLLphi-304.1 The phase 3 IMforte trial (NCT05091567) - Lurbinectedin (Zepzelca; lurbi) + atezolizumab (Tecentriq; atezo) as first-line (1L) maintenance treatment (tx) in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC): primary results of the phase 3 IMforte trial.2 The phase 3 CheckMate 816 trial (NCT02998528) - Overall survival with neoadjuvant nivolumab (Opdivo; NIVO) + chemotherapy (chemo) in patients with resectable NSCLC in CheckMate 816.3 The phase 3 PACIFIC15 trial (NCT05549037) - Randomized trial of relevance of time-of-day of immunochemotherapy for progression-free and overall survival in patients with non–small cell lung cancer.4 The phase 3 Beamion LUNG-1 trial (NCT04886804) - Patient-reported outcomes (PRO) evaluating physical functioning and symptoms in patients with pretreated HER2-mutant advanced non–small cell lung cancer (NSCLC): results from the Beamion LUNG-1 trial.5 The phase 3 ARTEMIA trial (NCT06472245) - Phase 3 trial of the therapeutic cancer vaccine OSE2101 versus docetaxel in patients with metastatic non–small cell lung cancer and secondary resistance to immunotherapy. References Rudin C, Mountzios G, Sun L, et al. Tarlatamab versus chemotherapy (CTx) as second-line (2L) treatment for small cell lung cancer (SCLC): primary analysis of Ph3 DeLLphi-304. J Clin Oncol. 2025;43(suppl 17):LBA8008. doi:10.1200/JCO.2025.43.17_suppl.LBA8008 Paz-Ares L, Borghaei H, Liu SV, et al. Lurbinectedin (lurbi) + atezolizumab (atezo) as first-line (1L) maintenance treatment (tx) in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC): primary results of the phase 3 IMforte trial. J Clin Oncol. 2025;43(suppl 16):8006. doi:10.1200/JCO.2025.43.16_suppl.8006 Forde PM, Spicer JD, Provencio M, et al. Overall survival with neoadjuvant nivolumab + chemotherapy in patients with resectable NSCLC in CheckMate 816. J Clin Oncol. 2025;43(suppl 17):LBA8000. doi:10.1200/JCO.2025.43.17_suppl.LBA8000 Zhang Y, Huang Z, Zeng L, et al. Randomized trial of relevance of time-of-day of immunochemotherapy for progression-free and overall survival in patients with non-small cell lung cancer. J Clin Oncol. 2025;43(suppl 16):8516. doi:10.1200/JCO.2025.43.16_suppl.8516 Sabari JK, Nadal E, Hendriks L, et al. Patient-reported outcomes (PRO) evaluating physical functioning and symptoms in patients with pretreated HER2-mutant advanced non-small cell lung cancer (NSCLC): results from the Beamion LUNG-1 trial. J Clin Oncol. 2025;43(suppl 16):8620. doi:10.1200/JCO.2025.43.16_suppl.8620 Liu SV, Guibert C, Tostivint EP, et al. Phase 3 trial of the therapeutic cancer vaccine OSE2101 versus docetaxel in patients with metastatic non-small cell lung cancer and secondary resistance to immunotherapy. J Clin Oncol. 2025;43(suppl 16):TPS8651. doi:10.1200/JCO.2025.43.16_suppl.TPS8651

In this episode, Dr. Ned McNamee discusses the latest advancements in lung cancer treatment presented at ASCO 2025, focusing on significant studies such as the Phase 3 DeLLphi-304 study and Checkmate 816. They explore the implications of these findings for clinical practice, including the challenges of managing immune-related side effects and the potential for neoadjuvant immunotherapy to improve patient outcomes. The conversation also touches on the economics of oncology and the surprising results regarding the timing of immunotherapy administration.Studies discussed in the episode:Phase 3 DeLLphi-304NeoADAURACheckmate816IMFORTE studyRandomized trial of relevance of time-of-day of immunochemotherapy for progression-free and overall survival in patients with non-small cell lung cancer.AND MORE!For more episodes, resources and blog posts, visit www.inquisitiveonc.comPlease find us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of AlisiaBeats: https://pixabay.com/users/alisiabeats-39461785/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice.Oncology for the Inquisitive Mind is recorded with the support of education grants from our foundation partners Pfizer, Gilead Pharmaceuticals and Merck Pharmaceuticals. Our partners have access to the episode at the same time you do and have no editorial control over the content. Hosted on Acast. See acast.com/privacy for more information.

In tonight’s podcast, we give the latest updates regarding the ongoing war in the Middle East between Israel and Iran. The Supreme Leader of Iran has just rejected Trump’s request to surrender and has made new threats against US interests in the Mideast. Will Trump take the final step and use the M.O.A.B. to be […]

Today, we cover ASCO 2025 in the genitourinary space, specifically bladder and renal cancer. Dr. Enrique Grande, a renowned oncologist and Program and Clinical Research lead of MD Anderson Cancer Centre, Madrid, joins us. This is a mega episode where we cover AMPLITUDE, JAVELIN MEDLEY, CHECKMATE 901 and NIAGARA, advancing urothelial cancer care; SEAR 02 and the CReST trial, pushing boundaries in bladder cancer; CHECKMATE 214; LITESPARK-005 and LITESPARK-004, showcasing belzutifan's promise; and KEYNOTE-564, adjuvant therapy for kidney cancer. Stay tuned for an insightful conversation on how these trials may be transforming patient outcomes!Studies discussed in the episode:CHECKMATE 901NIAGARACHECKMATE 214CREST trialSEAR 02LITESPARK 004/005AMPLITUDEJAVELIN MEDLEYFor more episodes, resources and blog posts, visit www.inquisitiveonc.comPlease find us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of AlisiaBeats: https://pixabay.com/users/alisiabeats-39461785/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice.Oncology for the Inquisitive Mind is recorded with the support of education grants from our foundation partners Pfizer, Gilead Pharmaceuticals and Merck Pharmaceuticals. Our partners have access to the episode at the same time you do and have no editorial control over the content. Hosted on Acast. See acast.com/privacy for more information.

La Dra. María Teresa Bourlon, oncóloga médica de México, y el Dr. Martín Ángel, oncólogo médico de Argentina, comparten su análisis de los estudios más relevantes en tumores genitourinarios presentados durante la Reunión Anual 2025 de la Sociedad Americana de Oncología Clínica, celebrada en Chicago. Su revisión se enfoca en los avances más destacados en cáncer urotelial, renal y de próstata, con base en la información disponible al momento de esta grabación.Carcinoma urotelialCREST (abstract #4517)EV-302 (abstract #664)CheckMate 901 (abstract #664)Cáncer renalCheckMate 214 (abstract #4505)KEYNOTE-564 (abstract #4514)Cáncer de próstataIRONMAN (abstract #5002)AMPLITUDE (abstract #LBA5006)ARCHES (abstract #5005)ARANOTE (abstract #5004) Material exclusivo para profesionales de la salud. Este material ha sido desarrollado únicamente con fines educativos e informativos y no tiene la intención de sustituir el juicio clínico de los profesionales de la salud.Las opiniones y declaraciones presentadas en este contenido son responsabilidad exclusiva de los ponentes y no reflejan necesariamente la postura institucional de ScienceLink ni de terceros mencionados. La información presentada se basa en el conocimiento y la experiencia profesional de los ponentes. La veracidad, exactitud y actualidad científica de los datos son de su exclusiva responsabilidad. Así mismo garantizan que el contenido utilizado no infringe derechos de autor de terceros y asumen toda responsabilidad por su uso.Se deberán de revisar las indicaciones aprobadas en el país con estricto apego al marco regulatorio aplicable para cada uno de los tratamientos y medicamentos comentados. ASCO® es una marca registrada de la American Society of Clinical Oncology. Este material ha sido producido de manera independiente y no está autorizado, patrocinado ni avalado por dicha organización.

In this episode of Around the School Table, host Steve Davis talks with Craig Ainsworth from Westport Public School about how a modest chess program in a low socio-economic school achieved elite educational outcomes over 18 years. Far from just a lunchtime club, Craig’s program developed students’ physical control, emotional intelligence, intellectual stamina, and creative thinking—all through the game of chess. Ainsworth shares that success wasn’t about innate giftedness, but about effort and process. Using a structured approach—such as the KM-PPS framework (King safety, Material, Pawn structure, Position, Space)—students learned to handle pressure, make strategic decisions, and apply consistent critical thinking under stress. Chess became more than a game; it was a vehicle for building resilience and a growth mindset. The program had broad academic impacts, boosting students’ performance in both maths and literacy. Notably, it also shattered stereotypes: many of the top players were athletic or quiet students who, through chess, discovered untapped cognitive strengths. Craig emphasises that coaching was not passive—it required active engagement, questioning students about their decisions, and creating an environment where learning was mutual. A key to the program’s longevity was its self-sustaining culture of mentoring. Elite players trained the next cohort, creating a legacy of peer-led excellence. Even though the program paused when Craig left in 2018, its ripple effects are seen in students now pursuing high-level studies and careers. When asked why chess still matters in the age of AI, Craig affirms that machines can analyse but not create. It’s human creativity, developed through tools like chess, that remains irreplaceable. This episode is a testament to how traditional games, paired with intentional teaching, can unlock transformative educational experiences—especially in places where they’re least expected. See omnystudio.com/listener for privacy information.

Checkmate by Kinte Fergerson

In this episode of Around the School Table, host Steve Davis talks with Craig Ainsworth from Westport Public School about how a modest chess program in a low socio-economic school achieved elite educational outcomes over 18 years. Far from just a lunchtime club, Craig’s program developed students’ physical control, emotional intelligence, intellectual stamina, and creative thinking—all through the game of chess. Ainsworth shares that success wasn’t about innate giftedness, but about effort and process. Using a structured approach—such as the KM-PPS framework (King safety, Material, Pawn structure, Position, Space)—students learned to handle pressure, make strategic decisions, and apply consistent critical thinking under stress. Chess became more than a game; it was a vehicle for building resilience and a growth mindset. The program had broad academic impacts, boosting students’ performance in both maths and literacy. Notably, it also shattered stereotypes: many of the top players were athletic or quiet students who, through chess, discovered untapped cognitive strengths. Craig emphasises that coaching was not passive—it required active engagement, questioning students about their decisions, and creating an environment where learning was mutual. A key to the program’s longevity was its self-sustaining culture of mentoring. Elite players trained the next cohort, creating a legacy of peer-led excellence. Even though the program paused when Craig left in 2018, its ripple effects are seen in students now pursuing high-level studies and careers. When asked why chess still matters in the age of AI, Craig affirms that machines can analyse but not create. It’s human creativity, developed through tools like chess, that remains irreplaceable. This episode is a testament to how traditional games, paired with intentional teaching, can unlock transformative educational experiences—especially in places where they’re least expected. See omnystudio.com/listener for privacy information.

En este programa especial, los Dres. Diego Ballén y Mauricio Lema, oncólogos clínicos colombianos, entrevistarán al Dr. Jorge Gallardo, oncólogo médico de la clínica Las Condes, Santiago de Chile, miembro de grupo de trabajo, SLAGO y presentarán lo más destacado en tumores gastrointestinales, presentado durante la Reunión Anual 2025 de la Sociedad Americana de Oncología Clínica, celebrada en Chicago, con base en la información disponible al momento de esta grabación.Los trabajos comentados son:CheckMate-577 (abstract #4000): estudio fase III, aleatorizado, multicéntrico, doble ciego, que evaluó nivolumab adyuvante en pacientes con cáncer de esófago o de la unión gastroesofágica resecado (R0) con enfermedad patológica residual después de quimiorradioterapia neoadyuvante. El objetivo primario fue la supervivencia libre de eventos (SLE). El objetivo secundario fue la supervivencia global (SG).MATTERHORN (abstract #LBA5): estudio fase III, aleatorizado, doble ciego y controlado con placebo, que evalúa la eficacia y seguridad de durvalumab, en combinación con quimioterapia FLOT (5-fluorouracilo, leucovorina, oxaliplatino y docetaxel) en pacientes con adenocarcinoma gástrico o de la unión gastroesofágica resecable en estadio II o superior. El objetivo primario fue la SLE. Los objetivos secundarios fueron la SG y la tasa de respuesta patológica completa.DESTINY-Gastric04 (abstract #LBA4002): estudio fase III, multicéntrico, aleatorizado, abierto, que evalúa trastuzumab deruxtecan en pacientes con adenocarcinoma gástrico o de la unión gastroesofágica metastásico o irresecable con HER2 positivo que han progresado durante o después de un régimen con trastuzumab. El objetivo primario fue la SG. Los objetivos secundarios, incluyen la supervivencia libre de progresión (SLP), la tasa de respuesta objetiva confirmada (TRO), la tasa de control de la enfermedad y la seguridad.ATOMIC (Abstract #LBA1): estudio fase III, aleatorizado y multicéntrico, que evalúa el uso de quimioterapia adyuvante con 5-fluorouracilo, leucovorina más oxaliplatino (FOLFOX) con o sin atezolizumab en pacientes con cáncer de colon en estadio III con inestabilidad de microsatélites (MSI-H, por sus siglas en inglés) o deficiencia en la reparación de errores de apareamiento de bases (dMMR, por sus siglas en inglés)). El objetivo primario fue la SLE. Los objetivos secundarios incluyeron la SG y el perfil de seguridad.BREAKWATER (abstract #LBA3500): estudio fase III, abierto, global y aleatorizado, que evalúa en primera línea el tratamiento con encorafenib más cetuximab, con o sin quimioterapia, frente al tratamiento estándar (quimioterapia con o sin bevacizumab) en pacientes con cáncer colorrectal metastásico con mutación BRAF V600E no tratados previamente. Los pacientes fueron asignados aleatoriamente en proporción 1:1:1 a recibir encorafenib más cetuximab, encorafenib más cetuximab y mFOLFOX6, o el tratamiento estándar. Los objetivos primarios fueron la tasa de respuesta objetiva confirmada y la SLP evaluadas por revisión central ciega, y como objetivo secundario se evaluó la SG.CHALLENGE (abstract #LBA3510): estudio fase III, aleatorizado que se diseñó para probar la hipótesis de que es posible lograr un aumento significativo de la actividad física recreativa después de la terapia adyuvante y que mejorará la SLE en el cáncer de colon en etapa 3 o en etapa 2 de alto riesgo. El objetivo primario fue la SLE comparada mediante una prueba de log-rank estratificada realizada sobre una base de intención de tratar. Los objetivos secundarios fueron la SG y los resultados informados por el paciente. ASCO® es una marca registrada de la American Society of Clinical Oncology. Este material ha sido producido de manera independiente y no está autorizado, patrocinado ni avalado por dicha organización.

The globalist resistance, pro-America, media has been completely exposed as nothing more than a new form of mockingbird press. The big patriot leaders are in unison calling for the end of “third world immigration” and even “non-white immigration,” becoming the very thing the left accused them of all along - while ignoring the fact that Asians, for example, commit little crime, use few drugs, and are some of the top earners and contributors to the country. All the hopes and dreams of “promises made, promises kept,” are evaporating in real time, with few able to further justify the increasingly obvious: the downfall of the Republic has been monetized and archetypically framed. With riots all across the country, fears of a black and white racial war have instead manifested as Mexican and American; the fear of outright civil war has manifested as a problem-reaction-solution of absolute information control and military martial law in the name of defending the country. Now the “No Kings” movement has nationwide protests planned for June 14th, 2025, the day of Saturn. Rather than arresting the organizers behind that, and the riots via the communist Indivisible, the AG has instead sued a coffee shop for antisemitism. The protests are meant to resist the massive military parade and presidential birthday parade in Washington on the same day. Don't like it? You will be met with “very big force,” says the President, if you don't like his “big parade.” BIG beautiful bill anyone? Not even Roman emperors held military parades for their birthdays, but they did hold them for victories in battle. So either the Trump camp is totally delusional, considering nationwide civil war as victory, or the display is meant to put the final nail in the Constitutional coffin. It all culminates with the US suddenly pulling all nonessential staff from embassies across the Middle East and putting the country on high alert the same week. The word is Iran is prepared to strike Israel's nuclear sites and Israel is fully poised to strike Iran (thus, the Houthis are warning of war too), and regardless of what the fake Donald-Benjamin feud suggests, the US will sacrifice its own citizens for the jewish state, which itself will, under the Samson Option, destroy the entire world if it doesn't get its way. Hence, the fake (maybe real) threat of Benjamin Netanyahu circulating the Internet: “if we do fall, many parts of the world will fall with us.” *The is the FREE archive, which includes advertisements. If you want an ad-free experience, you can subscribe below underneath the show description.-FREE ARCHIVE (w. ads)SUBSCRIPTION ARCHIVEX / TWITTER FACEBOOKYOUTUBEMAIN WEBSITECashApp: $rdgable Paypal email rdgable1991@gmail.comEMAIL: rdgable@yahoo.com / TSTRadio@protonmail.comBecome a supporter of this podcast: https://www.spreaker.com/podcast/the-secret-teachings--5328407/support.

When was Checkpoint Charlie created in Berlin? What triggered Stalin to enact a blockade on West Berlin? And how did the Western powers airlift over 2.3 million tons of supplies to their occupied zone of the city from 1948 to 1949? William and Anita are joined once again by Giles Milton, author of Checkmate in Berlin: The Cold War Showdown That Shaped the Modern World, to discuss the Berlin Blockade, the Berlin Airlift, and the way in which the Iron Curtain hardened towards the end of the 1940s. ----------------- Empire Club: Become a member of the Empire Club to receive early access to miniseries, ad-free listening, early access to live show tickets, bonus episodes, book discounts, our exclusive newsletter, and access to our members' chatroom on Discord! Head to empirepoduk.com to sign up. For more Goalhanger Podcasts, head to www.goalhanger.com.  ----------------- Email: empire@goalhanger.com Instagram: @empirepoduk  Blue Sky: @empirepoduk  X: @empirepoduk Assistant Producer: Becki Hills Producer: Anouska Lewis Senior Producer: Callum Hill Learn more about your ad choices. Visit podcastchoices.com/adchoices

MeidasTouch host Ben Meiselas reports on Donald Trump getting easily outmaneuvered, outplayed, and mocked by world leaders and often to his face. Dose: Save 30% on your first month of subscription by going to https://dosedaily.co/MEIDAS or entering MEIDAS at checkout. Visit https://meidasplus.com for more! Remember to subscribe to ALL the MeidasTouch Network Podcasts: MeidasTouch: https://www.meidastouch.com/tag/meidastouch-podcast Legal AF: https://www.meidastouch.com/tag/legal-af MissTrial: https://meidasnews.com/tag/miss-trial The PoliticsGirl Podcast: https://www.meidastouch.com/tag/the-politicsgirl-podcast The Influence Continuum: https://www.meidastouch.com/tag/the-influence-continuum-with-dr-steven-hassan Mea Culpa with Michael Cohen: https://www.meidastouch.com/tag/mea-culpa-with-michael-cohen The Weekend Show: https://www.meidastouch.com/tag/the-weekend-show Burn the Boats: https://www.meidastouch.com/tag/burn-the-boats Majority 54: https://www.meidastouch.com/tag/majority-54 Political Beatdown: https://www.meidastouch.com/tag/political-beatdown On Democracy with FP Wellman: https://www.meidastouch.com/tag/on-democracy-with-fpwellman Uncovered: https://www.meidastouch.com/tag/maga-uncovered Coalition of the Sane: https://meidasnews.com/tag/coalition-of-the-sane Learn more about your ad choices. Visit megaphone.fm/adchoices

Welcome to the Oncology Brothers podcast! In this episode, hosts Drs. Rahul and Rohit Gosain are joined by Dr. Stephen Liu from Georgetown Lombardi Comprehensive Cancer Center to discuss the latest and most impactful findings from the ASCO 2025 meeting, focusing on lung cancer. Join us as we dive into five key studies that could change clinical practice: 1. CheckMate 816: Discover the significant overall survival benefits of neoadjuvant chemotherapy combined with nivolumab in resectable non-small cell lung cancer. 2. Timing of Immunotherapy: Explore a groundbreaking study that reveals how the timing of immunotherapy infusions can dramatically affect patient outcomes. 3. NeoADAURA Trial: Learn about the use of osimertinib in the neoadjuvant setting for EGFR-mutated lung cancer and how it compares to established adjuvant therapies. 4. IMforte Study: Understand the implications of maintenance therapy in small cell lung cancer and how it can improve overall survival rates. 5. DeLLphi 304: Get insights into the efficacy of tarlatamab as a second-line treatment for small cell lung cancer and its potential to become the new standard of care. Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Tune in for an engaging discussion filled with expert insights, clinical pearls, and the latest advancements in lung cancer treatment. Don't forget to like, subscribe, and check out our other conference highlights! #OncologyBrothers #LungCancer #ASCO2025 #CancerResearch #Immunotherapy #EGFR #SmallCellLungCancer #NeoadjuvantTherapy #Podcast

Recorded live in Chicago, your hosts explore the latest in kidney cancer, discussing new five-year follow-up data from KEYNOTE-564, the long-term results of CheckMate 214, insights from the ongoing PDIGREE trial, and much more.The View on GU with Lalani & Wallis integrates key clinical data from major conferences and high impact publications, sharing meaningful take home messages for practising clinicians in the field of genitourinary (GU) cancers. Learn more about The View on GU: theviewongu.caThis podcast has been made possible through unrestricted financial support by Novartis, Bayer, Astellas, Tolmar, Ipsen, J&J, Merck, Pfizer, Eisai and AbbVie.

What was life like in Berlin in the immediate aftermath of the Second World War? Why did the Red Army steal taps from Berlin houses when they reached the city? Was the famous photo of the red flag on the Reichstag staged or authentic? Anita and William are joined by Giles Milton, author of Checkmate in Berlin: The Cold War Showdown That Shaped the Modern World, to discuss the division and destitution of the capital city after the Second World War.  ----------------- Empire Club: Become a member of the Empire Club to receive early access to miniseries, ad-free listening, early access to live show tickets, bonus episodes, book discounts, our exclusive newsletter, and access to our members' chatroom on Discord! Head to empirepoduk.com to sign up. For more Goalhanger Podcasts, head to www.goalhanger.com.  ----------------- Email: empire@goalhanger.com Instagram: @empirepoduk  Blue Sky: @empirepoduk  X: @empirepoduk Assistant Producer: Becki Hills Producer: Anouska Lewis Senior Producer: Callum Hill Learn more about your ad choices. Visit podcastchoices.com/adchoices

Most traders buy and sell with their gut and never get ahead of the market - so how can you follow the smart money without being in the weeds every day?  This week Ted Coaldrake and Pav Hundal are joined by James Check aka @_checkmate from X to talk about how to read the market, how to finally stop reacting to it and start looking ahead instead. Checkmate started as a data scientist at Glass Node in the early days of Bitcoin and is most well known for his educational videos that even Ted watched back in the day.  You'll hear: How everyone else's mistakes can give you the upper hand in the next cycle Why you need to stop reacting every time the market fluctuates - do this instead How can you tell if it's a pullback, correction or the end of a cycle? Where Bitcoin's going in 2025 based on how it's evolved over the years The metric James uses to divide the bulls and bears to stay in the game Are we on the way to Bitcoin's next bull cycle? You can find James on X over at @_Checkmatey_ and check out _checkonchain over at https://www.checkonchain.com/  Want to see what we're looking at every episode? Watch the YouTube version of the podcast here. Keen to join in TIC Tipping? Reset your demo mode and let us know your picks on @tappingintocrypto on instagram or X @tappingintocrypto Ready to start? Get $10 of FREE Bitcoin on Swyftx when you sign up and verify:  https://trade.swyftx.com.au/register/?promoRef=tappingintocrypto10btc  To get the latest updates, hit subscribe and follow us over on the gram @tappingintocrypto or X @tappingintocrypto If you can't wait to learn more, check out these blogs from our friends over at Swyftx. The Tapping into Crypto podcast is for entertainment purposes only and the opinions on this podcast belong to individuals and are not affiliated with any companies mentioned. Any advice is general in nature and does not take into account your personal situation, if you're looking to get advice, please seek out a licensed financial advisor

This is the final episode in the chapter of spiritual warfare, family betrayal, and psychic manipulation that Shelby and her husband have lived through. In this heartfelt, powerful closure, Shelby shares the final unraveling of the POA, the family power plays, and how surrendering everything brought total energetic freedom. Learn what really happened, how the curse was finally broken, and why walking away was the most powerful move they could make. This is the energetic conclusion. The new timeline begins now. Official Website #familykarma #breakingthecurse #spiritualfreedom #energeticsovereignty #walkawaystrong #soulcontracts #divinejustice #checkmate #psychicrelease

Keith Murphy and Andy Fales recap the eventful weekend before discussing the Pacers-Thunder matchup in the NBA Finals, and Magnus Carlsen losing. OTD in history, ThrowDowns and MORE! Presented by Ramsey Subaru. Learn more about your ad choices. Visit megaphone.fm/adchoices

Luke 22:1-23 (Checkmate) - Jamie Borchik by Park Community Church

Michiel Van Der Heijden joins us to discuss the Ipi/Nivo vs chemo randomization in this trial from his ASCO 2025 presentation

Dr. John Sweetenham shares highlights from Day 3 of the 2025 ASCO Annual Meeting, including new research for the treatment of advanced renal cell carcinoma and 2 studies on novel approaches in non-small cell lung cancer. Transcript Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham, the host of the ASCO Daily News Podcast, with my takeaways on selected abstracts from Day 3 of the 2025 ASCO Annual Meeting. Today's selection features studies addressing the treatment of advanced renal cell carcinoma and 2 studies exploring novel approaches in non-small cell lung cancer. My disclosures are available in the transcript of this episode. The first abstract is number 4505. This study, led by Dr. Toni Choueiri of the Dana-Farber Cancer Institute, describes the final analysis of the CheckMate 214 trial, which compared the combination of nivolumab and ipilimumab with sunitinib for the first-line treatment of advanced renal cell carcinoma. The ipi-nivo combination is approved for the frontline treatment of intermediate and poor-risk advanced renal cell carcinoma based on the primary analysis of the CheckMate 214 trial, which demonstrated a higher response rate and longer overall survival compared with sunitinib. Today's presentation provided the final safety and efficacy results for the trial with long-term follow-up of more than 9 years.  The intent-to-treat (ITT) population in this trial comprised 550 patients randomized to nivo and ipi versus 546 who received sunitinib. The final analysis showed sustained long-term benefit for the combination therapy. Patients given nivolumab plus ipi had a 29% reduction in the risk for death compared with sunitinib. For patients with intermediate or poor-risk disease, there was a 31% reduction in the risk of death.   The probability of remaining in response through 8 years was more than doubled with nivolumab plus ipilimumab versus sunitinib in the ITT population at 48% versus 19%, and in the intermediate and poor-risk population at 50% versus 23%. The other important observation is that patients with favorable-risk disease appeared to have a 20% reduction in the risk for death at 9 years and more durable responses. This suggests a possible delayed benefit for ipi and nivo in this group since these differences were not seen in the earlier analysis.   No new safety signals emerged with longer follow-up, and the results confirm the use of ipi and nivo as a standard front-line combination therapy in this disease. Since this combination has been in widespread use for some years, the results are not surprising although the subgroup analysis suggesting benefit in favorable-risk patients is likely to inform practice in the future.   Today's second abstract is number is 8506, which was presented by Dr. Tony Mok from the Chinese University of Hong Kong, describing results from the phase 3 HERTHENA-Lung02 trial. This trial compared the antibody-drug conjugate patritumab deruxtecan with platinum-based chemotherapy in patients with EGFR-mutated advanced non-small cell lung cancer following a third-generation tyrosine kinase inhibitor (TKI).  Patritumab deruxtecan, also known as HER3-DXd, comprises a fully human anti-HER3 IgG3 monoclonal antibody conjugated to a topoisomerase 1 inhibitor payload, and showed activity in a previous phase 2 trial in patients relapsing after EGFR TKI and chemotherapy.   In this phase 3 study, this agent was compared with platinum-based chemotherapy in eligible patients with an EGFR-activating mutation who had previously received 1 or 2 EGFR TKIs, at least one of which was a third-generation drug, with relapse or progression after this therapy. Five hundred and eighty-six patients were enrolled, with progression-free survival as the primary endpoint.  The primary analysis showed a 9-month progression-free survival of 29% for the experimental arm compared with 19% for platinum-based chemotherapy, for a hazard ratio of 0.77 and a P value of 0.011. With higher progression-free survival rates at 6 months and 12 months, HER3-DXd also had a better objective response rate (35.2% versus 25.3%) compared with platinum-based chemotherapy (PBC), and HER3-DXd also extended intracranial progression-free survival compared with PBC in patients with brain metastases, with a hazard ratio of 0.75. Grade 3 or more treatment-related adverse events occurred in 73% of patients treated with HER3-DXd and 57% of patients who received PBC. HER3-DXd had a higher rate of grade or more 3 thrombocytopenia, and drug-related interstitial lung disease occurred in 5% of patients in the HER3-DXd arm.   The follow-up will need more time to mature since no overall survival data are currently available, but definitely an agent to watch with interest. Moving on to today's final abstract, 8500, was presented by Dr. Pasi Jänne from the Dana-Farber Cancer Institute, describing results from the phase 2 portion of the KRYSTAL-7 study. This study is exploring the use of a potent KRAS inhibitor, adagrasib, in combination with pembrolizumab in patients with advanced or metastatic KRASG12C- mutated non-small cell lung cancer.  Adagrasib has already received accelerated approval in the U.S. for previously treated locally advanced or metastatic NSCLC with a KRASG12C mutation. A previous report from the KRYSTAL-7 study demonstrated encouraging activity in combination with pembrolizumab in the frontline setting for this patient group who also had more than 50% expression of PD-L1. The presentation today described efficacy and safety data for this drug combination across all PD-L1 expression levels.  One hundred and forty-nine patients with a median age of 67 years were treated with the combination, 104 of whom had PD-L1 expression level results available, representing the so-called biomarker population in this trial. The overall response rate for the entire study population was 44%. In the biomarker population, the overall response rate ranged from 36% in those with less than 1% PD-L1 expression to 61% for those with more than 50% expression. For all patients, the median response duration was just over 26 months, and the median progression-free and overall survival rates were 11 and 18.3 months respectively.    For the biomarker population, the median progression-free and overall survival were highest in those patients with more than 50% PD-L1. No new safety issues emerged from this analysis; the most frequent toxicities were nausea, diarrhea, and increases in transaminases. Immune-related toxicities included pneumonitis, hypothyroidism, and hepatitis. These are important results and the results of the phase 3 portion of KRYSTAL-7, which compares first-line therapy with adagrasib plus pembro versus pembro alone in the KRASG12C mutated/PD-L1 more than 50% group, will be informative. For those patients with lower levels of PD-L1 expression, the authors suggest that the treatment escalation may be beneficial, possibly including the addition of chemotherapy.  That concludes today's report. Thanks for listening and I hope you will join me again tomorrow to hear more top takeaways from ASCO25. If you value the insights that you hear on the ASCO Daily News Podcast, please remember to rate, review, and subscribe wherever you get your podcasts.  Disclaimer:  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  Find out more about today's speaker:    Dr. John Sweetenham    Follow ASCO on social media:     @ASCO on Twitter    @ASCO on Bluesky    ASCO on Facebook    ASCO on LinkedIn     Disclosures:   Dr. John Sweetenham:    No relationships to disclose

Shirley Collier, President and Founder of Scale2Market and Host of the Growth Masters Federal podcast was interviewed by Ken Rochon and Dr. Ken Smiley on how changes in the federal marketplace are affecting small contractors.

Making strides against melanoma: how can medical oncologists and interventional oncologists join forces to deliver smarter, patient-centered care? In this episode of BackTable, Dr. Tyler Sandow, hosts Dr. Sunandana Chandra, medical oncologist at Northwestern, and Dr. Riad Salem, interventional oncologist at Northwestern to discuss the evolving management of advanced melanoma. --- This podcast is supported by an educational grant from Replimune. --- SYNPOSIS The doctors open the episode with an overview of melanoma and recent advances in its treatment, highlighting key trials such as DREAMseq and CheckMate 067. The discussion explores the shift from medical oncologist as solo primary providers to a dynamic, multidisciplinary approach to advanced cancer care—emphasizing cutting-edge treatments like immunotherapy and intratumoral oncolytic viruses. Dr. Salem shares practical insights on the procedural techniques of administering intratumoral oncolytics like Replimune, emphasizing the importance of thorough documentation and patient-centered care. The doctors also provide an overview of the ongoing IGNYTE-3 Trial, a Phase 3 study assessing the safety and efficacy of the oncolytic immunotherapy RP1 in combination with nivolumab for the treatment of advanced melanoma. The episode underscores the transformative potential of innovative melanoma treatments and the crucial role of integrated, team-based approaches in improving cancer patient outcomes. --- TIMESTAMPS 00:00 - Introduction03:48 - The Evolution of Melanoma Treatment: From Chemotherapy to Immunotherapy14:05 - The Role of Oncolytic Viruses in Melanoma Treatment20:14 - Interventional Radiology's Role in Cancer Treatment27:00 - Collaborative Approach to Cancer Care32:53 - Hyper Documentation and Communication Efficiency44:47 - Future of Intratumoral Oncolytics48:10 - Multidisciplinary Approach in Advanced Cancer Management51:46 - Conclusion and Final Thoughts --- RESOURCES DREAMseq Trial: Atkins MB, Lee SJ, Chmielowski B, et al. Combination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced BRAF-Mutant Melanoma: The DREAMseq Trial-ECOG-ACRIN EA6134. J Clin Oncol. 2023;41(2):186-197. doi:10.1200/JCO.22.01763 CheckMate 067 trial: Wolchok JD, Chiarion-Sileni V, Rutkowski P, et al. Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma. N Engl J Med. 2025;392(1):11-22. doi:10.1056/NEJMoa2407417

We warmly welcome you to join Pastor Barry Blankenship in this Sunday morning message!

How God 'flipped the script' on Haman; learning that God will give victory no matter what it takes; a summary of Esther chapters 5-7. To support this ministry financially, visit: https://www.oneplace.com/donate/1213/29

Voice AI at the drive-thru is one or two years away from being ready to be rolled out to hundreds of thousands of locations, Checkmate CEO and founder Vishal Agarwal tells Bloomberg Intelligence. In this episode of the Choppin’ It Up podcast, Agarwal sits down with BI’s senior restaurant and foodservice analyst Michael Halen to discuss the rapid evolution of voice AI technology. He also comments on how kiosks have become a must have, the rapid growth of catering and what problems AI is best suited to solve. See omnystudio.com/listener for privacy information.

The OncoAlert

How God 'flipped the script' on Haman; learning that God will give victory no matter what it takes; a summary of Esther chapters 5-7. To support this ministry financially, visit: https://www.oneplace.com/donate/1213/29

In a legal sleight of hand, Republicans want to strip judges of their power to enforce rulings — because holding Trump in contempt might actually work…See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Vintage City Church // Checkmate // Steve AndersonWhen things go wrong in our lives, and unexpected circumstances shake our world, it can be easy to lose hope. But despite what happens, Jesus is always our Savior, Lord, and Hope.

On a stormy night filled with board games and boredom, two siblings answer a knock at the door — only to find two very strange visitors whose motives are anything but clear.FREE Word Search and Crossword puzzles, plus a fun Q&A for you and your kids to see how closely they were paying attenetion to the story! https://weirddarkness.com/mt-checkmateFind more family-friendly frights and creepy games to play on our website at http://MicroTerrors.com!Facebook page: https://www.facebook.com/microterrorsOther stories, novels, and more from author Scott Donnelly: https://amzn.to/3LymHaUOther narrations, podcasts, and audiobooks from voice artist Darren Marlar: https://WeirdDarkness.com= = = = = = = = = = = = = = = = = = = = = = = = = = = = = =Weird Darkness©, 2025Micro Terrors: Scary Stories for Kids™, 2025

On a stormy night filled with board games and boredom, two siblings answer a knock at the door — only to find two very strange visitors whose motives are anything but clear.FREE Word Search and Crossword puzzles, plus a fun Q&A for you and your kids to see how closely they were paying attenetion to the story! https://weirddarkness.com/mt-checkmateFind more family-friendly frights and creepy games to play on our website at http://MicroTerrors.com!Facebook page: https://www.facebook.com/microterrorsOther stories, novels, and more from author Scott Donnelly: https://amzn.to/3LymHaUOther narrations, podcasts, and audiobooks from voice artist Darren Marlar: https://WeirdDarkness.com= = = = = = = = = = = = = = = = = = = = = = = = = = = = = =Weird Darkness©, 2025Micro Terrors: Scary Stories for Kids™, 2025

Orrin 'Checkmate' Hudson | Mastering Chess, Inspiring Minds, and Changing Lives in Inner Cities. Chess Coach Based in Atlanta GA.

Hybrid Puzzle: The audio will tell you where each of the pieces on the board are, then read a series of moves from that position. When prompted, try to identify the best next move. To learn more about Don't Move Until You See It and get the free 5-day Conceptualizing Chess Series, head over to https://dontmoveuntilyousee.it/conceptualization FEN for today's exercise: 8/8/1pp5/2P4k/8/5K2/8/2Q5 b - - 0 1 PGN for today's exercise: 1... bxc5 2. Qxc5+ Kh4 { White to move. Checkmate in two. } * And the answer is... 3. Qf5 c5 4. Qg4#

Watch The X22 Report On Video No videos found (function(w,d,s,i){w.ldAdInit=w.ldAdInit||[];w.ldAdInit.push({slot:17532056201798502,size:[0, 0],id:"ld-9437-3289"});if(!d.getElementById(i)){var j=d.createElement(s),p=d.getElementsByTagName(s)[0];j.async=true;j.src="https://cdn2.decide.dev/_js/ajs.js";j.id=i;p.parentNode.insertBefore(j,p);}})(window,document,"script","ld-ajs");pt> Click On Picture To See Larger Picture As time goes on the people now can see the green new scam was a hoax, Bernie Sanders flies on private jet and Hawaii sues oil industry but spares refinery because they donate to the D party. Inflation is down, the fake news and the Fed were wrong. Trump once again calls on the Fed, he has now boxed them in.Transition to a people's economy is happening. The [DS] has lost all power. Trump has now signaled that he has the power and that the old guard has failed and it in the process of being replaced. What we are witnessing the forced exposure of the corrupt system, the people are seeing it. Now the offensive begins and those who were treasonous to this country will be held accountable. Checkmate. Economy https://twitter.com/mkhammer/status/1921181550239993909 https://twitter.com/libsoftiktok/status/1922302004904280481 https://twitter.com/thehill/status/1922270983534129248 (function(w,d,s,i){w.ldAdInit=w.ldAdInit||[];w.ldAdInit.push({slot:18510697282300316,size:[0, 0],id:"ld-8599-9832"});if(!d.getElementById(i)){var j=d.createElement(s),p=d.getElementsByTagName(s)[0];j.async=true;j.src="https://cdn2.decide.dev/_js/ajs.js";j.id=i;p.parentNode.insertBefore(j,p);}})(window,document,"script","ld-ajs");   https://twitter.com/WSJ/status/1922270583930167754 The inflation rate in the United States for April 2021, as measured by the Consumer Price Index (CPI), was 4.2% over the 12 months from April 2020 to April 2021 TRUMP ECONOMIC UPDATE: Inflation Drops to 2.3%, Lowest Since 2021, and US Treasury Records Second Biggest Surplus in History Thanks to Trump's Record Tariff Revenues  https://twitter.com/KobeissiLetter/status/1922268438912798730   https://twitter.com/RapidResponse47/status/1922277662560526415?ref_src=twsrc%5Etfw%7Ctwcamp%5Etweetembed%7Ctwterm%5E1922277662560526415%7Ctwgr%5E9a0647d641b176e03f79d37607411d8da3baf9a9%7Ctwcon%5Es1_c10&ref_url=https%3A%2F%2Fwww.thegatewaypundit.com%2F2025%2F05%2Ftrump-economy-update-inflation-drops-2-3-lowest%2F   Source: thegatewaypundit.com https://twitter.com/Peoples_Pundit/status/1922021412983730442 https://twitter.com/charliekirk11/status/1922286454119829804 https://twitter.com/TrumpWarRoom/status/1908318952838594601 @Taylor47 political class didn't do anything about it—they allowed it to happen!" @USTradeRep"The goal very clearly was to remove U.S. tariffs and trade barriers to make it easier for people to outsource to China." TAKE A LISTEN Trump Just Got Britain To Hit China, UK Politicians Say  British politicians are expressing alarm that the new U.S.–UK trade deal gives President Donald Trump the power to block Chinese investments in critical British infrastructure. The deal announced last week requires the UK to “promptly meet U.S. requirements” to shield supply chains and “relevant production facilities” from foreign investment. If the European country does not meet these requirements, the U.S. can reimpose tariffs, effectively using trade pressure to dictate which countries can invest in the UK's core infrastructure. That clause triggered immediate backlash from British lawmakers and media, who say the U.S. now has a de facto “veto” over foreign investment — specifically Chinese money flowing into the UK's steel and aluminum sectors.   “Washington wants the UK and others to peel away from Chinese trade and investment, especially in sensitive areas like steel,” said Allie Renison, a former trade official, speaking to the FT. Source: dailycaller.com

We are back with The Ledgermain parts 3 and 4. Which is also the conclusion to the Mystery of The Atom... We're looking at issues 61 and 62 of Suicide Squad... Batman, Superman, and Aquaman find out the truth about the death of Ray Palmer... and as the team's name implies... someone dies..... Feel free to e-mail us at taskforcex@headspeaks.com with your thoughts. Visit us on the web at http://taskforcex.headspeaks.com And let us know what you think.

Do product/CRO people REALLY know well? There may be some Dunning Kruger happening, and maybe we really don't get why they keep complaining about our initiatives. Spoiler: Many times, they have a VERY legitimate point! Who better than the freaking VP of Nielsen Norman Group "Checkmate" Kate Moran to come dish all the things we're getting wrong about UX, and how to better work together. We got into: - What product teams/CRO can learn from UX, and vice versa- Why product teams really need to focus on longer term relationships with the customer (and not chasing short term gains)- Amazing (and not so amazing) use cases for AI in UX Timestamps:00:00 Episode Start1:52 How Does UX View Experimentation / CRO?6:51 What Are The Biggest Problems UX Faces As An Industry?13:03 What Can CROs/Product Learn from UX (And Vice Versa)17:22 UX/Product Share This In Common: No One Knows What The Fuck We Do20:55 AI in UX - DON'T (!!!) Blindly Trust It26:56 What Is “Google Gullibility”? 30:51 Context Matters in UX38:05 Shiva Is Kinda Agegist (My Bad lol)Go follow Kate on LinkedIn: https://www.linkedin.com/in/kate-m-moran/ And check out Nielsen Norman's new live online courses!https://www.nngroup.com/training/live-courses/ Subscribe to our newsletter for more memes, clips, and awesome content! https://fromatob.beehiiv.com/If you have listener questions, submit them at https://tinyurl.com/askfromatob for a chance to be featured too!

In this Easter Sunday message, Greg shared with us how on the cross, God lured the rulers of this age into thinking that God could be defeated. However, what looked like defeat was ultimately the path to divine victory. Therefore, we can declare that what looks like Good Friday death is actually a precursor to resurrection victory.

Watch The X22 Report On Video No videos found Click On Picture To See Larger PictureDoug Burgum halted offshore wind project near NY, Gov Hochul tries to fight back. Foreign investors are dumping stocks.IMF issues warning, Trump is destroying their system. Trump is getting ready to drill baby drill. The Art of the Deal is in action. The [DS] has lost the narrative on MS-13 who was deported. The question is why are the Ds and the fake news concerned about this individual, does he know where the bodies are buried? Scavino sends a message puts up a picture of the President of El Salvador playing chess. What is the objective, in the end it will be checkmate king.   (function(w,d,s,i){w.ldAdInit=w.ldAdInit||[];w.ldAdInit.push({slot:13499335648425062,size:[0, 0],id:"ld-7164-1323"});if(!d.getElementById(i)){var j=d.createElement(s),p=d.getElementsByTagName(s)[0];j.async=true;j.src="//cdn2.customads.co/_js/ajs.js";j.id=i;p.parentNode.insertBefore(j,p);}})(window,document,"script","ld-ajs"); Economy Trump Admin Orders Halt To Offshore Wind Project Near New York Secretary of the Interior Doug Burgum said on April 16 that he had ordered a halt to the construction of a major wind project off the coast of New York “until further review.” Burgum, posting to the social platform X on Wednesday, said he had consulted with Commerce Secretary Howard Lutnick to direct the Bureau of Ocean Energy Management to “halt all construction activities” on Equinor's Empire Wind project. The Biden administration approved the project in 2023, with construction beginning last year. The interior secretary accused the former administration of “rush[ing] through its approval without sufficient analysis.” He did not provide further details on potential faults identified. “On day one, [President Donald Trump] called for comprehensive reviews of federal wind projects and wind leasing, and at Interior, we are doing our part to make sure these instructions are followed,” Burgum wrote in a follow-up post.   In response to the pause, New York Gov. Kathy Hochul said the project had already generated roughly 1,000 “good-paying union jobs” and is contributing to the state's economy. “This fully federally permitted project has already put shovels in the ground before the President's executive orders—it's exactly the type of bipartisan energy solution we should be working on,” Hochul wrote in a statement. “As Governor, I will not allow this federal overreach to stand. I will fight this every step of the way to protect union jobs, affordable energy, and New York's economic future.” According to the University of Maryland Center for Environmental Science, offshore wind farms “can be damaging to fish and other marine species” due to the noise and vibration from both the construction and operation of the wind turbines. Disturbing the sea floor during construction can also “affect plankton in the water column.” Source: zerohedge.com   https://twitter.com/KobeissiLetter/status/1912952517346070939  According to Apollo, foreigners own a massive $18.5 trillion of US stocks, or 20% of the total US equity market. Moreover, foreign holdings of US Treasuries are at $7.2 trillion, or 30% of the total. Investors from abroad also hold 30% of the total corporate credit market, for a total of $4.6 trillion. Foreign investors want out amid the volatility. IMF issues global economy warning The global economy is expected to grow more slowly this year and face higher inflation, the International Monetary Fund (IMF) has said, citing global trade disruptions and rising “protectionism.” Sweeping tariffs imposed by US President Donald Trump, which he says are focused on prioritizing domestic manufacturing and renegotiating trade deals in favor of the US, have caused a sharp rift with trade partners, including the European Union and China.

Watch The X22 Report On Video No videos found Click On Picture To See Larger PictureCEO Jamie Dimon is calling it, recession is coming. We are already in a recession, Trump will pull us out of it. Ds trying to stop Trump's tariffs. Countries ready to negotiate, Trump pauses tariffs for those countries. China and the EU fight back with reciprocal tariffs, this will not end well for them. Trump main target is the Fed. The [DS] is still trying to use judges to stop Trump's agenda, in the end this will fail. They are trying to use judges in the correct jurisdiction. Trump has set the timeline for the [DS] treasonous acts. Trump will show how the [DS] committed treasonous against the US. In the end Trump will have the final move, checkmate.   (function(w,d,s,i){w.ldAdInit=w.ldAdInit||[];w.ldAdInit.push({slot:13499335648425062,size:[0, 0],id:"ld-7164-1323"});if(!d.getElementById(i)){var j=d.createElement(s),p=d.getElementsByTagName(s)[0];j.async=true;j.src="//cdn2.customads.co/_js/ajs.js";j.id=i;p.parentNode.insertBefore(j,p);}})(window,document,"script","ld-ajs"); Economy https://twitter.com/KobeissiLetter/status/1909947842845614115   https://twitter.com/WallStreetMav/status/1909935573772738708 Schumer: We Want to Take Tariff Authority from Trump We Allowed Biden to Have Because Trump's ‘Going So Overboard'  Chuck Schumer (D-NY) r  “Congress has always had the power to deal with tariffs, and we've always had these fights in the past on some of the tariff issues as well. But now that Trump is going so overboard, Congress can, has every legal authority to take those powers back, and that's what we aim to do.”  Source: breitbart.com https://twitter.com/disclosetv/status/1909961646929301808 China is the Auto Capital of the World  China is the world's largest car producer and exporter. A little-known fact is that China first became the world's largest car exporter back in 2023, with low-cost EV companies BYD and Chery in the spotlight. The nation's auto sector has been steadily expanding since then, with Chinese brands reaching an all-time high of 69.4% of domestic passenger vehicle market share in Q1 2025. Overall, China exported 5.86 million vehicles in 2024, a 19.3% annual increase. Mexico, Russia, Brazil, and the UAE were the top buyers. China sold 4.96 million passenger vehicles (19.7% YoY increase), 900,000 commercial vehicles (17.5% YoY increase), and 1.28 million new energy vehicles, as well as 987,000 battery-electric vehicles. Japan is the world's second-largest car exporter, exporting 4.22 million vehicles in 2024. This marked a -4.5% decline from 2023. Toyota remains Japan's leading vehicle, accounting for $312.28 billion in revenue and 830,048 million vehicles. Germany is holding onto third place in auto exports. In 2024, Germany exported 3.4 million passenger cars, marking a 2.5% annual increase. Around 25.9% of all vehicles exported from Germany last year were electric. Volkswagen Group remains Germany's star, generating $354.86 billion in revenue for the year. Source: armstrongeconomics.com Scott Bessent Reminds China They Need Access To US Market Far More Than America Needs Access To Their Economy Treasury Secretary Scott Bessent warned that China's decision to retaliate against President Donald Trump's tariffs will ultimately backfire. China announced it is raising tariffs on American goods from 34% to 84% in response to Trump hiking tariffs on Chinese goods from 54% to 104%,   Bessent  thats because China exports far more to the U.S. than it imports, it has more to lose in a trade war. China exported $438.9 billion worth of goods to the United States in 2024 while the U.S. exported $143.5 billion to China, according to the U.S. Trade Representative. Consumer spending in America makes up nearly 70% of its Gross Domestic Product (GDP), according to J.P. Morgan Asset Management.

China has been taking advantage of America for years and Donald Trump has finally showed them who is in charge! Tariffs are being paused for dozens of nations but not for China, their tariffs have just been raised. Who will blink first? Guest: Tim Doesher - Executive Director, Committee to Unleash Prosperity Sponsor: My Pillow Www.MyPillow.com/johnSee Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Today's human civilization is still challenged by wars, atrocities, adversity, disturbing events, hardships, losses and so much more. But why? And how is this still possible? Aren't humans good? Aren't humans compassionate and caring? The truth is, not all humans are these very things, instead there is so much darkness and evil still occurring on this planet and people driven by things unexplainable to instigate and cause so much pain and suffering. In this episode you will begin to learn about Demons and demonic influence. The information in this episode stems from the Original Audio, Medical Medium Angels, Demons and Spiritual Tools. There are ways we can protect ourselves from so much we can't see. Get ready to hear the truth and to begin a journey applying powerful tools to protect yourself and the ones you love. In this episode… Discover why you should not fear the word “Demon”. Uncover how Demons might be affecting your life. Learn about “accidents” that happen, relationships that turn sour, dark actions that occur and what these incidents are truly about. Discover if, when bad things happen to someone, whether that person brought it upon themselves or not. Uncover the constant coverups that occur out there to hide the ongoing darkness that keeps truth from showing. Learn about the forces at work and the 16 Spiritual Lights of Free Will. All this and more, tune in and don't miss out on this important episode. You can revisit this episode anytime you need it. For more information visit www.medicalmedium.com