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This week Jordan and Lyndsey wrap up the series WandaVision, join us as we close out this series but open up Phase 4 of the MCU!

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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

In dieser Folge erhältst du praktische, tiefgehende Tipps, wie du mit deinen Schattenanteilen arbeiten kannst – also mit jenen verletzten inneren Anteilen, die dich unbewusst beeinflussen. Gerade jetzt, in dieser intensiven Phase der Zeitqualität, ist es entscheidend, Trigger bewusst zu erkennen, alte Muster zu durchbrechen und Heilung auf Herz- und Seelenebene zuzulassen.

Nach über vier Jahren eigener Erfahrung mit der Perimenopause, intensiver Selbsterforschung und vielen Weiterbildungen möchte ich heute mal wieder meine wertvollsten Erkenntnisse und auch Fehler, auf dem Weg, mit dir teilen. Ich hoffe, diese Folge ist hilfreich für dich und erkenntnisreich.1.) Intervallfasten kann kontraproduktiv sein, besonders wenn das Frühstück ausgelassen wird, da die morgendliche Leptin-Signalisierung für den Hormonstoffwechsel wichtig ist2.) "Intuitives Essen" funktioniert nicht immer - das Tracken von Blutzucker, Kalorien und Makronährstoffen kann wichtige Informationen liefern und langfristig zu mehr Freiheit führen3.) Krafttraining sollte individuell an den Hormontyp und die genetische Disposition angepasst werden, blinde Begeisterung kann zu Erschöpfung führen4.) Bioidentische Hormone können eine Option sein, sollten aber genotypisch passend eingesetzt werden5.) Unterschätzung des Schlafbedarfs ist in der Perimenopause besonders problematisch - viele Frauen benötigen in dieser Phase mehr als die gewohnten 6-7 Stunden6.) Bei Nahrungsergänzungsmitteln ist der Mineralstoffwechsel entscheidend - Eisen, Kupfer und Magnesium müssen im Gleichgewicht sein.Du musst meine Fehler nicht wiederholen. In meiner Hormon Glow Academy und meinen Masterclasses teile ich dieses Wissen, damit du leichter durch diese Lebensphase navigieren kannst. Denn der Glow steckt bereits in dir – er muss nur aktiviert werden.Wenn dir dieser Podcast gefällt, freue ich mich über dein Herzchen und Rating bei Apple, Spotify und Co. Spread the Glow und teile diese Folge gerne mit all deinen Freundinnen. Möchtest du mehr über meine Angebote, Yoga und Coachings erfahren? GANZ NEU: Mach den Leptin-Test: Finde heraus, ob du "Leptin-Resistent" bist und ob das vielleicht der Grund für deine hormonellen Schwankungen ist. www.soulglowveda.de Mehr über meine Angebote für Deine Hormongesundheit: www.soulglowveda.com oder folge mir auf Instagram Buch dir dein kostenloses Beratungsgespräch- ob Coaching, Hormon Glow Academy, Astrologie. Ich berate dich gerne:https://www.soulglowveda.com/consultationHormon Glow Academy - im Oktober 2025 geht es wieder los. Jetzt Early Bird sichernHormon Glow Academy- AusbildungsbroschüreDu findest mich auf Instagram unter: https://www.instagram.com/soulglowveda_claudia/

Mit "Ironheart" (3:42) geht die letzte Marvel-Serie aus Phase V des MCU an den Start - eine Phase, die mit "Secret Invasion" katastrophal begonnen hat. Kann die Serie über ein junges, weibliches, afroamerikanisches Pendant zu "Iron Man" für einen versöhnlichen Abschluss sorgen? Die Tatsache, dass Disney+ sie innerhalb von nur acht Tagen versendet spricht zumindest für wenig Selbstvertrauen seitens der Macher. Andererseits erinnert Holger, Michael und Rüdiger das Abenteuer grundsätzlich an "Ms. Marvel", die ihrer Meinung nach frischen Wind in das MCU gebracht hatte. Im Anschluss geht es um die letzte Staffel des Netflix-Überhits "Squid Game" (32:50), der in der zweiten Staffel allerdings 30% an Zuschauerschaft und einiges an Goodwill verloren hatte. Können die letzten sechs Folgen, von denen Netflix die ersten fünf zur Verfügung gestellt hat, das Ruder wieder herumreißen? Cold-Open-Frage: "Wo sollte die nächste Staffel ,White Lotus' gedreht werden?"

Die Temperaturen steigen immer weiter und wir befinden uns auf der heißen Phase was Transfers angeht. Ein paar Vereine spielen im Moment noch um den Titel bei der Klub-WM und andere werden sich bald für die Pre-Season melden. Doch was hat sich bisher getan? Genau hier setzen Niki & Chrisi in der neuesten Ausgabe an. Der englische Meister beispielsweise lockt Florian Wirtz an mit einem großen Transferpaket. Was bedeutet das für die Aufstellung der Mannschaft von Slot. Manchester City war auch bereits sehr aktiv und Verstärkung ist hier um Kevin De Bruyne zu ersetzen. Wie wird das Leben der Citiyzens ohne den Belgier aussehen? Außerdem sprechen wir über den momentanen Zwangsabstieg von Olympique Lyon. Was ist passiert und gibt es noch eine Rückkehr aus der Misere? All das und noch viel mehr in der neuesten Folge des Halbzeit Podcast! 

MLB: Shohei Ohtani Earns Most Phase 1 All-Star Votes in National League

Los Angeles Dodgers superstar Shohei Ohtani earned most votes in the National League in Phase 1 of All-Star voting, Major League Baseball said Thursday.

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

AP's Lisa Dwyer reports on another well known company that is fazing out artificial dyes.

大谷翔平選手【ロサンゼルス時事】米大リーグ機構は２６日、オールスター戦の先発野手を選ぶファン投票の１次の結果を発表し、ナ・リーグ指名打者部門の大谷翔平がナ最多の３９６万７６６８票を集め、５年連続５度目の選出が決まった。 Los Angeles Dodgers superstar Shohei Ohtani earned most votes in the National League in Phase 1 of All-Star voting, Major League Baseball said Thursday.

Parents know well the high costs of raising children. Certainly, this affects our ability to save for retirement or meet other financial goals, but what about when our kids leave home? How do empty nesters tend to respond financially, and psychologically? Work from Andrew Biggs, a Senior Fellow at the American Enterprise Institute and author of The Real Retirement Crisis: Why (Almost) Everything You Know About the US Retirement System is Wrong, finds that the period after our children become financially independent can have a big impact on retirement readiness. On this episode of The Behavioral Divide, host Hal Hershfield, discusses the research with Dr. Biggs along with real-world perspective from Certified Financial Planner Robin Sherwood, who serves as a Principal at HTG Investment Advisors. We look at how the empty-nester phase—and life transitions in general—can shape financial choices and personal fulfillment, and what can be done to make both better. The book The Real Retirement Crisis: Why (Almost) Everything You Know About the US Retirement System is Wrong is not affiliated with, sponsored by, or endorsed by Avantis Investors or American Century Investments.  If you enjoy the show, please let us know by giving our series a five-star rating. We'd also love to hear from you. To join in on the discussion, send us a note at BehavioralDivide@AvantisInvestors.com. Important Disclosures The views expressed in this presentation are the speaker's own and not necessarily those of American Century Investments. This presentation is for general information only and is not intended to provide investment, tax or legal advice or recommendations for any particular situation or type of retirement plan. Please consult with a financial, tax or legal advisor on your own particular circumstances. Hal Hershfield is not affiliated with American Century Investments. Follow us on social media: LinkedIn: https://a.vant.is/409KwhI X: https://a.vant.is/3HKHwSL

Der FC Bayern hat den Gruppensieg bei der Klub-WM gegen Benfica verspielt und muss nun gegen Flamengo ran. Woran es in der Hitze von Charlotte scheiterte und was Bayern in der nächsten Runde erwartet, erklärt kicker-Reporter Georg Holzner. Außerdem: Wirtz weg, Frimpong weg, Tah weg - wie geht es in Leverkusen weiter?

Wed, 25 Jun 2025 03:45:00 +0000 https://jungeanleger.podigee.io/2363-borsepeople-im-podcast-s19-14-markus-leitgeb 6c1271378f508e3119d10c17817a671f Markus Leitgeb ist Postler, Pressesprecher, Kommunikationsmanager und Storyteller bei der Österreichischen Post. Und er ist mein erster Gast, der seine Anmoderation selbst übernommen hat, also jetzt nicht direkt, aber ich wars auch nicht. Mit einem Kärntner starte ich natürlich in Kärnten und dort im Medien- und Social Media-Geschäft, dann reden wir über eine spannende Phase bei Wiener Wohnen beim Gasometer und schliesslich den Wechsel zur Post wenige Tage vor Covid Und wir holen weit aus: KI, Postcrossing, Markus 4 Weekly, die Dittelgasse mit Ernst Nevrivy, Nachhaltigkeit, Videocalls mit Katzen, das Laufen, es gibt diesmal sogar einige Prüfungsfragen, sehr souverän beantwortet alles. https://www.linkedin.com/in/markusleitgeb/ https://www.post.at About: Die Serie Börsepeople des Podcasters Christian Drastil, der im Q4/24 in Frankfurt als "Finfluencer & Finanznetworker #1 Austria" ausgezeichnet wurde, findet im Rahmen von http://www.audio-cd.at und dem Podcast "Audio-CD.at Indie Podcasts" statt. Es handelt sich dabei um typische Personality- und Werdegang-Gespräche. Die Season 19 umfasst unter dem Motto „25 Börsepeople“ 25 Talks. Presenter der Season 19 ist die Volksbank https://www.volksbank.at. Welcher der meistgehörte Börsepeople Podcast ist, sieht man unter http://www.audio-cd.at/people. Der Zwischenstand des laufenden Rankings ist tagesaktuell um 12 Uhr aktualisiert. Bewertungen bei Apple (oder auch Spotify) machen mir Freude: http://www.audio-cd.at/spotify , http://www.audio-cd.at/apple . 2363 full no Christian Drastil Comm. 1856

Input geben - Networking starten!Die Welt der Conversational AI hat sich mit dem Aufkommen von ChatGPT fundamental verändert. Wie reagieren etablierte Plattformen auf diese Revolution? In diesem faszinierenden Gespräch treffe ich Sebastian von Rasa, einem Pionier im Bereich der Chatbot-Entwicklung, mit dem meine eigene KI-Reise einst begann.Nach einer Phase der Zurückhaltung gegenüber Large Language Models hat Rasa nun ein beeindruckendes Comeback hingelegt. Sebastian stellt das innovative CALM-Framework vor – Conversational AI mit Large Language Models. Dieses verbindet die strukturierte Welt der klassischen Natural Language Understanding mit der Flexibilität moderner Sprachmodelle. Das Ergebnis? Vollständige Kontrolle über die KI-Antworten ohne auf die Vorteile von LLMs verzichten zu müssen.Besonders spannend: Die "Temperatur"-Einstellung ermöglicht eine präzise Steuerung, wie kreativ das System antworten darf – von strikt vordefinierten Antworten bis hin zu personalisierten Formulierungen, die sich an unterschiedliche Zielgruppen anpassen. Mit einer Zeitersparnis von 80% bei der Entwicklung und der Möglichkeit, jedes beliebige LLM zu nutzen, bietet Rasa eine vielversprechende Lösung für Unternehmen mit hohen Sicherheitsanforderungen, die dennoch von den Fortschritten der KI profitieren möchten.Entdeckt mit uns, wie die Zukunft der Conversational AI aussehen könnte – eine Welt, in der wir nicht mehr "prompt and pray" praktizieren müssen, sondern echte Kontrolle über KI-gestützte Kommunikation behalten. Hört jetzt rein und schreibt uns eure Gedanken zur Verbindung von strukturierter KI und Large Language Models! Support the showVielen Dank an unsere Starken Podcast-Partner CreaLog Software-Entwicklung und Beratung GmbH und VIER. Und als Medienpartner mit dabei CMM360.Ihr wollt mehr Networking? Dann kommt in meine WhatsApp Gruppe zu aktuellen Trends und News rund um AI und Chatbots: https://chat.whatsapp.com/BilAa1OLfELKJwuyodKgkXWeitere Links:Sophie auf WhatsApp kontaktierenSophie per Mail anfragenSophies WebseiteUnd noch mehr zu AI und Bots könnt ihr hier lesen.

Trump announced a ceasefire, claiming that Israel and Iran both approached him asking for peace. Plus, IDF says Iran launched missiles towards Israel as ceasefire nears. And, FBI and DHS warn of heightened threat environment in U.S. Learn more about your ad choices. Visit podcastchoices.com/adchoices

Episode Summary Join Dr. Eric Balcavage and Dr. Kelly Halderman for this milestone 200th episode of Thyroid Answers! This comprehensive discussion covers the evolution of thyroid care, key lessons learned from treating hundreds of patients, and the future of thyroid recovery. Dr. Eric shares his 70% patient recovery rate and explains why the shift from management to recovery is revolutionizing thyroid care. Key Topics & Timestamps

Jackson Moody has been the Foundation Phase Lead Coach at Aston Villa for 8 years. Jackson discusses his role at one of the biggest clubs and most successful academies in the country.

It wasn't a phase, mom will go over the life and crimes of teens and young adultsIn this episode of Murder Bucket, part of the It Wasn't a Phase, Mom series, we dive deep into the harrowing case of the Richardson Family Murders. What started as a seemingly normal family life took a dark and devastating turn that shocked the community. Join us as we explore the events leading up to the tragedy, the chilling details of the crime, and the aftermath that left an indelible mark. Prepare for a gripping true crime story that reminds us just how fragile life can be.Follow us on all social media!Facebook - ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.facebook.com/bucketmurd⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Twitter - ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://twitter.com/TheMurderBucket⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Instagram - ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.instagram.com/murdbucket/⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠TikTok -⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.tiktok.com/@murderbucketpod⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://murderbucketpod.wordpress.com/⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠

„Jetzt beginnt Phase zwei der Zeitenwende“, sagte gerade der deutsche Außenminister in einem Interview mit dem Spiegel. Wenn aktuell die zweite Phase einer Politik der Kriegstreiberei anläuft, wie sieht dann die dritte Phase aus? Der offene Weltkrieg? Die „Zeitenwende“ ist eines der schlimmsten Propagandastücke, das die Mächtigen je auf der Bühne der Republik aufgeführtWeiterlesen

Finishing up a cycle of relief and refreshment

The Taoiseach Micheal Martin has rejected comments that the Irish government's co-operation with the Omagh Bombing Inquiry has been “wholly unsatisfactory”. Reporter Una Kelly was at the inquiry to discuss.

In dieser Episode sprechen wir mit Martina Konrad – erfahrene Hebamme, die seit mittlerweile 25 Jahren mit Leidenschaft werdende Eltern begleitet. Sie teilt in dieser Folge ihr geballtes Wissen und wertvolle Praxistipps. Wir hoffen, diese Folge gibt euch wertvolle Einblicke und begleitet euch auf dem Weg zu einer sicheren und entspannten Schwangerschaft!Wir möchten darauf hinweisen, dass wir über ein aufwühlendes Thema sprechen. Wenn ihr euch aktuell in einer schwierigen Phase befindet oder euch das Thema belastet, hört diese Episode bitte nur, wenn ihr euch dazu bereit fühlt. Denkt daran, es ist völlig in Ordnung, Pausen einzulegen oder die Episode zu einem späteren Zeitpunkt anzuhören. Wir klären heute folgende Fragen:Was sind die häufigsten Ursachen und Risikofaktoren für eine Frühgeburt?Wie wirken sich Infektionen auf das Frühgeburtsrisiko aus, und welche Vorsichtsmaßnahmen gibt es?Warum sind Mehrlingsschwangerschaften oft risikobehaftet?Welche Rolle spielt Ernährung in der Schwangerschaft?Warum sind regelmäßige Vorsorgeuntersuchungen essenziell?Wie beeinflussen Rauchen und Alkohol das Frühgeburtsrisiko?Was ist eine Progesterontherapie, und wie hilft sie?Welche Rolle spielen Lungenreifespritzen und Tokolyse?Wann wird eine Zervixcerclage empfohlen, und wie funktioniert sie?Wie kann Stress das Risiko einer Frühgeburt erhöhen?Welche Entspannungstechniken und Routinen helfen in der Schwangerschaft?Warum ist emotionale Unterstützung durch Familie und Fachleute so wichtig?Welche Alltagsroutinen und Selbstpflege-Tipps könne helfen, eine Frühgeburt vorzubeugen?Wie kann man Veränderungen oder Warnsignale des Körpers besser erkennen?Für die aufregenden Monate vor der Geburt schau doch mal in unsere Schwangerschafts-App [https://keleya.de/schwangerschafts-app/]. Interessante Informationen, hilfreiche Praxistipps und wertvolle Anregungen warten auf dich. Außerdem gibt es eine tägliche Hebammensprechstunde sowie viele Livekurse rund um Schwangerschaft, Geburt und Babyzeit zu entdecken.Du bist schon Mama? In der keleya Mama App findest du unsere Kurse zur Rückbildung, zum Stillen sowie zur Beikosteinführung, für mehr Mindfulness, zum Babyschlaf, für das Wochenbett, zur Ersten Hilfe sowie Vieles mehr. Zudem haben wir für dich interessante Artikel, Videos und Audios speziell für das erste Baby-Lebensjahr zusammengestellt. Hier geht's zur Mama-App [https://keleya.de/mama-app/].Vielen Dank an Martina. Du kannst sie in unserer Hebammensprechstunde [https://keleya.de/hebammen-sprechstunde/] und unseren Livekursen [https://kinderheldin.de/kursuebersicht] antreffen.Danke für dein Interesse und Vertrauen. Von Herzen,Dein keleya Team… folge uns gern bei Instagram [@keleya.app] und Facebook [@getkeleya]. Hosted on Acast. See acast.com/privacy for more information.

Send us a textMany direct-to-consumer brands get stuck in the early stages of growth. This video breaks down the four phases every brand faces, from founder-led growth to omnichannel expansion. Understand what holds back revenue at $50K, $250K, and beyond.Ready to grow faster on Amazon? Book a call and let the experts take over: https://bit.ly/4jMZtxu#DirectToConsumer #EcommerceGrowth #BrandScaling #StartupTips #amazonDTCTimestamps:00:00 - Why Direct-to-Consumer Brands Struggle00:27 - Phase 1: Founder Growth Explained01:23 - Phase 2: The Paid Media Trap02:55 - Phase 3: Lifetime Value and Conversion Rate Focus04:46 - Phase 4: Omnichannel Expansion06:13 - Secret Phase 5: Becoming a Household Name06:51 - When Should You Hand Over the Reigns?----------------------------------------------Follow us:LinkedIn: https://www.linkedin.com/company/28605816/Instagram: https://www.instagram.com/stevenpopemag/Pinterest: https://www.pinterest.com/myamazonguys/Twitter: https://twitter.com/myamazonguySubscribe to the My Amazon Guy podcast: https://podcast.myamazonguy.comApple Podcast: https://podcasts.apple.com/us/podcast/my-amazon-guy/id1501974229Spotify: https://open.spotify.com/show/4A5ASHGGfr6s4wWNQIqyVwSupport the show

In this live episode from the LSI conference in California, Etienne Nichols is joined by Ashkon Rasooli to break down what it really takes to build a high-performing quality management system (QMS) in medtech—from startup chaos to post-market scale. Ashkon shares a phased approach to aligning QMS implementation with product development, explains the concept of "enforcement points," and reveals how founders can reduce the burden of compliance by starting small and planning ahead. If you're navigating regulatory requirements while trying to stay innovative, this episode is your roadmap to smarter, leaner quality.Key Timestamps00:02 – Introduction to Greenlight Guru and medtech process integration01:15 – QMS evolution from startup to commercialization03:00 – Phase-based product development overview (Phases 0–6)06:35 – Why QMS should follow product needs, not just regulatory triggers09:10 – Agile vs. proceduralism in quality systems11:50 – Building a quality culture during the feasibility phase15:25 – When to implement QMS controls and how to prepare for “enforcement points”18:40 – Investor-driven and regulatory QMS triggers21:10 – How early QMS planning saves time and reduces future remediation26:20 – Ashkon's final advice for startups: start small and stay proactiveStandout Quotes"You've got to take the BS—being burdensome—out of QMS."Ashkon Rasooli redefines QMS as a project management tool, challenging the notion that compliance must be a burden. This quote encapsulates his philosophy of proactive, phased implementation that actually enhances product development."Start small and do a little bit at a time—it won't seem like a burden."A practical mantra for startups, this advice underscores how a gradual, well-aligned QMS rollout can prevent last-minute fire drills and wasted effort.Top TakeawaysUse the "Phase 0–6" Model to Guide QMS Rollout – Align QMS implementation with the stages of product development to ensure each step supports the next.Don't Wait for Enforcement Points – Start building your QMS before regulators or investors demand it to avoid remediation-heavy implementations.Prioritize Culture Before Controls – In early feasibility, focus on aligning your team with medtech's safety responsibilities, rather than formal procedures.Procedures Should Support Outcomes, Not Just Check Boxes – Avoid proceduralism by tying every process back to its intended quality objective.Regulatory Strategy = Investor Strategy – QMS maturity is increasingly scrutinized during due diligence. Treat it as a value driver, not just a cost.ReferencesAshkon Rasooli on LinkedInGreenlight Guru – Quality management software for medical devicesEtienne Nichols on LinkedIn – Connect with the hostISO 13485 vs. ISO 9001 – Explains how medical device quality systems build on general standardsISO 14155 Overview – Relevant for clinical validation proceduresMedTech 101: What Are “Enforcement Points”?In the context of QMS, enforcement points are moments when external stakeholders (regulators or investors) require proof of formalized processes. Think of it like a driver's license checkpoint—you may be cruising just fine, but at that moment, you must prove you're compliant. The earlier you prep for them, the smoother your...

The trial of Jesus is really a trial of all those around him. Peter hits rock bottom as he denies Jesus three times, and Annas fails to grasp his own need for Jesus. Peter's story is our story: repeated failing, yet restored by the faithfulness of Christ. His story reminds us that Jesus can bring us back from the brink if only we would turn to Him. Our God is high and lifted up, but He also has compassion on those who have hit rock bottom: “For thus says the One who is high and lifted up, who inhabits eternity, whose name is Holy: ‘I dwell in the high and holy place, and also with him who is of a contrite and lowly spirit, to revive the spirit of the lowly, and to revive the heart of the contrite.” (Isaiah 57:15) Take-Home Message: Christ's faithfulness triumphs over my failures.  Christ's faithfulness triumphs over… My failure to see reality (12-14). The Trial of Jesus Phase 1 of Jewish trial: Jesus before Annas (Jn. 18:12-14, 19-23). Phase 2 of Jewish trial: Jesus before the Sanhedrin (Matt. 26:57-68). Phase 1 of Roman trial: Jesus before Pilate (Jn. 18:28-38a; Matt. 27:11-14). Phase 2 of Roman trial: Jesus before Herod Antipas (Lk. 23:6-12). Phase 3 of Roman trial: Jesus before Pilate again (Jn. 18:38b-19:16; Matt. 27:15-31). My failure to follow boldly (15-18). Why did Peter deny Jesus?Wrong expectation Wrong confidence Wrong urgency My failure to recognize authority (19-24). My failure to stop failing (25-27). Message: The Trial and Denial of Jesus Scripture: John 18:12-27 Simple. Authentic. Jesus. Prairiebible.org

A solicitor representing some of the bereaved families and survivors of the Omagh bombing has criticised the Irish government for what he called a failure to co-operate fully with the inquiry process. He was speaking at a hearing in Omagh today at the second phase of the inquiry into the atrocity, our reporter Una Kelly was there.

In dieser Folge nehmen Dich Rieke und Katharina mit in die letzten Tage vor der Geburt von Riekes drittem Kind. Nach zwei schweren Geburten war diesmal vieles anders: Die Geburt sollte als Kaiserschnitt stattfinden – aber erst, wenn das Baby bereit war. Wie Rieke diese besondere Phase erlebt hat, welche körperlichen und emotionalen Prozesse sie durchlaufen hat – und welche 3 Learnings sie rückblickend aus dieser Geburt für sich mitnimmt, erfährst Du in dieser Folge. ✨ Eine ehrliche, persönliche Episode über Loslassen, Vertrauen und den eigenen Weg. Viele Spaß beim Zuhören, deine Mamacademy Mehr zu unseren Kursen & Social Media, sowie unseren Werbepartnern findest Du hier: Shownotes

Die Zeichen stehen weltweit auf Krieg: Vor den Toren Europas eskaliert der Krieg zwischen Israel und Iran im Nahen Osten. Mit dem Angriff der USA auf den Iran ist nun eine neue Phase erreicht worden – darin ist sich die Presseclub-Runde einig. Von WDR 5.

FBI Releases Secret Docs Exposing Mass Voter Fraud, Article by John Zmirak. Trump- Don't Let the Rioters Win and Gold Has Entered 3rd & FINAL Phase: Why $10,000 oz Could Be Coming.   FBI Releases Secret Docs Exposing Mass Voter Fraud John Zmirak. Trump Learned the Bitter Lesson of 2020: Don't Let the Rioters Win Gold Has Entered 3rd & FINAL Phase: Why $10,000 oz Could Be Coming   FBI Releases Secret Docs Exposing Mass Voter Fraud to Rig 2020 Election Against Trump! FAKE Ballots Watch this video at- https://youtu.be/SfK7CHs9ABw?si=39TbBb7dcAc39zo4 Benny Johnson 4.77M subscribers 158,699 views Jun 17, 2025 This story is INSANE! BECOME A MEMBER:    / @bennyjohnson   FOLLOW OUR NEW CHANNELS: Benny On The Block:    / @bennyontheblock   Benny's Brews:    / @bennysbrews   FOLLOW BENNY ON SOCIALS: https://www.bennyjohnson.com/follow CHECK OUT OUR MERCH: https://shop.bennyjohnson.com/ Sign up for The Benny Newsletter: https://www.bennyjohnson.com/newsletter SUBSCRIBE TO THE PODCAST https://www.bennyjohnson.com/thebenny...   Gold Has Entered 3rd & FINAL Phase: Why $10,000 oz Could Be Coming | Mike Maloney Join Mike Maloney, best-selling author and seasoned gold investor, as he unveils the third and final stage of gold's monumental bull market. In this eye-opening presentation, Mike draws compelling parallels between today's gold surge and the infamous 1970s gold rush — when prices soared 25x in just months. Discover why gold and silver are “Giffen goods” — assets that gain demand as prices rise — and how global fear, greed, and economic instability could ignite the Great Gold & Silver Rush of the 21st Century. Backed by 20+ years of research, historic data, and insider insights, this video reveals: Why institutional and media attention signals a coming stampede How modern markets are primed for a price explosion Why gold could surpass $3,000... $5,000... even $10,000 per ounce If you think gold's best days are behind it, think again. Watch this video at- https://youtu.be/dxr_9zdGmZA?si=E_kn2PyAHqR7-E04 GoldSilver 824K subscribers 58,592 views Jun 17, 2025 Get Mike Maloney's 1st book for free here: http://www.GoldSilver.com/freebook ----------------------------------------------------------------- GoldSilver is one of the most trusted names in precious metals. Since 2005, we've provided investors with both education and world-class bullion dealer services. We offer a wide selection of bullion products, private vault storage, global shipping, and easy payment choices. Buy Precious Metals at: https://www.goldsilver.com Get Free content from Mike's new book here: http://www.ggsr21.com Subscribe to our channel: https://www.youtube.com/c/goldsilver?... Get Essential Gold & Silver News—Delivered Twice a Week: https://goldsilver.com/join-our-newsl... Follow Mike on Twitter:   / goldsilver_com   Follow us on Facebook:   / goldsilverdotcom   Check out our sister channel Wealthion @Wealthion featuring regular guests such as Jim Rickards, Rick Rule, Stephanie Pomboy, Lance Roberts, John Hathaway, Alisdair McLeod, Simon Hunt, John Rubino, Jim Rogers, Marc Faber and more. As always, thank you for your support. M.   Article by John Zmirak: John Zmirak. Trump Learned the Bitter Lesson of 2020: Don't Let the Rioters Win Find the article at- https://stream.org/trump-learned-the-bitter-lesson-of-2020-dont-let-the-rioters-win/   Trump Learned the Bitter Lesson of 2020: Don't Let the Rioters Win By John Zmirak Published on June 12, 2025 As gangs of illegal aliens and radical activists attack ICE officers and now local police in the streets of Los Angeles, I'm reminded of the race riots of 2020, and the mistakes most of us made while they were happening. In case you've blotted those ugly memories from your mind, let's review what happened in the aftermath of the botched arrest of career criminal George Floyd:   The police officers involved were immediately pulled from duty, then quickly arrested and charged. The System was working. There was literally nothing to riot about, except the vague and tendentious claim that “systemic racism” was killing black Americans. The Marxist group Black Lives Matter used Floyd's accidental death as a bloody shirt to wave around, demanding (and getting) hundreds of millions of dollars from large corporations to spend however it wished (for instance, on fancy homes and salaries). Conservative pundits and churches adopted that organization's mantra and offered uncritical support — desperate to establish their “antiracist” bona fides and protect their reputations. A series of coordinated “protests” erupted across the country, demanding that governments defund the police. Over and over, these protests turned violent, devolving into riots that saw the looting of neighborhoods poor and rich alike. Our media gaslit us with reports that these events were “mostly peaceful,” even as fires lit by arsonists raged on camera in the background. In blue states like Minnesota and California, Democrat governors who were savagely enforcing COVID lockdowns allowed the rioters to run free — pulling police from the scene and refusing to use their National Guards to protect citizens and their property. This was the starkest example of anarcho-tyranny in U.S. history … until the January 6 fedsurrection, that is. People who sneered when black entrepreneur and former presidential candidate Herman Cain died of COVID after attending a Trump campaign event and insisted that in-person voting was too dangerous to be allowed defended the riots publicly from the charge that they were “superspreader events.” Their excuse? “Racism is a threat to public health.” Trump did not federalize the National Guard in those rogue states to impose law and order. Like many of his supporters, and likely the advisors who convinced him to remain inert, I reasoned, “Let the blue cities burn. We'll make sure the federal government doesn't pay to rebuild them. The Left is trying to trap Trump into overreacting by using force in the hope that civilians will suffer and he will look like the dictator they've been calling him since Election Night 2016.” I now realize Step 6 was a huge mistake, as I'm sure Trump and his team had the chance to reflect on during the four years of lawfare and chaos they all endured under The Secret Committee Formerly Known As Joe Biden.   Now, we need to analyze why this is true so we can give full-throated support to restoring the rule of law today.   Abandoning Territory to Marxist Gangs Is Wrong Donald Trump is president of the entire United States, and he works for every American. That includes law-abiding citizens in blue states and cities who might not support mayors and governors committed to flouting U.S. laws on immigration, citizenship, and public order. Trump represents the harried, hunted police who work in Los Angeles and the taxpayers forced to fund the health care, education, and even transgender treatments of millions of illegal aliens the Biden regime let in.   We're supposed to love our neighbor. At minimum that includes our fellow Americans — even those deluded enough to believe that we owe citizenship and welfare payments to foreigners who broke into our national home. Just as we shouldn't hand out free heroin to addicts and shrug at the thought that they might OD, we shouldn't hand anarchy to Californians and Minnesotans, even if it's what they say they want. “Stinks to be you” isn't a New Testament maxim.   When Moderation Looks Like Weakness, It Is Weakness Letting blue cities burn or sink in their own squalor sounds tempting. However, it's not just a crime: it's a blunder, as political philosopher Yoram Hazony points out.   The spectacle of U.S. cities roiling with chaos, falling into the hands of Leftist mobs waving foreign flags, makes America look weak and vulnerable in the eyes of its foreign enemies. Furthermore, it makes any president who presides over it seem like a wounded, crippled giant. That was true in 2020, and it's even truer today — when the riots are aimed not at some nebulous, made-up bogeyman like “systemic racism” or “whiteness,” but directly at the law enforcement policies that got Trump elected and are, rightly, very popular: mass repatriation of blatantly illegal aliens.   These riots are aimed at Trump as a leader and his voters as citizens. They are armed, organized efforts to deprive the U.S. government of its legitimate monopoly on violence in large swathes of its territory. If Trump isn't willing to take every legal, constitutional measure to crush them and punish the perpetrators, he might as well resign right now and flee with his family into exile like the former Shah of Iran. Of course, that would leave all of us under a revolutionary tyranny every bit as ugly as Iran's.   Mobs Follow the Strong and Scorn the Weak It's a sad fact of fallen human nature: A high percentage of people don't join causes or adopt opinions because of rational argumentation, or even moral sentiments. People flock to the strong and steadfast, and naturally feel contempt for those who lack the courage of their convictions.   One of the main reasons that George Washington became first a national hero, then our leader in the fight for independence, was his obvious personal fearlessness. Bullets whizzed past him, shot through his hat and even his coat, and he was unperturbed. By contrast, the rival General Horatio Gates who sought to replace Washington at the head of the Continental Army disgraced himself by fleeing a 1780 military defeat at Camden, S.C., leaving his beaten troops behind. Trump can't afford to do the same today.   Please Support The Stream: Equipping Christians to Think Clearly About the Political, Economic, and Moral Issues of Our Day. Even thugs who stand for evil ideas can gather a following for their bravery. In their case, it's the gumption of bullies, and attracts other would-be bullies. But that's how warlords have triumphed all too often for millennia.   The thugs of illegal alien mobs, backed by the bullies in power in cities like Los Angeles, are counting on decent people to hide in their homes and on Trump to hide in the White House. We cannot let these lawless, unpatriotic, un-American mobs raise foreign flags over our cities. There's a word for that: It's “surrender.”   We didn't vote for a white flag, but for the man who stood tall while bleeding and shouted, “Fight, fight, fight!” -----------------------------------------------------------------------     John Zmirak is a senior editor at The Stream and author or coauthor of 14 books, including The Politically Incorrect Guide to Immigration and The Politically Incorrect Guide to Catholicism. His newest book is No Second Amendment, No First.   --------------------------------------------------------------------  Check out our ACU Patreon page: https://www.patreon.com/ACUPodcast   HELP ACU SPREAD THE WORD!  Please go to Apple Podcasts and give ACU a 5 star rating. Apple canceled us and now we are clawing our way back to the top. Don't let the Leftist win. Do it now! Thanks. Also Rate us on any platform you follow us on. It helps a lot. Forward this show to friends. Ways to subscribe to the American Conservative University Podcast Click here to subscribe via Apple Podcasts Click here to subscribe via RSS You can also subscribe via Stitcher FM Player Podcast Addict Tune-in Podcasts Pandora Look us up on Amazon Prime …And Many Other Podcast Aggregators and sites ACU on Twitter- https://twitter.com/AmerConU . Warning- Explicit and Violent video content.   Please help ACU by submitting your Show ideas. Email us at americanconservativeuniversity@americanconservativeuniversity.com   Endorsed Charities -------------------------------------------------------- Pre-Born! Saving babies and Souls. https://preborn.org/ OUR MISSION To glorify Jesus Christ by leading and equipping pregnancy clinics to save more babies and souls. WHAT WE DO Pre-Born! partners with life-affirming pregnancy clinics all across the nation. We are designed to strategically impact the abortion industry through the following initiatives:… -------------------------------------------------------- Help CSI Stamp Out Slavery In Sudan Join us in our effort to free over 350 slaves. Listeners to the Eric Metaxas Show will remember our annual effort to free Christians who have been enslaved for simply acknowledging Jesus Christ as their Savior. As we celebrate the birth of Christ this Christmas, join us in giving new life to brothers and sisters in Sudan who have enslaved as a result of their faith. https://csi-usa.org/metaxas   https://csi-usa.org/slavery/   Typical Aid for the Enslaved A ration of sorghum, a local nutrient-rich staple food A dairy goat A “Sack of Hope,” a survival kit containing essential items such as tarp for shelter, a cooking pan, a water canister, a mosquito net, a blanket, a handheld sickle, and fishing hooks. Release celebrations include prayer and gathering for a meal, and medical care for those in need. The CSI team provides comfort, encouragement, and a shoulder to lean on while they tell their stories and begin their new lives. Thank you for your compassion  Giving the Gift of Freedom and Hope to the Enslaved South Sudanese -------------------------------------------------------- Food For the Poor https://foodforthepoor.org/ Help us serve the poorest of the poor Food For The Poor began in 1982 in Jamaica. Today, our interdenominational Christian ministry serves the poor in primarily 17 countries throughout the Caribbean and Latin America. Thanks to our faithful donors, we are able to provide food, housing, healthcare, education, fresh water, emergency relief, micro-enterprise solutions and much more. We are proud to have fed millions of people and provided more than 15.7 billion dollars in aid. Our faith inspires us to be an organization built on compassion, and motivated by love. Our mission is to bring relief to the poorest of the poor in the countries where we serve. We strive to reflect God's unconditional love. It's a sacrificial love that embraces all people regardless of race or religion. We believe that we can show His love by serving the “least of these” on this earth as Christ challenged us to do in Matthew 25. We pray that by God's grace, and with your support, we can continue to bring relief to the suffering and hope to the hopeless.   Report on Food For the Poor by Charity Navigator https://www.charitynavigator.org/ein/592174510   -------------------------------------------------------- Disclaimer from ACU. We try to bring to our students and alumni the World's best Conservative thinkers. All views expressed belong solely to the author and not necessarily to ACU. In all issues and relations, we hope to follow the admonitions of Jesus Christ. While striving to expose, warn and contend with evil, we extend the love of God to all of his children. ----------------------------------------------------------------------------------------- 

The Iranian regime is receiving an education of sorts this week, and while we await President Trump's decision on the extent of America's role in busting up the nuclear site at Fordow, the Free Press's Eli Lake (and host of the Breaking History podcast) returns to educate us on why surgical involvement in Iran fits with the "America First" agenda that voters signed up for last November.Plus, the reunited James, Charles, and Steve talk Skrmetti and Mamdani.- Music from this week's open: The Israeli Air Force has a hit on Iranian State Television

As most of you know, our Patreon audience has the INSIDE access to the KF Show. The year 2025 will be an important one for Patreon specifically and if you'd consider jumping up to the $5 level it would sure help. The $10 level will remain and we now have a brand new $20 level as well! All members who join at that level will receive a sticker swag pack in the mail, you'll be IMMEDIATELY entered in the monthly prize grab, and you'll receive a phone call from one (or all) of us to chat up whatever you want for 30 minutes! Thank you SO MUCH to those of you who have joined in for the extra content that is only for Patreon supporters. To get in on the action and support the show with a minor financial contribution just click the link below to sign up. Join up via Patreon at patreon.com/KFSHOW ======================================== Presented with Holley - Back for 2025!  Phase 3 of Kibbe and Friends is officially here, and Holley is back for more fun, foolishness, and flying orange Chargers! Once again we're proud to be associated with the historic name that has made cars fast for years and years, and their innovations continue forward (as always)! Make sure that you visit Holley.com to place your speed parts orders - and THANK THEM for continuing on as the Title Sponsor of the KF Show!  ======================================== Ron Francis Wiring Brings you the Celebrity Automotive Birthday! https://www.ronfrancis.com ======================================== Dallas Kibbe Racing Update! This episode featured the Dallas Kibbe Legends Car Racing Update segment! Dallas joined the show himself after his last race on June 13 at Hawkeye Downs in Cedar Rapids, IA. Long story short.....he won! It was his first win in a Legends car, ever!! To follow Dallas Kibbe Racing you can watch his stats and other racing information here. Check it out! https://www.facebook.com/DallasKibbeRacing https://www.instagram.com/dallaskibbe_13/ https://www.tiktok.com/@dallaskibbe_13 MyRacePass.com/drivers/178661.  ======================================== Dukes Review: S7E1 Happy Birthday General Lee The greatest race of the General Lee is not in this episode…..but it's the first win of the General, and I have recently been reminded that your first win is irreplaceable. There's no doubt about the fact that in the course of the Dukes of Hazzard, this is the race that put him on the map. Thomas Steven Wopat presents the birth of the General Lee and - whether he meant to or not - creates the canon of the entire series by answering what every little boy needed to know most. Why are the doors welded shut? It's here. What's under the hood of the General? It's here. Why is the General orange, with a rebel flag on the roof, a dixie horn under the hood, and why is it named General Lee? It's here. More importantly, how does an old dead wreck from a junkyard become able to fly leaps and bounds, win every race, catch every bad guy, win every girl for the Duke Boys, respond to it's name on command, be so much of a family member it gets it's own birthday cake, and become the most magical car in the history of the known universe and the most famous car in the world? It's here! Legit Episode Info Season 7, Episode 1 “Happy Birthday, General Lee” Written by Si Rose Directed by Tom Wopat 9/21/1984  ======================================== National Parts Depot Presents: Bernie on the News! https://www.npdlink.com. The post K&F Show #332: Hollywood Cars – Props Vs Copyrightable Characters; All Racing June Dukes Review: S7E1 “Happy Birthday General Lee” first appeared on The Muscle Car Place.

The Iranian regime is receiving an education of sorts this week, and while we await President Trump's decision on the extent of America's role in busting up the nuclear site at Fordow, the Free Press's Eli Lake (and host of the Breaking History podcast) returns to educate us on why surgical involvement in Iran fits […]

Welcome to the Mind Muscle Connection Podcast!In this solo episode, I break down How I Coach Clients Through Their Next Body Recomp Phase with Strategy Not Emotion.I discuss the mistakes many people make in their fitness journey and how to make smarter, phase-based decisions based on your current body composition, biofeedback, stress load, and recent methods. If you're feeling stuck, unsure if you should cut or build, or just want to understand the strategy behind long-term results, this one's for you!Let's talk about:IntroductionPicking your next phase based on emotionWhat should guide your next moveTakeawayFollow me on Instagram for more information and education: @jeffhoehn_FREE 30 Min Strategy Call: HEREBody Recomp Checklist 2.0 HERENutrition Periodization Masterclass: HEREHow You Can Work With Me?: HERECoaching application: HEREBody Recomp Checklist 2.0: HERE

Dr. John Sweetenham and Dr. Marc Braunstein highlight top research on hematologic malignancies from the 2025 ASCO Annual Meeting, including abstracts on newly diagnosed chronic phase CML, relapsed B-cell lymphoma, and multiple myeloma. Transcript Dr. John Sweetenham: Hello, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. John Sweetenham. On today's episode, we'll be discussing promising advances in newly diagnosed chronic phase CML, relapsed B-cell lymphoma, multiple myeloma, and other hematologic malignancies that were presented at the 2025 ASCO Annual Meeting. Joining me for this discussion is Dr. Marc Braunstein, a hematologist and oncologist at the NYU Perlmutter Cancer Center. Our full disclosures are available in the transcript of this episode.  Marc, there were some great studies in the heme space at this year's Annual Meeting, and it's great to have you back on the podcast to highlight some of these advances. Dr. Marc Braunstein: Yes, I agree, John, and thank you so much for inviting me again. It's great to be here.  Dr. John Sweetenham: Let's start out with Abstract 6501. This was a study that reported on the primary endpoint results of the phase 3B ASC4START trial, which assessed asciminib versus nilotinib in newly diagnosed chronic phase CML. And the primary endpoint of this, as you know, was time to treatment discontinuation because of adverse events. Can you give us your insights into this study? Dr. Marc Braunstein: Absolutely. So, like you mentioned, you know, asciminib is an allosteric inhibitor of the BCR-ABL kinase that has activity in CML, and that includes patients with the T315I mutation that confers resistance to first- and second-generation TKIs. So, the ASC4FIRST study, which was published last year in the New England Journal of Medicine, showed superior efficacy of asciminib compared to investigator-selected first- or second-generation TKIs, actually leading to the FDA approval of asciminib in first-line CML. So, the authors of that study presented data at this year's ASCO meeting from the phase 3 ASC4START comparing safety and time to discontinuation due to adverse events of asciminib versus nilotinib, a second-generation TKI. So, 568 patients with newly diagnosed CML were randomized one-to-one to once-daily asciminib or twice-daily nilotinib. So, at a median follow-up of 9.7 months, about 11% in the asciminib group and 17% in the nilotinib group discontinued treatment, with significantly fewer discontinuations with asciminib due to adverse events. There was also a secondary endpoint of major molecular response, which was also better with asciminib. For example, the MR 4.5, which is a deep response, was 2.5% versus 0.4% favoring asciminib by week 12. So, I think in conclusion, these results build on the ASC4FIRST study, making the case for the superior safety and efficacy of asciminib versus other first- or second-generation TKIs in newly diagnosed CML. Dr. John Sweetenham: Thanks, Marc. Do you think this is going to change practice? Dr. Marc Braunstein: I think so. I think there are still some questions to be answered, such as what resistance mutations occur after first-line treatment with asciminib. But I think the sum of these studies really make the case for using asciminib upfront in CML. Dr. John Sweetenham: Okay, great. Thank you. And let's move on to our second abstract. This was Abstract 7015 and was reported from Mass General Hospital. And this was a study in patients with relapsed and refractory diffuse large B-cell lymphoma and reported the 2-year results of the so-called STARGLO study. This is a comparison of glofitamab, a T-cell engaging bispecific antibody, with gemcitabine and oxaliplatin in this group of patients. Can you tell us a little bit about your impressions of this study? Dr. Marc Braunstein: Absolutely. So just for background, the treatment landscape for relapsed/refractory large B-cell lymphoma is expanding, now with two bispecific antibodies targeting CD20 that are approved after two or more lines of therapy. Among these, glofitamab was approved in 2023 based on phase 2 data showing an objective response rate of 52%, with 39% complete responses in relapsed/refractory large B-cell lymphoma patients after a median of three prior lines of therapy. Distinguishing glofitamab from epcoritamab, the other approved bispecific, glofitamab was given for 12 cycles and then stopped. Additionally, when combined with gemcitabine and oxaliplatin in the phase 3 STARGLO study, there was significantly improved overall survival compared to rituximab plus gemcitabine and oxaliplatin in transplant-ineligible relapsed/refractory large B-cell lymphoma patients at a median follow-up of 11 months.  The authors of that study published last year in Lancet now present at ASCO this year the 2-year follow-up of the STARGLO study. Two hundred and seventy-four patients with a median of one prior line of therapy were randomized two-to-one to glofitamab plus GemOx versus rituximab plus GemOx, with the primary endpoint of overall survival. Here, the median overall survival was not reached versus 13.5 months, with a median PFS also significantly improved at about 14 months versus 4 months in the control. CRS of note in the glofitamab arm was mostly grade 1 or 2, with only about 2.3% grade 3 events. And three of the four patients had grade 1 or 2 neurotoxicity. So, John, putting this into context, I think it's encouraging that we now have randomized data showing the superiority of a bispecific plus chemotherapy over rituximab plus chemotherapy in transplant-ineligible patients. And while only 8% of the patients in the STARGLO study had prior anti-CD19 CAR T-cell therapy, I think this regimen could be considered in those patients who are ineligible for transplant or CAR T-cell therapy. Dr. John Sweetenham: Yeah, I agree. I think a couple of other compelling numbers to me were the fact that around 55% of these patients were alive at 2 years in the group who'd received glofitamab, and that almost 90% of those having that arm of the study who had a CR at the end of treatment were alive at 12 months. So, clearly, it's an active agent and also a kind of great off-the-shelf fixed-duration alternative in these relapsed and refractory patients. Dr. Marc Braunstein: I agree, and I would also note that the phase 3 SKYGLO study is looking at glofitamab plus Pola-R-CHP versus Pola-R-CHP alone. So, we may even be using these eventually in the first-line setting. Dr. John Sweetenham: Absolutely. Let's stay on the theme of diffuse large B-cell lymphoma and look at one other abstract in that space, which was Abstract 7000. This was a study from the HOVON group in the Netherlands, which looked at the prospective validation of end-of-treatment circulating tumor DNA in the context of a national randomized trial. What are your thoughts on this? Dr. Marc Braunstein: So, non-invasive liquid biopsies to detect and monitor cancers via circulating tumor-derived DNA or ctDNA, you know, is really emerging as a valuable tool in both solid and liquid tumors to understand disease biology, and also for drug development. So, to date, the most established application of ctDNA in lymphoma, I would say, is really for monitoring of minimal residual disease. So, in this correlative study by Steven Wang and colleagues in the HOVON group, they evaluated the prognostic significance of MRD status as assessed by ctDNA following first-line treatment with curative intent with either R-CHOP or dose-adjusted R-EPOCH. At the end of treatment, encouragingly, 76% of patients were MRD-negative, and 24% were MRD-positive. Now, of note, MRD-positive status at the end of treatment predicted inferior progression-free survival at 2 years, with only 28% of patients who are MRD-positive being progression-free versus 88% who are MRD-negative. And in fact, all the patients who failed to achieve a complete response after first-line treatment and were MRD-positive ultimately relapsed. So, circulating tumor cells are rarely found in large B-cell lymphomas, and so this study really builds on accumulating data that ctDNA has clinical value to detect residual disease with a non-invasive approach. So, there are many implications of how we could potentially use this to detect early signs of relapse, to potentially escalate treatment for consolidation if patients remain MRD-positive. So, I think this will eventually become utilized in clinical practice. Dr. John Sweetenham: Yeah, I agree. I think it's interesting that it provided an independent assessment of response, which was independent, in fact, of the results of PET-CT scanning and so on, which I think was very interesting to me. And the authors of the abstract actually commented in their presentation that they think this should be integrated as part of the standard response assessment now for patients with large B-cell lymphoma. Would you agree with that? Dr. Marc Braunstein: I would. For one thing, it allows repeated sampling. It's a non-invasive approach; it doesn't necessarily require a bone marrow biopsy, and it may have more sensitivity than conventional response measures. So, I think having a standardized system to assess ctDNA will be helpful, and definitely, I think this will be a valuable biomarker of disease response. Dr. John Sweetenham: Okay, great. Thanks. We're going to change gear again now, and we're going to highlight two abstracts in the multiple myeloma space. The first one of these is Abstract 7507. And this abstract reported on the long-term results of the CARTITUDE study for patients with relapsed and refractory multiple myeloma. What are your comments on this presentation? Dr. Marc Braunstein: So, this study actually got a lot of press, and I've already had multiple patients asking me about CAR T-cells as a result. Just as some background, CAR T-cells targeting BCMA, which is pretty much universally expressed on malignant plasma cells in myeloma, have really shown remarkable responses, especially in heavily pretreated patients, showing superior progression-free survival in both later and earlier phases of the disease, including in randomized studies in patients with second-line or beyond. So, the CARTITUDE-1 was really the original Phase 1/2 study of ciltacabtagene autoleucel, one of the two approved anti-BCMA CAR T-cell products, which was investigated in patients with a median of six to seven prior lines of therapy. So, these were patients who were pretty heavily pretreated. So, in the study presented by Voorhees at this year's ASCO meeting, this was the long-term follow-up at a median of 5 years from the one-time CAR infusion in these patients with a median of five prior lines of therapy. And remarkably, of the 97 patients, 33% remained progression-free at 5 years plus, without needing any further myeloma treatment during that time. And among those 33% of patients, 23% had high-risk cytogenetics, which we know are notoriously difficult to achieve responses in. What was interesting that they presented as correlative studies was there were some biomarkers that were distinguishing the patients who had the long PFS, including enrichment of more naive T-cells in the product, lower neutrophil-to-T-cell ratio, higher hemoglobin and platelets at baseline, and higher CAR T-cell levels relative to soluble BCMA levels. And the fact that they reported a median overall survival of 61 months in these really heavily pretreated patients, I think these data are impressive. I think we're going to continue to be using CAR T even earlier in the disease status than fifth or sixth line, as it was studied in CARTITUDE-1. There are even ongoing studies looking at first-line treatment with CAR T-cells. Dr. John Sweetenham: So, do you think that those 33% of patients who are disease-free at 5 years, do you think any of those are cured?  Dr. Marc Braunstein: That was one of the headlines in the press. I think if we're going to discuss things like "operational cures," where we're transforming myeloma into really a chronic disease, where patients can live practically a normal life expectancy, I think the measure of 5 years, especially in this population that was explored in CARTITUDE-1, I think we can call that close to a cure. Dr. John Sweetenham: Okay. Well, thank you. Exciting data, for sure. We're going to conclude today with another abstract in the multiple myeloma space. And this was Abstract 7500, which looked at an MRD, minimal residual disease-driven strategy following induction and transplant-eligible newly diagnosed multiple myeloma patients and reported on the primary endpoints of the phase 3 MIDAS trial. Can you walk us through this one, Marc? Dr. Marc Braunstein: Absolutely. It is a bit more complicated than the prior one we discussed because this is a randomized study with four arms. So, I'll start by saying that anti-CD38-based quadruplet regimens continue to show superior outcomes in both transplant-eligible and -ineligible newly diagnosed multiple myeloma patients. The MIDAS study mentioned is an open-label phase 3 trial with four arms in transplant-eligible newly diagnosed myeloma patients.  And initially, these patients were all treated with quadruplet therapy with the anti-CD38 antibody isatuximab combined with carfilzomib, lenalidomide, and dexamethasone in 718 newly diagnosed myeloma patients. So, they received the quadruplet regimen for six cycles and then were randomized based on their MRD status at 10 to the negative fifth following six cycles of induction. And that first randomization, if they were MRD-negative, was to either consolidation with six more cycles of the quadruplet regimen or transplant, autologous transplant, plus two cycles additionally of the quadruplet regimen. And both arms were followed by lenalidomide maintenance. The primary endpoint was MRD negativity at 10 to the negative sixth prior to entering the lenalidomide maintenance component. And in addition, the patients who were MRD-positive after induction were randomized to transplant plus two cycles of consolidation or a tandem autologous transplant. So, the median follow-up of the study was about 16 months, and the pre-maintenance rate of MRD negativity was high, between 84 to 86% between the two arms who were MRD-negative, which was not significantly different. And as far as the 233 patients who were MRD-positive, the pre-maintenance MRD negativity was also not significantly different at 40% for those who received autologous transplant, and 32% who received a tandem transplant. So, there's a lot of debate in the myeloma field about the evolving role of autologous transplant and whether transplant still plays a significant role in patients who are either MRD-negative after induction or who have deep remissions and are of standard risk. So, I think these data suggest that patients who are MRD-negative after induction with a quadruplet regimen studied here, which was Isa-KRd, plus consolidation, may possibly be able to forego consolidation with autologous transplant. And likewise, for those patients who are MRD-positive after induction, tandem transplant didn't seem to provide much of a benefit compared to single transplant, which is consistent with prior studies such as the StaMINA study. Dr. John Sweetenham: So, where do you think this leaves us, Marc? Are we going to need more studies before we have any definitive guidance on whether an autologous transplant is still appropriate for those patients who are MRD-negative? Dr. Marc Braunstein: Well, as clinicians, we want to do what's best for our patient. And in myeloma, the best we can do is to get as deep remissions as possible, meaning MRD negativity. And so, I think it's clear from the MIDAS study and others that quadruplet regimens provide the deepest remissions when given upfront. We can debate the role of autologous transplant. I think certainly the role of tandem autologous transplant is fading. But as far as a single autologous transplant as consolidation, I think it's reasonable as a goal to try to achieve MRD negativity after the transplant, especially for patients who remain MRD-positive after induction. Dr. John Sweetenham: Okay, great. Marc, thanks as always for sharing your insights on the heme malignancies studies from the ASCO meeting this year and for joining us on the ASCO Daily News Podcast. Always appreciate hearing your thoughtful and balanced input on these. Dr. Marc Braunstein: My pleasure. Thank you, John. Dr. John Sweetenham: And thank you to our listeners for joining us today. You'll find links to the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your 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 guest:  Dr. John Sweetenham Dr. Marc Braunstein   @docbraunstein     Follow ASCO on social media:   @ASCO on Twitter  ASCO on Bluesky  ASCO on Facebook   ASCO on LinkedIn     Disclosures:  Dr. John Sweetenham:  Consulting or Advisory Role: EMA Wellness  Dr. Marc Braunstein:  Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb/Celgene, Adaptive Biotechnologies, GlaxoSmithKline, ADC Therapeutics, Janssen Oncology, Abbvie, Guidepoint Global, Epizyme, Sanofi, CTI BioPharma Corp  Speakers' Bureau: Janssen Oncology  Research Funding (Institution): Janssen, Celgene/BMS

Russlands Präsident Wladimir Putin hat sich zu einem Treffen mit dem ukrainischen Präsidenten Wolodymyr Selenskyj bereit erklärt - allerdings erst in einer „finalen Phase“ der Verhandlungen mit Kiew über den seit drei Jahren andauernden Konflikt.

We are celebrating the one-year anniversary of the podcast with a cornerstone of the psychedelic renaissance: Amy Emerson. Amy is a respected leader in the field of psychedelic-assisted therapy. She was Lykos Therapeutics CEO for an important period in advancing MDMA-assisted psychotherapy for post-traumatic stress disorder as a drug with the FDA. In 2003, she began volunteering with the Multidisciplinary Association for Psychedelic Studies (MAPS), assisting with clinical research monitoring. Her expertise was instrumental in establishing MAPS' clinical department and managing the MDMA Clinical Development Program. When MAPS founded its Public Benefit Corporation in 2014 to develop and commercialize MDMA-assisted therapy, Amy was appointed CEO. The organization, later rebranded as Lykos Therapeutics, completed multiple Phase 2 and Phase 3 clinical trials and raised a successful Series A all working toward the goal of obtaining FDA approval for MDMA-assisted therapy for PTSD. Amy resigned from her CEO role in September 2024. Currently she is an advisor in the psychedelic research field.    In this episode, Amy shares about her own personal psychedelic use and how that led her to her early volunteer work with MAPS. We discuss what happened with the FDA approval process with MDMA, what went right, what went wrong and where the process goes from here. As part of the what-went-wrong focus, we explore what can be done to minimize the harm from inappropriate sexual encounters in psychedelic therapy, including the importance of therapists doing their own shadow work to help mitigate such abuse. We do a deep dive into the world of trauma and how these medicines can help provide healing on a number of levels. Amy also provides her dream scenario for where the psychedelic world could ideally be in ten years.   Learn More About Amy Emerson https://www.linkedin.com/in/amy-emerson-5ab7473/   Connect with Carla If you're inspired by this episode and want to stay connected, follow Carla and Psychedelic Divas on social media or visit the website to get your Psychedelic Safety Guide Including What to Do When Things Go Wrong: ·        Website: PsychedelicDivas.com ·        Carla's Coaching: CarlaDetchon.com ·        Instagram: https://www.instagram.com/psychedelicdivas ·        YouTube: https://www.youtube.com/@carladetchon ·        Subscribe & Review: If you enjoyed this episode, please subscribe, rate, and review Psychedelic Divas. Your support helps amplify these important conversations and grow our community.

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To watch Gerald Pollack's presentation from Confluence 2025, become a platinum member of https://www.TheWayFwrd.com. Platinum members also get access to live community calls, podcast guest Q&As, as well as our new platform helping you find like-minded community near you. Turn online alignment into an offline community — join us at TheWayFwrd.com to connect with like-minded people near you. It's the best way to support this podcast and the movement we're building together: https://thewayfwrd.com/join/ Alec is joined by Dr. Gerald Pollack, professor at the University of Washington, to explore the “fourth phase” of water and its vital role in biological energy. They discuss how structured water near cell surfaces, called the Exclusion Zone, challenges traditional biology, the energy sources behind it, and its implications for cell health and cancer. Dr. Pollack also reflects on the scientific pioneers who first proposed these ideas and the resistance faced by revolutionary research. For more details, links, and resources mentioned in this episode, visit our website: https://thewayfwrd.com/   Resources and Links Pollack Lab Website – https://www.pollacklab.org/   The Way Forward podcast is sponsored by: New Biology Clinic: Experience individually tailored terrain-based health services with virtual consults, practitioner livestreams, movement classes, and more. The New Biology Clinic's motivation is to make you healthy and keep you that way. Visit https://NewBiologyClinic.com and enter code TheWayForward for $50 off your activation fee. Members of The Way Forward get the full activation fee waived. Become a member of The Way Forward here: https://thewayfwrd.com/membership-sign-up/ ————————— RMDY Collective: Dedicated to making homeopathy accessible with high-quality remedies and hands-on training. Discover how this holistic approach supports natural healing and empowers you to take charge of your wellness.  Explore more at RMDY Collective at https://rmdycollective.org/?bg_ref=MKho6KZowa Enroll in RMDY Academy at https://rmdyacademy.org/?bg_ref=MKho6KZowa ————————— Medicamentum Authentica: Boost energy, mental clarity, and vitality with Authentica Shilajit™, a mineral-rich supplement trusted for holistic wellness. It supports stamina, focus, hormonal balance, and detoxification while promoting long-term health. Get 10% off with code WAYFORWARD at https://medauthentica.com/wayforward

Send us a textThe transformation and Phase 0 planning for SAP ECC are pivotal in setting the stage for a smooth transition to a more agile and future-ready ERP environment. This initial phase focuses on a comprehensive assessment of the existing system landscape, uncovering opportunities for business process enhancements, and crafting a clear strategic roadmap for migration or optimization. Crucial activities include evaluating data readiness, securing stakeholder alignment, and implementing robust governance frameworks to mitigate risks and ensure accountability. The challenge lies in establishing a solid foundation for Phase 0 that minimizes operational disruptions, boosts efficiency, and ultimately maximizes the return on the SAP ECC investment—key considerations for any organization embarking on this critical journey. In this episode, Sam Gupta engages in a LinkedIn live session with Sana Asher, Global Vice President, Integrity Resource Management, to discuss transformation and phase 0 planning for SAP ECC.Background Soundtrack: Away From You – Mauro SommFor more information on growth strategies for SMBs using ERP and digital transformation, visit our community at wbs. rocks or elevatiq.com. To ensure that you never miss an episode of the WBS podcast, subscribe on your favorite podcasting platform. 

The NFU has confirmed it sent a private letter to the Prime Minister, raising concerns over a prospective trade deal with the Gulf States. It said the deal could open the UK up to imports of low-welfare meat from the Gulf, and more importantly, many other countries around the world. Although meat from the Gulf States might come up to UK hygiene standards, some welfare groups are concerned about the conditions animals are kept in, and the intensive nature of production, especially poultry.Annual payments farmers in England receive based on the amount of land they have will be capped at just £600 next year. New details have emerged after last week's Spending Review.And there's evidence that humans have been using seaweed as a fertiliser for thousands of years. When chemical fertilisers were developed a century ago, that use of seaweed largely died out, but for some, it's making a comeback.Presented by Anna Hill Produced by Heather Simons

Is your child constantly saying "I'm tired"? If they're between 10 and 14, Dr. Roger Smith explains why it's likely more than just a complaint! In this episode of Parenting Matters Now, discover the neurodevelopmental shifts happening during pre-pubescence and puberty that genuinely increase a child's need for sleep. Learn how their developing emotional brain influences their expression of fatigue, and why compassion and providing downtime are crucial. Understand the internal changes your child is experiencing, even before external signs of puberty appear, and how to best support them through this naturally exhausting stage of growth. Visit me at: https://rogersmithmd.com/ This has been a production of ThePodcastUpload.com 

In this episode, I'm diving into the hot topic of 48-hour fasting during your follicular phase. I talk about the real science-backed benefits that fasting does provide & my recommendations for whether or not I think it could be beneficial for your fertility! Chapters in this episode: 00:00 Exploring the Benefits of Fasting03:00 Who Should Avoid Fasting?05:50 Alternatives to Fasting for Fertility09:07 Cleansing vs. Fasting: What's Best?11:54 Practical Fasting Tips for Hormonal Health14:46 Creating a Sustainable Lifestyle for FertilityWays to work with Corinne: Join the Mind Your Hormones Method, HERE! (Use code PODCAST for 10% off!!)Join the Mind Your Hormones Community to connect more with me & other members of this community!Come hang out with me on Instagram: @corinneangealicaOr on TikTok: @corinneangelicaEmail Fam: Click here to get weekly emails from meMind Your Hormones Instagram: @mindyourhormones.podcast Disclaimer: always consult your doctor before taking any supplementation. This podcast is intended for educational purposes only, not to diagnose or treat any conditions. 

Today is a REALLY big day! After months of teasing and planning, I'm finally announcing my major surprise: a brand new limited series podcast called "How to Find Clients: Tips for Coaches and Entrepreneurs." This isn't just another podcast - it's a bingeable, step-by-step audio course designed to solve the #1 problem coaches face: finding clients consistently and sustainably. After surveying my newsletter list, they confirmed what I suspected: the biggest struggle for coaches is getting clients. So I created this 21-episode limited series that contains everything I wish I'd known when I was struggling to find my first clients. The series is designed to be consumed like a Netflix show - all 21 episodes in less than 3 hours, meant to be listened to in order starting with Episode 1. Each episode builds on the previous one to create a complete client-finding system. I've also created a comprehensive workbook with homework assignments, visual infographics, and action items for each episode. You can download it free at amanda-walker.com/howtogetclients. In today's episode, I share why I created this series and give you a preview of Episode 3: "The Profitable Coach Formula." I break down the three phases every coaching business goes through: Phase 1: Thinking About Making Money - excited about coaching but unsure how to get paid consistently Phase 2: Prepping to Make Money - starting to post on social and set up basic systems Phase 3: Making Consistent Money - established authority with systems and flows that work Most coaches get stuck trying to go from social media posts directly to high-ticket offers without building the crucial "middle" of their ecosystem - the trust-building phase that establishes authority and credibility. To celebrate the launch, I'm hosting a giveaway! Subscribe to the new podcast, leave a review, and share episodes on social media for chances to win my favorite recording microphone. Search "How to Find Clients: Tips for Coaches and Entrepreneurs" on any podcast platform to start your binge-listening session! FREE WORKBOOK: amanda-walker.com/howtogetclients

Today's guest is chef, writer, and Emmy-nominated host Sophia Roe. The culinary creative has lots of pots on the stove, so to speak, including a YouTube channel, a new outpost of her Apartment Miso studio, and her biggest project to date: motherhood. Sophia and host Kerry Diamond talk about Sophia's early years in culinary school, working as a private chef, meeting her fiancé Chris, thoughts on being a working mom, and the surprising phase she finds herself in. “I am happier than I probably have been in my life, and I definitely didn't think that would happen,” she says. They also chat about the new Power Issue of Cherry Bombe Magazine with Sophia on the cover. Click here for tickets for our Summer Tastemaker Tour. Subscribe to Cherry Bombe's print magazine. More on Sophia: Instagram, Apartment Miso, websiteMore on Kerry: InstagramPast episodes and transcripts

It's ... Indicators of the Week! Our weekly look at some of the most fascinating economic numbers from the news. On today's episode: the monetary cost of Trump's military parade, looks like FEMA could be phased out, and another change to Warner Bros. Discovery.Related episodes: Coyote vs. Warner Bros. Discovery (Apple / Spotify) Gilded Age 2.0? (Apple / Spotify)For sponsor-free episodes of The Indicator from Planet Money, subscribe to Planet Money+ via Apple Podcasts or at plus.npr.org.Fact-checking by Sierra Juarez. Music by Drop Electric. Find us: TikTok, Instagram, Facebook, Newsletter. Learn more about sponsor message choices: podcastchoices.com/adchoicesNPR Privacy Policy