Podcasts about ADC

This episode I am reading from Admir Serrano's book 'Nights on the Other Side: How I Discovered My Immortality' Nights on the Other Side” is a book that invites us to look at life from a different perspective: more lucid, more open, and less fearful. Admir describes out-of-body experiences with clarity, combining his personal testimony with scientific references. But above all, he conveys the sense that we are not alone and that we are something more than we believe. Bio I am a Brazilian-American researcher, writer and lecturer on paranormal phenomena such as out-of-body experiences (OBEs), near-death experiences (NDEs), deathbed visions (DBVs), after- death communication (ADC), reincarnation, mediumship and the afterlife. And an unabashed believer in our survival of physical death and the immortality of the spirit. My interest in these subjects was triggered after I began having spontaneous OBEs, back in the year 2000, and I wanted to understand the phenomenon. Since then, I have had hundreds of lucid and amazing experiences which have proven to me beyond a shadow of a doubt that we are immortal beings. Aware of the sadness that death of a loved one can cause – and I have experienced it myself – I have made it my life's mission to spread the notion that there is no death, that only the body dies, and since we are not our body, we survive death – unscathed. For my own edification regarding the dynamics of physical death, I have worked as a hospice volunteer providing spiritual support to terminally ill patients as they waited for their time to cross over to the other side of life. And this is what death is, a change of worlds, the end of one mode of living, the physical, to the beginning of a spiritual existence. I have bachelor's degrees in psychology and liberal studies, and a master's in theology. I am an avid reader with a broad interest in world and religious history, anthropology, geography, world affairs, and the humanities. I have written five books in my native Portuguese language on death, dying and the afterlife, and two in English on related topics. I write and lecture in both languages, as well as Spanish, the third language I speak. I live in Homestead, Florida, with my wife, two daughters and my lovely grandson. https://www.admirserrano.com/ https://www.pastliveshypnosis.co.uk/https://www.patreon.com/ourparanormalafterlifeMy book 'Verified Near Death Experiences' https://www.amazon.com/dp/B0DXKRGDFP Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

 It was hailed as the "Mega-Alliance" that would reshape Nigeria's political future. The African Democratic Congress, ADC, became the unlikely home for former rivals, bringing together the heavyweights of the opposition. But today, the cracks in the foundation are becoming impossible to ignore. Whispers of a fallout between the Atiku Abubakar camp and the Peter Obi movement are growing louder. With ego, ambition, and the 2027 presidential ticket at stake, is this coalition headed for a divorce before the honeymoon even ends?Today on Nigeria Daily, we go inside the ADC to examine the internal friction, the rumors of Peter Obi's exit, and what this misalignment means for the opposition's chances in the next election.

This week I'm talking to Admir Serrano about his book 'Nights on the Other Side: How I Discovered My Immortality' Nights on the Other Side” is a book that invites us to look at life from a different perspective: more lucid, more open, and less fearful. Admir describes out-of-body experiences with clarity, combining his personal testimony with scientific references. But above all, he conveys the sense that we are not alone and that we are something more than we believe. Bio I am a Brazilian-American researcher, writer and lecturer on paranormal phenomena such as out-of-body experiences (OBEs), near-death experiences (NDEs), deathbed visions (DBVs), after- death communication (ADC), reincarnation, mediumship and the afterlife. And an unabashed believer in our survival of physical death and the immortality of the spirit. My interest in these subjects was triggered after I began having spontaneous OBEs, back in the year 2000, and I wanted to understand the phenomenon. Since then, I have had hundreds of lucid and amazing experiences which have proven to me beyond a shadow of a doubt that we are immortal beings. Aware of the sadness that death of a loved one can cause – and I have experienced it myself – I have made it my life's mission to spread the notion that there is no death, that only the body dies, and since we are not our body, we survive death – unscathed. For my own edification regarding the dynamics of physical death, I have worked as a hospice volunteer providing spiritual support to terminally ill patients as they waited for their time to cross over to the other side of life. And this is what death is, a change of worlds, the end of one mode of living, the physical, to the beginning of a spiritual existence. I have bachelor's degrees in psychology and liberal studies, and a master's in theology. I am an avid reader with a broad interest in world and religious history, anthropology, geography, world affairs, and the humanities. I have written five books in my native Portuguese language on death, dying and the afterlife, and two in English on related topics. I write and lecture in both languages, as well as Spanish, the third language I speak. I live in Homestead, Florida, with my wife, two daughters and my lovely grandson. https://www.admirserrano.com/ https://www.pastliveshypnosis.co.uk/https://www.patreon.com/ourparanormalafterlifeMy book 'Verified Near Death Experiences' https://www.amazon.com/dp/B0DXKRGDFP Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

Lauren Coyle, Launch Commissioning Editor, Bioconjugate Insights, speaks with Antoine Yver, Board Chair, Ona Therapeutics, with more than three and a half decades of experience shaping global cancer drug development. In this conversation, they explore what determines whether an ADC successfully crosses the critical threshold and how teams should rethink dose finding, toxicity, and what it truly takes to set a program up for long-term success in the clinic. 

This weekend's 1 in 31: Autism Today guest is Alan Day. Alan is the founder and CEO of Autism Double Checked (ADC), an innovative organization committed to making travel more accessible and inclusive for individuals on the autism spectrum. ADC classifies travel companies into three levels of "autism readiness": Autism Aware, Autism Ready, and Autism Double-Checked. At each level, the commitment to inclusivity deepens, and every participant is actively working to welcome guests traveling with autistic family members. Recently, ADC certified Bradley International Airport in Connecticut (the first in the U.S) as Autism Double Checked. Tune in to learn more about their certification process. You can also visit the ADC website to learn more about their service offerings including Autism Passport, Autism Concierge, Autism Stays, and Autism Flies, or see their directory of certified providers: https://autismchecked.com/     

In this episode of the Oncology Brothers podcast we navigated the rapidly evolving treatment landscape of Metastatic Hormone Receptor-Positive Breast Cancer. We were joined by Dr. Kevin Kalinsky, Director of the Breast Cancer Program at the Winship Cancer Institute, Emory University, to discuss the implications of new targeted therapies, optimal sequencing strategies, and practical toxicity management. Listen us on: Spotify: https://open.spotify.com/show/31BXhY9FM4gPWG10WgE11o Follow us on social media: •⁠  YouTube: https://www.youtube.com/@oncologybrothers •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ The discussion covered: • The critical role of NGS testing (tissue vs. liquid biopsy) in identifying PIK3CA, ESR1, AKT1 and PTEN alterations. • Frontline management of high-risk, endocrine-resistant disease with the inavolisib triplet (INAVO120) and its overall survival benefit. • Choosing between CDK4/6 inhibitors (abemaciclib vs. ribociclib) in de novo metastatic disease. • Post-CDK4/6 inhibitors on progression we covered, the use of oral SERDs (imlunestrant) and AKT inhibitors (capivasertib). • The "ADC explosion", sequencing T-DXd (DESTINY-Breast06), sacituzumab govitecan (TROPiCS-02), and datopotamab deruxtecan (TROPION-Breast01). • Clinical pearls for managing toxicities: stomatitis, hyperglycemia, rash, neutropenia, and ILD. Join us as we break down the latest data and provide actionable insights for the practicing oncologist. Don't forget to subscribe for more episodes in our breast cancer algorithm series! #MetastaticBreastCancer, #HRPositive, #ADCsequencing, #PIK3CA-AKT, #OncologyPodcast, #OncologyBrothers

From new cancer drugs to batteries and robotics – China's top-tier growth companies are forging paths of their own rather than following in the west's footsteps. Investment manager Sophie Earnshaw names companies that have caught her eye and explains why being a long-term stock picker differs in China from elsewhere. Background:Sophie Earnshaw is a decision-maker on our China Equities Strategy and joint manager of the Baillie Gifford China Growth Trust. In this conversation, she tells Short Briefings… host Leo Kelion about a select group of Chinese companies breaking new ground, supported by the state's efforts to become self-sufficient in more of today's critical technologies and a leader in some of those of the future. Earnshaw also details how the “phenomenal rate” at which companies are born, scale and die in the country makes stock-picking a challenging task – making the access we have to company leaders, academics and other local expertise core to our mission of finding the best firms to invest in on behalf of our clients. Portfolio companies discussed include:- CATL – the battery maker whose products power electric vehicles worldwide and increasingly support the renewable energy sector- BeOne and Innovent Biologics – pharmaceutical firms developing the next generation of cancer drugs - AMEC and NAURA – semiconductor equipment makers enabling China to develop increased self-reliance in computer chips - Alibaba, ByteDance and Tencent – China's ‘big tech' companies, whose artificial intelligence tools are becoming embedded into people's daily lives- MiniMax – the AI startup rolling out video and agentic tools at a fraction of the cost of western counterparts- Horizon Robotics – the automated driving tech provider with its eye on an even bigger opportunity. Resources:Baillie Gifford podcastsChina: a tale of two storiesChina investment strategy hub (institutional clients only)House of HuaweiPrivate investor forum 2025: investing in great growth companiesTrip notes: on the road with Baillie Gifford China Growth Trust  Companies mentioned include:AlibabaAMECASMLBeOneByteDanceCATLHorizon RoboticsInnovent BiologicsJiangsu HengruiHuaweiMiniMaxSamsungNAURATencentTSMCXiaohongshu Timecodes:00:00  Introduction01:55   Joining the China Equities Strategy02:40  Intense competition04:00  The government's influence06:10   CATL, the electrification champion08:45  Investing with a 5-year time horizon10:25   Shanghai office, local expertise11:45   Regulations and geopolitics14:30   China's next Five-year Plan16:15   Innovent Biologics' new cancer drugs18:10   Lower-cost clinical trials19:45   Being selective in semiconductors21:25   Investing in chip equipment makers23:00  China's ‘big tech and AI'25:10   MiniMax making AI like ‘tap water'27:45  The road to robotics29:35  A market you can't ignore30:30  Book choice Glossary of terms (in order of mention): Third plenum: a major policy meeting of China's ruling Communist Party, often used to set big economic/political direction.Sovereign bond issuance: The government raising money by selling bonds (IOUs) to investors.Opportunity set: the range of investable companies available to choose from.Capex: capital expenditure – money spent on long-term assets like factories, equipment, or data centres.Fiscal deficit target: how much more the government plans to spend than it collects in revenue (taxes plus other income), expressed as a share of the economy.GDP: gross domestic product – the total value of goods and services a country produces in a year.Market capitalisation: the total value of a company's shares (share price × number of shares).ESG: environmental, social and governance – how a company manages environmental impact, people issues, and corporate oversight.Large-form batteries: big battery packs used in things like electric vehicles and grid storage.Energy storage systems: large batteries that store electricity for later use (helping balance the grid).Generic drugs: copies of medicines whose patents have expired; usually cheaper, same active ingredient.Bi-specific (bispecific) drugs: drugs designed to bind to two targets at once (often to direct immune cells to cancer).ADC drugs: antibody–drug conjugates – antibodies that deliver a toxic payload to cancer cells.Out-licensing: selling rights to your drug/technology to another company (often for upfront + milestone payments).EUV machines: extreme ultraviolet lithography equipment used to make the most advanced chips.Foundry: a factory business that manufactures chips for other companies.Etch and deposition: steps in chipmaking – etch removes material to form patterns, deposition adds thin layers.Picks and shovels: a metaphor for companies that sell essential tools to an industry (rather than end products).Digitalisation: moving processes and services from offline to software and data-driven systems.Compute: the processing power (chips and servers) used to train/run AI.Large language model (LLM): an AI trained on lots of text to generate and understand language.Margins: how much profit a company makes per pound/dollar of revenue (after costs).Cloud business: selling computing power/storage/software over the internet instead of on a local machine.Algorithm layer: the method or software logic that makes the AI work (as distinct from the hardware).Gross margin: revenue minus direct costs (before overheads), a rough measure of product profitability.Assisted driving: features that help a driver (lane-keeping, adaptive cruise control, etc) but don't fully replace them.Autonomous driving: a car driving itself with minimal or no human input.Software attachment rate: the percentage of customers who add paid software features and/or subscriptions.

Alex Moss and Burton DeWitt are back with a new episode of your go-to darts podcast after the first PDC ProTour events of 2026!   The boys start the show with a brand-new game as Burton attempts to predict the quarter-final results of this week's Premier League night in Antwerp the day after with no prior knowledge of the results! Alex and Burton then take a look back at this week's Players Championship double-header in Germany and focus on the two title winners James Wade and Wessel Nijman.   New PDC tour card holder Samuel Price (24:44) joins the show to look back on a dramatic UK Q-School, which saw him secure a tour card on the final day as one of the top-up players from the First Stage Order of Merit. Samuel talks through his time in the game so far, from how he first got introduced to darts and then taking a break after suffering with dartitis, to making a comeback during lockdown, the influence of the ADC and UKDA in improving his game and a memorable start to 2026 that saw him become a PDC tour card holder for the first time.   Alex and Burton continue their review of the last week in darts and look back on the Dutch Open, which saw Germany's Paul Krohne and home favourite Priscilla Steenbergen win the two main titles in Assen.   The newly crowned Junior World Masters champion Kaya Baysal (1:07:18) calls in to reflect on his landmark win in Milton Keynes last month. The teenager looks back on a whirlwind last 12 months which saw him make history as the youngest winner of a WDF senior title in Hungary, breaking Luke Littler's record, play in youth events on the Lakeside and Alexandra Palace stages, and then defeat Mitchell Lawrie in the final of the inaugural Junior World Masters on the Arena MK stage just a few weeks ago.   The boys wrap up the show with a dip into the mailbag to answer your listeners questions.   Join the Darts Strava King group on Strava *** Get your own Alex Moss replica shirt (as worn by our co-host at the Las Vegas Open 2026) from DJD here! A % of the profits will be donated to The Ethan King Fund for Ewing Sarcoma Research *** This podcast is brought to you in association with Darts Corner - the number one online darts retailer! Darts Corner offers the widest selection of darts products from over 30 different manufacturers.  This podcast is sponsored by Darts Atlas - the platform for darts players, venues, and organisations. Darts Atlas is the home of the Amateur Darts Circuit (ADC) with hundreds of tournaments held on the platform every week.  Have you used Darts Atlas before? Share your feedback and experiences with Darts Atlas with us by sending an email to weeklydartscast@gmail.com and be in with a chance of winning some new logo Weekly Dartscast stickers! Check out Condor Darts here: UK site *** Enjoy our podcast? Make a one-off donation on our new Ko-Fi page here: ko-fi.com/weeklydartscast Support us on Patreon from just $2(+VAT): patreon.com/WeeklyDartscast Thank you to our Patreon members: Phil Moss, Gordon Skinner, Connor Ellis, Dan Hutchinson

Estamos convencidas de que hay dos tipos de personas, las que te llaman “guapa” y las que no. El guapa! casi nunca tiene nada que ver con el aspecto físico es un lubricante léxico, una caricia social o, dicho en modo ADC, un shortcut de la sociabilidad femme. A todo esto le damos vueltas hasta llegar al territorio Fascismo del Cuerpo. Que ahora se concentra en la cara, la cara de guapa. Lo explicamos rodeadas de gente guapa, guapísima, en un directo en el Cupra City Garage de Madrid.

Los Ratones should not be allowed in the LEC! In this episode, Thorin, Peter Dun, and guest jinjo break down one of the spiciest weeks in the LEC. The discussion covers the controversy around Los Ratones fans and Nemesis calling for franchising removal , Ice's development and limitations as an ADC, Humanoid's resurgence and Vitality's strong performances, KCorp's standout form and rising stars, G2's meta issues and drafting struggles, Fnatic's macro concerns and mid/top lane instability, and MKOI's long-standing difficulty in becoming a truly dominant team. Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

We start this episode discussing the latest international and local developments in the last few months. We begin with the massive display of wealth in the midst of growing inequality in the South East by Igbo bigwigs during the festive period. We use this as an entry point to discuss poverty and wealth gaps in Nigeria.We also reflect on what has been taking place in Nigeria namely the airstrike in Sokoto before briefly reacting to Venezuela and the US's strong hand in international geopolitics. We delve extensively into the actions of ADC, LP, APC and Peter Obi. Is any of it worth paying attention to? Or is it all pointless in the context of ideological similarities and the chances of genuine political change. Are they all the same? We do a breakdown of LP situation, the split in SE political elites over Peter Obi and the possible meaning of symbolism of Peter Obi's latest political moves.We then turn our attention to US intervention in Nigeria and Venezuela. Have we entered a new phase of US belligerence? Is this an increase or is it just more available to view? how much are the imperial vulgarities down to Trump as a person versus textbook US foreign policy? Listen and let us know your thoughts.

Editor-in-Chief of the Archives of Disease in Childhood, Dr Nick Brown, and Senior Editor of ADC, Dr Rachel Agbeko brings you the monthly Atoms - the highlights of the February 2026 issue. Read it on the Archives of Disease in Childhood website: https://adc.bmj.com/content/111/2/i     Please listen to our regular podcasts and subscribe in Apple Podcasts, Google Podcasts, Stitcher and Spotify to get episodes automatically downloaded to your phone and computer. And if you enjoy the podcast, please leave us a review at https://podcasts.apple.com/gb/podcast/adc-podcast/id333278832 

Dr. Joshua Reuss is back on the podcast to discuss the full update to the living guideline on stage IV NSCLC without driver alterations. He discusses the new evidence and how this impacts the latest recommendations on first-line and subsequent therapeutic options. Dr. Reuss emphasizes the need for shared decision-making between clinicians and patients. He shares ongoing research that the panel will review in the future for further updates to this living guideline, and puts the updated recommendations into context for clinicians treating patients with stage IV NSCLC. Read the full living guideline update "Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2026.3.0" at www.asco.org/thoracic-cancer-guidelines" TRANSCRIPT This guideline, clinical tools and resources are available at www.asco.org/thoracic-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology,  https://ascopubs.org/doi/10.1200/JCO-25-02825    Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I am interviewing Dr. Joshua Reuss from Georgetown University, co-chair on "Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2026.3.0." It is great to have you back on the show today, Dr. Reuss. Dr. Joshua Reuss: Happy to be here, Brittany. Brittany Harvey: Just before we discuss this guideline, I would like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Reuss who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. Dr. Reuss, this living clinical practice guideline for systemic therapy for patients with stage IV non-small cell lung cancer without driver alterations is updated on an ongoing basis. So, what prompted this latest update to the recommendations? Dr. Joshua Reuss: Our committee is tasked with making routine updates to the living guidelines and really keeping them living, right? So, evaluating new data as it is coming in to see, is this practice changing? Is this data that should inform and potentially alter our guideline recommendations so that practitioners and other care providers could really make the best treatment decisions for their patients? So that is something that happens on a more routine basis, but periodically, we are tasked with performing a more comprehensive update of our guideline where we really evaluate every one of our point recommendations, the data associated with these recommendations, to be sure that these are up to date, these are comprehensive, and to see if we need to alter anything in the language of these updates. Brittany Harvey: Excellent. Thank you for providing that background. And yes, this is truly a comprehensive update that goes through all the latest literature. Given that, I would like to review what has changed and what is new in the recommendations. So, what are the updated recommendations on first-line therapy for patients with stage IV non-small cell lung cancer without driver alterations? Dr. Joshua Reuss: So there are two main guidelines that we recommend from this panel. One is a driver mutation-positive guideline and the other is a driver mutation-negative guideline. And I think on first blush, one might look at kind of the recent flurry of approvals and new data and say, well, all the excitement, you know, is in the driver mutation-positive guideline. But I would say that the driver mutation-negative guideline is equally as important and really has several unique challenges associated with it. You know, first and foremost is that there are really a multitude of regimens that can be considered for any one patient. And how to choose between one can be quite difficult and a stressful challenge that clinicians can have, particularly since there are really no randomized studies comparing these regimens in a head-to-head fashion. In addition, you know, these guidelines are really broken down by two key factors. One is disease histology, so namely squamous versus non-squamous histology. And the other is PD-L1 status, broken down into one of three tertiles: PD-L1 high, which is greater than or equal to 50% expression; PD-L1 low, which is 1% to 49% expression; and then PD-L1 negative or unknown. So what you are really looking at, if you do that math, is really six unique patient subpopulations where we need to make a recommendation on one of the multitude of treatment regimens that is approved. And what that means is you are oftentimes really looking at subset and sub-subset level data to help inform clinicians in their treatment decision making, which can be quite challenging because as those small subsets of data is more and more parsed, there are many confounders that can be interjected there. And so I think the committee is tasked with really quite a challenge in terms of how to really communicate and broadcast that data in a way that informs clinicians in making a decision on what is the right treatment for their patient. Brittany Harvey: Absolutely. It can be challenging to interpret that subgroup data across several different studies that are reporting on different regimens and different outcomes. And I appreciate you mentioning the driver mutation-positive guideline as well. Listeners can check out the companion episode with Dr. Puri for more information on what is changed in the driver mutation-positive guideline. Based on that primer, what is new for first-line therapy for patients with stage IV non-small cell lung cancer without driver alterations? Dr. Joshua Reuss: Even though I will say there is not a lot of new trial data that was incorporated into this guideline, there were some updates and just some meaningful long-term data that we incorporated. I think first and foremost, there is a new top-level recommendation in this guideline pertaining to molecular testing, which is absolutely critical in both the driver mutation-positive and driver mutation-negative space. I think we tend to think that, oh, well, molecular testing really only pertains to then finding a driver mutation. But the lack of a mutation is absolutely critical as well, right? Because that is what leads us down the mutation-negative pathway. We also need this molecular testing to assess PD-L1 status. We are seeing emerging data on molecular mutations that might confer resistance to certain immunotherapy-based strategies. So the committee felt strongly that a recommendation on molecular testing is critical to include in both the driver mutation-positive guideline and the driver mutation-negative guideline. I will also say that we are now seeing five and six-year updates from some of the landmark trials of immunotherapy in driver mutation-negative non-small cell lung cancer. It is really incredible to see that in some of these trials, we are seeing very impressive durability of the treatment in the patient subsets that we are commenting on. In others, perhaps that durability is less clear, and I think that leads to challenges in making a recommendation on any one particular regimen. And I think that is nowhere more clear than in the squamous subset. I think that was one perhaps subtle change that is in this guideline where, particularly in the PD-L1 negative squamous population, the committee felt that no one regimen really was worthy of standing above the others. Sometimes I think it is important to really champion one unique regimen if we feel that the data is there to support it. But I think it is equally important to list multiple regimens where the data is less clear. I think another point is that while perhaps there were no new regimens that we have added or that led to other clear changes in the prioritization of one regimen over another, there are other unique data subsets that I think come into play in making a decision and that really are important when looking at the discussion on any one recommendation from this guideline. For example, we know there is emerging data on perhaps the significance of molecular alterations in KEAP1 or STK11 and how that might influence frontline decision-making. You know, there is not a prospective phase III trial in this population, but I think we still need to use that data in certain scenarios to make recommendations for a particular patient. Another example of a trial that, again, did not change our recommendations, but I think one can incorporate in their decision making is the KEYNOTE-598 trial. Now, this is not a new study, but what it studied was pembrolizumab versus pembrolizumab plus ipilimumab in a PD-L1 high subset, and found that the addition of ipilimumab to pembrolizumab in the PD-L1 high population did not significantly improve clinical efficacy. And so while pembrolizumab plus ipilimumab is not an approved regimen, it is hard to extrapolate that to our combination treatments that are approved. I think some clinicians might find that data valuable when making a frontline treatment decision on a patient who has PD-L1 high status. So a bit of a whirlwind tour, but I think there are still multiple factors that went into this guideline that are important to review when making treatment decisions for any one patient. Brittany Harvey: Absolutely. I think what you just mentioned in having that upfront molecular testing is really key for individualized patient care. And the evidence summaries that you provide in addition to the recommendations are really important for clinicians to be able to refer to as they are making decisions in their clinic. So then beyond those changes for first-line therapy, what is updated for second-line and subsequent therapies? Dr. Joshua Reuss: For second-line and subsequent therapies, we did see one new treatment recommendation join these ranks, and that was telisotuzumab vedotin. Telisotuzumab vedotin, quite a mouthful. That is an antibody-drug conjugate. I like to think of that as smart chemotherapy, targeted chemotherapy, where you are trying to utilize some aspect of a marker that is selectively expressed or overexpressed on the cancer surface to then shepherd in the anticancer molecule, a highly potent chemotherapeutic in the case of currently approved antibody-drug conjugates, to exert antitumor killing effect. So in this case, the antibody-drug conjugate telisotuzumab vedotin targets MET overexpression. So telisotuzumab is an antibody targeting MET, and that is conjugated to an MMAE highly potent chemotherapeutic payload called vedotin. So we know MET can be selectively expressed and overexpressed in non-small cell lung cancer in both driver mutation-positive and mutation-negative subsets. The data that led to this approval was from the phase II LUMINOSITY trial which evaluated telisotuzumab vedotin, or Teliso-V, in many subsets. But the subset that really showed promise and was expanded was the EGFR wild-type, non-squamous, non-small cell lung cancer population with MET overexpression. And so in 78 patients with high levels of expression, the response rate here was 34.6%, median progression-free survival of 5.5 months, and a median overall survival of 14.6 months. With an overall acceptable safety profile; grade 3 or higher adverse events, neuropathy was perhaps the most common at 7%, also increased ALT at 3.5%, and pneumonitis at 2.9%. Now this was phase II data that led to an accelerated approval. There is an ongoing phase III study randomizing patients with high expression to Teliso-V versus docetaxel. That is the phase III TeliMET study. But it is nice that we now have another option for patients, perhaps a more biomarker-directed option with, again, this MET overexpression. And again, it further reinforces the importance of molecular testing in patients with traditionally driver mutation-negative non-small cell lung cancer, whether that is upfront or at progression, and in particular utilizing immunohistochemistry to assess MET expression in these patients. And this does join another ADC that we had previously made an update in our recommendation, which is trastuzumab deruxtecan, which is approved for those patients with HER2-overexpressing non-small cell lung cancer. So just again to reiterate the importance of molecular testing in patients both at the outset of their treatment and upon progression on frontline therapy. Brittany Harvey: Definitely. It is great to have this new antibody-drug conjugate join the treatment options, and as you mentioned, very important in this case to have that molecular testing done at the outset and at progression. So then in your view, what should clinicians know as they implement this living guideline, and how do these changes impact patients with non-small cell lung cancer? Dr. Joshua Reuss: Because there are so many different regimens that one can consider for any one patient, I think it is easy to become overwhelmed and stress on, "Am I making the right choice for my patient?" And I think one of the key take home points is that in many cases, there is no one right regimen. And I think one has to weigh several factors. It is the treatment schedule. It is the toxicity profile. It is the molecular profile of the patient. It is the patient preference. You know, there are so many factors here. And I would like to draw the reader and viewer's attention to an important section of these guidelines, particularly the Patient and Clinician Communication section, where we have a box focused on discussion points between patients and clinicians, which I think focuses on several of the high-level points that one can emphasize in making these decisions, ranging on things from: what are the goals of the treatment? What are the risks and benefits to any one approach? What are comorbidities that should be factored in? Common concerns, toxicity management, clinical trial consideration. All of these factors that I think are incredibly important in making that frontline treatment decision and implementing a regimen that both the clinician and, more importantly, the patient feels comfortable with. Brittany Harvey: It is really important that there is shared decision-making in these scenarios. And I think that patient-clinician communication section can tease out some of those preferences from the patient end and talk through the risks and benefits of different regimens as well. As we mentioned at the top of this episode, this guideline is a living guideline and updated on an ongoing basis. So what is the panel examining and keeping an eye on for future updates to this guideline? Dr. Joshua Reuss: So I think there are a lot of exciting new therapies and more up-to-date trials that we are anxiously awaiting the results of on our committee, and I think the oncology community in general is awaiting the results of. When we will have these results, I think, is a bit of an open-ended question, but I can give some insight on several of the trials that our committee is really keeping a close eye on. One that we have mentioned for several guideline iterations is the ECOG-ACRIN INSIGNA trial. This is a phase III clinical trial comparing pembrolizumab versus pembrolizumab plus carboplatin and pemetrexed chemotherapy in PD-L1 positive, non-squamous, non-small cell lung cancer. We talk about there being different regimens that can be considered in PD-L1 positive and PD-L1 high subsets, namely immunotherapy alone or immunotherapy plus chemotherapy, but there is no direct head-to-head comparison here. So this trial hopefully will answer that question. It has now finished accrual. There are other very interesting molecules and trials. I think another interesting compound is ivonescimab. This is a PD-1/VEGF bispecific antibody that is currently approved in China as monotherapy in patients with PD-L1 positive non-small cell lung cancer based off of the HARMONi-2 trial, where the progression-free survival of this bispecific antibody, ivonescimab, appeared superior to pembrolizumab. And we are looking closely at ongoing trials to see if these results will be replicated in an ex-China population. And if so, I think it could have a real impact and change on our guidelines. Still other very interesting things. There are obviously confirmatory studies for antibody-drug conjugates, such as the TeliMET study that I alluded to earlier, and many promising antibody-drug conjugates, both bispecific and trispecific antibody-drug conjugates, that hopefully can inform practice. And then there are several unique subsets of populations that I think we now are utilizing data on to make decisions, but a lot of that is retrospective in small subsets where we do not have that prospective data. And there are several trials ongoing in some of these subsets to try to gain clarity on what regimen may be the best for patients. One example is the phase III TRITON trial, which is looking at comparing CTLA-4 containing regimen, particularly the POSEIDON regimen of durvalumab plus tremelimumab and chemotherapy, versus the KEYNOTE-189 regimen, which is pembrolizumab plus carboplatin and pemetrexed, in patients with non-squamous, non-small cell lung cancer that have alterations in either KRAS, KEAP1, and/or STK11. There is a lot of both preclinical and clinical data to suggest that patients with these alterations in STK11 and KEAP1 may be more resistant to a PD-1 based treatment approach, and perhaps the incorporation of CTLA-4 can lead to a more meaningful response in this unique subset. Obviously, that data, it is retrospective, it is in small subsets. And when you add in a CTLA-4 molecule, you are also introducing greater risk for toxicity. So this trial is going to be very important in elucidating: is there a benefit in that unique subset? Does that data that we see retrospectively in this small subset hold true when evaluated in a prospective fashion? So while our guideline, our most recent comprehensive panel update, may not have had a lot of new data in it that has influenced frontline treatment decision-making, I think the future is bright and there are a lot of novel studies and novel treatments on the horizon that will hopefully improve the outcomes for our patients. Brittany Harvey: Absolutely. We will look forward to the results of those ongoing trials to provide more options and particularly clarity for patients with non-small cell lung cancer and to inform this guideline and its many updates to come. So I want to thank you so much for your work to rapidly and continuously update this guideline, and thank you for your time today, Dr. Reuss. Dr. Joshua Reuss: Thank you so much. Brittany Harvey: And finally, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/thoracic-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines App available in the Apple App Store or the Google Play Store. If you have enjoyed what you have heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  

In this episode of the Mic On Podcast, Seun Okinbaloye speaks with political activist and BBOG co-convener Aisha Yesufu, who delivers a blunt assessment of Nigeria's leadership and the state of governance under President Bola Tinubu. She says the country lacks direction and argues that public frustration cuts across regions, driven by lived realities rather than party loyalty.Yesufu explains her alignment with the ADC as a strategic move, not an emotional one, describing the coalition as united enough to challenge the APC in 2027. While admitting that Peter Obi influenced her decision, she insists her loyalty is to competence and accountability, not party sentiment.She strongly backs Obi as the most credible opposition candidate, dismissing claims that he cannot win Northern votes and predicting internal fractures within the APC ahead of 2027. For Yesufu, the coming election hinges on credible leadership and the integrity of the process, which she believes will define Nigeria's future.Guest:Aisha Yesufu(Political Activist / Co-Convener, Bring Back Our Girls Movement)

Promises, Promises: Nigeria's election cycle is in full swing, and politicians are dusting off their playbooks, making grand promises to woo voters. But as the campaign rhetoric fades and the votes are cast, one question lingers: when is enough, enough? How long should Nigerians wait for leaders to deliver on their promises? Is four years too long for roads to be fixed, hospitals to be built, and jobs to be created? In this episode of Nigeria Daily, we take a hard look at the perennial gap between promise and delivery. We'll explore the reasons behind the disconnect and ask the tough questions: what's holding our leaders back? And what will it take for Nigerians to see real change on the ground?"

In this episode of the Mic On Podcast, Seun Okinbaloye speaks with the Minister of Arts. Culture, Tourism and the Creative Economy, Hannatu Musawa, on the future of Nigeria's creative industry and the political outlook ahead of 2027. She traces her resilience to her upbringing and family influences, describing her father as the most significant figure in her life.Musawa outlines the government's creative economy agenda, citing plans to expand “Detty December,” create millions of jobs, and boost GDP through global best practices. She said the ministry was focused on funding, distribution, and global competitiveness to help Nigerian creatives thrive.On politics, the minister strongly backed President Bola Tinubu's re-election, arguing that opposition figures lack the reach to unseat him, especially in the North. She also weighed in on party dynamics, the rise of the ADC, and insisted that her focus remains on delivering results, not pursuing electoral office.Guest:Hannatu Musawa(Minister of Arts, Culture, Tourism & the Creative Economy)

Katie talks to Palestinian-American lawyer Jenin Younes about the settlement reached by NY Attorney General Tish James and Betar, the zionist hate group, which has gone after Jenin's own clients; the attacks on free Speech criticizing Israel and her spat with JD Vance that landed her on The Daily Show. Then Katie talks to Immigration and Civil Rights lawyer James Carleson about how the Trump administration is using immigration enforcement to unleash a broader techno-fascist agenda in league with Peter Thiel and the billionaires, which the Democrats enable. He also talks about the rapid response networks being built out in major cities which offers a roadmap for how ordinary people resist. To watch the full interview with Mohammad Marandi & Moeed Pirzada, sign up for Patreon: https://www.patreon.com/posts/patreon-full-148479202 Or you can now watch as a YouTube member: https://youtu.be/MeubrKgKxTo Jenin Younes is a palestinian-American attorney, and the national legal director of the ADC, The American-Arab Anti-Discrimination Committee. She's also the co-host of the podcast Previously Prohibited. She describes herself as cancelled by the left for her Covid views & cancelled by the right for Palestine views. This is the horizontal/landscape aspect ratio of the broadcast. For the vertical/portrait aspect ratio, go here: https://youtube.com/live/_sCNlTdE6GI ***Please support The Katie Halper Show *** For bonus content, exclusive interviews, to support independent media & to help make this program possible, please join us on Patreon - https://www.patreon.com/thekatiehalpershow Get your Katie Halper Show Merch here! https://katiehalper.myspreadshop.com/all Follow Katie on Twitter: https://x.com/kthalps Follow Katie on Instagram: https://www.instagram.com/kthalps Follow Katie on TikTok: https://tiktok.com/@kthalps_

Esportmaníacos 2473: En el programa de hoy hemos tenido información del nuevo MMO de League of Legends, por lo menos en lo que respecta a una nueva contratación de un ex de World of Warcraft para Riot Games. Hemos charlado sobre Ferra yéndose a Heretics y hemos revisado unas declaraciones de Vladi, mid laner de Fnatic, sobre Caliste, ADC de Karmine Corp. APÓYANOS AQUÍ https://www.patreon.com/Esportmaniacos https://www.twitch.tv/esportmaniacos 🔁Nuestras redes🔁 https://twitter.com/Esportmaniacos https://www.tiktok.com/@esportmaniacos 💙Referido de AMAZON: https://amzn.to/36cVx3g 00:00:00 - Intro 00:22:00 - Repaso a la LPL 00:26:25 - Novedades del MMO de League of Legends 00:40:10 - Lo de Ferra 01:10:15 - Momento exprimir a Champi a ver si nos dice algo de las scrims 01:13:20 - Vladi responde a unas declaraciones de Caliste 01:27:30 - Vladi también habla del nivel de Fnatic

Justin Fris and Tom Zaunmayr discuss Tony Galati's apple ambitions. Plus BHP share dip after cost blowout; Victor Goh's hotel given a hurry up; ADC plan pivot for Perth Girls School.

Since Nigeria returned to democratic rule in 1999, the Fourth Republic has promised inclusion, representation and opportunity for all citizens.But for many years, young Nigerians remained spectators in a political system dominated by older leaders.The signing of the Not Too Young To Run Act in 2018 marked a turning point, lowering age limits and giving young people a legal pathway into leadership.On Nigeria Daily, we examine how this law has reshaped youth participation in Nigeria's Fourth Republic, the challenges young politicians still face, and whether Nigeria's democracy is truly opening its doors to the next generation.

The League of Legends Betting Podcast  Friday, January 16th, 2025 - LCK, LPL Recorded on: Thursday, January 15th at 507pm Eastern   Intro/Recap (0:26) Brief discussion about ADC / meta and possible DFS / prop site implications LCK Slate (13:05) LPL Slate (16:31)     You can find more, exclusive content to go along with this show on My Patreon. My Twitter/X is @GelatiLOL P&L Sheet for 2025 can be found here and pinned to the top of my Twitter.

Dr. Hope Rugo and Dr. Vivek Subbiah discuss innovative trial designs to enable robust studies for smaller patient populations, as well as the promise of precision medicine, novel therapeutic approaches, and global partnerships to advance rare cancer research and improve patient outcomes. TRANSCRIPT  Dr. Hope Rugo: Hello and welcome to By the Book, a podcast series from ASCO that features engaging conversations between editors and authors of the ASCO Educational Book. I am your host, Dr. Hope Rugo. I am the director of the Women's Cancers Program and division chief of breast medical oncology at the City of Hope Cancer Center [in Los Angeles]. The field of rare cancer research is rapidly transforming thanks to progress in clinical trials and treatment strategies, as well as improvements in precision medicine and next-generation sequencing that enable biomarker identification. According to the National Cancer Institute, rare cancers occur in fewer than 150 cases per million each year, but collectively, they represent a significant portion of all cancer diagnoses. And we struggle with the appropriate treatment for these rare cancers in clinical practice. Today, I am delighted to be joined by Dr. Vivek Subbiah, a medical oncologist and the chief of early-phase drug development at the Sarah Cannon Research Institute in Nashville, Tennessee. Dr. Subbiah is the lead author of a paper in the ASCO Educational Book titled "Designing Clinical Trials for Patients with Rare Cancers: Connecting the Zebras," a great title for this topic. He will be telling us about innovative trial designs to enable robust studies for small patient populations, the promise of precision medicine, and novel therapeutic approaches to improve outcomes, and how we can leverage AI now to enroll more patients with rare cancers in clinical trials. Our full disclosures are available in the transcript of this episode.  Dr. Subbiah, it is great to have you on the podcast today. Thanks so much for being here. Dr. Vivek Subbiah: Thank you so much, Dr. Rugo, and it is an honor and pleasure being here. And thank you for doing this podcast for rare cancers. Dr. Hope Rugo: Absolutely. We are excited to talk to you. And congratulations on this fantastic paper. It is such a great resource for our community to better understand what is new in the field of rare cancer research. Of course, rare cancers are complex and multifaceted diseases. And this is a huge challenge for clinical oncologists. You know, our clinics, of course, cannot be designed as we are being very uni-cancer focused to just be for one cancer that is very rare. So, oncologists have to be a jack of all trades in this area. Your paper notes that there are approximately 200 distinct types of rare and ultra-rare cancers. And, by definition, all pediatric cancers are rare cancers. Of course, clinical trials are essential for developing new treatment strategies and improving patient outcomes, and in your paper, you highlight some unique challenges in conducting trials in this rare cancer space. Can you tell us about the challenges and how really innovative trial designs, I think a key issue, are being tailored to the specific needs of patients with rare cancer and, importantly, for these trials? Dr. Vivek Subbiah: Rare cancers present a perfect storm of challenges. First, the patient populations are very small, which makes it really hard to recruit enough participants for traditional type trials. Second, these patients are often geographically dispersed across multiple cities, across multiple states, across multiple countries, across multiple zip codes. So, logistics become complicated. Third, there is often limited awareness among clinicians, which delays referrals and diagnosis. Add to that regulatory hurdles, funding constraints, and you can see why rare cancer trials are so tough to execute. To overcome these barriers, we are seeing some really creative novel trial designs. And there are four different types of trial designs that are helping with enrolling patients with rare cancers. The first one is the basket trial. So let us talk about what basket studies are. Basket studies group patients based on shared genetic biomarkers or shared genetic mutations rather than tumor type. So instead of running separate 20 to 30 to 40 trials, you can study one therapy across multiple cancers. The second type of trial is the umbrella trial. The umbrella trials flip that concept of basket studies. They focus on one cancer type but test multiple targeted therapies within it. The third category of innovative trials are the platform studies. Platform trials are another exciting innovation. They allow new treatment arms to be added or removed as the data matures and as the data evolves, making trials more adaptive and efficient. The final category are decentralized tools in traditional trials, which are helping patients participate closer to where they are so that they can sleep in their own bed, which is, I think, a game changer for accessibility.  These designs maximize efficiency and feasibility for rare cancer research and rare cancer clinical trials. Dr. Hope Rugo: I love the idea of the platform trials that are decentralized. And I know that there is a trial being worked on with ARPA-H (Advanced Research Projects Agency for Health) funding in triple-negative breast cancer as well as in lung cancer, I think, and others with this idea of a platform trial. But it is challenged, I think, by precision medicine and next-generation sequencing where some patients do not have targetable markers, or there isn't a drug to target the marker. I think those are almost the same thing. We have really seen that these precision medicine ideas and NGS have moved the needle in helping to identify genetic alterations. This helps us to be more personalized. It actually helps with platform studies to customize trial enrollment. And we hope that this will result in better outcomes. It also allows us, I think, to study drugs even in the early stage setting more effectively. How can these advances be best applied to the future of rare cancers, as well as the challenges of not finding a marker or not having a drug? Dr. Vivek Subbiah: Thank you so much for that question. I think precision medicine and next-gen sequencing, or NGS, are truly the backbone of modern precision oncology. They have transformed how we think about cancer treatment. Instead of treating based on where the tumor originated or where the tumor started, we now look at the genetic blueprint of cancer. The NGS or next-gen sequencing allows us to sequence millions of DNA fragments quickly. Twenty, 30 years ago, they said we cannot sequence a human genome. Then it took almost a decade to sequence the first human genome. Right now, we have academic centers and commercial sequencing companies that are really democratizing NGS across all sites, not just in academic centers, across all the community sites, so that NGS is now accessible. This means that we can identify these actionable alterations like picking needles in haystacks, like NTRK fusions, RET fusions, or BRAF V600E alterations, high tumor mutational burden. This might occur across not one tumor type, across several different tumor types. So for rare cancers, this is critical because some of these mutations often define the best treatment option. Here is why this matters. Personalized therapy, right? Instead of a one-size-fits-all approach, we can tailor treatment to the patient's unique molecular profile. For trial enrollment, this can definitely help because patients can join biomarker-driven trials even if their cancer type is rare or ultra-rare. NGS technology has also helped us in designing rational studies. Many times monotherapy does not work in these cancers. So we are thinking about rational combination strategies. So NGS technology is helping us. Looking ahead, I see NGS becoming routine in clinical practice, not just at major niche academic centers, but everywhere. We will see more tumor-agnostic approvals, more molecular tumor boards guiding treatment decisions in real time. And I think we are seeing an expanded biomarker setup. Previously, we used to have only a few drugs and a handful of mutations. Now with homologous recombination defects, BRCA1/2 mutation, and expanding the HRD and also immunohistochemistry, we are expanding the biomarker portfolio. So again, I personally believe that the future is precision. What I mean by precision is delivering the right drug to the right patient at the right time. And for rare cancers, this isn't just progress. It is survival. And it is maybe the only way that they can have access to these cutting-edge precision medicines. Dr. Hope Rugo: That is so important. You mentioned an important area we will get to in a moment, the tumor-agnostic therapies. But as part of talking about that, do you think that the trials should also include just standard therapies? You know, who do you give an ADC to and when with these rare cancers? Because some of them do not have biomarkers to target and it is so disappointing for patients and providers where you are trying to screen a patient for a trial or a platform trial where you have one arm with this mutation, one arm with that, and they do not qualify because they only have a p53 loss, you know? They just do not have the marker that helps them. But we see this in breast cancer all the time. And it is tough because we don't have good information on the sequencing. So I wonder, you know, just because for some of these rare cancers it is not even clear what to use when with standard treatments. And then that kind of gets into this idea of the tumor-agnostic therapies that you mentioned. There are a lot of new treatments that are being evaluated. We have seen approval of some treatments in the last few years that are tumor-agnostic and based on a biomarker. Is that the best approach as we go forward for rare cancers? And what new treatment options are most exciting to you right now? Dr. Vivek Subbiah: Tumor-agnostic therapies, really close to my heart, are real breakthrough therapies and represent a major paradigm shift in oncology. Traditionally, for the broad listeners here, we are used to thinking about designing clinical trials and therapy like where the cancer originated, breast cancer, kidney cancer, prostate cancer, lung cancer. A tumor-agnostic therapy flips that model. Instead of focusing on the organ, they target the specific genetic alteration or biomarker that drives cancer growth regardless of where the tumor started, regardless of the location of the tumor, regardless of the zip code of the tumor. So why is this so important for rare cancers? Because many rare cancers share molecular features with more common cancers. For instance, NTRK fusion might occur in pediatric sarcoma, a salivary gland tumor, or a thyroid cancer. Historically, each of these would require separate trials, which is nearly impossible, unfeasible to conduct in these ultra-rare cancers like salivary gland cancer or pediatric sarcomas. Tumor-agnostic therapies allow us to treat all those cancers with the same targeted drug if they share that biomarker. Again, we are in 2025. The first tissue-agnostic approval, the historic precedent, was in fact an immunotherapy. Pembrolizumab was approved in 2017, May 2017, as the first immunotherapy to be approved in a tumor-agnostic way for a genomic biomarker, for MSI-High and dMMR cancers. Then came the NTRK inhibitors. So today we have not one, not two, but three different NTRK inhibitors: larotrectinib, entrectinib, and repotrectinib, which show response rates of nearly more than 60 to 75% across a handful of dozens and dozens of cancer types. Then, of course, we have RET inhibitors like selpercatinib, which is approved tissue-agnostic, and pralsetinib, which also shows tissue-agnostic activity across multiple cancers. And more recently, combination therapy with a BRAF and MEK combination, dabrafenib and trametinib, received tumor-agnostic approval for all BRAF V600E tumors with the exception of colorectal cancer. And even recently, you mentioned about antibody drug conjugates. Again, I think we live in an era of antibody drug conjugates. And Enhertu, trastuzumab deruxtecan, which was used first in breast cancer, now it is approved in a histology-agnostic manner for all HER2-positive tumors defined by immunohistochemistry 3+. So again, beyond NGS, now immunohistochemistry for HER2 is also becoming a biomarker. So again, for the broad listeners here, in addition to comprehensive NGS that may allow patients to find treatment options for these rare cancers for NTRK, RET, and BRAF, immunohistochemistry for HER2 positivity is also emerging as a biomarker given that we have a new FDA approval for this. So I would say personally that these therapies are game changers because they open doors for patients who previously had no options. Instead of waiting for years for a trial in their specific cancer type, they can access a treatment based on their molecular profile. I think it is precision medicine at its finest and best. Looking ahead, the third question you asked me is what is exciting going on? I think we will see more of these approvals. My hope is that today, I think we have nine to ten approvals. My hope is that within the next 25 to 50 years, we will have at least 50 to 100 drugs approved in this space based on a biomarker, not based on a location of the tumor type. Drug targeting rare alterations like FGFR2 fusions, FGFR amplifications, ALK fusions, and even complex signatures like high tumor mutational burden. I think we will be seeing hopefully more and more drugs approved. And as sequencing becomes routine, we will identify more patients for these therapies. I think for rare cancers, this is not just innovative approach. This is essential for them to access these novel precision medicines. Dr. Hope Rugo: Yeah, that is such a good point. I do think it is critical. Interestingly in breast cancer, it hasn't been, you know, there is always like two patients in these tumor-agnostic trials, or if that. You know, I think I have seen one NTRK fusion ever. I think that highlights the importance for rare cancers. And you know, I am hoping that that will translate into some new directions for some of our rarer and impossible-to-treat subtypes of breast cancer. It is this kind of research that is really going to make a difference. But what about those people who do not have biomarkers? What if you do not fit into that? Do you think there is a possibility of trying to do treatments for rare cancers in some prospective way that would help with that? You know, it is really a huge challenge. Dr. Vivek Subbiah: Absolutely. I think, you know, you're right, usually many of these rare cancers are driven by specific biomarkers. And again, some of the pediatric salivary gland tumors or pediatric sarcomas like fibrosarcomas, they are pathognomonic with NTRK fusions. And again, given that we have a tumor-agnostic approval, now these patients have access to these therapies. And I do not think that we would have had a trial just for pediatric fibrosarcomas with NTRK fusions. So that is one way. Another way is SWOG, right? The SWOG DART [1609] had this combination dual checkpoint, it was called the DART study dual combination chemotherapy with ipi/nivo. Now here the rare cancer subtype itself becomes a biomarker and they showed activity across multiple rare cancer subtypes. They didn't require a biomarker. As long as it was a rare or ultra-rare cancer, these patients were enrolled into the SWOG DART trial and multiple arms have read out. Angiosarcoma, Kaposi sarcoma, even gestational trophoblastic disease. Again, they have shown responses in these ultra-rare, rare cancers. Sometimes they might be seeing one or two cases a whole year. And I think this SWOG effort, this cooperative group effort, really highlighted the need for such studies without biomarkers as well. Dr. Hope Rugo: That is such a fantastic example of how to try and treat patients in a collaborative way. And in the paper, you also emphasize the need for collaborative research efforts, you know, uniting resource expertise across different ways of doing research. So cooperative groups, advocacy organizations that can really help advance rare cancer research, improve access to new therapies, and I think importantly influence policy changes. I think this already happened with the agnostic approvals. Could you tell us more about that? How can we move forward with this most effectively? Dr. Vivek Subbiah: Personally, I believe that collaboration is absolutely critical and essential for rare cancer research. No single institution, no single individual, or no single state or entity can tackle these challenges alone. The patient populations are small and dispersed. So pooling resources is the only way to run these meaningful trials. Again, it is not like singing, it is like putting a huge, huge, I would say, an opera piece together. It is not a solo, vocal therapy, but rather putting a huge opera piece like Turandot. You know, you mentioned cooperative groups. Cooperative groups, as I mentioned earlier, the SWOG DART program, the ASCO [TAPUR study]. ASCO is doing a phenomenal work of the TAPUR study. Again, this ASCO TAPUR program has enrolled so many patients with rare cancers who otherwise would not have treatment options. NCI-MATCH, the global effort, right? NCI-MATCH and the ComboMATCH are great examples. They bring together hundreds of sites, thousands of clinicians to run large-scale trials that would be impossible for any individual center or institution. These trials have already changed practice. For instance, the DART demonstrated the power of immunotherapy in rare cancers and influenced NCCN guidelines. One of the arms of the NCI-MATCH study from the BRAF V600E arm contributed towards the BRAF V600E tissue-agnostic approval. So, the BRAF V600E tissue-agnostic approval was by a pooled analysis of several studies. The ROAR study, the Rare Oncology Agnostic Research study, the NCI-MATCH dataset of tumor-agnostic cohort, and another pediatric trial, and also evidence from literature and evidence of case reports. And all this pooled analysis contributed to the tissue-agnostic approval of BRAF V600E across multiple rare cancers. There are several patient advocacy organizations which are the real unsung heroes here. Groups like, for instance, we mentioned in the paper, Target Cancer Foundation, don't just raise awareness for rare cancer research, they actively connect patients to trials providing financial, emotional support, and even run their own studies like the TRACK trial. They also influence policy to make access easier. On a global scale, initiatives like DRUP in the Netherlands, the ROME study in Italy, the PCM4EU in Europe are expanding precision medicine across these borders. These collaborations accelerate research, improve trial enrollment, and ensure patients everywhere can have access to these cutting-edge therapies. Again, it is truly a team effort, right? It is a multi-stakeholder approach. Researchers, clinicians, investigators, industry, regulators, academia, patients, patient advocates, and their caregivers all working together. And it takes a village. Dr. Hope Rugo: Absolutely. I mean, what a nice response to that. And I think really exciting and it is great to see your passion about this as well. But it helps all of us, I think, getting discouraged in treating these cancers to understand what is happening moving forward. And I think it is also a fabulous opportunity for our junior colleagues as they rise up in academics to be involved in these international collaborative efforts which are further expanding. One of the things that comes up for clinical trials for patients, and I think it is highlighted with rare cancers because, as you mentioned, people are all over the place, you know, they are so rare. They are all far away. Our patients are always saying to us, "Should I go here for a phase 1 trial?" Can you talk a little bit about how we can overcome these financial and geographic burdens for the patients? You talked about having trials locally, but it is a big financial and just social burden for patients. Dr. Vivek Subbiah: Great point. Financial cost is a major barrier in rare cancer clinical trials. It is a major barrier not just in rare cancer clinical trials, but in clinical trials in general. The economics of rare cancer research are one of the toughest challenges we face. Developing a new drug is already expensive, often billions of dollars. On an average, it takes 2 billion dollars or 2.8 billion dollars according to some data from drug discovery to approval. For rare cancers, the market is tiny, which means the pharmaceutical companies have really little financial incentive to invest. That is why initiatives like the Orphan Drug Act were created to provide tax credits, grants, and market exclusivity to encourage development for rare diseases. Clinical trials themselves are expensive because the small patient populations mean longer recruitment times and higher per-patient costs. Geographic dispersion, as you mentioned, for the patients adds travel, coordination. That is why we need to think out of the box about decentralized trial infrastructure so that we can mitigate some of these expenses. Complex trial designs like basket or platform trials sometimes require sophisticated data systems and regulatory oversight. That is a challenge. And I think some of the pragmatic studies like ASCO TAPUR have overcome those challenges. Advanced technologies like next-gen sequencing and molecular profiling also add significant upfront cost to this. Funding is also limited because rare cancers receive less attention compared to common cancers. Public funding and cooperative group trials help a lot, but I think they cannot cover everything. Patient advocacy organizations sometimes step in to bridge these gaps, but sustainable financing remains a huge challenge. So, the bottom line is without financial incentives and collaborating funding models, many promising therapies for rare cancers would never make it to patients. That is why we need system-wide policy changes, global partnerships, and innovative, effective, seamless trial designs which are so critical so that they can help reduce the cost and make research feasible so that we can deliver the right drug to the right patient at the right time. Dr. Hope Rugo: There is a lot of excitement about the future integration of AI in screening. Just at the San Antonio Breast Cancer meetings, we have a number of different presentations about AI to find markers, even like HER2, and using AI where you would screen and then match patients to clinical trials. Do you have any guidance for the rare cancer community on how to leverage this technology in order to optimize patient enrollment and, I think, identification of the best treatment matches? Dr. Vivek Subbiah: I think artificial intelligence, AI, is a game-changer in the making. Right now, clinical trial is clunky. Matching patients to trial is often manual, time consuming, laborious. You need a lot of personnel to do that. AI can automate this process by analyzing genomic data, medical records, and trial eligibility criteria to find the best matches quickly, accurately, and effectively. For the community, the key is to invest in data standardization and interoperability because AI needs clean, structured data to work effectively. Dr. Hope Rugo: Thank you so much, Dr. Subbiah, for sharing these fantastic insights with us on the podcast today and for your excellent article. Dr. Vivek Subbiah: Thank you so much. Dr. Hope Rugo: We thank you, our listeners, for joining us today. You will find a link to Dr. Subbiah's Educational Book article in the transcript of this episode. And please join us again next month on By the Book for more insightful views on key issues and innovations that are shaping modern oncology.  Thank you. 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. Hope Rugo   @hoperugo   Dr. Vivek Subbiah @VivekSubbiah Follow ASCO on social media:        ASCO on X  ASCO on Bluesky       ASCO on Facebook        ASCO on LinkedIn        Disclosures:       Dr. Hope Rugo:    Honoraria: Mylan/Viatris, Chugai Pharma   Consulting/Advisory Role: Napo Pharmaceuticals, Sanofi, Bristol Myer   Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Hoffman La-Roche AG/Genentech, In., Stemline Therapeutics, Ambryx   Dr. Vivek Subbiah: Consulting/Advisory Role: Loxo/Lilly, Illumina, AADI, Foundation Medicine, Relay Therapeutics, Pfizer, Roche, Bayer, Incyte, Novartis, Pheon Therapeutics, Abbvie Research Funding (Inst.): Novartis, GlaxoSmithKline, NanoCarrier, Northwest Biotherapeutics, Genentech/Roche, Berg Pharma, Bayer, Incyte, Fujifilm, PharmaMar, D3 Oncology Solutions, Pfizer, Amgen, Abbvie, Mutlivir, Blueprint Medicines, Loxo, Vegenics, Takeda, Alfasigma, Agensys, Idera, Boston Biomedical, Inhibrx, Exelixis, Amgen, Turningpoint Therapeutics, Relay Therapeutics Other Relationship: Medscape, Clinical Care Options

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we delve into a series of transformative updates reshaping drug development and patient care across the globe.Starting with a major collaboration between Roche and Medilink Therapeutics that has captured industry attention. Roche is making a strategic move by committing $570 million to partner on an antibody-drug conjugate, or ADC, targeting the B7-H3 immune checkpoint protein. This partnership underscores a broader industry trend focusing on immuno-oncology. ADCs have become pivotal due to their ability to deliver cytotoxic agents precisely to tumor cells, reducing systemic exposure and minimizing side effects. This precision not only enhances efficacy but also improves patient experience, marking a significant stride in cancer treatment modalities.In another strategic alliance, Pfizer has entered into a $50 million deal with Madrigal Pharmaceuticals for a DGAT2 inhibitor. Madrigal plans to pair this with its liver disease treatment, Rezdiffra, aiming to amplify therapeutic outcomes in liver conditions. This highlights an increasingly popular approach in medicine: polypharmacy and combination therapies. By tackling diseases from multiple angles, these therapies promise more comprehensive management of complex conditions, reflecting a shift towards more personalized and effective treatment strategies.Turning our attention to the startup landscape, "Baby KJ" Scientist has launched a new personalized CRISPR therapy company with $16 million in initial funding from Menlo Ventures. This venture signals growing interest in CRISPR technology for crafting bespoke genetic therapies. The potential for CRISPR lies in its ability to edit genomes precisely, opening possibilities for treating genetic disorders at their root cause and tailoring interventions to individual patients' genetic profiles.On the financial front, Aktis Oncology's successful IPO stands out, raising an impressive $318 million through an upsized offering. This achievement not only illustrates investor confidence in biotech but also suggests a more favorable atmosphere for upcoming biotech ventures seeking public funding. A robust financial ecosystem is crucial for fostering innovation and bringing cutting-edge therapies from the lab bench to the bedside.In another exciting development, Airnexis Therapeutics has secured $200 million to advance its COPD treatment asset in collaboration with a Chinese pharmaceutical firm. The total deal could reach up to $955 million in what's known as biobucks—a term used for milestone payments in biotech partnerships. This collaboration exemplifies the globalization of biotech partnerships, emphasizing the strategic importance of tapping into diverse markets for drug development and commercialization.Meanwhile, Ollin Biosciences is making waves with promising results from its bispecific antibody trial. The antibody showed superior efficacy in treating diabetic macular edema compared to Genentech's Vabysmo. This success potentially sets a new benchmark for retinal disease therapies and highlights the rapid evolution of bispecific antibodies. These agents can engage multiple targets simultaneously, offering enhanced therapeutic potential across various conditions.Leadership dynamics are also influencing the sector. Charles Fuchs has transitioned from his role as Roche's Global Head of Oncology and Hematology Product Development to Tubulis. Such moves suggest potential shifts in strategic focus for both companies involved, reflecting broader trends in leadership realignments within the industry. Additionally, Illumina's appointment of Eric Green as Chief Medical Officer showcases another instance of experienced leaders taking pivotal roles within companies at the forefront of genomic research. Such appointments underscore the imSupport the show

Dr. Monty Pal and Dr. Hope Rugo discuss advances in antibody-drug conjugates for various breast cancer types as well as treatment strategies in the new era of oral SERDs for HR-positive breast cancer. TRANSCRIPT Dr. Monty Pal: Hello, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. Monty Pal. I'm a medical oncologist and vice chair of academic affairs here at the City of Hope Comprehensive Cancer Center, Los Angeles. Today, I'm thrilled to be joined by Dr. Hope Rugo, an internationally renowned breast medical oncologist and my colleague here at City of Hope, where she leads the Women's Cancers Program and serves as division chief of breast medical oncology. Dr. Rugo is going to share with us exciting advances in antibody-drug conjugates (ADCs) that are expanding treatment options in various breast cancer types. She'll also address some of the complex questions arising in the new era of oral SERDs (selective estrogen receptor degraders) that are revolutionizing treatment in the hormone receptor-positive breast cancer space. Our full disclosures are available in the transcript of this episode.  Dr. Rugo, welcome, and thanks so much for being on the podcast today. Dr. Hope Rugo: Thank you. Pleasure to be here. Dr. Monty Pal: So, I'm going to switch to first names if you don't mind.  The first topic is actually a really exciting one, Hope, and this is antibody-drug conjugates. I don't know if I've ever shared this with you, but I actually started my training at UCLA, I was a med student and resident there, and it was in Dennis Slamon's lab. I worked very closely with Mark Pegram and a handful of others. This is right around the time I think a lot of HER2-directed therapies were really evolving initially in the clinics. Now we've got antibody-drug conjugates. Our audience is well-familiar with the mechanism there but tell us about how ADCs have really started to reshape therapy for HER2-positive breast cancer. Dr. Hope Rugo: Yeah, I mean, this is a really great place to start. I mean, we have had such major advances in breast cancer just this year, I think really changing the paradigm of treating patients. But HER2-positive disease, we've been used to having sequenced success of new agents. And I think the two biggest areas where we've made advances in HER2-positive disease, which were remarkably advanced this year in 2025, have been in antibody-drug conjugates with trastuzumab deruxtecan and with new oral tyrosine kinase inhibitors (TKIs) that have less of a target on EGFR and more on HER2, so they have an overall more tolerable toxicity profile and therefore a potentially better efficacy in the clinic. At least that's what we're seeing with these new strategies that we couldn't really pursue in the past because of toxicities of the oral TKIs. So, although our topic is ADCs, I'm going to include the TKI because it's so important in our thinking about treating HER2-positive disease. In the metastatic setting, we've seen these remarkable improvements in progression-free and overall survival in the second-line setting with T-DXd, or trastuzumab deruxtecan, compared to T-DM1. And then sequencing ADCs with giving T-DXd after T-DM1 was better than an oral tyrosine kinase or a trastuzumab combination with standard chemotherapy. That was DESTINY-Breast03 and DESTINY-Breast02. So, then we've had other trials since then, and T-DXd has moved into the early-stage setting, which I'll talk about in just a moment. But the next big trial for T-DXd in HER2-positive disease was moving it to the first-line setting to supplant what has become an established treatment for now quite a long time: the so-called CLEOPATRA regimen, which used the combined antibodies trastuzumab, pertuzumab with a taxane as first-line therapy. And then we've proceeded on with maintenance with ongoing HP for patients with responding or stable disease. And we'd seen long-term data showing, you know, at 8 years there was a group of patients whose cancers had never progressed and continued improved overall survival. So, T-DXd was studied in DESTINY-Breast09, either alone or in combination with pertuzumab compared to THP. The patient population had received a little bit more prior treatment, but interestingly, not a lot compared to CLEOPATRA. And they designed the trial to be T-DXd continued until progression with or without pertuzumab versus THP, which would go for six cycles and then stop around six cycles, and then stop and continue HP. Patients who had hormone receptor-positive disease could use hormone therapy, and this is one of the issues with this dataset because, surprisingly in this dataset and one other I'll mention, very few patients took hormone therapy. And even in the maintenance trial, the HER2CLIMB-05, less than 50% took hormone therapy as maintenance. This is kind of shocking to me and highlights an area of really important education, that outcome is improved when you add endocrine therapy for hormone receptor-positive HER2-positive metastatic disease in the maintenance phase, and it's a really important part of treatment. But suffice it to say, you know, you're kind of studying continued chemo versus stopping chemo in maintenance. And T-DXd, as we all expected, in combination with pertuzumab was superior to THP in terms of progression-free survival, really remarkably improved. And you could stop the chemo with toxicity, but most people continued it with T-DXd. Again, not a lot of people got hormone therapy, which is an issue, and you stop the chemo in the control arm. So, this has brought up a lot of interest in trying to use T-DXd as an induction and then go to maintenance, much as we do with the CLEOPATRA regimen with hormone therapy. But it brings up another issue. So first, T-DXd is superior; it's a great treatment. Not everybody needs to have it because we don't know whether it's better to give T-DXd first or second with progression - that we need a little bit longer follow-up. But just earlier this week, interestingly, the third week of December, the U.S. FDA approved T-DXd in the DESTINY-Breast09 approach with pertuzumab. So as I mentioned earlier, there was a T-DXd-alone arm; that arm has not yet reported. So very interesting, we don't know if you need pertuzumab or not. So what about the maintenance? That's the other area where we've made a huge advance here. So, we all want to stop chemo and we want to stop T-DXd. You don't want somebody being nauseated for two years while they're on treatment, and also there's a small number of patients with mostly de novo metastatic HER2-positive disease who are cured of their disease. We'd like to expand that, and I think these new drugs give us the opportunity to improve the number of patients who might be cured from metastatic disease. So the first maintenance study we saw was adding palbociclib, the CDK4/6 inhibitor, to endocrine therapy and HP, essentially. There, we had a remarkable improvement in progression-free survival difference of 15.2 months: 29 to 44 months, really huge. At San Antonio this year, we saw data with this oral tyrosine kinase inhibitor tucatinib, already showed it was great in a triplet, but as maintenance in combination with HP, it showed also a remarkable improvement in progression-free survival. But the numbers were all shifted down. So in PATINA, the control arm was in the 24-month range; here it was the tucatinib-HP arm that was in the 25 months and 16 months for control. So there was a differential benefit in ER-negative and ER-positive disease. So I think we're all thinking that our ideal approach moving forward would be to give T-DXd to most patients, we see how they do, and treat to best response. And then, stop the T-DXd, start HP, trastuzumab, pertuzumab for ER-negative, with tucatinib for ER-positive with palbociclib. We also have early data that suggests that both approaches may reduce the development of brain metastases, an issue in HER2-positive disease, and delay time to progression of brain metastases as seen in HER2CLIMB-05 in very early data - small numbers, but still quite intriguing that you might delay progression of brain metastases with tucatinib that clearly has efficacy in the brain.  So, I think that this is a hugely exciting advance for our patients, and these approaches are quickly moving into the early stage setting. T-DXd compared to standard chemo, essentially followed by THP, so a sequenced approach resulted in more pathologic complete responses than a standard THP-AC-type neoadjuvant therapy. T-DXd alone for eight cycles wasn't better, and that's interesting. We still need the sequenced non-cross-resistant chemo. But I think even more importantly, the data from DESTINY-Breast05 looking at T-DXd versus T-DM1 in patients with residual disease after neoadjuvant HER2-targeted therapy showed a remarkable improvement in invasive disease-free survival with T-DXd versus T-DM1, and quite early. It was a high-risk population, higher risk than the T-DM1 trial with KATHERINE, but earlier readout with a remarkable improvement in outcome. We expect to be FDA approved sometime in the first half of 2026. So then we'll get patients who've already had T-DXd who get metastatic disease. But my hope is that with T-DXd, maybe with tucatinib in the right group of patients or even sequenced in very high-risk disease, that we could cure many more patients with early-stage HER2-positive breast cancer and cure a subset, a greater subset of patients with de novo metastatic disease. Dr. Monty Pal: That's brilliant. And you tackled so many questions that I was going to follow up with there: brain metastases, etc. That was sort of looming in my mind. I mean, general thoughts on an ADC versus a TKI in the context of brain mets? Dr. Hope Rugo: Yeah, it's an interesting question because T-DXd has shown quite good efficacy in this setting. And tucatinib, of course, had a trial where they took patients with new brain mets, so a larger population than we've seen yet for the T-DXd trials, and saw that not only did they delay progression of brain metastases and result in shrinkage of existing untreated brain mets, but that patients who develop a new brain met, they could stay on the same assigned treatment. They got stereotactic radiation, and then the patients who were on tucatinib with trastuzumab and capecitabine had a further delay in progression of brain mets compared to those on the placebo arm, even after treatment of a new one that developed on treatment. So, I think it's hard. I think most of us for a lot of brain mets might start with the tucatinib approach, but T-DXd is also a very important treatment. You know, you're kind of trading off a diarrhea, some liver enzyme elevations with tucatinib versus nausea, which you really have to work on managing because it can be long-delayed nausea, and this risk of ILD, interstitial lung disease, that's about 12%, with most but not all trials showing a mortality rate from interstitial lung disease of just under 1 percent. In the early-stage setting, it was really interesting to see that with T-DXd getting four cycles in the neoadjuvant setting, a lot less ILD noted than the patients who got up to 14 cycles, as I think they got a median of 10 cycles in the post-surgical setting, there was a little bit more ILD. But I think we're going to be better and better at finding this earlier and preventing mortality by just stopping drug and treating earlier with steroids. Dr. Monty Pal: And this ILD issue, it always seems to resurface. There are drugs that I use in my kidney cancer clinic, everolimus, common to perhaps the breast cancer clinic as well, pembrolizumab, where I think the pattern of pneumonitis is quite different, right? What is your strategy for recognizing pneumonitis early in this context? Dr. Hope Rugo: Well, it is, and you know, having done the very early studies in everolimus where we gave it in the neoadjuvant setting and we're like, "Hmm, the patient came in with a cough. What's going on?" You know, we didn't know. And you have mouth sores, you know, we were learning about the drug as we were giving it. What we don't do with everolimus and CDK4/6 inhibitors, for example, is grade 1 changes like radiation pneumonitis, we don't stop, we don't treat it. We only treat for symptoms. But because of the mortality associated with T-DXd, albeit small, we stop drug for grade 1 imaging-only asymptomatic pneumonitis, and some of us treat with a half dose of steroids just to try and hasten recovery. We've actually now published or presented a couple of datasets from trials, a pooled analysis and a real-world analysis, that have looked at patients who were retreated after grade 1 pneumonitis or ILD and tolerated drug very well and none of them died of interstitial lung disease, which was really great to see because you can retreat safely and some of these patients stayed on for almost a year benefiting from treatment. So, there's a differential toxicity profile with these drugs and there are risk factors which clearly have identified those at higher risk: prior ILD, for example. A French group said smoking; other people haven't found that, maybe because they smoked more in France, I don't know. And being of Japanese descent is quite interesting. The studies just captured that you were treated in Japan, but I think it's probably being of Japanese descent with many drugs that increases your risk of ILD. And, you know, older patients, people who have hypoxia, those are the patients. So, how do we do this? With everolimus, we don't have specific monitoring. But for T-DXd we do; we do every nine weeks to start with and then every 12 weeks CT scans because most of the events occur relatively early. Somebody who's older and at higher risk now get the first CT at six weeks. Dr. Monty Pal: This is super helpful. And I have to tell you, a lot of these drugs are permeating the bladder cancer space which, you know, is ultimately going to be a component of my practice, so thank you for all this. We could probably stay on this topic of HER2-positive disease forever. I'm super interested in that space still. But let me shift gears a little bit and talk about triple-negative breast cancer and this evolving space of HR-positive, HER2-low breast cancer. I mean, tell us about ADCs in that very sort of other broad area. Dr. Hope Rugo: So triple-negative disease is the absolute hardest subset of disease that we have to treat because if you don't have a great response in the early stage setting, the median survival is very short, you know, under two years for the majority of TNBCs, with the exception of the small percentage of low proliferative disease subsets. The co-question is what do we do for these patients and how do we improve outcome? And sacituzumab govitecan has been one strategy in the later line setting that was shown to improve progression-free and overall survival, the Trop-2 ADC. We had recently three trials presented with the two ADCs, sacituzumab govitecan and the other Trop-2 ADC that's approved for HR-positive disease, datopotamab deruxtecan. And they were studied in the first-line setting. Two trials with SG, sacituzumab govitecan, those trials, one was PD-L1 positive, ASCENT-04. That showed that SG with a checkpoint inhibitor was superior, so pembrolizumab was superior to the standard KEYNOTE-355 type of treatment with either a taxane or gemcitabine and carboplatin with pembrolizumab for patients who have a combined positive score for PD-L1, 10 or greater. So, these are patients who are eligible for a checkpoint inhibitor, and SG resulted in an improved progression-free survival.  The interesting thing about that dataset is that few patients had received adjuvant or neoadjuvant checkpoint inhibitor, which is fascinating because we give it to everybody now. But access is an issue and timing of the study enrollment was an issue. The other thing which I think we've all really applauded Gilead for is that there was automatic crossover. So, you could get from the company, to try and overcome some of the enormous disparities worldwide in access to these life-saving drugs, you could get SG through the company for free once you had blinded independent central review confirmation of disease progression. Now, a lot of the people who got the SG got it through their insurance, they didn't bill the company, but 80 percent of patients in the control arm received SG in the second-line setting. So that impacts your ability to look at overall survival, but it's an incredibly important component of these trials. So then at ESMO, we saw the data from SG and Dato-DXd in the first-line metastatic setting for patients who either had PD-L1-negative disease or weren't eligible for an immunotherapy. For the Dato study, TROPION-Breast02, that was 10 percent of the patients who had PD-L1-positive disease but didn't get a checkpoint inhibitor, and for the ASCENT-03 trial population it was only 1 percent. Importantly, the trials allowed patients who relapsed within a year of receiving their treatment with curative intent, and the Dato study, TB-02, allowed patients who relapsed while on treatment or within the first six months, and that was 15 percent of the 20 percent of early relapsers. The ASCENT trial, ASCENT-03, had 20 percent who relapsed between 6 and 12 months. The drugs were better than standard of care chemotherapy, the ADCs in both trials, which is very nice. Different toxicity profiles, different dosing intervals, but better than standard of care chemotherapy in the disease that's hardest for us to treat. And importantly, when you looked at the subset of early relapsers, those patients also did better with the ADC versus chemotherapy, which is incredibly important. And we were really interested in that 15 percent of patients who had early relapse. I actually think that six months thing was totally contrived, invented, you know, categorization and doesn't make any sense, and we should drop it. But the early relapsers were 15 percent of TB-02 and Dato was superior to standard of care chemo. We like survival, but the ASCENT trial again allowed the crossover to an approved ADC that improved survival and 80 percent of patients crossed over. In the Dato trial, they did not allow crossover, they didn't provide Dato, which isn't approved for TNBC but is for HR-positive disease, and they didn't allow, of course, pay for SG. So very few patients actually crossed over in their post-treatment data and in that study, they were able to show a survival benefit. So actually, I think in the U.S. where we can use approved drugs already before there's a fixed FDA approval, that people are already switching to use SG or Dato in the first-line setting for metastatic TNBC that's both PD-L1 positive for SG and PD-L1 negative for both drugs. And I think understanding the toxicity profiles of the two drugs is really important as well as the dosing interval to try and figure out which drug to use. Dr. Monty Pal: Brilliant. Brilliant. Well, I'm going to shift gears a little bit. ADCs are a topic, again, just like HER2-positive disease we could stay on forever. Dr. Hope Rugo: Huge. Yes. Dr. Monty Pal: But we're going to shift gears to another massive topic, which is oral SERDs. In broad strokes, right, this utilization of CDK4/6 inhibitors in the context of HR-positive breast cancer is obviously, you know, a paradigm that's been well established at this point. Where do we sequence in oral SERDs? Where do they fit into this paradigm? Dr. Hope Rugo: Ha! This is a rapidly changing area; we keep changing what we're saying every other minute. And I think that there are three areas of great interest. So one is patients who develop ESR1 mutations that allow constitutive signaling through the estrogen receptor, even when there's not estrogen around, and that is a really important mutation that is subclonal; it develops under the pressure of treatment in about 40 percent of patients. And it doesn't happen when you first walk in the door. And what we've seen is that oral SERDs as single agents are better than standard single-agent endocrine therapy in that setting. The problem that we've had with that approach is that we're now really interested in giving targeted agents with our endocrine therapies, not just in the first-line setting where CDK4/6 inhibitors are our standard of care with survival benefit for ribociclib and, you know, survival benefit in subsets with other CDK4/6 inhibitors, and abemaciclib with a numeric improvement. So we give it first line. The question is, what do you do in the second-line setting? Because of the recent data, we now believe that oral SERDs should be really given with a targeted agent. And some datasets which were recently presented, which I think have helped us with that, have been EMBER-3 and then the most recently evERA BC, or evERA Breast Cancer, that looked at the oral SERD giredestrant with everolimus compared to standard of care endocrine therapy with everolimus, where 100 percent of patients received prior CDK4/6 inhibitor and showed a marked improvement in progression-free survival, including in the subsets of patients with a short response, 6-12 months of prior response to CDK4/6 inhibitor and in those who had a PIK3CA pathway mutation. The thing is that the benefit looks like it's much bigger in the ESR1 mutant population, although response was better, PFS wasn't better in the wild type. So, we're still trying to figure that out. We also saw EMBER-3 with imlunestrant and abemaciclib as a second line. Not everybody had had a prior CDK4/6 inhibitor; they compared it to imlunestrant alone, but still the data was quite striking and seemed to cross the need for ESR1 mutations. And then lastly, we saw data from the single arms of the ELEVATE trial looking at elacestrant with everolimus and abemaciclib and showed these really marked progression-free survival data, even though single-arm, that crossed the mutation status. At least for the everolimus combination, abemaciclib analysis is still to come in the mutated subgroups. But really remarkable PFS, much longer.  Single-agent fulvestrant after CDK4/6 inhibitor AI has a PFS in like the three-month range and in some studies, maybe close to five months. These are all at 10-plus months and really looking very good. And so those questions are, is it ESR1 mutation alone? Is it all comers? We'd like all comers, right? We believe in the combination approach and we're learning more about combinations with drugs like capivasertib and other drugs as we move forward. Everybody now wants to combine their targeted agent with an oral SERD because they're clearly here to stay with quite remarkable data. The other issue, so the second issue in the metastatic setting is, does it make a difference if we change to an oral SERD before radiographic imaging evidence of progression? And that was the question asked in the SERENA-6 trial where patients had serial monitoring for the presence of ESR1 mutations in ctDNA. And those who had them without progression on imaging could be randomized to switch to camizestrant with the same CDK4/6 inhibitor or stay on their same AI CDK4/6 inhibitor. And they showed a difference in progression-free survival that markedly favored camizestrant. But interestingly, the people who were on the standard control arm had an ESR1 mutation, we think AIs don't work, they stayed on for nine more months. The patients who were on the camizestrant stayed on for more than 16 months. And they presented some additional subset data which showed the same thing: follow-up PFS data, PFS2, all beneficial in SERENA-6 at the San Antonio [Breast Cancer Symposium]. So, we're still a little bit unclear about that. They did quality of life, and pain was markedly improved. They had a marked delayed time to progression of pain in the camizestrant arm. So this is all a work in progress, trying to understand who should we switch without progression to an oral SERD based on this development of this mutation that correlates with resistance. And, you know, it's interesting because the median time to having a mutation was 18 months and the median time to switch was almost 24 months. And then there were like more than 3,000 patients who hadn't gotten a mutation, hadn't switched, and were still okay. So screening everybody is the big question, and when you would start and who you would change on and how this affects outcome. Patients didn't have access to camizestrant in the control arm, something we can't fix but we have experimental drugs. We're actually planning a trial, I hope in collaboration with the French group Unicancer, and looking at this exact question. You know, if you switch and you change the CDK4/6 inhibitor and then you also allow crossover, what will we see? Dr. Monty Pal: We're coming right to the tail end of our time here, and I could probably go on for another couple of hours with you here. But if you could just give us maybe one or two big highlights from San Antonio, any thoughts to leave our audience with here based on this recent meeting? Dr. Hope Rugo: Yeah, I mean, I talked about a lot of those new data already from San Antonio, and the one that I'd really like to mention which I think was, you know, there were a lot of great presentations including personalized screening presented from the WISDOM trial by my colleague Laura Esserman, fascinating and really a big advance. But lidERA was the big highlight, I think, outside of the HER2CLIMB-05 which I talked about earlier in HER2-positive disease. And this study looked at giredestrant, the oral SERD versus standard of care endocrine therapy as treatment for medium and high-risk early-stage breast cancer. And what they showed, which I think was really remarkable with just about a three-year median follow-up, was an improvement in invasive disease-free survival with a hazard ratio of 0.7. I mean, really quite remarkable and so early. It looked as though this was all driven by the high-risk group, which makes sense, not the medium risk, it's too early. And also that there was a bigger benefit in patients who were on tamoxifen compared to giredestrant versus AI, but for both groups, the confidence intervals didn't cross 1. There's even a trend towards overall survival, even though it's way too early. I think that, you know, really well-tolerated oral drug that could improve outcome in early-stage disease, this is the first advance we've seen in over two decades in the treatment of early-stage hormone receptor-positive disease with just endocrine therapy. I think we think that we don't want to give up CDK4/6 inhibitors because we saw a survival benefit with abemaciclib and a trend with giving ribociclib in the NATALEE trial. So we're thinking that maybe one approach would be to give CDK4/6 inhibitors and then switch to an oral SERD or to have enough data to be able to give oral SERDs with these CDK4/6 inhibitors for early-stage disease. And that's all in the works, you know, lots of studies going on. We're going to see a lot of data with both switching 8,000 patients with an imlunestrant switching trial, an elacestrant trial going on, and safety data with giredestrant with abemaciclib and soon to come ribociclib. So, this is going to change everything for the treatment of early-stage breast cancer, and I hope cure more patients of the most common subset of the most common cancer diagnosed in women worldwide. Dr. Monty Pal: Super exciting. It's just remarkable to hear how this has evolved since 25 years ago, which is really the last time I sort of dabbled in breast cancer.  Thank you so much, Hope, for joining us today. These were fantastic insights. Appreciate you being on the ASCO Daily News Podcast and really want to thank you personally for your remarkable contribution to the field of breast cancer. Dr. Hope Rugo: Thank you very much, and thanks for talking with me today. Dr. Monty Pal: You got it. And thanks a lot to our listeners today as well. You'll find links to all the studies we discussed today in the transcript of this episode. Finally, if you value the insights that you hear today on the ASCO Daily News Podcast, please 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 opinion 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. Monty Pal @montypal Dr. Hope Rugo   @hoperugo Follow ASCO on social media:        ASCO on X  ASCO on Bluesky       ASCO on Facebook        ASCO on LinkedIn        Disclosures:     Dr. Monty Pal:    Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview   Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical   Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis   Dr. Hope Rugo:    Honoraria: Mylan/Viatris, Chugai Pharma   Consulting/Advisory Role: Napo Pharmaceuticals, Sanofi, Bristol Myer   Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Hoffman La-Roche AG/Genentech, In., Stemline Therapeutics, Ambryx  

Esportmaníacos 2454: En el programa de hoy hemos repasado los cambios de la nueva temporada de League of Legends ya que hoy ha dado inicio. Desde las misiones por rol, los cambios a objetivos y los nuevos objetos. También hemos visto un leak sobre la nueva ERL de España llevada por Cabal y Lastlap. Leak al cuál hemos añadido algo de información. APÓYANOS AQUÍ https://www.patreon.com/Esportmaniacos https://www.twitch.tv/esportmaniacos 🔁Nuestras redes🔁 https://twitter.com/Esportmaniacos https://www.tiktok.com/@esportmaniacos 💙Referido de AMAZON: https://amzn.to/36cVx3g 00:00:00 - Intro 00:17:40 - El leak de la ERL española 00:30:50 - Muere el Código del Invocador 00:33:20 - El nuevo sistema de baneo a trolls en selección de campeón 00:40:20 - Todos los cambios de la nueva temporada 00:56:50 - Royal se rinde 01:00:35 - La misión de mid lane 01:08:00 - La misión de ADC/bot lane 01:18:50 - La misión de support 01:23:30 - Cambios a los objetivos 01:35:15 - Los nuevos objetos, ¿qué será lo más OP?

Election preparations in Nigeria traditionally follow a clear path INEC releases a timetable, political parties adjust, and campaigns officially begin.But ahead of the 2027 general elections, that order appears to be shifting.Even without an official election calendar from INEC, some aspirants have declared interest, supporters are mobilising, and campaign-like activities are already unfolding raising questions about legality, fairness, and the future of Nigeria's electoral process.On Nigeria Daily, we examine when INEC will release the 2027 election calendar, why some politicians are moving ahead of schedule, and what the law says about early declarations and campaigns.

Alex Moss and Andrew Sinclair are back with a new episode of your go-to darts podcast after the 2025/26 PDC World Darts Championship! The boys start the show with a look back at the finale at Alexandra Palace, reflecting on Luke Littler becoming a back-to-back PDC world champion and also discussing Gian van Veen's run to his first senior world final. The ADC's Scott Hunt (20:00) calls in following the ADC Global Championship finale at the weekend. Scott looks back on the ADC's 2025 and the start of 2026 which saw Jack Tweddell pocket the £60,000 top prize for winning the Global Championship, before looking ahead to the rest of this year, the expansion to the Championship Tour in 2026, along with what the future holds for the organisation's flagship event later this year. Alex and Andrew continue their review of the PDC World Darts Championship, picking out their favourite moments from the last three weeks at Alexandra Palace, before giving their thoughts on the Premier League line up for 2026. Ahead of opening in select theatres on Friday, some of the cast and crew from BULLS The Movie join Alex to look ahead to the first darts movie's big release this week. Director Dan Meyer, lead actors Meir Steinberg and Matt Trudeau, and producer/actress Kelsey Bunner talk through their roles in the movie and the excitement of BULLS finally coming to our screens. The boys wrap up the show by giving their picks for the final stage at Q-School and then look ahead to 2026 and what they are most looking forward to darts wise from the year ahead. BULLS The Movie is being released from Vertical Films to select theatres and streaming on January 9. Join the Darts Strava King group on Strava *** This podcast is brought to you in association with Darts Corner - the number one online darts retailer! Darts Corner offers the widest selection of darts products from over 30 different manufacturers.  This podcast is sponsored by Darts Atlas - the platform for darts players, venues, and organisations. Darts Atlas is the home of the Amateur Darts Circuit (ADC) with hundreds of tournaments held on the platform every week.  Have you used Darts Atlas before? Share your feedback and experiences with Darts Atlas with us by sending an email to weeklydartscast@gmail.com and be in with a chance of winning some new logo Weekly Dartscast stickers! Check out Condor Darts here: UK site *** Enjoy our podcast? Make a one-off donation on our new Ko-Fi page here: ko-fi.com/weeklydartscast Support us on Patreon from just $2(+VAT): patreon.com/WeeklyDartscast Thank you to our Patreon members: Phil Moss, Gordon Skinner, Connor Ellis, Dan Hutchinson

Alexandre Kazuo Kubo & Lucas Ribeiro, authors of Principle: 128 Kazuo Kubo and Lucas Ribeiro are Brazilian advertising creatives with over 20 years of experience at top global agencies, including McCANN New York , CP+B, BETC, Hill Holliday, and Africa. They've contributed to campaigns for brands like The Coca-Cola Company, BMW Group, Gatorade, PUMA Group, Smirnoff, and ESPN, earning recognition at Cannes Lions International Festival of Creativity, D&AD, One Show, Clio, and ADC. Both also mentor emerging talent and co‑authored Principle: @128 Principles to Become a Creative in an Advertising Agency, a career guide offering practical advice for newcomers navigating agency life.

The year 2025 was one marked by political tension, policy decisions, and difficult choices for Nigeria.From economic reforms and tax debates to security operations and party politics, government actions continued to shape public conversation and daily life.On today's episode of Nigeria Daily, we take a closer look at the political events and policies that defined 2025, and what they reveal about Nigeria's governance and democratic journey.

Featuring perspectives from Dr Lisa A Carey and Dr Rita Nanda, including the following topics:  Overview: Molecular basis of antibody-drug conjugate (ADC) toxicities — Sequencing of ADCs and mechanisms of resistance (0:00) Case: A woman in her late 60s with localized triple-negative breast cancer develops myocarditis during neoadjuvant therapy with chemotherapy/pembrolizumab — Richard Zelkowitz, MD (8:22) Case: A woman in her mid 70s with recurrent ER-negative, HER2-low, PD-L1-positive metastatic breast cancer (mBC) who experiences disease progression on nab paclitaxel/atezolizumab responds to sacituzumab govitecan — Ranju Gupta, MD (26:43) Case: A woman in her early 80s with recurrent ER-positive, HER2-low (IHC 1+) mBC experiences disease progression on trastuzumab deruxtecan (T-DXd), then receives datopotamab deruxtecan and develops pulmonary symptoms — Laila Agrawal, MD (32:11) Data Review: T-DXd (37:51) Case: A woman in her early 70s with recurrent ER-positive, HER2-low (IHC 1+) mBC, including bladder metastases, experiences disease progression after palbociclib/letrozole, then capivasertib/fulvestrant, then nab paclitaxel — Justin Favaro, MD, PhD (44:02) Case: A woman in her late 70s with ER-positive, HER2-low mBC who experiences disease progression after 1 year of ribociclib/letrozole receives sacituzumab govitecan — Erik Rupard, MD (55:19) CME information and select publications

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world.In a dynamic landscape marked by both advancements and challenges, the pharmaceutical and biotech sectors continue to evolve with notable scientific, regulatory, and strategic updates. Ipsen's recent $1 billion acquisition of Simcere's preclinical LRRC15-targeting asset underscores a growing focus on antibody-drug conjugates (ADCs). These conjugates leverage the targeted action of antibodies combined with the cytotoxic effects of drugs, representing a promising approach to cancer treatment by potentially minimizing systemic toxicity. Ipsen's strategic move reflects its commitment to expanding its oncology portfolio and staying competitive within the rapidly advancing ADC landscape.AstraZeneca has been active in its pursuit of innovative cancer treatments. The company has invested $100 million in Jacobio's clinical-stage pan-KRAS inhibitor, a promising development targeting KRAS mutations prevalent in various cancers. This investment aligns with AstraZeneca's strategy to tackle challenging oncogenic targets. However, their efforts faced a setback as their Phase 3 trial for ceralasertib, an ATR inhibitor for lung cancer, failed to meet its primary endpoint. Despite this setback, AstraZeneca maintains confidence by investing significantly in promising areas like KRAS inhibitors, highlighting the inherent risks involved in pioneering novel therapeutic strategies, particularly those aiming to overcome resistance mechanisms in immuno-oncology.BioMarin has quietly discontinued its liver disease candidate amid a $4.8 billion deal with Amicus. This decision points to the complex nature of pipeline prioritization and resource allocation within high-stakes financial environments. The company's strategic shifts reflect ongoing evaluations of their development priorities in light of evolving market demands.Boehringer Ingelheim has demonstrated a commitment to renal therapeutics with a $448 million investment in Rectify Pharmaceuticals for a preclinical chronic kidney disease program. This partnership seeks to address significant unmet medical needs within kidney disease treatment. Meanwhile, Gilead Sciences has entered into a $35 million licensing agreement with Assembly Biosciences for herpes simplex virus (HSV) assets, diversifying its infectious disease portfolio and expanding its reach within antiviral therapies.Novo Holdings-backed Windward Bio's acquisition of rights to Qyun's clinical-stage immunology bispecifics for $700 million highlights robust activity in the immunology space. Bispecific antibodies are gaining traction due to their ability to target two antigens simultaneously, offering enhanced therapeutic efficacy. This acquisition illustrates ongoing interest in this area as companies seek innovative solutions to complex immunological challenges.The broader industry is also witnessing strategic partnerships such as Aditum Bio's launch of a new biotech venture with Fosun Pharma. This collaboration aims to foster novel therapies through a synergistic blend of biotechnology innovation and pharmaceutical expertise. These alliances reflect an industry trend towards collaborative efforts that leverage diverse strengths to advance therapeutic development.In regulatory news, nine major pharmaceutical companies have reached agreements with the U.S. government to lower certain drug prices in exchange for tariff relief. This development signals ongoing negotiations aimed at balancing drug affordability with industry sustainability amid growing scrutiny over pricing practices.In December 2025, significant developments emerged, impacting scientific innovation, regulatory approvals, mergers, and strategic partnerships across the industry. Notably, the U.S. Food and Drug Administration (FDA) granted early approval to Cytokinetics' MyqorzSupport the show

JCO PO author Dr. Shilpa Gupta at Cleveland Clinic Children's Hospital shares insights into her article, "Fibroblast Growth Factor Receptor 3 (FGFR3) Alteration Status and Outcomes on Immune Checkpoint Inhibitors (ICPI) in Patients with Metastatic Urothelial Carcinoma". Host Dr. Rafeh Naqash and Dr. Gupta discuss how FGFR3 combined with TMB emerged as a biomarker that may be predictive for response to ICPI in mUC. TRANSCRIPT Dr. Rafeh Naqash: Hello and welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I'm your host, Dr. Rafeh Naqash, podcast editor for JCO Precision Oncology and Associate Professor at the OU Health Stephenson Cancer Center. Today I am excited to be joined by Dr. Shilpa Gupta, Director of Genitourinary Medical Oncology at the Cancer Institute and co-leader of the GU Oncology Program at the Cleveland Clinic, and also lead author of the JCO PO article titled "Fibroblast Growth Factor Receptor 3 Alteration Status and Outcomes on Immune Checkpoint Inhibitors in Patients With Metastatic Urothelial Carcinoma." At the time of this recording, our guest's disclosures will be linked in the transcript. Shilpa, welcome again to the podcast. Thank you for joining us today. Dr. Shilpa Gupta: Thank you, Rafeh. Honor to be here with you again. Dr. Rafeh Naqash: It is nice to connect with you again after two years, approximately. I think we were in our infancy of our JCO PO podcast when we had you first time, and it has been an interesting journey since then. Dr. Shilpa Gupta: Absolutely. Dr. Rafeh Naqash: Well, excited to talk to you about this article that you published. Wanted to first understand what is the genomic landscape of urothelial cancer in general, and why should we be interested in FGFR3 alterations specifically? Dr. Shilpa Gupta: Bladder cancer or urothelial cancer is a very heterogeneous cancer. And while we find there is a lot of mutations can be there, you know, like BRCA1, 2, in HER2, in FGFR, we never really understood what is driving the cancer. Like a lot of old studies with targeted therapies did not really work. For example, we think VEGF can be upregulated, but VEGF inhibitors have not really shown definite promise so far. Now, FGFR3 receptor is the only therapeutic target so far that has an FDA approved therapy for treating metastatic urothelial cancer patients, and erdafitinib was approved in 2019 for patients whose tumors overexpressed FGFR3 mutations, alterations, or fusions. And in the landscape of bladder cancer, it is important because in patients with non-muscle invasive bladder cancer, about 70 to 80% patients can have this FGFR3. But as patients become metastatic, the alterations are seen in, you know, only about 10% of patients. So the clinical trials that got the erdafitinib approved actually used archival tumor from local cancer. So when in the real world, we don't see a lot of patients if we are trying to do metastatic lesion biopsies. And why it is important to know this is because that is the only targeted therapy available for our patients right now. Dr. Rafeh Naqash: Thank you for giving us that overview. Now, on the clinical side, there is obviously some interesting data for FGFR3 on the mutation side and the fusion side. In your clinical practice, do you tend to approach these patients differently when you have a mutation versus when you have a fusion? Dr. Shilpa Gupta: We can use the treatment regardless of that. Dr. Rafeh Naqash: I recently remember I had a patient with lung cancer, squamous lung cancer, who also had a synchronous bladder mass. And the first thought from multiple colleagues was that this is metastatic lung. And interestingly, the liquid biopsy ended up showing an FGFR3-TACC fusion, which we generally don't see in squamous lung cancers. And then eventually, I was able to convince our GU colleagues, urologists, to get a biopsy. They did a transurethral resection of this tumor, ended up being primary urothelial and synchronous lung, which again, going back to the FGFR3 story, I saw in your paper there is a mention of FGFR3-TACC fusions. Anything interesting that you find with these fusions as far as biology or tumor behavior is concerned? Dr. Shilpa Gupta: We found in our paper of all the patients that were sequenced that 20% had the pathognomonic FGFR3 alteration, and the most common were the S249C, and the FGFR3-TACC3 fusion was in 45 patients. And basically I will say that we didn't want to generate too much as to fusion or the differences in that. The key aspect of this paper was that historically there were these anecdotal reports saying that patients who have FGFR alterations or mutations, they may not respond well to checkpoint inhibitors because they have the luminal subtype. And these were backed by some preclinical data and small anecdotal reports. But since then, we have seen that, and that's why a lot of people would say that if somebody's tumor has FGFR3, don't give them immunotherapy, give them erdafitinib first, right? So then we had this Phase 3 trial called the THOR trial, which actually showed that giving erdafitinib before pembrolizumab was not better. That debunked that myth, and we are actually reiterating that because in our work we found that patients who had FGFR3 alterations or fusions, and if they also have TMB-high, they actually respond very well to single agent immunotherapy. And that is, I think, very important because it tells us that we are not really seeing that so-called potential of resistance to immunotherapy in these patients. So to answer your question, yeah, we did see those differences, but I wouldn't say that any one marker is more prominent. Dr. Rafeh Naqash: The analogy is kind of similar to what we see in lung cancer with these mutations called STK11/KEAP1, which are also present in some other tumors. And one of the questions that I don't think has been answered is when you have in lung cancer, if you extrapolate this, where doublet or single agent immunotherapy doesn't do as well in tumors that are STK11 mutated. But then if you have a high TMB, question is does that TMB supersede or trump the actual mutation? Could that be one reason why you see the TMB-high but FGFR3 altered tumors in your dataset responding or having better outcomes to immunotherapy where potentially there is just more neoantigens and that results in a more durable or perhaps better response to checkpoint therapy? Dr. Shilpa Gupta: It could be. But you know, the patients who have FGFR alterations are not that many, right? So we have already seen that just patients with TMB-high respond very well to immunotherapy. Our last podcast was actually on that, regardless of PD-L1 that was a better predictor of response to immunotherapy. So I think it's not clear if this is adding more chances of response or not, because either way they would respond. But what we didn't see, which was good, that if they had FGFR3, it's not really downplaying the fact that they have TMB-high and that patients are not responding to immunotherapy. So we saw that regardless, and that was very reassuring. Dr. Rafeh Naqash: So if tomorrow in your clinic you had an individual with an FGFR3 alteration but TMB-high, I guess one could be comfortable just going ahead with immunotherapy, which is what the THOR trial as you mentioned. Dr. Shilpa Gupta: Yes, absolutely. And you know, when you look at the toxicity profiles of pembrolizumab and erdafitinib, really patients really struggle with using the FGFR3 inhibitors. And of course, if they have to use it, we have to, and we reserve it for patients. But it's not an easy drug to tolerate. Currently the landscape is such that, you know, frontline therapy has now evolved with an ADC and immunotherapy combinations. So really if patients progress and have FGFR3 alterations, we are using erdafitinib. But let's say if there were a situation where a patient has had chemotherapy, no immunotherapy, and they have FGFR3 upregulation and TMB-high, yes, I would be comfortable with using only pembrolizumab. And that really ties well together what we saw in the THOR trial as well. Dr. Rafeh Naqash: Going to the clinical applications, you mentioned a little bit of this in the manuscript, is combination therapies. You alluded to it a second back. Everything tends to get combined with checkpoint therapy these days, as you've seen with the frontline urothelial, pembrolizumab with an ADC. What is the landscape like as far as some of these FGFR alterations are concerned? Is it reasonable to combine some of those drugs with immune checkpoint therapy? And what are some of the toxicity patterns that you've potentially seen in your experience? Dr. Shilpa Gupta: So there was indeed a trial called the NORSE trial. It was a randomized trial but not a comparative cohort, where they looked at FGFR altered patients. And when they combined erdafitinib plus cetrelimab, that did numerically the response rates were much higher than those who got just erdafitinib. So yeah, the combination is definitely doable. There is no overlapping toxicities. But unfortunately that combination has not really moved forward to a Phase 3 trial because it's so challenging to enroll patients with such kind of rare mutations on large trials, especially to do registration trials. And since then the frontline therapy has evolved to enfortumab vedotin and pembrolizumab. I know there is an early phase trial looking at a next generation FGFR inhibitor. There is a triplet combination looking in Phase 1 setting with a next generation FGFR inhibitor with EV-pembro. However, it's not a randomized trial. So you know, I worry about such kinds of combinations where we don't have a path for registration. And in the four patients that have been treated, four or five patients in the early phase as a part of basket trial, the toxicities were a lot, you know, when you combine the EV-pembro and an FGFR3 inhibitor, we see more and more toxicity. So the big question is do we really need the "kitchen sink" approach when we have a very good doublet, or unless the bar is so high with the doublet, like what are we trying to add at the expense of patient toxicity and quality of life is the big question in my mind. Dr. Rafeh Naqash: Going back to your manuscript specifically, there could be a composite biomarker. You point out like FGFR in addition to FGFR TMB ends up being predictive prognostic there. So that could potentially be used as an approach to stratify patients as far as treatment, whether it's a single agent versus combination. Maybe the TMB-low/FGFR3 mutated require a combination, but the TMB-high/FGFR mutated don't require a combination, right? Dr. Shilpa Gupta: No, that's a great point, yeah. Dr. Rafeh Naqash: But again, very interesting, intriguing concepts that you've alluded to and described in this manuscript. Now, a quick take on how things have changed in the bladder cancer space in the last two years. We did a podcast with you regarding some biomarkers as you mentioned two years back. So I really would like to spend the next minute to two to understand how have things changed in the bladder cancer space? What are some of the exciting things that were not there two years back that are in practice now? And how do you anticipate the next two years to be like? Maybe we'll have another podcast with you in another two years when the space will have changed even more. Dr. Shilpa Gupta: Certainly a lot has happened in the two years, you know. EV-pembro became the universal frontline standard, right? We have really moved away from cisplatin eligibility in metastatic setting because anybody would benefit from EV-pembro regardless of whether they are candidates for cisplatin or not, which historically was relevant. And just two days ago, we saw that EV-pembro has now been approved for localized bladder cancer for patients who are cisplatin ineligible or refusing. So, you know, this very effective regimen moving into earlier setting, we now have to really think of good treatment options in the metastatic setting, right? So I think that's where a lot of these novel combinations may come up. And what else we've seen is in a tumor agnostic trial called the DESTINY-PanTumor trial, patients who had HER2 3+ on immunohistochemistry, we saw the drug approval for T-DXd, and I think that has kind of reinvigorated the interest in HER2 in bladder cancer, because in the past targeting HER2 really didn't work. And we still don't know if HER2 is a driver or not. And at ESMO this year, we saw an excellent study coming out of China with DV which is targeting HER2, and toripalimab, which is a Chinese checkpoint inhibitor, showing pretty much similar results to what we saw with EV-pembro. Now, you know, not to do cross-trial comparisons, but that was really an amazing, amazing study. It was in the presidential session. And I think the big question is: does that really tell us that HER2-low patients will not benefit? Because that included 1+, 2+, 3+. So that part we really don't know, and I think we want to study from the EV-302 how the HER2 positive patients did with EV and pembro. So that's an additional option, at least in China, and hopefully if it gets approved here, there is a trial going on with DV and pembro. And lastly, we've seen a very promising biomarker, like ctDNA, for the first time in bladder cancer in the adjuvant setting guiding treatment with adjuvant atezolizumab. So patients who were ctDNA positive derived overall survival and recurrence-free survival benefit. So that could help us select moving forward with more studies. We can spare unnecessary checkpoint inhibitors in patients who are not going to benefit. So I think there is a lot happening in our field, and this will help do more studies because we already have the next generation FGFR inhibitors which don't have the toxicities that erdafitinib comes with. And combining those with these novel ADCs and checkpoint inhibitors, you know, using maybe TMB as a biomarker, because we really need to move away from PD-L1 in bladder cancer. It's shown no utility whatsoever, but TMB has. Dr. Rafeh Naqash: Well, thank you so much, Shilpa, for that tour de force of how things have changed in bladder cancer. There used to be a time when lung and melanoma used to lead this space in terms of the number of approvals, the biomarker development. It looks like bladder cancer is shifting the trend at this stage. So definitely exciting to see all the new changes that are coming up. I'd like to spend another minute and a half on your career. You've obviously been a leader and example for many people in the GU space and beyond. Could you, for the sake of our early career especially, the trainees and other listeners, describe how you focused on things that you're currently leading as a leader, and how you shaped your career trajectory over the last 10 years? Dr. Shilpa Gupta: That's a really important question, Rafeh, and you and I have had these discussions before, you know, being an IMG on visas like you, and being in different places. I think I try to make the most of it, you know, instead of focusing on the setbacks or the negative things. Like tried to grab the opportunities that came along. When I was at Moffitt, got to get involved with the Phase 1 trial of pembrolizumab in different tumor types. And just keeping my options open, you know, getting into the bladder cancer at that time when I wanted to really do only prostate, but it was a good idea for me to keep my options open and got all these opportunities that I made use of. I think an important thing is to, like you said, you know, have a focus. So I am trying to focus more on biomarkers that, you know, we know that 70% patients will respond to EV-pembro, right? But what about the remaining 30%? Like, so I'm really trying to understand what determines hyperprogressors with such effective regimens who we really struggle with in the clinic. They really don't do well with anything we give them after that. So we are doing some work with that and also trying to focus on PROs and kind of patient-reported outcomes. And a special interest that I've now developed and working on it is young-onset bladder cancer. You know, the colorectal cancer world has made a lot of progress and we are really far behind. And bladder cancer has historically been a disease of the elderly, which is not the case anymore. We are seeing patients in their 30s and 40s. So we launched this young-onset bladder cancer initiative at a Bladder Cancer Advocacy Network meeting and now looking at more deep dive and creating a working group around that. But yeah, you know, I would say that my philosophy has been to just take the best out of the situation I'm in, no matter where I am. And it has just helped shape my career where I am, despite everything. Dr. Rafeh Naqash: Well, thank you again. It is always a pleasure to learn from your experiences and things that you have helped lead. Appreciate all your insights, and thank you for publishing with JCO PO. Hopefully we will see more of your biomarker work being published and perhaps bring you for another podcast in a couple of years. Dr. Shilpa Gupta: Yeah, thank you, Rafeh, for the opportunity. And thanks to JCO PO for making these podcasts for our readers. So thanks a lot. Dr. Rafeh Naqash: Thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcast. 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. DISCLOSURES Dr. Shilpa Gupta Stock and Other Ownership Interests: Company: BioNTech SE,  Nektar Consulting or Advisory Role: Company: Gilead Sciences, Pfizer, Merck, Foundation Medicine, Bristol-Myers Squibb/Medarex, Natera, Astellas Pharma, AstraZeneca, Novartis, Johnson & Johnson/Janssen Research Funding: Recipient: Your Institution Company: Bristol Myers Squibb Foundation, Merck, Roche/Genentech, EMD Serono, Exelixis, Novartis, Tyra Biosciences, Pfizer, Convergent Therapeutics, Acrivon Therapeutics, Flare Therapeutics, Amgen Travel, Accommodations, Expenses: Company: Pfizer, Astellas Pharma, Merck    

In this episode, we sit down with Riot Phroxzon, Lead Gameplay Designer at Riot Games, for a deep-dive into the future of League of Legends.We cover what Riot learned from the 2025 champion releases (Mel, Yunara, and Zaahen), why some designs missed the mark with players, and how those lessons are shaping champion philosophy going forward. Phroxzon breaks down Zaahen's kit design, community reaction to Mel, and whether Riot is satisfied with Yunara's long-term impact.The conversation then shifts to Summoner's Rift changes, including what worked, what didn't, and why Atakhan is being removed. We explore Riot's evolving vision for macro gameplay in 2026, including split pushing, objective control, and how the overall pace of the game is changing.We also tackle one of the most controversial topics in League right now: role balance. Why does Riot believe jungle is overtuned, why ADC and top lane are struggling, and how jungle lost its identity in 2025. Phroxzon explains Riot's internal data, the goals behind role quests, and what role balance will look like moving into 2026.Later in the episode, we discuss matchmaking and Solo Queue, including autofill philosophy, what it actually takes to climb, and how Riot plans to reduce time to get into games. We also touch on bringing back old items, Aegis of Valor, duo queue across ranks (excluding Korea), and what Riot learned from WASD movement testing.

"I'll go back to the backpack analogy. When your kids come home with a backpack, all of a sudden their homework is not on the desk where it's supposed to be. It's in the kitchen; it kind of spreads all over the place, but it's still in the house. When we give antibody–drug conjugates (ADCs), the chemotherapy does go in, but then it can kind of permeate out of the cell membrane and something right next to it—another cancer cell that might not look exactly like the cancer cell that the chemotherapy was delivered into—is affected and the chemotherapy goes over to that cancer cell and kills it," ONS member Marisha Pasteris, OCN®, office practice nurse in the breast medicine service at Memorial Sloan Kettering Cancer Center in New York, NY, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a conversation about ADCs in metastatic breast cancer. Music Credit: "Fireflies and Stardust" by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0  This podcast is sponsored by Gilead and is not eligible for NCPD contact hours. ONS is solely responsible for the criteria, objectives, content, quality, and scientific integrity of its programs and publications.  Episode Notes  This episode is not eligible for NCPD. ONS Podcast™ episodes: Episode 391: Pharmacology 101: Antibody–Drug Conjugates Episode 378: Considerations for Adolescent and Young Adult Patients With Metastatic Breast Cancer Episode 368: Best Practices for Challenging Patient Conversations in Metastatic Breast Cancer Episode 350: Breast Cancer Treatment Considerations for Nurses Episode 303: Cancer Symptom Management Basics: Ocular Toxicities ONS Voice articles: An Oncology Nurse's Guide to Cancer-Related Ocular Toxicities Black Patients With Metastatic Breast Cancer Are Less Informed About Their Clinical Trial Options Communication Case Study: Talking to Patients About Progressive Metastatic Breast Cancer What Is HER2-Low Breast Cancer? ONS Voice drug reference sheets: Belantamab mafodotin-blmf Datopotamab deruxtecan-dlnk Enfortumab vedotin-ejfv Fam-trastuzumab deruxtecan-nxki ONS books: Chemotherapy and Immunotherapy Guidelines and Recommendations for Practice (second edition) Guide to Breast Care for Oncology Nurses Guide to Cancer Immunotherapy (second edition) ONS courses: ONS Fundamentals of Chemotherapy and Immunotherapy Administration™ ONS/ONCC® Chemotherapy Immunotherapy Certificate™ Clinical Journal of Oncology Nursing article: Antibody–Drug Conjugates and Ocular Toxicity: Nursing, Patient, and Organizational Implications for Care The Association Between Hormone Receptor Status and End-of-Life Care Among Patients With Metastatic Breast Cancer Oncology Nursing Forum article: Impact of Race and Area Deprivation on Triple-Negative Metastatic Breast Cancer Outcomes ONS huddle cards: Altered Body Image Huddle Card Chemotherapy Huddle Card Targeted Therapy Huddle Card Foundations of Antibody–Drug Conjugate Use in Metastatic Breast Cancer: A Case Study ONS Biomarker Database (refine by breast cancer) ONS Breast Cancer Learning Library American Society of Clinical Oncology (ASCO) homepage Drugs@FDA package inserts National Comprehensive Cancer Network homepage Susan G. Komen metastatic breast cancer page To discuss the information in this episode with other oncology nurses, visit the ONS Communities.  To find resources for creating an ONS Podcast club in your chapter or nursing community, visit the ONS Podcast Library. To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org. Highlights From This Episode "What an ADC is doing is taking the antibody and linking it to a cytotoxic chemotherapy with the idea of delivering it directly into the cell. How I explain this to new nurses or patients is a backpack analogy. If we think of it as a HER2 molecule wearing a chemo backpack, it's going to find the HER2 receptor attached to it and then drop the chemotherapy into the cell via the backpack. Similar to how we come home from work, we open the key to our door, we're carrying all of our items, and then we drop our own personal items in our house." TS 2:30 "The reason that so many patients with metastatic breast cancer are able to receive ADC therapy is because they are targeting two very common antibodies that we see in breast cancer. One is HER2 and the other is trophoblast cell surface antigen 2 (TROP2). These are seen across the board. We see these on triple-negative breast cancers, hormone receptor–positive cancers, and HER2-positive breast cancers. And now we have a new way to talk about HER2, which is a HER2-low. ... Recently, we have found that patients who express low levels of HER2 are able to receive ADC therapy, specifically fam-trastuzumab deruxtecan." TS 4:21 "Another [ADC] that has just been approved is datopotamab deruxtecan. This is another ADC that targets the TROP2 receptor on a cancer cell. This one carries a lot of side effects. I mentioned earlier that you need an ophthalmology clearance because there is a lot of ocular toxicity around this one. We see a lot of blepharitis, conjunctivitis, there can be blurred vision. Another thing we monitor on this one is mucositis. In the package insert, there's a recommendation for using ice chips while receiving the treatment. ... Then in the HER2-positive and HER2-low space is the big one, which is fam-trastuzumab deruxtecan. This was approved in 2019 for the HER2-positive patients, then more recently in the HER2-low [patients]. The big [side effect] with this one is interstitial lung disease." TS 10:11 "Interstitial lung disease is an inflammation or a little bit of fibrosis within the lung that causes an impaired exchange between the oxygen and carbon dioxide. This was seen in the clinical trials, specifically around fam-trastuzumab deruxtecan. During the trials, they had a very small percentage, I think it was 1%, that died due to interstitial lung disease. So, this is a very important side effect for us as nurses to be aware of. It typically presents in patients like a dyspnea. A lot of times, it's like, 'Well, I used to be able to walk my kid to the bus stop, but now when I walk there, I feel really short of breath.' Or 'I've had this dry cough for the past couple weeks and I've tried medications, but haven't had that relieved.' So, we really need to be aware of that because early intervention in interstitial lung disease is key." TS 12:57 "ADCs are toxic drugs. They have the benefit of being targeted, but we know that they carry a lot of side effects. ... Their specificity makes them so wonderful and we've seen amazing responses to these drugs. But also, we want patients to be safe. We want to give these drugs safely. So, we have to assess our patients and make sure that this is an appropriate patient to give this therapy to. I think that's an open conversation that clinicians need to have with patients regarding these drugs." TS 18:08

Please visit answersincme.com/860/IME-69386-replay1 to participate, download slides and supporting materials, complete the post test, and get a certificate. In this activity, experts in NSCLC discuss how to harness targeted ADCs with practical, case-based insights to personalize care and improve outcomes in advanced lung cancer. Upon completion of this activity, participants should be better able to: Interpret the latest clinical trial data for approved and emerging antibody-drug conjugates (ADCs) in NSCLC; Recognize biomarker-driven strategies to guide treatment management in patients with NSCLC; and Apply evidence-based strategies for the individualized management of patients with NSCLC receiving ADC therapy.

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we're diving into a series of pivotal events and breakthroughs shaping the future of this dynamic industry.The pharmaceutical and biotech sectors are experiencing a wave of significant advancements, regulatory shifts, and strategic maneuvers. Recently, Bristol Myers Squibb faced a delay in their Alzheimer's psychosis treatment, Cobenfy, due to site irregularities detected in the ADEPT-2 study. This highlights the critical importance of rigorous clinical trial management. The postponement could influence stakeholders' confidence in timelines for breakthrough treatments in neuropsychiatric disorders.Richard Pazdur, M.D., is preparing to retire from his leadership role at the FDA's Center for Drug Evaluation and Research. This transition period could have profound implications for how new therapies are evaluated, potentially altering approval processes and timelines. His departure marks a significant shift within an agency renowned for its role in drug approvals and regulatory oversight.On the scientific front, Cosmo Pharmaceuticals has reported promising results from two Phase 3 trials of clascoterone, a topical cream designed to treat male-pattern hair loss. The findings suggest that clascoterone could become a transformative treatment by offering a novel mechanism to address androgenetic alopecia through the inhibition of dihydrotestosterone activity at the follicular level. This development underscores an expanding focus on dermatological conditions within biopharma research and offers new hope to millions affected by hair loss.In legal developments, Daiichi Sankyo's successful appeal in its antibody-drug conjugate (ADC) patent dispute with Seagen marks a significant victory with substantial financial implications. The overturning of a $41.8 million verdict illustrates the competitive dynamics in ADC technology, which plays a crucial role in targeted cancer therapies. This case emphasizes the importance of robust intellectual property strategies in maintaining competitive advantages in innovative therapeutic modalities.On the funding front, Excelsior Sciences has secured $95 million to enhance its "smart bloccs" platform for small molecule discovery and production. This investment aims to support advancements in chemical synthesis technologies crucial for accelerating drug development pipelines and fostering collaborations across therapeutics and materials science sectors. Such initiatives underscore the growing emphasis on technological innovation to streamline drug discovery processes.The European Union is making strides toward bolstering supply chain resilience with new regulations aimed at preventing drug shortages. By diversifying local biopharma supply chains and encouraging domestic production, these measures address vulnerabilities exposed by recent global disruptions. This policy shift could lead to more sustainable drug manufacturing practices within Europe, ensuring better preparedness against future crises.Pharvaris has achieved a significant milestone with its Phase 3 trial of deucrictibant meeting primary endpoints. This sets the stage for regulatory filings as a competitor to KalVista Pharmaceuticals' Ekterly in hereditary angioedema treatment. This progress highlights ongoing innovation in addressing rare genetic diseases and fostering competitive therapeutic landscapes.The FDA's approval of Cleveland Diagnostics' IsoPSA test marks a notable advancement in prostate cancer diagnostics. By detecting specific PSA protein variants associated with malignancy risk, IsoPSA represents a step forward in precision medicine. It offers enhanced diagnostic accuracy and potentially improves patient outcomes through early intervention strategies.Overall, these developments reflect the dynamic nature of the pharmacSupport the show

Now, and??? Okay! Just another dime, And just enough to find Before I count them up to dollars— But you're turning into wine. What did you ever want? This is my other world. Go shatter you tantric catwalk elsewhere! Don't you know there is a show to put on? A wool to pull over the eyes of the unknown? Why do you have to groan at the quantifiable harm known but justice undone. No harm, no foul No food, no valid excuse for betraying my sacred dopamine, but hopefully you know only no good But words can come from it, And words that fall on blind eyes have no context at all. {Enter The Multiverse} Uncorrected transcript. [excuse my neighbors in the background they're determined to make my life miserable more than likely in exchange for dollar signs.] Okay, my Wi-Fi is off, my Bluetooth is off. Oh, my laptop is open, my Wi-Fi is on. I can give me a second to remedy that. Hello. Hello. I'm Atticus's tail says hello. What's going on? Oh, I wasn't planning on oh, my WiFi on my computers off. That is good. Uh, I keep all my devices uh, at minimum on off the grid as often as possible. Um, there there actually it's crazy how much of a difference this makes. I gotta pour myself some coffee. it is almost midnight, o'clock. Hello, um, what's up, we're missing talking episodes. Um, we're missing talking episodes from season 12. I can't find anything like past October, and I know it's on one of my hard drives, but all of my hard drives are full, um, I have like something like 10 terabytes altogether of stuff that needs to be like moved around and not all of it. Some of it's like really personal, like not personal, but like sensitive information that I can't necessarily utilize a cloud for. So I am it's taking me some time to organize some stuff. I I try to do between like eight and 12 hours of just organizing on any typical night after my uh exercise or whatever, or between I would say that exercise is definitely like the primary function of like my life. And that's like the priority right now, especially with the things that I've been going through. I think it's really important to keep my physical and mental health as um in in it's not gonna be at its peak, um, because of the noise pollution that I've been dealing with, and it's actually made me really sick over this extended period of two times. um, and I'm trying to um seek treatment for that, but it's a uh it's a long road, I have a long road ahead of me. We could just say that. Um, which is why I am giving you guys, um, some stuff that I've been working on that's not necessarily finished, and I'm actually really like, I'm embarrassed because I don't necessarily um I I actually have a hard rule of not releasing any music until it's absolutely finished. like even if it is a first draft, like it still has to be finished. um, but I actually and I gave you, I think, I think two tracks, which is actually four. um because this upcoming project, it's a concept album called a symposia. um and the concept for it is um a lot. I don't necessarily have to explain right now. Um, but all of the tracks so far on it are double tracks, and so it is typically I've always really loved albums that have that are like gapless. I don't think through my distributor, like I can never technically um, like put out an album that has no um technical stop or start between songs, like they would have to be cut a certain type of way that, like my distributor does it. There's always gonna be a gap between my music, but um all of the tracks are um double tracks, so they're all two tracks in one, um that are kind of along the same theme or idea and um like lead into the next track. I've always loved albums like that. uh, one of my favorite compilation albums, um like just to give you an example, just to throw it out there, is like, the Beatles love album, which is not actually a Beatles album. It's just a, um, it's a compilation of their um songs made for the Cirus Sole show that I think is still playing in Vegas. I don't know if it is it's been playing for like 10 years, and I still haven't seen it. um I really I really want to take mushrooms and go uh see that show. I've wanted to do that since it came out, but my favorite one of my favorite albums in the world is the love album, which is is basically a mash up of like their greatest hits, crafted by, um engineers and people who used to work with the Beatles and stuff for this uh Cir dis soet show um in Vegas that I hope I get to see I hope it's just one of those like long standing like like Siegfried and Roy. I just realized that they were in Vegas for like 40 years, like they were just there, they were just a stable, so hopefully that show is um kind of like that and one day I'll get the, uh one day I'll get the opportunity to see it. Like my my bucket list, like destination, like vacation at one point was to go see the Beatles love on like an EDC week. um that's still something that I want to do. I promise myself I wouldn't go to EDC unless I like ever got booked there. Um, and I think this year is like 30 years or something of EDC, and so they um they sold out in like five minutes. um so it's it's not it's not something I'd consider doing by myself anyway, unless I was gonna go with my best friend, and um and I was like I was talking to my best friend and I was like, oh, maybe I should check on, like the early bird tickets for ADC, and they were like, they was sold out, and was this celebrating 30 years, and I'm like, okay, well, I guess I should uh work on getting a booking agent, but my music is not my music is kind of turned into like a passion project. um, since everything that I've been going through over the last couple of years kind of just like took me off my path in that sort of way and DJing, I kind of wanna preserve it as like, I really love being a DJ. I really love producing music and because it's so consumer, there's a bunch of people in the industry that are not necessarily like music oriented or love oriented, and it's just like a whole different vibration from like the peace and the love and the unity respect of that. Like I like the scene for. I really want to check out, like as far as a festival goer is concerned, I really wanna check out some of these new festivals that are popping up that are doing like no cell phones. I kind of wanna check those out, cause I feel like the quality of of the experience has been preserved or will have been preserved in in certain spaces like that, um, but anyway, I'm uh I have been physically ill for like a few months now. um, and so the best that I can do for you guys my audience just because I'm not sure if I will get symposium out this year in which case it will come out next year. um, and then I think this track, I'm not sure, this track is definitely like a track that was in my mind. um implementing all of the like sound design stuff that I'm doing for symposium and is also a double track. um it's called Forget me nots. uh and then the second track is followed through. uh,get me nots/follow through. I think it's like an eight or nine. um minute track or whatever. It's not finished. Um, actually, the only finished track that you guys have heard, and even this even bitter butter and southwest of your scars is like a double track that is finished, that is on symposium, but it's still the version one, like it's not um I haven't done like any of the final mastering or any of the things that I do in the process of getting ready for a a release. I do have like a a like an implemented ritual structure of doing things like that, even for projects that seem like mindless, or, you know, things that are seem seemingly just like thrown together, like chasing dragons, was kind of like not necessarily even a concept until the three tracks were like sandwiched together, and I was like, oh, okay, like, this does tell a story and and they were all created in a certain way so that they'd go together. I think I fixed that. um, because, um, chasing dragons, the EP was for some reason, when chasing dragons got released to, like all the major platforms, it had chasing dragons was the first and the last track, and then dishes and the sink was just in the middle, which was weird. um so the third track on chasing dragons is actually immortalist and I got that all fixed. and I also got the regular like the normal version of the songightfall is out on the platforms now. Those were two er errors um that I needed to fix that I finally did. um but I'm slower to do music things now because like I said, my health is the priority. So it's like, yo, if it comes down to like getting a good meal in or like some good exercise or like right now I'm doing active recovery because I'm dumb. I went from like not really running anymore and only walking for an hour every day on the treadmill and doing like an hour between one and two hours on the pelotone, a day which is technically still three hours of work, um, but then I went back into heavy training the way that I preferred to do like I prefer to be at the gym between two and three hours every day. That is my ideal. That is where my body feels comfortable, um and flexible and like happy. Um, and if I can do that in the very beginning, like to start my day, cause I don't necessarily have 24 hour, like days anymore. um like what's technically the end of my day is oftentimes the very beginning of other people's days, and so I'm kind of just on on night, like, routine because it is like, I'm I'm basically just like protecting myself from the uh, you know, like my my nervous system can't take any further damage. Like, I do have really pronounced synesthesia and, um, I wasn't necessarily like planning to be exposed to extreme like noise pollution for an extended period of time without having the financial security or stability to escape from it, cause honestly, if I could have moved, I would have moved or if I could have just left, I would have just left, um, but I obviously wasn't in a situation that I could, and so I became very vulnerable um, to this type of attack, which I learned was actually very common. It's not something that is just like, oh, you know, um, this is just something that I'm going through. It's actually a very common for people of color to be, um vulnerable to this kind of disease that comes from um an implementation of using sound as a weapon. And I mean, like the irony is is that I was already kind of studying synesthetics and the way that, you know, as a culture or the way that in as as far as like mass consumerism is concerned, that's why people pay so much for a, you know, festiv for the festival experiences because sound can be a very much uh manipulated to be a physical thing. It's not, you know, it's not invisible. And so the fact that those same kind of um those that same kind of engineering can be implemented also in a negative way to have a negative effect. Like, you don't have to punch somebody in the face, like, you can just back up your exhaust, your engine exhaust, and, you know, fire at point blank to somebody that is, you know, caught off guard. and in that way, um sound can be used as a weapon, it uses the same dynamics, the same kind of dynamics as, you know, the reason why we go in the th you know, in flocks by the thousands and the millions to these festivals to feel the vibrations that that are on the opposite end of the same spectrum, the healing vibrations of, you know, certain things. and so I've been doing my best to try and, you know, maintain a certain level of health through, you know, using, um, you know, certain frequencies to block out. But when it's your physical person is in a space that's being manipulated to be on a certain frequency, um, uh, the exposure to this negative frequency that is unnatural to your body over a period of time. um, you begin to get very, very sick and that's what's happened to me. And so I'm trying my best to like keep my head above water and, you know, stay afloat. Um, but I didn't expect it especially after, you know, a period of like two or three years before that, where I was just like on the go all the time. Um, and, you know, not necessarily having like a a suitable foundational stability or a place to call home and then going straight into something else that was like more traumatic and more violent than, um then I expected, and so I've been trying to remedy that. um, the best that I can and because I'm putting my mental health and my physical health first, I'm not necessarily like, I it was weird. I was kind of in like a meditative space and I had, you know, like this this kind of spirit come over me that was like music, you know, music is gonna be there forever. like, as long as you're as long as you exist, you know, whether it's in like a physical realm or like an infinite realm or whatever, like as long as you exist, there's always gonna be music. and that was kind of like the sign that like, K, as much as I do like having a streak of, you know, like being an Ableton every day for several hours a day. um, the way that I am using these techniques that I'm applying in symposium and as seen on TV, which reminded up being a double album, because I actually have, um, like several, um, tracks that are like honestly on TV, I've been working on since, like, 2023., like, early 2023. Um, and so, the things that I've like collected, it's kind of interesting because my evolution as an artist or like my technique as a producer will be, um represented here in this project, which I hope comes out next year, but I can't say for sure, cause it's probably the it's definitely the biggest, most um important album I've ever worked on and I I put a lot of care and thought into those as seen on TV tracks because it does um like creatively, I guess, run alongside this series into the multiverse and all the series within the festival project, uh Ascension Death Wish, legends, um the legend of uh, the secret life and the sweet life of sunny Blue, just to name a few, there are I keep trying to make like a list of all of the shows within the festival project, but then I'm like, oh, like there are so many that it would it just falls apart. And so I mean like I'm getting a little bit more organized with the with the actual structure of, like, the television and movie, like, script part of the project. um, while I'm cleaning out my hard drives, but having to organize everything so that it's, you know, so that I can go to a certain hard drive and be like, okay, well, this is um, you know, this is this season to this season. I'm still archiving episodes from, you know, 2021 and and because a lot of those statistics can't be like once I delete an episode from the podcast, it goes away and all the all the statistical information about the number of downloads,, like all of its information, all of its metadata goes away. and that's very important for what I'm going through in my personal life right now in order to protect myself for those things to be taken down, but also for it to be archived in a way that I can reference as a creator like, okay, this is this day that this was published with this, that like, because it's it's a time travel concept that is multifaceted, and it is like based in this multiperceptory m multiperceptory multiimensional concept of technically technically infinite time and space, like it has to be organized in such a way that, like, all of the series and all of their all of the ways that they're connected to any particular parallels have to be, you know, they have to be organized and documented so that because I'm the more that I'm looking at it, the more it makes sense. I'll be like, oh, like, I thought this was just like nonsense or whatever, but when I'm putting it into like an organized space, um, and to me, that's like the god part about it is that like, oh, like, um like, I' I'll be looking at the writing and noticing how it takes like particular shapes or how the shapes will cut is sometimes like make pictures, like sometimes when you're looking at the clouds and you see, you know, shapes and the clouds. sometimes the riding for this project is like that, which is kind of incredible to me.c it's not something that I'm doing um, intentionally, it's kind of just something that's happening. I'm writing in a stream of consciousness that's also, you know, like artistic, creative in a way, that kind of has this, like, sense of divinity to it that I'm not necessarily, like, consciously doing. Um, so everything has to be organized in such a way that like it is gonna take time, um, and because it takes time and a lot of the other things that I did not foresee happening or also taking a lot of my time, like a lot of my my time and energy to document like how sick I've been getting a lot of time and energy has been focused on just like, doing the research on, you know, like crazy crazy shit that I never really took interest in, um, but could be applied here. um, could be applied to this situation and and kind of just finally being able to have a piece of mind to give myself the benefit of the doubt that, like, it wasn't in my head. like, I just had to be uh, I just had to be pushed to the point that I could understand, you know, that this um, sometimes very silent type of, um, you know, warfare is is like a documented not even necessarily historically, but like presently and present day. um, they're just I don't think haven't been enough survivors of this kind of thing, um, that it could be, um that it could be notably researched, like the amount of reports, but, you know, it's it's not it's not by choice, like it is taking up a lot of my time and I wish I was the kind of person that could just ignore it. Um, but I'm getting very physically ill. Um, so I can't, like, I can't ignore the fact that, like, you know, I'm running on zero pretty much all the time, and that my my patterns of speech have changed in my, you know, my thoughts have been intercepted and my, you know, like, because physical and mental health is such a priority to me, the fact that those things have been the primary uh, source of degradation has has affected me in such a way that it's not, I mean, like, it's less emotional than it is the logical answer to, you know, like if you have a cold, you take cold medicine or if you have the flu, you take, you know, it's it's like, well, remedying something that is a fi physical illness, you know. um, removing the cancer from the body, uh, you know, in such a way that it doesn't come back is kind of my main primary concern in this way. Um, so I am am especially because I can't but the talking episodes are actually more popular this season than any other season. and I can't find like six or seven of them, because I I don't know, I was just switching out all my, you know, uh my stuff so quickly and pulling things out of the cloud that it, you know, got saved under drive zip eight, seven six nine, you know, like. It's it's just a mess of of terabytes and tabyrites of creative work, um, and, you know, other things that I've had to dedicate my time to, which is not necessarily fair, but, you know what they say is life is not fair. Um, so, you know, life hasn't been fair, but I have, you know, been blessed in such a way that, like I I I've at least been able to um creatively channel some of the some of the energy and some of the time that I have left over that is technically mine. while in the sense that I've had a lot of my time and energy just stolen in siphoned, um, you know, I have been able to kind of forge a medium through fighting this that allowed me to, you know, start doing art along the lines of, um more more the way that I want my music to to think and feel. And so I'm I'm still just working from a little tiny MacBook air. um, so my, you know, um, my projects get like overwhelmed really quickly. I can't necessarily implement all of my um my plugins or all of the tools that I like to use at once, and so everything is kind of segment segmented in the way that I'm working. um and like, yeah, my projects get overloaded very quickly. um so the tracks that I'm giving you are not finished, but they're more um I would say like they're more, like colored, they're more like filled out. It's not necessarily abstract in the way that some of my stuff is like very like, you know, like drag and drop and cut and go, well, I do a lot of like, even in my even in my like my cut and dry stuff, I do a lot of sample manipulation. I very rarely will keep a sample in the way that it is without doing something to it, you know, like, I don't do dragon drop, um, unless I'm planning on just, like, you know, giving a beat to a rapper a artist for free. like, sometimes I'll just be like, okay, for the next 15 minutes, just do, like, something, you know, like a two or three minute, like dragon drop or whatever. But those those are not necessarily tracks that I A share here or B like plan on doing anything with because the world of sampling has gotten to the point where it's like, yo, you gotta have some creativity, like you can't just open up a sample pack and drag it and drop it into place, because then you have eight or nine songs that sound exactly the same. Eight or nine songs that are the same because basically you're just putting together a, you know, you're putting together stems from a track that was already created, you know, by somebody that's trying to sell you something, so um, you know, I I take a little bit more creative uh integrity in the stuff that I do mean seriously. Um, a lot of it lately hasn't been serious, but I I actually did want to take an hour to talk about this not this track in particular, just talk about why I'm doing this because it was something that it was like, oh, I feel like this project is a little bit more special or is a little bit more like technical than some of the other work that I've shared here on this podcast or work that I've put out before and so I kind of wanted to keep it to myself um, but then I've kind of had a couple, like, you know, like heart shattering experiences that make me realize, like, you don't know. like, you don't really know what's gonna happen and life is, um, sometimes very cruel and sometimes life is, you know, it just takes turns that are not necessarily. um you know, like you don't you don't ever know. And my mindset has not necessarily been that negative. It's like, oh, everything, you know, there's a there's a reason for everything, and blah, blah, blah, and I still do believe that, but like, you know, two years of constant, like, torture and stress to the point where I don't necessarily have a medium for support or, you know, um, like, I don't necessarily have the foundation of community. um, being in a place that is not my home and coming from a family that's very, very small and doesn't necessarily have, you know, well, like, I don't have what some people have, I don't have a large network of family and friends and the kind of family and friends that you create for yourself in the business are not necessarily, um, you know, like people can't necessarily be trusted to have your best interests. Um, especially especially if you are coming from like a a margin for success that, you know, is documented, like you've done well, you can't necessarily still believe that, like, everyone in your immediate circle has the best interest for you, because it is in human nature that everybody has, you know, themselves as the primary interest, and so um, me being like a a solidly um you know, like self sufficient. I won't say independent person. um, driving towards independence or whatever. um, but being a person that spends a lot of time in solitude and with enough respect, like enough self-respect to understand what my when my spiritual and my personal boundaries are being pushed even even in a person you know, professional setting. um like I took today for active recovery because I'm dumb and I went straight back into training as if I'd never really stopped. like it okay, like I'm on the Peloton seven days a week and I have a treadmill that I walk on in for an hour a day, you know, five to six days a week, but it's not the same as like being in the gym and lifting in stri strength training and and um active recovery um but I was like, okay, if I was running like a Madonna or whatever, you know, for this amount of time, then I should be able to do that. I should be able to do that. No, I didn't run a Madonna, but I ran like a 3K and then a little bit. and I like, my body was like, yeah, this is good, but then I had, like the rest of the day and I did not properly hydrate, and I got, like even more sick. and so I'm like, oh, fuck. Like, I really got like I really got a prioritize, like, my physical health, because if I keep letting myself get pushed, you know, like over the summer, before requisite when I was just like, oh, you know, like, I'm just gonna record. I'm gonna go to Manhattan 20 fucking days in a row and not take a day off and I'm also gonna train, you know, and I'm also gonna do this, like the like, I'm maximized my potential for burnout, which also left me per like, personally vulnerable. to the, like, professional sabotage and, like, weird, underhanded, like, underbelly shit that, like people in the DJ circuit are doing because it's so hard to actually break through., from the level of like consumer professionalism right now. So people are doing like a lot of nasty things to try to get that main stage spot and I wasn't like in my head, I'm still very much like a Disney kid, like, I'm still like, I don't necessarily well, I mean, like Disney to teach us like, there's always gonna be a villain, but like, a society kind of undoes that teaching and is like, but that's just in movies and that's just in your head, but there's no like to me, I there is just this weird misst up between real life and what is told that like, okay, like anything that exists that is like in a certain field of negativity is just in your head. but, like, evil is it like a documented source of the opposite of good. since the beginning of time, and I just don't understand in how in a society we can philosophically and psychologically embrace therapy, however, when it when it comes to, like, real lived experiences, when you're dealing with something that is not necessarily, uh, like a normal part of societal living, like that stuff only happens in movies. I'm like, but it does happen. Sometimes you just have to, you know, like being having I've I've never really been such a socially dependent creature. like, a lot of people have to have some kind of validation. That's why social media is like ruling our society right now. is because people have to have the validation or the likes of whatever they're doing is like cool with the rest of the group. and to me, that this is dangerous group think. like, if you're all thinking the same way, then there's something being missed. There's always something being missed, you know, if you're all on the same frequency or the same form of thought, you know. And so, I've always been like a big, you know, maybe it's just because I don't have any siblings. I've been like a big believer in embracing, um, independent thought, like, okay, if everybody else is thinking one way, then what is the opposite of what everybody else is thinking and not necessarily alluding to the fact that the opposite might be the right thing, but anything between whatever the group think and the opposite is, is also like valid, could be valid, you know, it's not necessarily the opposite of what everybody's thinking, but it's somewhere along the spectrum of maybe that or maybe the opposite, like it could be anything else in between. And so I think I'm the kind of person or the kind of thinker that's motivated by the the spectrum, you know, the spectrum, uh process, anything in between, like not necessarily that, not necessarily the opposite of that, but like what other possibilities, you know? um, could be validated or verified through thinking outside of the box or outside of a you know, being forced to the point of conformity that, like, everything sounds the same and everything looks the same and everything has like a way. That's not necessarily wrong. um, but also not necessarily the only way or right. um, so that I' of been uh what what did I get on that round about? I don't know. I've just been playing with like a lot of different concepts, like not necessarily trying to sound like anything. or anyone, and also not necessarily having the opportunity or environmental expression, like the space to be able to sound like myself. Like I still don't artistically or musically think that I sound like myself. um, and that they are elements of myself there, but it's something that's kind of, um, in its, you know, convex form of being this thing that is potential, but not necessarily fully realized or realizable yet. Like, I haven't had I haven't had peace and I haven't had like full p I haven't had peak health in a long time, or a safe environment in a very long time. and I think that the disallowance of comfort, not necessarily the safity of um of complatancy, you know, or or being comfortable to a point that it's it becomes dangerous, um, but just being able to kind of be in a life that is not necessarily like violent or terrible all the time. I think removing these barriers has not necessarily been a foreseeable reality for nearly a decade and while some artists technically thrive in what is, you know, what is this, you know, tragedy and darkness? It's there's only so much of a certain space that my creative ingenuity can take up and not void. And so, understanding that this time is kind of transitional in the sense that eventually it has to in no matter what direction break free from its current state of, you know, entrapment and its current state of imprisonment. um and so in my artistry and not will change, but I don't think I don't think it's necessarily going to be like fully realized until I have a a a point that I'm in an environment that I can breathe and be and think clearly without the force of control or being subjugated to, you know, a certain level of violence that's not necessarily always physical, but is certainly not, um, you know, without it's notable, um, impact on my physical health, my physical and mental health. So that being said, um, this track, um, this track is somewhere between symposium and, um, as seen on TV, I think I began writing it before the concept for symposium was fully formed. and, um, I think it was like the first of its little group of double tracks and I didn't necessarily mean, like, for the story, cause it, you know, ideally, like a song is like five minutes or less or whatever. um five minutes or less or whatever, but I've again, not been, uh, trying to conform to what is supposed to be this, or what is supposed to be that, and, um I don't know. I I began writing it in with the mindset and the technicality of symposium, but also as I listen back to it, um, I'm also using elements that have been implementing for the last few years into as seen on TV. And so there's some like to me, it's very beautiful. Again, what what is more important or more, you know, like wh what is more palatable for my audience is always differed like my favorite tr tracks are not your guys's favorite tracks from what I'm looking at for for the numbers, you know, my favorite episodes of me talking are not your favorite episodes for me talking. So, I mean, like they're exists here, this obvious, like, it's weird because a lot of artists can be applied to their fans and to their listeners. It's like the the listeners are being projective of like they see themselves in their favorite artists, or they see themselves reflected back through an artist that they, you know, like Taylor Swift, like, all her fans are Taylor Swift and like, most artists are that way that, you know, they're reflective of the people that they look like and have the same experience of and that's how, you know, um, that's how mass that's how mass media works. It's reflected, you know, through the medium of sorts, you know, um it as a as a concept that is shared amongst all all of those, you know, people. um, but I'm looking at my numbers and I'm realizing that, like, oh, there there's like a distinctly different flavor from the way that, like, my perception of what is my best work is and what my audience thinks is the best or, you know, the like I look a lot at the numbers not as they happen, but like over time, whereas I'll be in hiatus for a certain amount of months and then I'll come back. and see what the numbers are reflecting in in what is more, you know, palatable for my audience, like what my audience is is actually agreeing with more is like my better work and it's always not it's not necessarily again, it's not necessarily opposite. but it's not um, you know, it's not always what I expect to be. So this to me, I like um, but it doesn't necessarily like that you, whoever you are as an audience is gonna agree. Um This is actually the least completed track. um I feel like I'm showing you yeah, like I'm showing you my my uh it just it's naked cause it's very much not done. This is probably the most incomplete thing that I've ever, like, put out for anybody else to listen to. Um, but just being audit honest as like a person, not like as a entertainer, cause I don't necessarily see myself as that anymore after these couple years. Um, but being honest, like as a human being, as like a person, um, I've had some times that feel as though are, you know, an indication of not having a very prolonged experience in this sort of way. And I don't, like, I don't wanna put a trigger warning on anything. And I don't wanna, you know, like I I also don't want to insinuate things that are not there. Um, but a lot of the time, that is just to say that I don't feel safe, um, that I don't feel, um safe or secure, um, and that there's not necessarily a like sh it's just New York City. There's no level of like autho like a there is no necessary authority complex that has any sort of like, ability to protect you, you know, from uh certain experiences that are not necessarily um, you know, there's there's no level of protection from from, you know, there there are more heavily funded organizations that are like banks and investments or are more funded than the police. So when you're telling the police, like, hey, I'm being, you know, stalked or harassed and like, there's a pattern and like, here's the evidence and they won't even look at your evidence. Um, even though technically by the law, like it is, you know, documented uh, verifiable, like verifiable, like, no, there's none in my head. Like, I have like the videos, I have pictures, I have audio recordings of like this is happening to me, and they won't even look at it, um, not necessarily because they don't want to, but maybe because they've been trained to look in the other way. Um, and then, you know, just the cultural disadvantage of like, youre snitch. I'm like, I'm also within inches of my life sometimes. and nobody's helping me. Um, and it's not necessarily a mental condition. I think that more now than ever, I would be like readily willing to admit like, oh yeah, like, I should just take the meds, but I'm like, this is I'm not hallucinating this. I'm not gonna take some kind of fucking pill for some kind of medication for something that's like, I'm experiencing this, and not only am I experiencing this with like my eyes, my nose, my ears, like, I'm now videotaping 100% of my life everywhere I go. If I walk out the door, I'm recording, like, that's how many times I've been stalked or followed. Like, if I walk outside of my apartment, like I'm I'm videotaping it, because if I don't, if something happens, then it's literally their word against mine. and the police is, like, literal their whole thing is like, if we didn't see it, it didn't happen. Like, you can get you can get, like beaten within an inch of your life and the police can show up and you can tell them and they can see you like bleeding from the face or whatever, and be like, that guy did it, but the police will straight up tell you. the police will straight up tell you like if we didn't see it, it didn't happen, like we can write the report, but like we like they will not investigate. Period. They will not investigate. And so understanding that, like that opens the, you know, the possibility of like way, way more heinous crimes, you know, being able to be, um, played out without, you know, without any possibility of you having help for that, as, you know, is like dangerous to me, and a lot of the time I feel like I'm in danger, um, to me, and so, my priority is not sitting down in Ableton and and you know, getting these cues just right, like, especially with this this track. um, like it's so, so far from complete, but when I hear it, it still sounds it sounds decent enough that, like, I'll give it to you guys just in case, like like the least sometimes that I feel is gonna happen is that I just get hit by a bus. uh, which does happen almost any time I go outside. It's like, I will not get a bicycle. I won't because I'm like, that's like the easiest way to ensure that I will get hit by something. I'll get hit by something. um I will get hit by something, so I don't um I don't, you know. I'm just trying to, uh, get along and protect myself and away that, you know, maybe possibly enables me to, like, disappear. I don't necessarily need to be anybody. I stopped fighting for that main stage spot a long time ago, cause I I see that it's not about like it can't necessarily be about the love when it's about the money. and I have so, so much love. like for the music, um, and for what used to be the scene. I mean, the scene's always been kind of dirty. You pick up any book about DJ culture, about festival culture, you know, about music in the in the sense that it's been meant in the rave world has always had like a CD side to it. um because it was previously a counterculture, you know, that became mainstream and it still definitely has its like flavor, it definitely has its like, you know it's flavors to it, which, you know, is is a magnetism or like a draw, that's like, oh, there is this darkness that exists, but like, at the core of it is the frequency, you know? And I think that if there was ever going to be like a place for like a placeholder for success for me and the industry, it would be somewhere in the future when it can be a more decisive. No, what am I trying to say? Oh, I don't know. I think that money really fucks things up sometimes, and because of the amount of inequality in the world and the fact that the the world has become such a competitive space, um, that there're actually less places for opportunity for artists, even though it seems like there should be more. um I think until it's like about wellness, yeah, I think in until music can be until we can create like spaces where wellness is like at the center of these, you know, gatherings, then I don't think it's necessarily going to be like a safe place. Um for anybody, but let alone for me, because I'm very much like a fragile person when it comes down to, um, like per like the protection of my spirit and the protection of my aura, I don't necessarily want to be in a place of uh tragedy or a place of defense all the time. I I wanna go outside and and be in defense mode 100% of the time. I am right now, so um, like anything I I I kind of take it with a grain of salt in the way that like anything I say can and will be used against me. And so I don't say so much. I I don't say so much, and I want to be sure to take care of my art in a way that it doesn't is not, um, you know, so that it doesn't necessarily exist in a place of toxicity or that it's not coming from. Like, I won't sit down and Ableton if I feel a certain way. It's not just me being lazy. Like it's if I have like a certain vibration that's incurable, like it's not uh it doesn't make sense for me to, like, you know, sit down and work on a track. So this this track, uh, forget me nots and follow through. um, I think it is the first track and symposium. I don't know, because when I listen back to it, I also hear um when I listen back to it, I also hear as seen on TV, like a lot. um like a lot. And so it's kind of interesting to see those two kind of elements of my artistic personality combined, because I think the tracks that I've shared with you that are from symposium or different in the way that they're um made only one way, but this one is definitely implementing um techniques from two projects. Um, so the what are the two other ones? I think it's like talked to me about it. Is that oneosium? I think so. and bitter butter and southwest of your scars. Ah, those are all from this project, but then I I look at this one, which is technically the first of the bunch and it's so not done. that I'm like, don't put it out until it's done. and I'm like, well, and might not ever be done with the shit that's happening is kind of scary. Like, it's I might I may not ever be able to get back to a place where this is possible because of the things that are continually happening uh, to me. Um, I I don't know what the source of evil is. Like, I really don't, like I am very much a spiritual person and I do have like the tendency to believe that like no matter what God has my back so if I'm removed from one situation or existence into another, it is for the protection of that aura, for the protection of that frequency, for the protection of, you know, keeping my, you know, um my source intact, like there's, you know, certain elements or certain frequencies that can't exist in in other realms. I think that, uh, a toxic environment. Like my energ is not going to sustain an intoxic environment. It's just not. It's just not. It's not necessarily even a personal or emotional preference. It's more of like a oh, this doesn't go in there. Like this doesn't go there or I don't exist over there. Like, I don't, you know, it's not. I think I wish that I could be applied to like every space and time, but I think that there are certain drawbacks to being in energy that is applicable to anything and everything. I think that, you know, in the very rare circumstances that an energy like that exists, um it's very magnetizing, it's very, uh enigmatic and it's very charismatic in the way that, like, everybody wants it, everybody wants a piece, everybody wants to be around it, but also for that person, you know, where that energy exists, you know, for that vehicle, I think that it becomes like exhausting to the point that, you know, um, the human of of that, um, you know, the human of that energy is entirely vulnerable all the time. And so those people that are, um designated to do those kinds of jobs, having that high level of power and energy are also, uh, you know, in every sense of the word, um, like exhausted to some effect, um, and I'm exhausted, um, but I think that this last two years has been a case study for all of the like I mean, like she's just horrible things people are doing to each other to try to get ahead, you know, like to try to get a little bit of the pie just to get the tiniest crumbs or to get you know, people are stepping on heads out here. Like people are doing what it takes and they're justifying things that are technically morally, you know. so very morally, uh, corrupt and so so so bad to other people with the justification of like, that's just the way it is. Or you you gotta do what you gotta do and I'm like, yo, dude, but like again, my energy just does not exist in that space for that mindset you know where it's like you know, um because I also believe that like a certain level of justifying, you know, morally uh, you know, morally corrupt behavior eventually just makes it so that you can't get ahead. I I honestly chronically believe that, like if you're constantly fucking other people over just to get to the top, like your top is not going to be consistent with what is actually success and what is actually um freedom, you know, like, you are gonna owe back energy to a certain extent, you know, um, because you stole it in the first place, like, you can't you can't sustain on stolen energy. Like you cannot do it. Like you cannot exist in a place that that was taken from somebody else without something else in turn being taken from you. I honestly truly believed that with every like with every last breath, with every last word, I honestly believe that like that that good overpowers evil. Like, you can't sustain on something that you robbed from somebody, you can't sustain on something that you you know, that that you took, eventually, you know, karmically, um, it comes back too, and so, I don't think energy is any different. I think if you suck the life out of somebody, eventually something' gonna get sucked out of you and, uh, it's one of those things where it's like one step forward, two steps back for people who uh subsist on energy that way. I just I don't know. um, I try more and more to be conscious of my self to point where I realized that um the effect that I have on people could be, you know, long lasting. It's it's something that could be like a ripple effect, and so I'm very careful with my energy in the way that, you know, I if I dole it out, I expect I expect 39%. I don't know why that's the number. 39% to get it back. um, you know, on a certain way. And uh understanding my limits and my like just understanding my ability and my placement. understanding the, you know, the the love you make. yeah, all that. and the love that you make is equal to the love that you take. And so um also, I think that love in itself is probably the most valuable heat source and that it overpowers what is um technically needed in the society of, you know, for survival. I think that love overpowers, you know, whatever material, you know, the material sense of existence is. I think that love overpowers, whatever is morally corrupt, whatever is systematically corrupt. I think that love at the end of the day, like, really does put in its place. um what is supposed to be and what is not supposed to be. And so in because I think like living in this spirit with the understanding that like it took me a really long time. I think I having a a a victim's mentality of like, I must deserve this in some sort of way, but then understanding also like I didn't do anything wrong. Um Sometimes these things just happen and the understanding of why that is is not always attainable. Um, and so to wallow in it and to be like, why, why? You know, like, why? I mean, I think in a from a philosophical standpoint, I do a lot of this because it's like this doesn't necessarily make sense, but it has to it has to be an art artistic way for me to be like, well, it doesn't make sense, but like, you know, now I have ten pages about trying to figure, like, instead of actually just wallowing it and being like, what? Well, now I have ten pages of like this, you know, something that can be considered beautiful. you know, something that can be considered, uh, useful to somebody, maybe not now, but at some point in time, you know, because all of my work is is stored in like this digital time space, kind of like encrypted into history in itself being like a digital marker for, you know, something that very much did exist or did happen. I still believe I still live in the belief that like this, well, it's just like the overall knowing that this part, this faction of history is a very, you know, uh verifiable part of ancient history, you know, to a culture that exists like beyond our time. And so with that understanding that, like it's so crazy, because I do have this overriding kind of factor of, you know, God that's just kind of like, oh, these are ancient times. this is an ancient world and it's hard to like wrap your mind around it because youth, you know, you think of yourself in the present time of like being a, you know, a being of existence in the future. Oh, I watched the jet the Jetsons. Oh, that was so good. I watched uh the Jetsons. which I didn't know is also the Simpsons. and like every animated show that came out on it like a lot, actually. It's a good show. I got I think I gotta watch it again because I was like, oh, this is like ten different shows. It was like ten different shows. um but I watched like the pilot, I think episode of the Jetsons and I was tripping. I I was tripping. um it was just really good. Anyway, um I think what what was I saying? Oh, like this time being like a marker for actual actually being a primitive civilization. Whereas like not necessarily compared to what we know as the primitive civilizations, you know, of human time, like, you think of primitive civilizations of being like the ancient Egyptians or, you know, the Mayans or, uh, you know, the Greeks, uh loved them. I really I I almost even favored them over the Romans. almost, almost, almost, I don't know, I could talk about history and culture forever. cause I'm like, but the other Romans really, like their architecture, but the Greeks more culturally, like artistically, I think where what is the word for them? Uh, the Greeks? What is the word for them? I think there were definitely more, uh yeah, yeah, definitely more artistic philosophical than the Romans, but the Romans had like a lot, like a lot to do with modern society to the point where that's also uh admirable. I do like the Romans. They're just like shitty and violent. They're just shitty and violent anyway. um what was I saying? I don't know. I'm wrapping this up. cause I'm hungry. I don't know about a taco, though. This is technically the start of my day. at midnight o'clock. Um, at midnight o'clock. oh, that's what I was talking about. Markers for ancient civilizations. Oh, yeah, this this time is so so far beyond. But I think the the incredible thing about this time that we're living in now presently, um, is that it is so, like there's so much record of it that it does exist beyond our time for, you know, potentially millions of years and into hire and further civilizations. So I kind of live with that, like, understanding of like this this also and itself being like, a part of the ancient world as far as time is concerned, you know? like, in as much a stipulation of like any apocalyptic or societal, you know, destruction is made, like nothing really sees past, like nothing really sees past the fact that, like, they're so much historical information about our present time in the future that it is consistently creating to an adding to like the what am I trying to say? Oh, something about the multiviverse. Something about the cosmos or something. constantly expanding, because it is, but whatever, I actually just kind of made this as a real time episode to so that I could share this song and then um not really like I don't necessarily have anything for you, anything else for you in this season. um it's there. like, there are six or seven other episodes. There might even be some music. oh, all the freaky Fridays or whatever, mix tapes. Did I even post what up Wednesday? I did I did a freaky Friday on a Wednesday and it was arguably the best. of all the freaky Fridays. I don't know if I posted that already. um I don't know if I posted that already. but it's not. Also, like my podcasting distributor is kind of archaic. So it takes a lot of work just to go check on what's been posted or whatever. um So I'm I'm not going to make any promises and be like, oh, go check if that was posted. And if it is posted, I'll just maybe post it again, cause it's worth it. Um, what up Wednesdays? I did it twice, actually. um because it got difficult to do freaky Fridays. It's still kind of fucking difficult to do it. And, uh, I it pains me to realize, like, how physically affected. I've I have been. um cause it sucks, cause it's not just something that's in my head, it's like ow, like, my body hurts. like, I cannot, you know. I can't withstand a certain frequency or electronic exposure that is negative over this much time. Like, I'm just like broken down right now. Um at least I'm still capable, cause I didn't ever think. I was like, I don't think I'll ever run more than a mile again. Um, I probably should um take the proper steps to make sure that, though, uh, now that I'm running again, I take the proper steps, like, I forgot to stretch, and I forgot to drink water. Stupid. Well, I I just felt so good to run. I love those woodway treadmills so much, so much, it just felt so good that I didn't that I couldn't stop and then when I did, like my body is like, okay, like you're stupid. Like it felt really good, so I'm like, all right, like active recovery. I'm gonna do like two hours on the pelotone and then a walk. um, before I run again. and that's what I'm about to do right now. I love getting to the reunion parts of the bad girls club because as the most fighting and I burn the most calories during the reunions, I just finished to season. I just watched the season for the second time. and uh I have a reunion episode coming up, so I'm a I'm— I don't know. I'm pretty boring person to be quite honest, but here's the song. okay, I'm at an hour yet. Here's the song forgetmenot// and follow through. It's not finished. Like if I could give you a percentage on the— what are you doing? Yo, this dudes are weird all day. I'm sorry. Um. He's so funny. He's so funny. Earlier he like earlier he like sneezed. Earlier he sneezed. But like also farted and this scared himself so bad that I could not contain myself. Because he was like embarrassed. but like, also he sneezed and farted and probably could not. He was like, oh, my God. Like, oh my God. And then, uh, I laughed for like a good five minutes after that. He seemed genuinely embarrassed. I was like, yeah. yeah, that that is shocking that you can manage to do something like that. like being a cat, but, you know, oh, he did. It was good. That's why we have emotional support animals, because I needed that laugh. I don't think I' laughed so hard at anything in a very, very long time, so I'm glad I have my little kitty. my satterat, my Mr. Cat, mush matters anyway. uh, was I wrapping something up? I was.ive meods to follow through. this song that's about to come up, and then I'm maybe I'll maybe I'll if it's not out already. Well, if it is, here it is again, what up Wednesday? I'll go dig it out of the fucking archives. you guys couldn't have that. decent. Um, keep in mind that the CDJs at the radio station, where do Freaky Fridays are also very archaic? Um, I'm not complaining, though. I don't know. I don't know if I got to the episode where I was talking about that. Uh, or maybe I got I got fi I gotta figure it out. um I gotta figure out where these episodes are. There's like six or seven. Should I uh honorable mentions or dishonorable mensions? I feel like it borders on both. because I just figured out what apparently the six seven phenomenon is. And I'm actually worried about suburban children, like, having act like, why are they saying this? Because I looked up I looked up where it came from, it came from this rapper called scrilla dude. not gonna lie. One of my personal favorites, cause I love rap, that is terrible to a certain extent. um and it is, like it's not only it's not only like it's not lyrically terrible. He's actually really good um He's actually really good whatever he's saying. I know what he's saying, which is what's terrifying that, like, apparently suburban upper middle class and upper class children are saying this. six seven thing, because it came from this video by this rapper called Skrilla do doot. Yup. and well, it's culture music, like it's it's trap culture music, it's not necessarily drill, but it's done in the style of drill. um, talking about like the culture the culture the culture um that is not necessarily like great. cause he was talking I was like yo. what the fuck are children saying this for? Um, what the fuck are children exposed to this for? Because there was no, like parental block on it or anything like that. And the dude was talking about like, straight up murderer. He was like, yeah, m, like this though. And I was like, oh no, like I I actually kind of dig his music because it's it's like it's the music that was born of like the Young Thug and the low Wayne and themehesine and it's bad. It's really bad. Like it's really bad. like if your kids are saying six seven, like, the origin of that is not, I'm like,o, shout out sc a d do, because that is facts, but also like, like like kids should not necessarily like, everything he was saying and all of his songs, I was like, that's bad. That's bad that you said that. not that you shouldn't, actually. I feel like there, like art exists as a medium to be able to have this level of freedom of speech, and that's why it exists. But also like, if you understand which I think kids obviously don't if they're just like, oh, six, seven, I'm like, okay, like, but obviously, like, this is where that came from. Like, and this is where that came from, and the dude is talking about some stuff that I'm like what? Like, I'm not confused. I know what he's talking about. But like, children should not necessarily like, even if they don't know what he's talking about, this is not like, this is different from like, when I was like, 10 and it's getting hot in here. So take off all your clothes, like that came out or like to the window to the wall, like this is mild, those things are mild, compared to like, the shit that scrill a do dude. talks about. I'm like, oh, what? What? And apparently we little kids are seeing this and exposed to it, like, they don't necessarily know what it means, but he's like, yo, these are the lyrics to my songs. Listen. I'm like, oh, like. That's troubling. That that exists. That's troubling. truly troubling. I'm I'm not talking shit. I actually really like it, but like parental controls, like, my kids should not be exposed to this, like via the Internet. Like, you should not like, this should be something especially if you live in the subrooms like if you live in a house that has rooms, like if you live in a house that has rooms in an all. like the culture that this is referencing and you know what? The only thing that actually made me look it up was like so many people were saying it in the circuit of television that I watched that I was like, it was bothering me. It was bothering me like Labubu was, but Labubu was far less disturbing, far less. I was like, oh, no. this is not cool. This is not cool, David Letterman. This is not cool, because he was like,Yo, what's up six seven? I'm like, you're 106. I don't know why you're saying this. So I looked it up. So I looked it up, and I was like, oh no, like, okay, like we know it's a cultural fucking phenomenon, but like, do you know why? Do you know why? Like, do you know why? And do you know what this man is talking about? Do you know what this man is saying? Anyway. I'm not I'm actually not gonna say it. Like I'm not gonna say it because I think it it exempt exemplifies that's what I'm trying to say right yeah. I think it exemplifies and represents a part of the culture that is deeply, deeply, deeply, deeply wrong. um in the history of the United States of America. I think it's just bad news. It's just bad news. And it's bad news, like it exists, but the reason why it exists is terrible, like it shouldn't exist is it's terrible. It's bad. It's bad and it's bad that kids are saying this. It's bad anyway. it's really bad. Anyway, I got Peloton time, bad girls' club reunion, some coffee to reheat. Here's this song, um there's no anything else for a while. I gotta make sure that like my uh I got to make sure if I get taken out, it's by like a city bus. And, you know, not just because my insides are uh imploding. um and yeah, my insides are imploding. Uh, gotta take care of number one, which is me. So, that self serving thing I get, but, you know, I'm just not the kind to to step on heads or like, I'm not gonna make it, like, purposely harder for you to do something. Like, I do believe in free will to the point where if you're not hurting anybody else, it's not affecting anybody else's, like vibe, like, do what you want, like, as long as you're not objectively or subjectively hurting anybody. Like, just don't hurt anybody, but besides this, you know, take care of yourself, but it's not, you know. I mean, you're not causing any quantifiable harm. Go ahead and, you know? I, um, but that's it. That's that's it for me. Thank you for listening. Is that it? Yeah, forget me nots. It's not finished. I've got a lot to do. Like, I actually had this is a song that actually has like a list, like a handwritten list on a piece of paper of like do this and do that and do this and do that. But like here's what I have so far just in case, you know, the city buses be getting awful close to the curb sometimes. where I stand, I am yep, they do. anyway. um I said more stories to tell and stuff, but now it's not the time or the place. did I say my thing? Yeah, I say my. Dave you were listening. something, you're listening, see you next time. That's it, yeah. Yeah, I don't have anything else. Thank you for listening. See you next time, bye.

Audio roundup of selected biopharma industry content from Scrip over the business week ended November 28, 2025. In this episode: 2027 Medicare price cuts likely not as large as CMS estimates; Zai Lab leads DLL3 lung cancer ADC race; Phase II failure for J&J's Alzheimer's asset posdinemab; Bayer's positive Phase III data for asundexian in stroke; and Pfizer/Astellas's Padcev's first big win in bladder cancer study. Story links: https://insights.citeline.com/scrip/podcasts/scrips-five-must-know-things/quick-listen-scrips-five-must-know-things-R4RCDF2RXVGVHPEX2WQ7A3JVKU/ This episode was produced with the help of AI text-to-voice and voice emulation tools. Playlist: soundcloud.com/citelinesounds/sets/scrips-five-must-know-things

"Antibody–drug conjugates (ADCs) have three basic parts: the antibody part, the cytotoxic chemo, and the linker that connects the two. First, the antibody part binds to the target on the surface of the cell. Antibodies can be designed to bind to proteins with a very high level of specificity. That's what gives it the targeted portion. Then the whole thing gets taken up by the cell and broken down, which releases the chemotherapy part. Some sources will call this the 'payload' or the 'warhead.'  That's the part that's attached to the 'heat-seeking' part, and that's what causes the cell death," Kenneth Tham, PharmD, BCOP, clinical pharmacist in general oncology at the University of Washington Medicine and Fred Hutchinson Cancer Center in Seattle, WA, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a conversation about antibody–drug conjugates. Music Credit: "Fireflies and Stardust" by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0  Earn 0.5 contact hours of nursing continuing professional development (NCPD) by listening to the full recording and completing an evaluation at courses.ons.org by November 28, 2026. The planners and faculty for this episode have no relevant financial relationships with ineligible companies to disclose. ONS is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation. Learning outcome: Learners will report an increase in knowledge related to the mechanism of action of antibody–drug conjugates. Episode Notes  Complete this evaluation for free NCPD. ONS Podcast™ episodes: Pharmacology 101 series Episode 303: Cancer Symptom Management Basics: Ocular Toxicities Episode 283: Desensitization Strategies to Reintroduce Treatment After an Infusion-Related Reaction ONS Voice articles: An Oncology Nurse's Guide to Cancer-Related Ocular Toxicities Antibody–Drug Conjugates Join the Best of Two Worlds Into One New Treatment Nursing Management of Adverse Events From Enfortumab Vedotin Therapy for Urothelial Cancer Oncology Nurses' Role in Translating Biomarker Testing Results The Pharmacist's Role in Combination Cancer Treatments ONS Voice drug reference sheets: Belantamab mafodotin-blmf Datopotamab deruxtecan-dlnk Enfortumab vedotin Fam-trastuzumab deruxtecan-nxki ONS book: Chemotherapy and Immunotherapy Guidelines and Recommendations for Practice (second edition) ONS course: ONS Fundamentals of Chemotherapy and Immunotherapy Administration™ Clinical Journal of Oncology Nursing articles: Antibody–Drug Conjugates and Ocular Toxicity: Nursing, Patient, and Organizational Implications for Care Nurse-Led Grading of Antineoplastic Infusion-Related Reactions: A Call to Action Other ONS resources: Antineoplastic Administration Huddle Card Biomarker Database Chemotherapy Huddle Card Monoclonal Antibodies Huddle Card Association of Cancer Care Centers (ACCC) antibody–drug conjugates page Drugs@FDA Hematology/Oncology Pharmacy Association (HOPA) National Cancer Institute cancer drugs page Network for Collaborative Oncology Development and Advancement (NCODA) clinical resource library ACCC/HOPA/NCODA/ONS Patient Education Sheets website To discuss the information in this episode with other oncology nurses, visit the ONS Communities.  To find resources for creating an ONS Podcast club in your chapter or nursing community, visit the ONS Podcast Library. To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org Highlights From This Episode "The mechanism of action of the chemo itself depends on what agent or what 'warhead' is attached. Generally, [ADCs] have some kind of cytotoxic mechanism related to many of the chemotherapies that we use in practice, without attachment to the antibody. Some of them can be microtubule inhibitors, vinca alkaloids like vincristine. Some of them can be topoisomerase I (TOP1) inhibitors like irinotecan. Some can be alkylating agents that cause DNA breaks. So, again, looking back at the arsenal we have of cytotoxic chemo, these can all be incorporated into the ADCs." TS 5:54 "I want to talk about a case where the biomarker is being tested, but the biomarker isn't the target that you're looking for. One good case of this is a newer agent that was approved called datopotamab deruxtecan. The datopotamab portion is specific to a target called 'trophoblast cell surface antigen 2' (TROP2), which is expressed on the surface of many epithelial cancers. This agent was first approved in hormone receptor-positive, HER2-negative breast cancer, and received accelerated approval in patients with non-small cell lung cancer (NSCLC) with an EGFR mutation. ... The antibody looks for a target, TROP2. But in both of these cases—in the breast cancer and the NSCLC—you're testing for expression of different mutations or lack thereof. You're not looking for expression of TROP2. There's more research that needs to be done about the relationship between TROP2 expression and the presence or absence of these other biomarkers, but until we know more, we're actually testing for biomarkers that aren't the target of the ADC." TS 10:22 "There are common adverse advents to antibodies and chemo in general. Because we have both of these components, we want to watch out for the adverse effects of both of them. Antibodies, as with most proteins, can trigger an immune response or an infusion reaction. So, many ADCs can also cause hypersensitivity or infusion reactions. The rates of that are really variable and depend on the actual antibodies themselves. Then you have the cytotoxic component, the chemotherapy component, which has its own characteristic side effects. So, if we think of general chemo side effects—fatigue, nausea, bone marrow suppression, alopecia—these can [occur] with a lot of ADCs as well." TS 15:34 "The rate of ocular toxicity in [mirvetuximab soravtansine] is quite high. The manufacturer reports that this can occur in up to 60% of patients. With rates so high, the manufacturer recommends a preventive strategy. For this particular agent, [they] recommend patients have required eyecare. ... This ocular toxicity is something we do see in other ADCs that don't have the same target and don't necessarily have the same payload component. For example, tisotumab vedotin and again, datopotamab deruxtecan, can both cause ocular toxicities and both would have required ocular supportive care." TS 20:08 "Overall, I feel like the future is incredibly bright for these agents. There have only been around a dozen therapies approved by the U.S. Food and Drug Administration (FDA) despite this idea—the first agent came out in 2000. So, 25 years later, there are only around a dozen FDA-approved treatments. But there are so many more that are coming through the pipeline. And as we're discovering more biomarkers and developing more specialized antibodies, it's only natural that more ADCs will follow." TS 26:50

Please visit answersincme.com/CAZ860 to participate, download slides and supporting materials, complete the post test, and obtain credit. In this activity, an expert in hematology-oncology answers the most commonly asked questions from clinicians about the management of relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) with antibody–drug conjugates (ADCs). Upon completion of this activity, participants should be better able to: Identify patients with R/R DLBCL who may benefit from ADC therapy in the third-line or later setting; Interpret current evidence to inform selection of ADC therapies for patients with R/R DLBCL in the third-line or later setting; and Discuss strategies to optimize the use of ADC therapies for patients with R/R DLBCL, particularly in the community setting.

Dr. Linda Duska and Dr. Kathleen Moore discuss key studies in the evolving controversy over radical upfront surgery versus neoadjuvant chemotherapy in advanced ovarian cancer. TRANSCRIPT Dr. Linda Duska: Hello, and welcome to the ASCO Daily News Podcast. I am your guest host, Dr. Linda Duska. I am a professor of obstetrics and gynecology at the University of Virginia School of Medicine.  On today's episode, we will explore the management of advanced ovarian cancer, specifically with respect to a question that has really stirred some controversy over time, going all the way back more than 20 years: Should we be doing radical upfront surgery in advanced ovarian cancer, or should we be doing neoadjuvant chemotherapy? So, there was a lot of hype about the TRUST study, also called ENGOT ov33/AGO-OVAR OP7, a Phase 3 randomized study that compares upfront surgery with neoadjuvant chemotherapy followed by interval surgery. So, I want to talk about that study today. And joining me for the discussion is Dr. Kathleen Moore, a professor also of obstetrics and gynecology at the University of Oklahoma and the deputy director of the Stephenson Cancer Center, also at the University of Oklahoma Health Sciences.  Dr. Moore, it is so great to be speaking with you today. Thanks for doing this. Dr. Kathleen Moore: Yeah, it's fun to be here. This is going to be fun. Dr. Linda Duska: FYI for our listeners, both of our full disclosures are available in the transcript of this episode.  So let's just jump right in. We already alluded to the fact that the TRUST study addresses a question we have been grappling with in our field. Here's the thing, we have four prior randomized trials on this exact same topic. So, share with me why we needed another one and what maybe was different about this one? Dr. Kathleen Moore: That is, I think, the key question. So we have to level-set kind of our history. Let's start with, why is this even a question? Like, why are we even talking about this today? When we are taking care of a patient with newly diagnosed ovarian cancer, the aim of surgery in advanced ovarian cancer ideally is to prolong a patient's likelihood of disease-free survival, or if you want to use the term "remission," you can use the term "remission." And I think we can all agree that our objective is to improve overall survival in a way that also does not compromise her quality of life through surgical complications, which can have a big effect. The standard for many decades, certainly my entire career, which is now over 20 years, has been to pursue what we call primary cytoreductive surgery, meaning you get a diagnosis and we go right to the operating room with a goal of achieving what we call "no gross residual." That is very different – in the olden days, you would say "optimal" and get down to some predefined small amount of tumor. Now, the goal is you remove everything you can see.  The alternative strategy to that is neoadjuvant chemotherapy followed by interval cytoreductive surgery, and that has been the, quote-unquote, "safer" route because you chemically cytoreduce the cancer, and so, the resulting surgery, I will tell you, is not necessarily easy at all. It can still be very radical surgeries, but they tend to be less radical, less need for bowel resections, splenectomy, radical procedures, and in a short-term look, would be considered safer from a postoperative consideration. Dr. Linda Duska: Well, and also maybe more likely to be successful, right? Because there's less disease, maybe, theoretically. Dr. Kathleen Moore: More likely to be successful in getting to no gross residual. Dr. Linda Duska: Right. Yeah, exactly. Dr. Kathleen Moore: I agree with that. And so, so if the end game, regardless of timing, is you get to no gross residual and you help a patient and there's no difference in overall survival, then it's a no-brainer. We would not be having this conversation. But there remains a question around, while it may be more likely to get to no gross residual, it may be, and I think we can all agree, a less radical, safer surgery, do you lose survival in the long term by this approach? This has become an increasing concern because of the increase in rates of use of neoadjuvant, not only in this country, but abroad. And so, you mentioned the four prior studies. We will not be able to go through them completely. Dr. Linda Duska: Let's talk about the two modern ones, the two from 2020 because neither one of them showed a difference in overall survival, which I think we can agree is, at the end of the day, yes, PFS would be great, but OS is what we're looking for. Dr. Kathleen Moore: OS is definitely what we're looking for. I do think a marked improvement in PFS, like a real prolongation in disease-free survival, for me would be also enough. A modest improvement does not really cut it, but if you are really, really prolonging PFS, you should see that-  Dr. Linda Duska: -manifest in OS. Dr. Kathleen Moore: Yeah, yeah. Okay. So let's talk about the two modern ones. The older ones are EORTC and CHORUS, which I think we've talked about. The two more modern ones are SCORPION and JCOG0602. So, SCORPION was interesting. SCORPION was a very small study, though. So one could say it's underpowered. 170 patients. And they looked at only patients that were incredibly high risk. So, they had to have a Fagotti score, I believe, of over 9, but they were not looking at just low volume disease. Like, those patients were not enrolled in SCORPION. It was patients where you really were questioning, "Should I go to the OR or should I do neoadjuvant? Like, what's the better thing?" It is easy when it's low volume. You're like, "We're going." These were the patients who were like, "Hm, you know, what should I do?" High volume. Patients were young, about 55. The criticism of the older studies, there are many criticisms, but one of them is that, the criticism that is lobbied is that they did not really try. Whatever surgery you got, they did not really try with median operative times of 180 minutes for primary cytoreduction, 120 for neoadjuvant. Like, you and I both know, if you're in a big primary debulking, you're there all day. It's 6 hours. Dr. Linda Duska: Right, and there was no quality control for those studies, either. Dr. Kathleen Moore: No quality control. So, SCORPION, they went 451-minute median for surgery. Like, they really went for it versus four hours and then 253 for the interval, 4 hours. They really went for it on both arms. Complete gross resection was achieved in 50% of the primary cytoreduced. So even though they went for it with these very long surgeries, they only got to the goal half the time. It was almost 80% in the interval group. So they were more successful there. And there was absolutely no difference in PFS or OS. They were right about 15 months PFS, right about 40 months OS.  JCOG0602, of course, done in Japan, a big study, 300 patients, a little bit older population. Surprisingly more stage IV disease in this study than were in SCORPION. SCORPION did not have a lot of stage IV, despite being very bulky tumors. So a third of patients were stage IV. They also had relatively shorter operative times, I would say, 240 minutes for primary, 302 for interval. So still kind of short. Complete gross resection was not achieved very often. 30% of primary cytoreduction. That is not acceptable. Dr. Linda Duska: Well, so let's talk about TRUST. What was different about TRUST? Why was this an important study for us to see? Dr. Kathleen Moore: So the criticism of all of these, and I am not trying to throw shade at anyone, but the criticism of all of these is if you are putting surgery to the test, you are putting the surgeon to the test. And you are assuming that all surgeons are trained equally and are willing to do what it takes to get someone to no gross residual. Dr. Linda Duska: And are in a center that can support the post-op care for those patients. Dr. Kathleen Moore: Which can be ICU care, prolonged time. Absolutely. So when you just open these broadly, you're assuming everyone has the surgical skills and is comfortable doing that and has backup. Everybody has an ICU. Everyone has a blood bank, and you are willing to do that. And that assumption could be wrong. And so what TRUST said is, "Okay, we are only going to open this at centers that have shown they can achieve a certain level of primary cytoreduction to no gross residual disease." And so there was quality criteria. It was based on – it was mostly a European study – so ESGO criteria were used to only allow certified centers to participate. They had to have a surgical volume of over 36 cytoreductive surgeries per year. So you could not be a low volume surgeon. Your complete resection rates that were reported had to be greater than 50% in the upfront setting. I told you on the JCOG, it was 30%. Dr. Linda Duska: Right. So these were the best of the best. This was the best possible surgical situation you could put these patients in, right? Dr. Kathleen Moore: Absolutely. And you support all the things so you could mitigate postoperative complications as well. Dr. Linda Duska: So we are asking the question now again in the ideal situation, right? Dr. Kathleen Moore: Right. Dr. Linda Duska: Which, we can talk about, may or may not be generalizable to real life, but that's a separate issue because we certainly don't have those conditions everywhere where people get cared for with ovarian cancer. But how would you interpret the results of this study? Did it show us anything different? Dr. Kathleen Moore: I am going to say how we should interpret it and then what I am thinking about. It is a negative study. It was designed to show improvement in overall survival in these ideal settings in patients with FIGO stage IIIB and C, they excluded A, these low volume tumors that should absolutely be getting surgery. So FIGO stage IIIB and C and IVA and B that were fit enough to undergo radical surgery randomized to primary cytoreduction or neoadjuvant with interval, and were all given the correct chemo. Dr. Linda Duska: And they were allowed bevacizumab and PARP, also. They could have bevacizumab and PARP. Dr. Kathleen Moore: They were allowed bevacizumab and PARP. Not many of them got PARP, but it was distributed equally, so that would not be a confounder. And so that was important. Overall survival is the endpoint. It was a big study. You know, it was almost 600 patients. So appropriately powered. So let's look at what they reported. When they looked at the patients who were enrolled, this is a large study, almost 600 patients, 345 in the primary cytoreductive arm and 343 in the neoadjuvant arm. Complete resection in these patients was 70% in the primary cytoreductive arm and 85% in the neoadjuvant arm. So in both arms, it was very high. So your selection of site and surgeon worked. You got people to their optimal outcome. So that is very different than any other study that has been reported to date. But what we saw when we looked at overall survival was no statistical difference. The median was, and I know we do not like to talk about medians, but the median in the primary cytoreductive arm was 54 months versus 48 months in the neoadjuvant arm with a hazard ratio of 0.89 and, of course, the confidence interval crossed one. So this is not statistically significant. And that was the primary endpoint. Dr. Linda Duska: I know you are getting to this. They did look at PFS, and that was statistically significant, but to your point about what are we looking for for a reasonable PFS difference? It was about two months difference. When I think about this study, and I know you are coming to this, what I thought was most interesting about this trial, besides the fact that the OS, the primary endpoint was negative, was the subgroup analyses that they did. And, of course, these are hypothesis-generating only. But if you look at, for example, specifically only the stage III group, that group did seem to potentially, again, hypothesis generating, but they did seem to benefit from upfront surgery.  And then one other thing that I want to touch on before we run out of time is, do we think it matters if the patient is BRCA germline positive? Do we think it matters if there is something in particular about that patient from a biomarker standpoint that is different? I am hopeful that more data will be coming out of this study that will help inform this. Of course, unpowered, hypothesis-generating only, but it's just really interesting. What do you think of their subset analysis? Dr. Kathleen Moore: Yeah, I think the subsets are what we are going to be talking about, but we have to emphasize that this was a negative trial as designed. Dr. Linda Duska: Absolutely. Yes. Dr. Kathleen Moore: So we cannot be apologists and be like, "But this or that." It was a negative trial as designed. Now, I am a human and a clinician, and I want what is best for my patients. So I am going to, like, go down the path of subset analyses. So if you look at the stage III tumors that got complete cytoreduction, which was 70% of the cases, your PFS was almost 28 months versus 21.8 months. Dr. Linda Duska: Yes, it becomes more significant. Dr. Kathleen Moore: Yeah, that hazard ratio is 0.69. Again, it is a subset. So even though the P value here is statistically significant, it actually should not have a P value because it is an exploratory analysis. So we have to be very careful. But the hazard ratio is 0.69. So the hypothesis is in this setting, if you're stage III and you go for it and you get someone to no gross residual versus an interval cytoreduction, you could potentially have a 31% reduction in the rate of progression for that patient who got primary cytoreduction. And you see a similar trend in the stage III patients, if you look at overall survival, although the post-progression survival is so long, it's a little bit narrow of a margin.  But I do think there are some nuggets here that, one of our colleagues who is really one of the experts in surgical studies, Dr. Mario Leitao, posted this on X, and I think it really resonated after this because we were all saying, "But what about the subsets?" He is like, "It's a negative study." But at the end of the day, you are going to sit with your patient. The patient should be seen by a GYN oncologist or surgical oncologist with specialty in cytoreduction and a medical oncologist, you know, if that person does not give chemo, and the decision should be made about what to do for that individual patient in that setting. Dr. Linda Duska: Agreed. And along those lines, if you look carefully at their data, the patients who had an upfront cytoreduction had almost twice the risk of having a stoma than the patients who had an interval cytoreduction. And they also had a higher risk of needing to have a bowel resection. The numbers were small, but still, when you look at the surgical complications, as you've already said, they're higher in the upfront group than they are in the interval group. That needs to be taken into account as well when counseling a patient, right? When you have a patient in front of you who says to you, "Dr. Moore, you can take out whatever you want, but whatever you do, don't make me a bag." As long as the patient understands what that means and what they're asking us to do, I think that we need to think about that. Dr. Kathleen Moore: I think that is a great point. And I have definitely seen in our practice, patients who say, "I absolutely would not want an ostomy. It's a nonstarter for me." And we do make different decisions. And you have to just say, "That's the decision we've made," and you kind of move on, and you can't look back and say, "Well, I wish I would have, could have, should have done something else." That is what the patient wants. Ultimately, that patient, her family, autonomous beings, they need to be fully counseled, and you need to counsel that patient as to the site that you are in, her volume of disease, and what you think you can achieve. In my opinion, a patient with stage III cancer who you have the site and the capabilities to get to no gross residual should go to the OR first. That is what I believe. I do not anymore think that for stage IV. I think that this is pretty convincing to me that that is probably a harmful thing. However, I want you to react to this. I think I am going to be a little unpopular in saying this, but for me, one of the biggest take-homes from TRUST was that whether or not, and we can talk about the subsets and the stage III looked better, and I think it did, but both groups did really well. Like, really well. And these were patients with large volume disease. This was not cherry-picked small volume stage IIIs that you could have done an optimal just by doing a hysterectomy. You know, these were patients that needed radical surgery. And both did well. And so what it speaks to me is that anytime you are going to operate on someone with ovary, whether it be frontline, whether it be a primary or interval, you need a high-volume surgeon. That is what I think this means to me. Like, I would want high volume surgeon at a center that could do these surgeries, getting that patient, my family member, me, to no gross residual. That is important. And you and I are both in training centers. I think we ought to take a really strong look at, are we preparing people to do the surgeries that are necessary to get someone to no gross residual 70% and 85% of the time? Dr. Linda Duska: We are going to run out of time, but I want to address that and ask you a provocative question. So, I completely agree with what you said, that surgery is important. But I also think one of the reasons these patients in this study did so well is because all of the incredible new therapies that we have for patients. Because OS is not just about surgery. It is about surgery, but it is also about all of the amazing new therapies we have that you and others have helped us to get through clinical research. And so, how much of that do you think, like, for example, if you look at the PFS and OS rates from CHORUS and EORTC, I get it that they're, that they're not the same. It's different patients, different populations, can't do cross-trial comparisons. But the OS, as you said, in this study was 54 months and 48 months, which is, compared to 2010, we're doing much, much better. It is not just the surgery, it is also all the amazing treatment options we have for these patients, including PARP, including MIRV, including lots of other new therapies. How do you fit that into thinking about all of this? Dr. Kathleen Moore: I do think we are seeing, and we know this just from epidemiologic data that the prevalence of ovarian cancer in many of the countries where the study was done is increasing, despite a decrease in incidence. And why is that? Because people are living longer. Dr. Linda Duska: People are living longer, yeah. Dr. Kathleen Moore: Which is phenomenal. That is what we want. And we do have, I think, better supportive care now. PARP inhibitors in the frontline, which not many of these patients had. Now some of them, this is mainly in Europe, will have gotten them in the first maintenance setting, and I do think that impacts outcome. We do not have that data yet, you know, to kind of see what, I would be really interested to see. We do not do this well because in ovarian cancer, post-progression survival can be so long, we do not do well of tracking what people get when they come off a clinical trial to see how that could impact – you know, how many of them got another surgery? How many of them got a PARP? I think this group probably missed the ADC wave for the most part, because this, mirvetuximab is just very recently available in Europe. Dr. Linda Duska: Unless they were on trial. Dr. Kathleen Moore: Unless they were on trial. But I mean, I think we will have to see. 600 patients, I would bet a lot of them missed the ADC wave. So, I do not know that we can say we know what drove these phenomenal – these are some of the best curves we've seen outside of BRCA. And then coming back to your point about the BRCA population here, that is a really critical question that I do not know that we're ever going to answer. There have been hypotheses around a tumor that is driven by BRCA, if you surgically cytoreduced it, and then chemically cytoreduced it with chemo, and so you're starting PARP with nothing visible and likely still homogeneous clones. Is that the group we cured? And then if you give chemo first before surgery, it allows more rapid development of heterogeneity and more clonal evolution that those are patients who are less likely to be cured, even if they do get cytoreduced to nothing at interval with use of PARP inhibitor in the front line. That is a question that many have brought up as something we would like to understand better. Like, if you are BRCA, should you always just go for it or not? I do not know that we're ever going to really get to that. We are trying to look at some of the other studies and just see if you got neoadjuvant and you had BRCA, was anyone cured? I think that is a question on SOLO1 I would like to know the answer to, and I don't yet, that may help us get to that. But that's sort of something we do think about. You should have a fair number of them in TRUST. It wasn't a stratification factor, as I remember. Dr. Linda Duska: No, it wasn't. They stratified by center, age, and ECOG status Dr. Kathleen Moore: So you would hope with randomization that you would have an equal number in each arm. And they may be able to pull that out and do a very exploratory look. But I would be interested to see just completely hypothesis-generating what this looks like for the patients with BRCA, and I hope that they will present that. I know they're busy at work. They have translational work. They have a lot pending with TRUST. It's an incredibly rich resource that I think is going to teach us a lot, and I am excited to see what they do next. Dr. Linda Duska: So, outside of TRUST, we are out of time. I just want to give you a moment if there were any other messages that you want to share with our listeners before we wrap up. Dr. Kathleen Moore: It's an exciting time to be in GYN oncology. For so long, it was just chemo, and then the PARP inhibitors nudged us along quite a bit. We did move more patients, I believe, to the cure fraction. When we ultimately see OS, I think we'll be able to say that definitively, and that is exciting. But, you know, that is the minority of our patients. And while HRD positive benefits tremendously from PARP, I am not as sure we've moved as many to the cure fraction. Time will tell. But 50% of our patients have these tumors that are less HRD. They have a worse prognosis. I think we can say that and recur more quickly. And so the advent of these antibody-drug conjugates, and we could name 20 of them in development in GYN right now, targeting tumor-associated antigens because we're not really driven by mutations other than BRCA. We do not have a lot of things to come after. We're not lung cancer. We are not breast cancer. But we do have a lot of proteins on the surface of our cancers, and we are finally able to leverage that with some very active regimens. And we're in the early phases, I would say, of really understanding how best to use those, how best to position them, and which one to select for whom in a setting where there is going to be obvious overlap of the targets. So we're going to be really working this problem. It is a good problem. A lot of drugs that work pretty well. How do you individualize for a patient, the patient in front of you with three different markers? How do you optimize it? Where do you put them to really prolong survival? And then we finally have cell surface. We saw at ASCO, CDK2 come into play here for the first time, we've got a cell cycle inhibitor. We've been working on WEE1 and ATR for a long time. CDK2s may hit. Response rates were respectable in a resistant population that was cyclin E overexpressing. We've been working on that biomarker for a long time with a toxicity profile that was surprisingly clean, which I like to see for our patients. So that is a different platform. I think we have got bispecifics on the rise. So there is a pipeline of things behind the ADCs, which is important because we need more than one thing, that makes me feel like in the future, I am probably not going to be using doxil ever for platinum-resistant disease. So, I am going to be excited to retire some of those things. We will say, "Remember when we used to use doxil for platinum-resistant disease?" Dr. Linda Duska: I will be retired by then, but thanks for that thought. Dr. Kathleen Moore: I will remind you. Dr. Linda Duska: You are right. It is such an incredibly exciting time to be taking care of ovarian cancer patients with all the opportunities.  And I want to thank you for sharing your valuable insights with us on this podcast today and for your great work to advance care for patients with GYN cancers. Dr. Kathleen Moore: Likewise. Thanks for having me. Dr. Linda Duska: And thank you to our listeners for your time today. You will find links to the TRUST study and other studies 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. More on today's speakers:   Dr. Linda Duska  @Lduska Dr. Kathleen Moore Follow ASCO on social media:     @ASCO on X (formerly Twitter) ASCO on Bluesky   ASCO on Facebook     ASCO on LinkedIn     Disclosures of Potential Conflicts of Interest:    Dr. Linda Duska:   Consulting or Advisory Role: Regeneron, Inovio Pharmaceuticals, Merck, Ellipses Pharma  Research Funding (Inst.): GlaxoSmithKline, Millenium, Bristol-Myers Squibb, Aeterna Zentaris, Novartis, Abbvie, Tesaro, Cerulean Pharma, Aduro Biotech, Advaxis, Ludwig Institute for Cancer Research, Leap Therapeutics  Patents, Royalties, Other Intellectual Property: UptToDate, Editor, British Journal of Ob/Gyn  Dr. Kathleen Moore: Leadership: GOG Partners, NRG Ovarian Committee Chair Honoraria: Astellas Medivation, Clearity Foundation, IDEOlogy Health, Medscape, Great Debates and Updates, OncLive/MJH Life Sciences, MD Outlook, Curio Science, Plexus, University of Florida, University of Arkansas for Medical Sciences, Congress Chanel, BIOPHARM, CEA/CCO, Physician Education Resource (PER), Research to Practice, Med Learning Group, Peerview, Peerview, PeerVoice, CME Outfitters, Virtual Incision Consulting/Advisory Role: Genentech/Roche, Immunogen, AstraZeneca, Merck, Eisai, Verastem/Pharmacyclics, AADi, Caris Life Sciences, Iovance Biotherapeutics, Janssen Oncology, Regeneron, zentalis, Daiichi Sankyo Europe GmbH, BioNTech SE, Immunocore, Seagen, Takeda Science Foundation, Zymeworks, Profound Bio, ADC Therapeutics, Third Arc, Loxo/Lilly, Bristol Myers Squibb Foundation, Tango Therapeutics, Abbvie, T Knife, F Hoffman La Roche, Tubulis GmbH, Clovis Oncology, Kivu, Genmab/Seagen, Kivu, Genmab/Seagen, Whitehawk, OnCusp Therapeutics, Natera, BeiGene, Karyopharm Therapeutics, Day One Biopharmaceuticals, Debiopharm Group, Foundation Medicine, Novocure Research Funding (Inst.): Mersana, GSK/Tesaro, Duality Biologics, Mersana, GSK/Tesaro, Duality Biologics, Merck, Regeneron, Verasatem, AstraZeneca, Immunogen, Daiichi Sankyo/Lilly, Immunocore, Torl Biotherapeutics, Allarity Therapeutics, IDEAYA Biosciences, Zymeworks, Schrodinger Other Relationship (Inst.): GOG Partners

Send us a textGood morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we delve into a host of transformative events reshaping the landscape, from strategic acquisitions and funding infusions to regulatory maneuvers and scientific breakthroughs.Johnson & Johnson has taken a decisive step in its oncology strategy with the $3 billion acquisition of Halda's cell death technology. This acquisition, focusing on the "hold and kill" bifunctional small molecule platform, is poised to enhance J&J's prostate cancer pipeline significantly. It underscores J&J's commitment to expanding its oncology portfolio through innovative platforms designed to improve therapeutic outcomes. The move highlights a broader industry trend toward personalized medicine and targeted cancer therapies, which are becoming pivotal in improving patient care.In another domain of cancer treatment, Nuvalent has unveiled promising Phase 1/2 data for its candidate neladalkib, which could position the company as a formidable competitor to Pfizer's established lung cancer drug, Lorbrena. The promising data might expedite regulatory discussions with the FDA, potentially leading to an accelerated approval process. This development illustrates the competitive landscape in oncology, where firms strive to introduce novel therapies with improved efficacy and safety profiles.The field of antibody-drug conjugates (ADCs) is also experiencing significant advancements. A San Diego-based biotech has secured $120 million in funding to develop a best-in-class ADC formula, with support from Merck & Co. This initiative aims to refine the precision and efficacy of ADCs by delivering cytotoxic agents directly to cancer cells while minimizing collateral damage to healthy tissues. Such innovations are crucial as they represent a new frontier in targeted cancer therapy.In terms of financial activities, Artios Pharma's successful $115 million Series D funding round is set to bolster its clinical efforts in exploring DNA damage response inhibitors for cancer treatment. These inhibitors target cancer cells' ability to repair DNA damage, holding potential for more effective therapies against resistant cancer types. Meanwhile, Sofinnova Partners' €650 million raise for biotech and medtech investments amid a volatile economic environment underscores continued investor confidence in life sciences despite market uncertainties.Bayer is making strategic moves in China by opening an incubator in Beijing. This facility will host local biopharma companies such as Suzhou Puhe Biopharma and Beijing Youngen Technology, fostering innovation and collaboration within China's burgeoning biotech landscape. Such initiatives reflect global efforts to leverage regional strengths and foster cross-border collaborations.On the operational side, Nxera Pharma is restructuring its workforce by laying off 15% of its staff as part of a strategic pivot towards profitability. This decision mirrors broader industry trends where companies refocus resources on core projects to streamline operations and enhance financial stability.A recent study has highlighted the impact of NIH grant cuts on clinical trials across the United States. Over 383 trials involving more than 74,000 patients have been disrupted due to funding terminations under the current administration. This situation raises concerns about the sustainability of clinical research funding and its implications for ongoing medical advancements.Jazz Pharmaceuticals has reported practice-changing Phase 3 results for its HER2-targeted drug Ziihera for gastroesophageal adenocarcinoma. These findings reaffirm Jazz's confidence in positioning Ziihera as a preferred first-line treatment option for HER2-positive cancers, poSupport the show

In this week's episode of Dividend Talk, we're back with a jam-packed Dividend Announcements & Earnings deep dive.We kick things off with PayPal initiating its first-ever dividend (welcome to the club, Monkey!), Hershey holding flat to stay off the aristocrat chopping block, and a wild stat on revenue-per-employee (OnlyFans crushes tech giants at $37.6M per head). Then it's over to dividend hikes from Iberdrola (+8.2%), Rockwell Automation, AbbVie, and ExxonMobil, before diving into earnings: Nestlé's volume rebound in China, Schneider Electric riding data-center tailwinds, Altria's cash-rich but growth-poor reality, UnitedHealth's margin squeeze, T. Rowe Price outflows, and Shell's $10B FCF buyback machine.In the Q&A, we tackle benchmarking vs. S&P 500, dollar-cost-averaging into falling knives, estate tax broker moves, covered-call ETFs, Finnish gems, Evolution's permanent pivot, and stock-specific takes on Novo Nordisk, APD, Qualcomm, and more.SEE YOU ON THE INSIDE!!Tickers discussed: PYPL, HSY, GOOGL, MSFT, EBAY, AMZN, IBM, MCD, IEP, IBDR.MC, MUM.DE, SIE.DE, APD, LIN, NOVO-B.CO, EVO.ST, QCOM, ARE, ADC, MO, BATS.L, PM, UNH, TROW, SHEL, XOM, TTE, ITW, ABT, ADP, SCHN.PA, ROC.AX, NOVN.SW, NESN.SW, MCD, APH, DHR, TXN, VFC, RELAS, VWS.CO, WSO, GRG.LJoin us:[Facebook] – Https://www.facebook.com/groups/dividendtalk[Twitter] – @DividendTalk_ , @European_DG[Discord] – https://discord.gg/nJyt9KWAB5[Premium Services] – https://dividendtalk.eu/download-your-free-samples/[Malmo Meetup] – https://t.co/STgV1nMWKj

On today's episode, Dr. Tabby Khan, senior director of analytics for Komodo Health, spoke about their newest data analysis measuring age and insurance disparities in antibody-drug conjugate, or ADC, treatment rates in patients with metastatic breast cancer. The analysis was in partnership with the Tigerlily Foundation, a national breast cancer advocacy organization, in celebration of the 40th anniversary of Breast Cancer Awareness Month.

Hear experts Matthieu Culié and Alessandro Agosti as they discuss how Olon stands out in a competitive landscape through its fully integrated end-to-end ADC manufacturing expertise, global operations, impurity control and strategic facilities.

This week's EYE ON NPI is as mysterious and powerful as the extra-dimensional being from Star Trek (https://en.wikipedia.org/wiki/Q_(Star_Trek)) - it's the new Arduino UNO Q (https://www.digikey.com/en/product-highlight/a/arduino/uno-q-microcontroller-board) microcontroller board, released as part of the Qualcomm/Arduino acquisition announcement (https://www.qualcomm.com/news/releases/2025/10/qualcomm-to-acquire-arduino-accelerating-developers--access-to-i). This Uno-shaped board is packed with both an STM32 microcontroller and a Qualcomm Dragonwing microprocessor so you get the best-of-both-worlds: 3.3V/5V logic compatibility with timers and ADCs, plus a full Debian install and AI support for running local vision models. We last checked in on Arduino we were reviewing their new announcements based on a partnership with Renesas: the Arduino Nano R4 SoC (https://www.youtube.com/watch?v=QLAI41ZfCfw) which is a miniaturized version of the UNO R4 (https://www.youtube.com/watch?v=uw0EU8urz5M). These boards feature an Arm microcontroller, with lots of fun on-board accessories like an LED grid, Qwiic connector, and WiFi/Bluetooth module. These boards represented a bump in capabilities over the classic UNO R3 (https://www.digikey.com/en/products/detail/arduino/A000073/3476357) but are still under-powered compared to the 'Portenta' line (https://www.digikey.com/en/products/detail/arduino/ABX00045/15294134). So, when we see the Arduino UNO Q (https://www.digikey.com/short/qc9d09fm) is a merging of three separate 'strands' of Arduino development history. One, it's shaped and has hardware-compatibility with the classic UNO which has been their mainstay for decades. Two, it has the powerful microcontroller type that the Pro line features. And three, it revives some of the Linux-based boards that Arduino had previously released like the Yun (https://www.digikey.com/en/products/detail/arduino/A000008/4486331), Tian (https://docs.arduino.cc/retired/boards/arduino-tian/) and Tre (https://docs.arduino.cc/retired/boards/arduino-tre). What sets the Q apart is that this time instead of being just a chip-supplier partnership, Arduino has been acquired as a subsidiary of Qualcomm (https://www.qualcomm.com/news/releases/2025/10/qualcomm-to-acquire-arduino-accelerating-developers--access-to-i) which means that there's going to be first-class engineering support for the onboard Dragonwing processor. Speaking of, let's take a look at the hardware included in the new Q! There's two chipsets on each board: the big processor is a Qualcomm Dragonwing™ QRB2210 (https://www.digikey.com/en/products/detail/qualcomm/QRB-2210-0-NSP752-TR-00-0/27904331) - 64-bit System-on-Chip with 4 × Arm Cortex-A53 running at 2.0 GHz and Adreno 702 GPU running at 845 MHz for 3D graphics. This chip runs mainline Debian OS with upstream support so you can configure a kernel and distribution image without needing patches. Arduino and Qualcomm distribute their own ready to go image too (https://docs.arduino.cc/tutorials/uno-q/update-image/). This chip has modern A/V support with both CSI camera and DSI MIPI display capability to match. Those high speed connects are available on the dual 60-pin bottom connects - while there isn't a sub-connect board right now, it's likely that Arduino will develop one soon. Meanwhile, you can use their documentation (https://docs.arduino.cc/hardware/uno-q/) such as STEP and Gerber files if you want to start adding a direct-plug integration into your hardware now. The second chipset is a STM32U585 Arm Cortex-M33 with 2 MB Flash, 786 kB SRAM and running at 160 MHz - it runs the Arduino Core via Zephyr OS and from the block diagram, looks like it communicates with the main core via UART and SPI. The STM is what handles GPIO, PWM, ADC, DAC, timers, etc since it is 3.3V logic and has some 5V logic-level compatibility. The main headers on the Arduino - and some of the bottom extra headers - expose the STM logic so you can connect standard sensors, OLEDs, relays etc. While there are some GPIO from the Dragonwing also available, they're 1.8V logic and are already allocated in the Linux Device tree. The Arduino UNO Q (https://www.digikey.com/short/qc9d09fm) is available for pre-order right now from DigiKey for a door-busting $44! We've already put in our order, and we'll do a project to check it out as soon as it arrives. After you get your pre-order in, check out some of the projects that have already been published to get a sense of the Q's capabilities like this MAME emulation arcade cabinet (https://projecthub.arduino.cc/jcarolinares/arduino-uno-q-arcade-cabinet-machine-39dd38) or face-recognition car (https://www.youtube.com/watch?v=EGDxAXpH_Ag). You can start dreaming of what you'll be able to do with a full computer + microcontroller board that fits where your old UNO R3 would fit, while you wait for the shipping notification.

What happens when the most complex molecules in biotech meet the organizational challenge of managing 300+ analytical scientists? The answer lies not just in the science, but in building systems that turn technical complexity into reliable delivery.In Part 2 of our deep dive with Amanda Hoertz, VP of Analytical and Formulation Sciences at KBI Biopharma, we shift focus from the molecular intricacies of ADCs to the operational mastery required to scale analytical development across multiple sites. Amanda reveals how her team achieves consistency across hundreds of scientists while maintaining the agility to pivot priorities in real time when critical programs need emergency support.This isn't just about managing people; it's about architecting systems that preserve institutional knowledge, accelerate method transfer, and deliver results when regulatory deadlines loom.What you'll discover:Seamless Project Handoffs Without Knowledge Loss: How KBI's stable team assignments eliminate the costly learning curves that plague most CDMO relationships, ensuring your molecule expertise stays with your program from development through commercial manufacturing.Organizational Scale Without Operational Chaos: The decision tree and layered reporting structure that allows 200+ analysts at a single site to function as a coordinated force, capable of rapid reprioritization and flood-level resource deployment when programs reach critical status.Digital Transformation That Actually Works: Beyond the automation buzzwords, Amanda walks through the practical realities of LIMS/ELN implementation, audit-compliant systems, and machine learning databases that transform raw data into defensible, actionable insights for complex biologics.Whether you're evaluating how analytical capabilities scale with program complexity, or seeking practical insights into leading technical teams through digital transformation, this episode delivers the operational intelligence that separates successful ADC programs from expensive failures.Connect with Amanda Hoertz:LinkedIn: www.linkedin.com/in/amanda-hoertz-3aba605KBI Biopharma: www.kbibiopharma.comKBI Portal: www.standalone.kbi.bioNext step:Book a 20-minute call to help you get started on any questions you may have about bioprocessing analytics: https://bruehlmann-consulting.com/call

Featuring an interview with Dr Laura Huppert, including the following topics: General overview of antibody-drug conjugate (ADC) structure and function; mechanisms of resistance to ADCs (0:00) Preventing and managing toxicities associated with trastuzumab deruxtecan (5:44) Selecting between sacituzumab govitecan and datopotamab deruxtecan for patients with metastatic breast cancer; common toxicities associated with these 2 agents (9:30) Potential use of ADCs in the first line for metastatic triple-negative breast cancer (mTNBC) (16:13) Case: A woman in her mid 40s with mTNBC receives sacituzumab govitecan and pembrolizumab in the first-line setting (18:25) CNS penetration and activity of ADCs in the treatment of breast cancer (22:27) Use of trastuzumab deruxtecan for HER2-ultralow mTNBC; promising trials of ADCs and other therapies for mTNBC (24:24) Treatment options in the second line and beyond for patients with HR-positive mBC that is HER2-negative, HER2 low or HER2 ultralow (27:05) Case: A woman in her late 50s with HR-positive, HER2-low mBC experiences disease progression on multiple lines of therapy (30:51) Ongoing evaluation of ADCs in the localized disease setting (35:42) Novel therapeutic approaches for leptomeningeal disease in patients with breast cancer (38:38) CME information and select publications

We break down Pobelter's thoughts on the ADC role and discuss how OP support is.Join an academy for coaching and guides: https://wtl.lol/thinkchallJoin our free community with courses: https://wtl.lol/skool

Send us a textPeaches and Aaron are back swinging at the nonsense. From Special Warfare's assessment model to Air Force Academy cadets racking up predatory loans, this episode rips into leadership fails, lazy commanders who hand out paperwork like candy, and the lost art of spot corrections. We go from stories of LOCs, LORs, and mustache games with Rangers, to watching Army football drop a quarter million dollars just to get smoked by Tarleton State. Oh, and Peaches gets dragged through camp in just a towel because Rangers can't handle beards. Add in college football meltdowns, fantasy league punishments, and some blistering hot takes on what “leadership” actually means—you've got a mix of cringe, comedy, and brutal honesty that only Ones Ready delivers.⏱️ Timestamps: 00:00 – Intro & Special Warfare assessment truth bombs 01:15 – Operator Training Summit Nashville & gear talk 03:10 – Booties in the pool: stop training slick 04:45 – AOCs gone wild with paperwork 07:00 – Progressive discipline vs lazy leadership 10:20 – Why real mentorship beats LOR inflation 12:50 – Spot corrections, life problems, and actually helping airmen 17:30 – Setting boundaries and predictable leadership 23:10 – Smoke sessions, “don't tell dad,” and better discipline tools 25:30 – Peaches' LOC story that turned his career around 29:30 – Pushing boundaries vs working the system 33:00 – Rangers, beards, and the towel walk of shame 36:00 – Mustache game rules and how to win (or lose) 40:00 – Always rebuttal your paperwork (and call ADC, not your buddy) 41:30 – The insane $416K Academy disenrollment bill 47:00 – The infamous Manitou Incline & OTS candidate pain fest 54:00 – Army football pays $250K to lose to Tarleton State 56:10 – Air Force uniforms: actually fire this year 01:02:00 – Bama gets stomped, SEC fan tears taste delicious 01:03:50 – Peaches unveils the Fantasy Loser Belt 01:04:55 – Wrap up & call-to-actions