Podcasts about adcs

“We were able to show multiple datasets that actually deliver against this vision that antibody drug conjugates can improve on and therefore displace chemotherapy” says Dr. Susan Galbraith, AstraZeneca’s EVP of oncology R&D. Galbraith joins Bloomberg Intelligence analyst Sam Fazeli to break down key findings from ESMO — from early-line HER2 breast cancer data to progress in bladder and lung cancer. She details the promise of Enhertu and Datopotamab, AstraZeneca’s antibody-drug conjugates (ADCs), and how their work may transform cancer treatment in curative settings.See omnystudio.com/listener for privacy information.

As part of the European Society for Medical Oncology (ESMO) Congress 2025, CancerNetwork® spoke with a variety of experts about key takeaways from different late-breaking abstracts, oral presentations, and other sessions focused on potential advancements across cancer care. Presenting investigators highlighted updated results from clinical trials evaluating novel therapeutic strategies across different cancer populations, including breast cancer and lung cancer.  Phase 3 VIKTORIA-1 Trial Sara A. Hurvitz, MD, FACP, the Smith Family Endowed Chair in Women's Health and senior vice president and director of the Clinical Research Division at the Fred Hutch Cancer Center, and tumor chair in breast oncology for the ONCOLOGY® editorial advisory board, first discussed findings from the phase 3 VIKTORIA-1 trial (NCT05501886). Her presentation highlighted how VIKTORIA-1 was “the first study to demonstrate a statistically significant and clinically meaningful improvement in progression-free survival [PFS] with PAM inhibition” for patients with PIK3CA wild-type advanced breast cancer. Data from the trial showed that gedatolisib plus fulvestrant (Faslodex) and palbociclib (Ibrance) produced a median PFS of 9.3 months (95% CI, 7.2-16.6) vs 2.0 months (95% CI, 1.8-2.3) with fulvestrant alone (HR, 0.24; 95% CI, 0.17-0.35; P

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 some of the most significant shifts occurring in these industries, touching on strategic restructuring, regulatory milestones, and groundbreaking scientific advancements that are shaping the future of drug development and patient care.Let's begin with a major corporate shakeup at Novo Nordisk. The company has announced a significant leadership transition as former CEO Lars Rebien Sorensen is set to become the new chairman of the board. This change follows the resignation of seven board members and indicates a strategic realignment within the company. The Novo Foundation's involvement suggests a deeper strategic shift, potentially aligning with new organizational objectives and innovations. Such moves are pivotal as they could influence Novo Nordisk's market position and future product development.Turning to scientific breakthroughs, Merck's collaboration with Kelun-Biotech has yielded promising results with their Trop2 antibody-drug conjugate, sacituzumab-tmt. This ADC has shown success in two Phase 3 trials targeting lung and breast cancers, underscoring the therapeutic potential of ADCs in oncology. By selectively targeting cancer cells while minimizing damage to healthy tissues, ADCs could significantly improve patient outcomes and represent a powerful modality in cancer treatment.In regulatory affairs, Kenvue is challenging the FDA over proposed safety warnings for Tylenol linked to autism during pregnancy. This dispute highlights the ongoing debates surrounding drug safety and regulatory oversight. The outcome could have significant implications for labeling practices and consumer trust in over-the-counter medications. Meanwhile, Summit Therapeutics plans to file for FDA approval of ivonescimab, highlighting ongoing innovation in drug development pipelines. Similarly, Novo Nordisk's semaglutide pill Rybelsus has received FDA expansion approval to reduce major adverse cardiovascular events. This sets a new benchmark for oral metabolism drugs by demonstrating their potential beyond glycemic control to positively impact cardiovascular health.As we explore industry trends, there's growing interest in direct-to-consumer drug sales. While this approach offers patients access to medications at reduced costs, it raises concerns about privacy and the quality of care without traditional healthcare provider interactions. Additionally, a notable decline in pharmaceutical TV ad spending by 19% in Q3 suggests a shift towards digital engagement strategies. Amidst these narratives, the Biotechnology Innovation Organization (BIO) has launched an awareness campaign to combat misinformation about vaccines. This effort underscores the importance of immunizations in public health and aims to reinforce trust amid rising disinformation.In another scientific advancement, GSK has released positive Phase 3 data for Spero Therapeutics' oral antibiotic candidate. The oral formulation's efficacy comparable to intravenous options could lead to broader use and improved patient adherence—critical advancements as antibiotic resistance remains a global health challenge.Investment activities reflect strategic shifts within the industry as well. Curewell Capital's investment in Wilmington PharmaTech aims to enhance U.S. active pharmaceutical ingredient production capacity—a crucial step given recent global supply chain disruptions. Similarly, India's ACG is making a $200 million investment in its first U.S. empty-capsule production facility, highlighting the strategic importance of manufacturing capabilities on American soil.Galapagos' decision to wind down its cell therapy unit marks a significant strategic pivot from its previous focus on this modality. This shift reflects broader industry trends where companies reassess priorSupport the show

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Recent developments in these industries underscore a period of significant scientific progress, regulatory maneuvers, and strategic investments.One notable event was AstraZeneca and Daiichi Sankyo's success at the European Society for Medical Oncology Congress 2025. Their antibody-drug conjugate, Datroway, demonstrated superior efficacy compared to Gilead's Trodelvy in the first global head-to-head trial involving Trop2-targeted therapies. This reflects the increasing focus on antibody-drug conjugates as precision medicine tools that offer targeted treatment options with potentially improved outcomes over traditional chemotherapy.In a move highlighting the ongoing trend of bolstering domestic production capacities, Merck is making a substantial $3 billion investment in a small molecule drug plant in Virginia. This is part of a broader $70 billion commitment to expand manufacturing and R&D capabilities in the U.S. Such strategic investments are crucial for maintaining competitive advantage and ensuring drug availability while meeting rising demands and streamlining supply chains.Turning to regulatory updates, the FDA has approved Amgen and AstraZeneca's Tezspire for chronic rhinosinusitis with nasal polyps. This marks Tezspire's second indication, following its initial approval for severe asthma in 2021. The expanded approval showcases the drug's versatility and represents a strategic push to enhance its market presence against competitors like Dupixent.In oncology, Merck's Keytruda and Astellas/Pfizer's Padcev have made headlines with compelling results in muscle-invasive bladder cancer. The combination therapy reduced the risk of death by 50%, reinforcing Keytruda's position as a cornerstone immunotherapy across multiple cancer types. This result not only augments treatment options but also signifies the potential for combination regimens to enhance patient outcomes.Roche has expanded the indication of its aging oncology drug Gazyva to treat lupus nephritis, demonstrating strategic repurposing efforts to extend the lifecycle of existing therapies. While this expansion into autoimmune diseases comes late in Gazyva's lifecycle, it highlights a growing trend of capitalizing on established drugs for new therapeutic areas.AstraZeneca and Daiichi Sankyo's Enhertu showed robust efficacy in early breast cancer treatment, potentially reshaping therapeutic strategies by offering new hope for early intervention. Similarly, Novartis' Pluvicto demonstrated promise in slowing hormone-sensitive prostate cancer progression, underscoring the potential of radioligand therapies in oncology.However, not all developments have been positive. AstraZeneca faced setbacks when its Imfinzi and Lynparza combination failed to meet survival goals in ovarian cancer, underscoring the challenges inherent in oncology drug development and the stringent benchmarks set by regulatory authorities like the FDA.The industry is also witnessing significant advancements in next-generation ADCs, as evidenced by Tubulis' 59% response rate in early clinical trials, which has attracted substantial investor interest. Additionally, Grail's Galleri cancer blood test is progressing towards FDA review with enhanced performance data, potentially revolutionizing cancer screening and early detection practices.These scientific and regulatory milestones are complemented by strategic investments in bioconjugation technologies. Cohance Life Sciences' $10 million investment in NJ Bio to enhance GMP bioconjugation capabilities exemplifies this trend. Such investments are crucial for advancing ADC development, which remains a focal point for innovative cancer therapies.Overall, these developments reflect a dynamic phase for the pharmaceutical and biotech sectors characterized by signSupport the show

Julia Radosa und Harald Müller-Huesmann diskutieren aktuelle ESMO-Daten zum Mammakarzinom: CDK4/6-Inhibitoren in der Adjuvanz, Antikörper-Wirkstoff-Konjugate beim triple-negativen Brustkrebs und positive Signale für Immuntherapie-Kombinationen im Ovarialkarzinom.

En esta cápsula de ESMO 2025 EXPRESS, el Dr. Gonzalo Giornelli, oncólogo clínico y jefe del Departamento de Gineco-Oncología del Instituto Alexander Fleming en Buenos Aires, Argentina, nos comenta brevemente los avances más relevantes en tumores ginecológicos presentados durante el congreso ESMO 2025.El gran protagonista de este ESMO fue, sin duda, el cáncer de ovario, particularmente en el contexto platino-resistente, una población de mal pronóstico y con necesidad de nuevas alternativas terapéuticas. En este escenario, tres estudios marcaron un antes y un después al demostrar beneficios en sobrevida global.El primero, KEYNOTE-B21, evaluó pembrolizumab más paclitaxel semanal ± bevacizumab frente al estándar de paclitaxel ± bevacizumab. Este estudio mostró una reducción del riesgo de progresión del 28 % y una disminución del riesgo de muerte del 24 %, con un incremento notable en la tasa de respuesta (50 % vs 40 %). El Dr. Giornelli subraya que este régimen se consolida como una nueva opción sin necesidad de selección por PD-L1, aunque advierte que la población estudiada tuvo menor exposición a inhibidores PARP que la práctica actual. Estos resultados llevaron a la aprobación acelerada por la FDA como nuevo estándar en pacientes con cáncer de ovario platino-resistenteEl segundo estudio mencionado fue MIRASOL, con el anticuerpo conjugado mirvetuximab soravtansine, que demostró una reducción del 37 % en el riesgo de progresión y del 32 % en el riesgo de muerte, junto con tasas de respuesta del 42 %. Sin embargo, requiere la sobreexpresión del receptor de folato alfa, presente en alrededor del 36 % de las pacientesEn otras patologías ginecológicas, el Dr. Giornelli resaltó un estudio chino en cáncer de cérvix, que evaluó camrelizumab + famitinib (una combinación similar a pembrolizumab + lenvatinib) frente a quimioterapia sola, mostrando beneficios en PFS, OS y tasa de respuesta, aunque con toxicidades relevantes.Finalmente, en cáncer de endometrio, destacó que se avanza hacia una mayor precisión molecular para definir tratamientos en pacientes sin alteraciones MSI-H o POLE. Además, subrayó la importancia de identificar el subgrupo HER2 positivo, dada la alta tasa de respuesta (> 76 %) observada con trastuzumab deruxtecán en este grupo.El especialista concluye que ESMO 2025 marcó un punto de inflexión en oncología ginecológica, con tres nuevas alternativas terapéuticas para cáncer de ovario platino-resistente y múltiples desarrollos en cáncer de cérvix y endometrio, reafirmando la relevancia de la inmunoterapia y los ADCs como ejes del futuro tratamiento en estos tumores

Carolin Groß-Ophoff-Müller und Harald Müller-Huesmann ordnen ESMO-Highlights der Thoraxonkologie ein: Follow-up-Analysen in NSCLC (treiberalteriert & nicht-treiberalteriert), frühe-Phasen-Entwicklungen beim SCLC (DLL3, ADCs, multispezifische Antikörper) und digitale Praxis-Tools.

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.

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we're delving into a series of fascinating updates that underscore a period of significant scientific advancement, strategic partnerships, and regulatory developments in the industry.Starting with Dianthus Therapeutics, which has taken a bold step by investing up to $1 billion to license a bifunctional fusion protein from Nanjing Leads Biolabs. This protein targets autoimmune disorders, a field of immense interest due to the unmet medical needs and potential for breakthrough treatments. Such substantial financial commitments highlight the ongoing trend in the biotech sector towards innovative therapies for autoimmune diseases. In parallel, Sanofi has secured a $500 million agreement with Evoq Therapeutics, continuing its strategic focus on next-generation autoimmune technologies. This partnership aligns with Sanofi's broader strategy to leverage cutting-edge science in managing autoimmune conditions more effectively. Sanofi's engagement with Evoq Therapeutics stands out as a significant step forward in conquering autoimmune diseases through nanodisc technology designed to facilitate the development of curative treatments for disorders like celiac disease and type 1 diabetes. This collaboration reflects a growing trend among pharmaceutical giants investing in advanced biotechnologies that promise transformative impacts on disease management and patient care.Meanwhile, AstraZeneca's renewed collaboration with Immunai, valued at $85 million, seeks to enhance therapies for inflammatory bowel disease through artificial intelligence. This collaboration is part of a wider industry movement towards utilizing AI in drug discovery and development, particularly for complex diseases like IBD. AI's ability to process large datasets and identify potential therapeutic targets faster and more accurately is revolutionizing how companies approach drug development.In clinical trial news, Praxis Precision Medicines has reported positive Phase 3 results for ulixacaltamide in treating essential tremor. This outcome reverses prior concerns from interim analyses and illustrates the persistent innovation in neurological disorder treatments. Similarly, AiCuris has announced successful results from its Phase 3 trial of pritelivir for refractory herpes simplex virus infections in immunocompromised patients. This success paves the way for an FDA filing, demonstrating ongoing progress in antiviral therapy development.Novartis is also making strides with favorable outcomes from its Phase 3 trial of fabhalta for IgA nephropathy. As a complement factor B inhibitor, fabhalta has shown efficacy in slowing kidney function decline, which may lead to a new standard of care for this chronic kidney disease. Novartis plans to file these findings with regulatory bodies soon, highlighting its strategic focus on diversifying into rare kidney diseases.Turning to industry trends, there is significant investment activity in antibody-drug conjugates (ADCs). French biotech company ADCytherix has raised $122 million to advance these targeted therapies into clinical trials. ADCs are gaining traction due to their precision in targeting cancer cells while minimizing damage to healthy tissues. Such advancements signal a potential shift in cancer treatment paradigms toward more targeted and less toxic therapies. Similarly, Tubulis raised an impressive Series C funding round to advance work on ADCs targeting ovarian and lung cancers, underscoring the growing interest in the potential of ADCs engineered to deliver cytotoxic drugs specifically to cancer cells.In another intriguing development, research has shown that a common diabetes drug can alleviate brain inflammation in female mice with multiple sclerosis. This finding exemplifies the growing interest in drug repurposSupport the show

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

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 major advancements and strategic moves that are shaping the future of healthcare.A significant development comes from AstraZeneca, which has committed a substantial $445 million investment to bolster production at its Texas facility for Lokelma, a treatment designed for hyperkalemia. Hyperkalemia is a condition characterized by elevated potassium levels in the blood, posing serious health risks if not managed properly. This investment highlights AstraZeneca's dedication to meeting growing global demand and enhancing patient access to this vital treatment. By strengthening its production capabilities, the company aims to ensure a more reliable supply chain, potentially leading to better outcomes for patients worldwide.Meanwhile, Pfizer is making noteworthy progress in the realm of oncology. Recent clinical trial results have positioned Tukysa, developed in collaboration with Seagen, as a promising candidate for first-line maintenance therapy in HER2-positive breast cancer. The potential shift from second-line to first-line treatment could significantly alter patient care by offering an effective therapeutic option earlier in the disease management process. This advancement underscores Pfizer's commitment to improving long-term outcomes for patients battling this aggressive form of cancer.In legal news, a dispute between Novo Nordisk and KBP Pharmaceuticals has underscored the critical importance of transparency and thorough due diligence in biotech transactions. The controversy involves "anomalous" phase 2 clinical trial results that Novo Nordisk claims were not adequately disclosed by KBP. Such cases highlight the necessity for rigorous investigation during mergers and acquisitions to prevent costly legal battles and ensure informed decision-making in drug development partnerships.On the HIV prevention front, GSK has released promising data for its long-acting pre-exposure prophylaxis drug, Apretude. This new data suggests Apretude holds higher acceptability compared to Gilead's competing product, Yetztugo. Improved patient adherence could shift market dynamics towards GSK's favor, potentially enhancing public health outcomes by preventing HIV infections more effectively.Manufacturing innovations are also taking center stage as Particle Dynamics collaborates with a former EuroAPI plant to introduce Codis, a new contract development and manufacturing organization (CDMO). Codis will offer comprehensive services such as spray drying and particle engineering, aligning with growing demand for specialized pharmaceutical manufacturing capabilities.Turning our attention to diabetes treatment advancements, Eli Lilly's oral GLP-1 candidate Orforglipron has demonstrated superiority over both placebo and AstraZeneca's Farxiga in phase 3 trials for type 2 diabetes. This success strengthens Eli Lilly's portfolio in a highly competitive market and could lead to regulatory approval next year. An oral treatment option could significantly enhance patient compliance compared to existing injectable GLP-1 therapies.In oncology, Boehringer Ingelheim has entered into a deal worth up to $991 million with AimedBio, focusing on antibody-drug conjugates (ADCs) that target proteins involved in tumor growth and resistance. This collaboration highlights the increasing interest in ADCs as targeted cancer therapies capable of minimizing systemic toxicity while delivering potent cytotoxic agents directly to cancer cells.The industry continues to be shaped by funding rounds and strategic acquisitions. Novo Nordisk's acquisition of Omeros' MASP-3 inhibitor Zaltenibart for $2.1 billion marks a significant move in rare disease therapeutics. Despite Omeros pausing development, Novo Nordisk sees potential in treating paroxysSupport the show

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

What if the key to unlocking ADC manufacturing success lies in abandoning the platform mindset entirely?Antibody-drug conjugates represent biotech's most promising weapon against cancer: precision-targeted therapeutics that deliver cytotoxic payloads directly to tumor cells while sparing healthy tissue. But beneath the clinical promise lies a manufacturing reality that's rewriting the rules of bioprocess development, demanding analytical strategies that most CDMOs simply aren't equipped to handle.In this deep-dive episode, David Brühlmann sits down with Amanda Hoertz, Vice President of Analytical and Formulation Sciences at KBI Biopharma, where she oversees 300+ scientists across the mammalian network. Amanda's team has cracked the code on some of the industry's most challenging ADC programs, achieving a remarkable 93% batch success rate by rejecting cookie-cutter approaches in favor of molecule-specific development strategies.What you'll discover:The Platform Fallacy: Why treating ADCs like standard monoclonals is costing companies millions and months of development time, and the bespoke analytical framework that's changing everything.Cytotoxic Payload Management: From free drug analysis to employee safety protocols, Amanda reveals the hidden complexities of handling molecules designed to kill cells, including the specialized facilities and analytical methods required for GMP manufacturing.Charge Heterogeneity Mastery: The analytical method that "keeps Amanda up at night," and the development strategies her team uses to achieve robust separation and qualification across multiple sites and analysts.This episode delivers the technical depth and strategic insights that bioprocess engineers need to navigate ADC development successfully. Whether you're evaluating CDMO partnerships, optimizing analytical methods, or scaling complex conjugates, Amanda's proven strategies will transform your approach to these game-changing therapeutics.Ready to master the analytical complexities that make or break ADC programs?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

Dr Laura Huppert from the University of California, San Francisco, discusses approved and investigational antibody-drug conjugates in the current and future management of HR-positive and triple-negative metastatic breast cancer. CME information and select publications here.

Dr. Hope Rugo and Dr. Giuseppe Curigliano discuss recent developments in the field of bispecific antibodies for hematologic and solid tumors, including strategies to optimize the design and delivery of the immunotherapy. 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. I am also the editor-in-chief of the Educational Book. Bispecific antibodies represent an innovative and advanced therapeutic platform in hematologic and solid tumors. And today, I am delighted to be joined by Dr. Giuseppe Curigliano to discuss the current landscape of bispecific antibodies and their potential to reshape the future of precision oncology. Dr. Curigliano was the last author of an ASCO Educational Book piece for 2025 titled, "Bispecific Antibodies in Hematologic and Solid Tumors: Current Landscape and Therapeutic Advances." Dr. Curigliano is a breast medical oncologist and the director of the Early Drug Development Division and chair of the Experimental Therapeutics Program at the European Institute of Oncology in Milan. He is also a full professor of medical oncology at the University of Milan. You can find our disclosures in the transcript of this episode. Dr. Curigliano, Giuseppe, welcome and thanks for being here. Dr. Giuseppe Curigliano: Thanks a lot for the invitation. Dr. Hope Rugo: Giuseppe, I would like to first ask you to provide some context for our listeners on how these novel therapeutics work. And then perhaps you could tell us about recent developments in the field of bispecific antibodies for oncology. We are at a time when antibody-drug conjugates (ADCs) are all the rage and, trying to improve on the targeting of specific antigens, proteins, receptors in the field of oncology is certainly a hot and emerging topic. Dr. Giuseppe Curigliano: So, thanks a lot. I believe really it was very challenging to try to summarize all the bispecific antibodies that are under development in multiple solid tumors. So, the first thing that I would like to highlight is the context and the mechanism of action of bispecific antibodies. Bispecific antibodies represent a groundbreaking advancement in cancer immunotherapy, because these engineered molecules have the unique ability to target and simultaneously bind to two distinct antigens. That is why we call them bispecific. So typically, one antigen is expressed on the tumor cell and the other one is expressed on the immune effectors, like T-cell or natural killer cells. So this dual targeting mechanism offers several key advantages over conventional monoclonal antibodies because you can target at the same time the tumor antigen, downregulating the pathway of proliferation, and you can activate the immune system. So the primary mechanism through which bispecific antibodies exert their therapeutic effects are: First, T-cell redirecting. I mean, many bispecific antibodies are designed to engage tumor-associated antigens like epidermal growth factor receptor, HER2, on the cancer cell and a costimulatory molecule on the surface of T-cell. A typical target antigen on T-cell is CD3. So what does it mean? That you activate the immune system, immune cells will reach the tumor bed, and you have a dual effect. One is downregulating cell proliferation, the other one is activation of the immune system. This is really important in hematological malignancies, where we have a lot of bispecifics already approved, like acute lymphoblastic leukemia or non-Hodgkin lymphoma.  The second, in fact, is the engagement of the tumor microenvironment. So, if you engage immune effector cells like NK cells or macrophages, usually the bispecific antibodies can exploit the immune system's ability to recognize and kill the immune cells, even if there is a lack of optimal antigen presentation.  And finally, the last mechanism of action, this may have a role in the future, maybe in the early cancer setting, is overcoming immune evasion. So bispecific antibodies can overcome some of the immune evasion mechanisms that we see in cancer. For example, bispecific antibodies can target immune checkpoint receptors, like PD-L1 and CTLA-4. Actually, there is a bispecific under development in breast cancer that has a dual targeting on vascular endothelial growth factor receptor and on PD-L1. So you have a dual effect at the same time. So, what is really important, as a comment, is we need to focus first on the optimal format of the bispecific, the optimal half-life, the stability, because of course even if they are very efficient in inducing a response, they may give also a lot of toxicities. So in clinical trials already, we have several bispecifics approved. In solid tumors, very few, specifically amivantamab for non-small cell lung cancer, but we have a pipeline of almost 40 to 50 bispecifics under development in multiple solid tumors, and some of them are in the context of prospective randomized trials. Dr. Hope Rugo: So this is really a fascinating area and it's really exciting to see the expansion of the different targets for bispecific antibodies. One area that has intrigued me also is that some of the bispecifics actually will target different parts of the same receptor or the same protein, but presumably those will be used as a different strategy. It's interesting because we have seen that, for example, in targeting HER2. Dr. Giuseppe Curigliano: Oh, yes, of course. You may consider some bispecifics like margetuximab, I suppose, in which you can target specifically two different epitopes of the same antigen. This is really an example of how a bispecific can potentially be more active and downregulating, let us say, a pathway, by targeting two different domains of a specific target antigen. This is an important point.  Of course, not all the bispecifics work this way, because some of the target antigen may dimerize, and so you have a family of target antigen; an example is epidermal growth factor receptor, in which you have HER1, HER2, HER3, and HER4. So some of them can inhibit the dimerization between one target antigen and the other one, in order to exert a more antiproliferative effect. But to be honest, the new generation of them are more targeting two different antigens, one on the tumor and one on the microenvironment, because according to the clinical data, this is a more efficient way to reduce proliferation and to activate the immune system. Dr. Hope Rugo: Really interesting, and I think it brings us to the next topic, which is really where bispecific antibodies have already shown success, and that is in hematologic malignancies where we have seen very interesting efficacy and these are being used in the clinic already. But the expansion of bispecific antibodies into solid tumors faces some key challenges. It's interesting because the challenges come in different shapes and forms. Tell us about some of those challenges and strategies to optimize bispecific antibody design, delivery, patient selection, and how we are going to use these agents in the right kind of clinical trials. Dr. Giuseppe Curigliano: This is really an excellent question because despite bispecific antibodies having shown a remarkable efficacy in hematological malignancies, their application in solid tumors may have some challenges. The first one is tumor heterogeneity. In hematological malignancy, you have a clear oncogene addiction. Let us say that 90% of the cells may express the same antigen. In solid tumors, it is not the same. Tumor heterogeneity is a typical characteristic of solid tumors, and you have high heterogeneity at the genetic, molecular, and phenotypic levels. So tumor cells can differ significantly from one another, even if within the same tumor. And this heterogeneity sometimes makes it difficult to identify a single target antigen that is universally expressed in an hematological malignancy. So furthermore, sometimes the antigen expressed on a tumor cell can be also present on the normal tissue. And so you may have a cross-targeting. So let's say, if you have a bispecific against epidermal growth factor receptor, this will target the tumor but will target also the skin with a lot of toxicity. The second challenge is the tumor microenvironment. The solid tumor microenvironment is really complex and often immunosuppressive. It is characterized by the presence of immunosuppressor cells like the T regulators, myeloid derived suppressor cells, and of course the extracellular matrix. All these factors hinder immune cell infiltration and also may reduce dramatically the effectiveness of bispecific antibodies. And as you know, there is also an hypoxic condition in the tumor. The other challenge is related to the poor tumor penetration. As you know also with antibody-drug conjugate, only 1 to 3% of the drug will arrive in the tumor bed. Unlike hematological malignancies where tumor cells are dispersed in the blood and easily accessible, the solid tumors have a lot of barriers, and so it means that tumor penetration can be very low. Finally, the vascularity also of the tumor can be different across solid tumors. That is why some bispecifics have a vascular endothelial growth factor receptor or vascular endothelial growth factor as a target. Of course, what do we have to do to overcome these challenges? First, we have to select the optimal antigen. So knowing very well the biology of cancer and the tumor-associated antigens can really select a subgroup of epitopes that are specifically overexpressed in cancer cells. And so we need to design bispecifics according to the tumor type. Second, optimize the antibody format. So there are numerous bispecific antibody formats. We can consider the dual variable domain immunoglobulin, we specified this in our paper. The single chain variable fragments, so FC variable fragments, and the diabodies that can enhance both binding affinity and stability. And finally, the last point, combination therapies. Because bispecific antibodies targeting immune checkpoint, we have many targeting PD-1 or PD-L1 or CTLA-4, combined eventually with other immune checkpoint inhibitors. And so you may have more immunostimulating effect. Dr. Hope Rugo: This is a fascinating field and it is certainly going to go far in the treatment of solid tumors. You know, I think there is some competition with what we have now for antibody-drug conjugates. Do you see that bispecifics will eventually become bispecific ADCs? Are we going to combine these bispecific antibodies with ADCs, with chemotherapy? What is the best combination strategy do you think looking forward? Dr. Giuseppe Curigliano: So, yes, we have a bispecific ADC. We have actually some bispecifics that are conjugated with a payload of chemotherapy. Some others are conjugated with immunoactivation agents like IL-2. One of the most effective strategies for enhancing bispecific activity is the combination therapy. So which type of combination can we do? First, bispecific antibodies plus checkpoint inhibitors. If you combine a bispecific with an immune checkpoint, like anti-PD-1, anti-PD-L1, or anti-CTLA-4, you have more activity because you have activation of T-cells, reduction of immunosuppressive effect, and of course, the capability of this bispecific to potentiate the activity of the immune checkpoint inhibitor. So, in my opinion, in a non-small cell lung cancer with an expression of PD-L1 more than 50%, if you give pembrolizumab plus a bispecific targeting PD-L1, you can really improve both response rate and median progression-free survival.  Another combination is chemotherapy plus bispecific antibodies. Combining chemotherapy with bispecific can enhance the cytotoxic effect because chemotherapy induces immunogenic cell death, and then you boost with a bispecific in order to activate the immune system. Bispecific and CAR T-cells, until now, we believe that these are in competition, but this is not correct. Because CAR T-cells are designed to deliver an activation of the immune system with the same lymphocytes engineered of the patients, with a long-term effect. So I really do not believe that bispecifics are in competition with CAR T-cells because when you have a complete remission induced by CAR T-cell, the effect of this complete remission can last for years. The activity of a bispecific is a little bit different. So there are some studies actually combining CAR T-cells with bispecifics. For example, bispecific antibodies can direct CAR T-cells in the tumor microenvironment, improving their specificity and enhancing their therapeutic effect.  And finally, monoclonal antibody plus bispecific is another next generation activity. Because if you use bispecific antibodies in combination with existing monoclonal antibodies like anti-HER2, you can potentially increase the immune response and enhance tumor cell targeting. In hematological malignancies, this has been already demonstrated and this approach has been particularly effective. Dr. Hope Rugo: That's just so fascinating, the whole idea that we have these monoclonal antibodies and now we are going to add them to bispecifics that we could maybe attach on different toxins to try and improve this, or even give them with different approaches. I suppose giving an ADC with a bispecific would sort of be similar to that idea of giving a monoclonal antibody with the bispecific. So it is certainly intriguing. We also will need to understand the toxicity and cost overall and how we are going to use these, the duration of treatment, the assessment of biomarkers. There are just so many different aspects that still need to be explored.  And then with that idea, can you look ahead five or ten years from now, and tell us how you think bispecific antibodies will shape our next generation cancer therapies, how they will be incorporated into precision oncology, and the new combinations and approaches as we move forward that will help us tailor treatment for patients both with solid tumors and hematologic malignancies? Are we going to be giving these in early-stage disease in solid tumors? So far, the studies are primarily focusing on the metastatic setting, but obviously one of the goals when we have successful treatments is to move them into the early stage setting as quickly as possible. Dr. Giuseppe Curigliano: Let us try to look ahead five years rather than ten years, to be more realistic. So, personally I believe some bispecifics can potentially replace current approaches in specifically T-cell selected population. As we gather more data from ongoing clinical trials and we adopt a deeper understanding of the tumor immuno microenvironment, of course we may have potentially new achievement. A few days ago, we heard that bispecifics in triple negative breast cancer targeting VEGF and PD-L1 demonstrated an improvement in median progression-free survival.  So, how to improve and to impact on clinical practice both in the metastatic and in the early breast cancer setting or solid tumor setting? First, personalized antigen selection. So we need to have the ability to tailor bispecific antibody therapy to the unique tumor profile of individual patients. So the more we understand the biology of cancers, the more we will be able to better target. Second, bispecific antibodies should be combined. I can see in the future a potential trial in which you combine a bispecific anti-PD-L1 and VEGF with immune checkpoint inhibitor selected also to the level of expression of PD-L1, because integration of antibody bispecific with a range of immunotherapies, and this cannot be only immune checkpoint inhibitors, but can be CAR T-cells, oncolytic viruses, also targeted therapy, will likely be a dominant theme in the coming years. This combination will be based on the specific molecular and immuno feature of the cancer of the patient.  Then we need an enhanced delivery system. This is really important because you know now we have a next generation antibody. An example are the bicyclic. So you use FC fragment that are very short, with a low molecular weight, and this short fragment can be bispecific, so can target at the same time a target antigen and improving the immune system. And so the development of this novel delivery system, including also nanoparticles or engineered viral vectors, can enhance the penetration in the tumor bed and the bioavailability of bispecific antibodies. Importantly, we need to reduce toxicity. Until now, bispecifics are very toxic. So the more we are efficient in delivering in the tumor bed, the more we will reduce the risk of toxicity. So it will be mandatory to reduce off-target effects and to minimize toxicity.  And finally, the expansion in new indication. So I really believe you raised an excellent point. We need to design studies in the neoadjuvant setting in order to better understand with multiple biopsies which is the effect on the tumor microenvironment and the tumor itself, and to generate hypotheses for potential trials or in the neoadjuvant setting or in those patients with residual disease.  So, in my opinion, as we refine design, optimize patient selection, and explore new combination, in the future we will have more opportunity to integrate bispecifics in the standard of care. Dr. Hope Rugo: I think it is particularly helpful to hear what we are going to be looking for as we move forward to try and improve efficacy and reduce toxicity. And the ability to engineer these new antibodies and to more specifically target the right proteins and immune effectors is going to be critical, of course, moving forward, as well as individualizing therapy based on a specific tumor biology.  Hearing your insights has been great, and it really has opened up a whole area of insight into the field of bispecifics, together with your excellent contribution to the ASCO Educational Book. Thank you so much for sharing your thoughts and background, as well as what we might see in the future on this podcast today. Dr. Giuseppe Curigliano: Thank you very much for the invitation and for this excellent interview. Dr. Hope Rugo: And thanks to our listeners for joining us today. You will find a link to the Ed Book article we discussed today in the transcript of this episode. It is also, of course, on the ASCO website, as well as on PubMed. Please join us again next month on By the Book for more insightful views on the key issues and innovations that are shaping modern oncology. 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  @hope.rugo  Dr. Giuseppe Curigliano @curijoey Follow ASCO on social media:       @ASCO on X (formerly Twitter)       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. Giuseppe Curigliano: Leadership: European Society for Medical Oncology, European Society of Breast Cancer Specialists, ESMO Open, European Society for Medical Oncology Honoraria: Ellipses Pharma Consulting or Advisory Role: Roche/Genentech, Pfizer, Novartis, Lilly, Foundation Medicine, Bristol-Myers Squibb, Samsung, AstraZeneca, Daiichi-Sankyo, Boerigher, GSK, Seattle Genetics, Guardant Health, Veracyte, Celcuity, Hengrui Therapeutics, Menarini, Merck, Exact Sciences, Blueprint Medicines, Gilead Sciences Speakers' Bureau: Roche/Genentech, Novartis, Pfizer, Lilly, Foundation Medicine, Samsung, Daiichi Sankyo, Seagen, Menarini, Gilead Sciences, Exact Sciences Research Funding: Merck Travel, Accommodations, Expenses: Roche/Genentech, Pfizer, Daiichi Sankyo, AstraZeneca      

Featuring a slide presentation and related discussion from Dr Laura Huppert, including the following topics: Overview of approved antibody-drug conjugates (ADCs) for metastatic hormone receptor-positive HER2-negative breast cancer — trastuzumab deruxtecan, sacituzumab govitecan and datopotamab deruxtecan(0:00) Approved and investigational ADCs for metastatic triple-negative breast cancer (17:18) Sequencing of ADCs for metastatic HER2-negative breast cancer; future research directions (26:10) CME information and select publications

Lisata Therapeutics Inc (NASDAQ:LSTA) CEO Dr David Mazzo talked with Proactive's Stephen Gunnion about the company's new collaboration with Catalent, which reinforces its strategy to leverage the broad applicability of its lead molecule, certepetide, across multiple cancer types and treatment modalities. Dr Mazzo said the Catalent deal “really has, to a great extent, unlimited revenue potential,” pointing to the rapid growth of antibody-drug conjugates (ADCs) as a therapeutic class. He explained that the agreement with Catalent is non-exclusive for ADCs, giving Lisata the flexibility to engage with a range of partners across the oncology space. The CEO added that this marks the first time a third party has used a certepetide-related molecule in a conjugated format, validating Lisata's hypothesis that the compound can be beneficial whether co-administered or conjugated. Lisata's ongoing strategy is to expand certepetide's use through partnerships that bring complementary technology or capital. Dr Mazzo emphasized that collaboration with an established company like Catalent is “a great step forward” as Lisata continues exploring additional partnership opportunities to maximize certepetide's potential applications. For more interviews and company updates, visit Proactive's YouTube channel. Don't forget to like this video, subscribe, and turn on notifications for future content. #LisataTherapeutics #DrDavidMazzo #Certepetide #Catalent #ADCTherapy #OncologyResearch #CancerTreatment #BiotechNews #PharmaPartnerships #ProactiveInvestors

Philip meets up with Dragan Grabulovski, CEO of the startup Araris, at Lake Zurich to chat about the company's work with antibody-drug conjugates (ADCs).They talk about Araris' huge $400M upfront buyout by Taiho Pharma of Japan, Dragan's extensive history as a biotech entrepreneur, and Araris' vision to replace chemotherapy with ADCs.⭐️ ABOUT THE SPEAKERDragan Grabulovski is a co-founder of the startup Araris and became CEO in 2023. He previously worked as a biotech consultant and startup coach in Switzerland. He co-founded the biotech company Covagen in 2007, which was acquired by Johnson & Johnson in 2014. Dragan has a Master's degree and a PhD in Pharmaceutical Sciences from ETH Zurich.

Please visit answersincme.com/YMJ860 to participate, download slides and supporting materials, complete the post test, and obtain credit. In this activity, experts in gynecologic oncology discuss the evolving clinical roles of antibody–drug conjugates (ADCs) in ovarian cancer, focusing on CDH6-targeted ADCs. Upon completion of this activity, participants should be better able to: Identify the rationale for using antibody–drug conjugates (ADCs) in the treatment of platinum-resistant ovarian cancer (PROC); Evaluate the evidence for emerging CDH6-targeted ADCs in the treatment of patients with PROC; Outline expected clinical implications of the evidence for emerging CDH6-targeted ADCs in the treatment of PROC.

JCO PO authors Dr. Abhishek Tripathi and Dr. Salvador Jaime-Casas at City of Hope Comprehensive Cancer Center share insights into their article, “Comparative Genomic Characterization of Small Cell Carcinoma of the Bladder Compared With Urothelial Carcinoma and Small Cell Lung Carcinoma.”  Host Dr. Rafeh Naqash and Drs. Tripathi and Jaime-Casas discuss a novel understanding of the genomic alterations underlying SCBC, revealing actionable mutations that could serve as potential targets for improved clinical outcomes. 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 am your host, Dr. Dr. Rafeh Naqash, Podcast Editor for JCO Precision Oncology and Associate Professor at the OU Health Stephenson Cancer Center at the University of Oklahoma. Today, I am thrilled to be joined by Dr. Abhishek Tripathi, Associate Professor in the Department of Medical Oncology and Experimental Therapeutics Research at the City of Hope Comprehensive Cancer Center, as well as his mentee, Dr. Salvador Jaime-Casas, postdoctoral research fellow and first author of the JCO Precision Oncology article entitled "Comparative Genomic Characterization of Small Cell Carcinoma of the Bladder Compared with Urothelial Carcinoma and Small Cell Lung Carcinoma". At the time of this recording, our guest disclosures will be linked in the transcript. Abhishek and Salvador, welcome to our podcast and thank you for joining us today. This is a very interesting topic given that at least the landscape for neuroendocrine carcinomas, where small cell lung cancer is on one end of the spectrum, has been changing, at least on the lung cancer side, with recent approvals and some new ADCs. So, of course, understanding the genomic and transcriptomic similarities or differences between pulmonary small cell and extrapulmonary small cell is of huge interest. Could you tell us a little bit about small cell bladder cancer, current approaches to treatment of small cell bladder cancer, and then why you wanted to investigate that in this project as far as the genomic differences or similarities are concerned? Dr. Salvador Jaime-Casas: Well, first of all, thank you very much for having me. I am very excited to be here. And really what served as backbone for this research project was the notion that there is a currently evolving genomic landscape in the area of bladder cancer. We know this is a highly heterogeneous disease when it comes to molecular underpinnings and mutational profile. Specifically, we know that the most common histologic subtype is urothelial carcinoma. Small cell bladder cancer represents a histology that is found in less than 1% of all bladder cancer cases. However, it is one of the most aggressive histologies. It presents with a very poor prognosis to patients and very poor response to treatment, which is why we attempted to really elucidate what is the mutational profile behind this and provide a comparison contrast between small cell bladder cancer, small cell lung cancer, and conventional urothelial carcinoma. As your question mentioned, in terms of treatment, the conventional urothelial carcinoma and small cell bladder cancer are two distinct pathways when it comes to treatment algorithms. We know that in the current era there are newer and newer drugs being developed for conventional urothelial carcinoma. We have perioperative immunotherapy in the context of metastatic disease. We have antibody-drug conjugates such as enfortumab vedotin. But really, this amazing track record of drug development hasn't been mirrored in small cell bladder cancer. And here most of the therapy is usually extrapolated from studies from other small cell histologies like you mentioned earlier, small cell lung cancer has given some form of background in terms of what therapies are used here. Cytotoxic chemotherapy, for some patients with localized disease and small cell bladder cancer, concurrent chemotherapy and radiotherapy or perioperative cytotoxic chemotherapy have been the cornerstone of treatment for many years now. However, like I mentioned, the oncologic outcomes are very suboptimal when it comes to comparing it with other disease histologies, which is why we really wanted to describe the landscape here and provide this comparison across three different groups. For this particular study, we leveraged the Tempus dataset. So, include patients with urothelial carcinoma with small cell bladder cancer and small cell lung cancer. We included their demographic information, as well as the frequency of most common genomic alterations identified. And really, it was a very comparable Table 1. We see the demographic data across the three groups was very similar. One key thing that we identified was the female prevalence was a little bit lower in patients with small cell bladder cancer when compared to small cell lung cancer. But other than that, the age, race, ethnicity, was comparable across groups, and even the smoking history. Most of the patients in this cohort were former smokers, which we believe comes to explain that regardless of any mutational profile that we talked about in a few minutes, there are shared commonalities between these histologies and shared environmental exposures and risk factors that are going to be implicated in the disease biology for these three histologies. Dr. Rafeh Naqash: Thank you so much, Salvador, for that useful background. I would like to shift to Abhishek real quick. Abhishek, you are a practicing clinician, you have led several studies in the GU space, especially bladder. Based on what you see in the small cell lung cancer space, how drug development is shaping up, which aligns with what you are trying to evaluate in this paper as targets, how do you see some of that being implemented for small cell bladder cancer in the current era and age? Abhishek Tripathi: Thanks so much for the excellent question, Rafeh. As a GU investigator, small cell bladder cancer has always lagged behind in some regards regarding enrollment abilities for the novel clinical trials. And small cell lung cancer has paved the way and led the development of a lot of these drugs across the board. With the most recent sort of drugs targeting DLL3 already approved and several antibody-drug conjugates currently in development. That actually translates really well to how we should approach drug development in bladder cancer. What we saw in the study is that although there are overlaps and similarities between small cell lung cancer and small cell bladder cancer, there are also certain differences. So the long-term assumption that all therapies for small cell bladder cancer can be extrapolated to small cell bladder], may or may not be true, and I think it is high time that we specifically investigate these novel agents in tissue-specific small cell carcinomas. To that effect, we are excited to be participating in trials that are looking at some of the novel DLL3 targeted agents, specifically bispecific antibodies and T cell engagers so to speak, and antibody-drug conjugates that are now starting to open enrollment specifically in non-lung cancer cohorts to evaluate its efficacy. So overall, I think studies like this have the opportunity to identify more putative targets for organ-specific development of these novel agents. Dr. Rafeh Naqash: Absolutely, I could not agree more. I think tumor-agnostic therapies definitely have a place, but not all therapies work the same in different tumors with a similar histological or genomic background because there are definitely differences. So now going to the comparison that Salvador, you guys did in this project, could you help us understand what are some of the things you looked at, what were some of the commonalities and the differences, and what were some of the conceptual thoughts that come out from those results? Dr. Salvador Jaime-Casas: Of course. So, the first thing that we identified was which were the most frequent molecular alterations across these histologies. We actually provided a table showcasing how the most common mutations that we identified were TP53, TERT, RB1. However, like Dr. Tripathi mentioned, the distinction between these histologies is notable in the sense that some are more predominant in small cell-pertaining cancers such as bladder cancer and lung cancer. While some others are more common in bladder-pertaining malignancies like urothelial carcinoma and small cell bladder cancer. For instance, we saw that TP53 and RB1 were significantly more evident in small cell histologies, both small cell bladder cancer and small cell lung cancer, as opposed to conventional urothelial carcinoma, which really this mirrors what is known about these mutations and what has been published. These are markers associated with more aggressive disease with a worse prognosis and even to resistance to treatment. We also identified how TERT mutations were characteristically more prevalent in small cell bladder cancer as opposed to small cell lung cancer, as well as in urothelial carcinoma. TERT mutations were more commonly identified than in small cell lung cancer. And we give a long list of these mutations that we identified, but really what we wanted to underscore here was, A, the most common mutations across histologies; B, the most common co-occurring mutations where we saw that these are not mutually exclusive. A lot of patients had co-occurring TP53 and RB1 or RB1 and TERT or RB1 and ARID1A, really elucidating how heterogeneous this molecular landscape is across histologies. And the third one that we believe really brings down the clinical impact of this research was evidencing the idea of clinically actionable mutations. We also provided a table here showcasing how mutations like FGFR, DLL notch pathway, HER2, were evident in these histologies, and what is the current status of some clinical trials evaluating different drug designs for these mutations. Like Dr. Tripathi mentioned in the context of FGFR, approximately 6% of our cohort with small cell bladder cancer showcased mutations in FGFR3. However, up to 14% of them had mutations in any FGFR gene, which really underscores the notion that drugs like erdafitinib, which have been introduced in the market in recent years, could potentially showcase some response in the space of small cell bladder cancer. We actually provide the description of two trials, phase two, phase three trials, that are evaluating erdafitinib in the context of high-risk non-muscle invasive bladder cancer and even metastatic urothelial carcinoma. Like Dr. Tripathi mentioned as well, antibody-drug conjugates, another very interesting area of drug development targeting HER2, we included evidence on how disitamab vedotin and trastuzumab deruxtecan are currently being explored across different phase two and phase three clinical trials, both as part of basket trial designs for solid malignancies expressing HER2, but also for patients with urothelial carcinoma where there is evidence of HER2 expression. So, we believe that the landscape is shifting in the right direction in the sense that therapies are becoming much more personalized and targeted against these known molecular profiles. Dr. Rafeh Naqash: Thank you, Salvador, for summarizing some of those very interesting results and providing a very unique conceptual context to that. I would like to go to Abhishek this last portion. Of course, I am sure you guys will expand on this work and there are a lot of other interesting things that will likely come out from this work and hopefully you will publish that in JCO PO. But one of the very important things that I wanted to highlight from this podcast specifically was the science is obviously very interesting, but I feel the more important interesting aspect is giving trainees and fellows, residents, mentorship opportunities, mentoring them and giving them lead roles in projects like this, which is what Dr. Tripathi has successfully done for you in this project, Salvador. So, Abhishek, as somebody I have known for a couple of years now, more than a couple of years, as a very successful clinical translational investigator in the GU space in the early phase setting, Abhishek, really briefly, within a minute, could you tell us about your journey and what are some of the things that have worked for you as an early career investigator that you have learned from, and then your journey of mentorship, how has that been for you and what are some of the things that you take home from your mentorship role? Abhishek Tripathi: Absolutely. And as you mentioned, mentorship has been pivotal for all early career investigators for them to really succeed. So, my journey, as you know, I started off as an early career investigator at another institution, and I think I owe it to my mentors even at that time and even now who are helping me develop some of these newer translational and clinical trial ideas, creating opportunities where we could really showcase some of the interesting work that we are doing. That actually goes a long way in terms of creating independence as an established investigator. And I think the sooner we start off with mentorship prospects, I think the better it is. And paying it forward, I think I have been lucky to have mentees like Salvador who are just extremely talented, really committed, and goal-oriented. He really led the project right from the beginning in terms of initial analyses and looking up all the sort of correlative studies that we could do and the contextual data between small cell lung cancer and bladder cancer that we have delved into for the past several years. And it really showcases the ability of young mentees like Salvador to really excel given the right guidance and the support. As a mentor, it has been a really rewarding experience. It is really helpful to actually learn from some of these mentees as well as to approach the same problem from a different angle and different thought process and guide them through the study. So, it has been incredibly helpful and rewarding both being a mentee and a mentor over the past several years as I have transitioned. Dr. Rafeh Naqash: Thank you, Abhishek, for those very insightful comments on how both being a mentee and being a mentor helps shape you as an individual as well. And then you take a lot of pride in the success of your mentees. Now real quick, Salvador, could you tell us a little bit about yourself, you know, how you ended up at City of Hope under Dr. Tripathi's mentorship and what are some of the next important things that you are looking forward to doing? Dr. Salvador Jaime-Casas: So, a little bit about who I am. I did medical school in Mexico City. I was born and raised there, and towards the end of my medical training, I started to be engaged in research projects. And through one of my mentors in Mexico, I was actually introduced to the team here at City of Hope, including Dr. Tripathi. And through this, we got the opportunity to have some conversations about what I wanted to do, become a physician-researcher in the area of genitourinary oncology and hopefully my transition to residency in a few years. And that is how I came to be his mentee here at City of Hope. I think it has been a very rewarding experience, like Dr. Tripathi said, having such an incredible mentor and really being with him both in the academic setting and in the clinical setting, in patients with clinic, seeing this curiosity and all these clinical trials, all of this evidence that we have coming together to generate this insight. Dr. Rafeh Naqash: Thank you so much for both the scientific insights, as well as the journey of being a mentee for you, Salvador, and as a mentor for you, Abhishek. I really enjoyed talking to you guys about both aspects here today and hopefully we will see more of your work, Abhishek and Salvador, as far as understanding the transcriptomic heterogeneity in neuroendocrine tumors or neuroendocrine cancers of the bladder. Dr. Salvador Jaime-Casas: Thank you very much. Thank you for having us. Dr. Rafeh Naqash: Thank you for listening to JCO Precision Oncology Conversations. Do not 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/podcasts. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.   Dr. Abhishek Tripathi Disclosures Consulting or Advisory Role:  Company: Aadi biosciences, Seattle Genetics/Astellas, Exelixis, Bayer, Gilead Sciences, Pfizer, Deka biosciences Speakers' Bureau: Company: Sanofi

Featuring an interview with Prof Peter Schmid, including the following topics: Response to immunotherapy in breast cancer subtypes (0:00) Tolerability of TROP2 antibody-drug conjugates (ADCs) for metastatic breast cancer (mBC) (3:51) Approaches to therapy for patients with HR-negative HER2-low and HER2-ultralow mBC (13:03) ADC structure and treatment-related adverse events (19:02) Available data from the Phase III ASCENT-04 trial evaluating sacituzumab govitecan with pembrolizumab as first-line therapy for patients with PD-L1-positive advanced triple-negative breast cancer (23:06) Novel ADCs and bispecific antibodies under investigation for mBC (28:30) Comparing datopotamab deruxtecan and sacituzumab govitecan for HR-positive disease (33:01) Clinical investigator perspectives on the Phase III DESTINY-Breast09 trial evaluating first-line trastuzumab deruxtecan with or without pertuzumab versus THP (docetaxel/rastuzumab/pertuzumab) for HER2-positive mBC (35:06) CME information and select publications

Drs. Liu and Scott discuss the future of small cell lung cancer treatment, reviewing emerging strategies including immunotherapy, antibody–drug conjugates (ADCs), and bispecific T-cell engagers, as well as other targeted agents.

Featuring a slide presentation and related discussion from Prof Peter Schmid, including the following topics: Evolution of the therapeutic landscape for metastatic triple-negative breast cancer; age of immunotherapy (0:00) Case: A woman in her early 40s with no actionable mutations (7:29) Evolution of antibody-drug conjugates (ADCs) in the management of metastatic breast cancer (11:13) TROP2-directed ADCs (15:22) Case: A woman in her early 50s with PD-L1-negative, HR-negative, HER2-low de novo metastatic breast cancer (20:21) Novel strategies utilizing approved and investigational ADCs (23:28) Case: A woman in her early 60s with loss of HER2 expression on disease progression (31:39) ADCs in combination with immunotherapy (32:51) CME information and select publications

Michael Glass, RF Systems Sales Engineer at Quantic Wenzel, talks with Pat Hindle about the rising demand for ultra-low phase noise frequency sources in digital RF systems. They cover how ADCs, PLLs, DDS synthesizers, and RF SoCs still depend on clean analog clocks to reach low noise floors, and how newer designs push for higher frequencies, smaller form factors, rugged construction, and multiple coherent outputs. Glass explains how low noise clocks improve radar resolution, SATCOM link reliability, and system performance. Sponsored by Quantic Wenzel.

The OncoAlert Weekly Roundup is your go-to podcast for the latest, most impactful updates in oncology from across the globe

Featuring an interview with Dr Neel Pasricha, including the following topics: Anatomy and physiology of the cornea; intersection of ophthalmology and oncology for patients receiving antibody-drug conjugates (ADCs) (0:00) Association of corneal toxicities with ADCs (4:56) Dose and schedule modifications to mitigate ocular toxicities associated with belantamab mafodotin and other ADCs (9:02) Spectrum and severity of corneal toxicities associated with datopotamab deruxtecan (14:44) Role of optometrists and ophthalmologists in screening for and management of ocular toxicities (17:55) Other ocular toxicities associated with cancer therapies (24:26) Prevention and management of corneal toxicity (33:58) Preexisting ophthalmic conditions as potential risk factors for development of ocular toxicities with ADCs (43:39) General clinical pearls on the management of ocular toxicities with cancer therapies (48:04) CME information and select publications

In this podcast, experts Virginia Kaklamani, MD, DSc, and Tiffany A. Traina, MD, FASCO, discuss the rationale for and data to support combining TROP2-targeting antibody-drug conjugates (ADCs) with immune checkpoint inhibitors (ICIs) to treat triple-negative breast cancer (TNBC).

In this podcast, experts Aditya Bardia, MD, MPH, FASCO, Erika P. Hamilton, MD, and Virginia Kaklamani, MD, DSc, discuss frequently asked questions regarding the use of antibody-drug conjugates (ADCs) in triple-negative breast cancer (TNBC).

Featuring perspectives from Prof Rebecca A Dent, Dr Hans Lee, Dr Neel Pasricha and Dr Tiffany A Richards, including the following topics:  Introduction: The Patient Experience (0:00) Managing Ocular Toxicities Associated with Antibody-Drug Conjugates and Other Cancer Therapies — Dr Pasricha (10:28) Ocular Toxicities in Multiple Myeloma (45:33) Ocular Toxicities in Breast Cancer (50:34) CME information and select publications

In this podcast, experts Filipa Lynce, MD, and Rita Nanda, MD, discuss recent clinical trial and real-world data for antibody-drug conjugates (ADCs) used to treat triple-negative breast cancer (TNBC).

In this podcast, experts Filipa Lynce, MD, and Rita Nanda, MD, discuss unmet needs in triple-negative breast cancer (TNBC) and the rationale for using TROP2-targeting antibody-drug conjugates (ADCs) in this disease.

Please visit answersincme.com/860/98320325-replay to participate, download slides and supporting materials, complete the post test, and obtain credit. In this activity, experts in oncology discuss the evolving role of HER2-targeted antibody–drug conjugates (ADCs) and how to integrate them into clinical practice. Upon completion of this activity, participants should be better able to: Recognize the role of biomarker testing for the management of HER2-overexpressing NSCLC; Evaluate the clinical significance of new and emerging HER2-targeting ADCs for HER2-overexpressing NSCLC; and Apply strategies to optimize the use of HER2 targeting ADCs in patients with NSCLC.

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

Featuring an interview with Dr Erika Hamilton, including the following topics: Monitoring, mitigating and managing adverse events with antibody-drug conjugates (ADCs) for breast cancer (0:00) Heist RS et al. Clinical management, monitoring, and prophylaxis of adverse events of special interest associated with datopotamab deruxtecan. Cancer Treat Rev 2024;125:102720. Abstract Management protocols for adverse events associated with sacituzumab govitecan (7:49) García JMP et al. Prevention of sacituzumab govitecan (SG)-related neutropenia and diarrhea in patients with triple-negative or HR+/HER2- advanced breast cancer (ABC; PRIMED): A phase 2 trial. ASCO 2024;Abstract 1101. Pérez-García JM et al. Prevention of sacituzumab govitecan-related neutropenia and diarrhea in patients with HER2-negative advanced breast cancer (PRIMED): An open-label, single-arm, phase 2 trial. eClinicalMedicine 2025;85:103309. Abstract Datopotamab deruxtecan for patients with breast cancer brain metastases or leptomeningeal disease (10:51) Tarantino P et al. DATO-Base: A phase II study of DATOpotamab deruxtecan for patients with breast cancer brain metastases or leptomeningeal disease. ASCO 2025;Abstract TPS1134. Sequencing ADCs in breast cancer (13:12) Pacholczak-Madej R et al. Sequencing of antibody drug conjugates in breast cancer: Evidence gap and future directions. Biochim Biophys Acta Rev Cancer 2025;[Online ahead of print]. Abstract CME information and select publications

Dr Erika Hamilton from Sarah Cannon Research Institute in Nashville, Tennessee, discusses the monitoring, mitigation and management of adverse events with available antibody-drug conjugates and novel strategies incorporating ADCs into the breast cancer treatment paradigm. CME information and select publications here.

Antibody-drug conjugates (ADCs) are a relatively new type of medicine for breast cancer. Enhertu (chemical name: fam-trastuzumab-deruxtecan-nxki) and Dato-DXd (brand name: Datroway) are two ADCs used to treat breast cancer. Dr Benjamin Schrank and colleagues have developed a new type of ADC that combines an antibody with a toxin — called an antibody-toxin conjugate — that teaches the immune system to recognize and attack cancer cells. Listen to the episode to hear Dr. Schrank explain: the antibody and the toxin component of the medicine how the new medicine works possible side effects next steps for the research Episode image photo credit: The University of Texas MD Anderson Cancer Center

In this episode, Dr. Daniel Morgensztern and Dr. Jonathan Strosberg discuss the emerging role of DLL3-targeted agents in the management of extrapulmonary neuroendocrine carcinomas, including:The clinical implications of using DLL3 as a therapeutic targetThe impact of emerging DLL3-targeted therapies on evolving treatment paradigmsHow to incorporate DLL3-based treatments into clinical practicePresenters:Daniel Morgensztern, MDProfessor of MedicineClinical Director of Thoracic OncologyWashington University School of MedicineSt Louis, MissouriJonathan Strosberg, MDProfessorDepartment of GI OncologyMoffitt Cancer Center and Research InstituteTampa, FloridaContent based on an online CME program supported by an independent educational grant from Boehringer Ingelheim Pharmaceuticals, Inc.Link to full program: https://bit.ly/4mjNPfy

This week on EYE ON NPI we're featuring some open source hardware from one of our favorite hardware manufacturers! It's the Arduino Nano R4 System on Module (https://www.digikey.com/en/product-highlight/a/arduino/nano-r4) a miniaturized version of the Arduino UNO R4 and Minima (https://blog.adafruit.com/2023/07/27/eye-on-npi-arduino-uno-r4-minima-and-uno-r4-wifi-boards-digikey-arduino-digikey-adafruit/) versions we covered on EYE ON NPI about two years ago! taking a cue from popular 'castellated single side' PCB proto boards on the market, the Nano comes in two options, one with headers (https://www.digikey.com/en/products/detail/arduino/ABX00143/26766495) for easy installation into existing Arduino Nano expansion kits or breadboards, and one with reflowable castellations (https://www.digikey.com/en/products/detail/arduino/ABX00142/26766490) The Arduino Nano (https://www.digikey.com/en/products/detail/arduino/A000005/2638989) is second only to the UNO as the definitive Arduino board that 'everyone got started with'. Many folks would start with the chunky UNO and then migrate to the Nano to get something that plugs into a breadboard for compact assembly. With a USB connector on one end, button and LEDs and programming header on the top, this board powered tens of thousands of builds. So it's not surprising that Arduino iterated on this design with a wide variety of chips like the RP2040 (https://www.digikey.com/en/products/detail/arduino/ABX00052/14123941) and ESP32 (https://www.digikey.com/en/products/detail/arduino/ABX00092/21219771) The latest generation is the Renesas RA4M1 series - which updates the original ATmega328 8-bit microcontroller to a beefy Cortex M4 with FPU. You get 48MHz clock, 256KB of Flash, 32KB of SRAM, ADC, DAC, CAN, captouch and other extras. The FPU in particular makes it a nice upgrade to the cortex M0/M0+. The best part is that with the 5V logic support of the R7FA4M1AB3CFM (https://www.digikey.com/en/products/detail/renesas-electronics-corporation/R7FA4M1AB3CFM-AA0/10447195), it makes for a great drop-in replacement when a 3V logic chip like the RP2040/ESP32 won't work as well. Plus you get lots of nice linear ADCs, the RP2040 only has 4 and the ESP32's are non-linear and sometimes don't work when WiFi is active. We also love that they added a Qwiic (https://www.sparkfun.com/qwiic) connector on the end! We use this for all our Stemma QT sensors, and between the many companies that have joined in the ecosystem there are easily a thousand different ons/displays/accessories that can plug in directly for instant expansion. If you want to get the latest Nano from the manufacturer of genuine Arduino boards, DigiKey is a authentic distributor and has tons of the Arduino Nano R4 (https://www.digikey.com/short/3brjrnjp) in stock right now for (https://www.digikey.com/en/products/detail/arduino/ASX00061/26744081) immediate shipment! Pick from the castellated flat or soldered-header variety, and don't forget to also grab some Arduino Nano accessories to get your design prototyped fast. Order today and your Nano will fly out of the DigiKey warehouse and arrive at your doorstep by tomorrow morning.

We love to hear from our listeners. Send us a message. On this week's episode, Oury Chetboun, co-founder and CEO of Seekyo, a French biotech, talks about the range of experiences that prepared him to lead a company focused on developing innovative solid tumor treatments that target functional proteins in the tumor micro-environment. Chetboun talks about raising money for preclinical research and navigating the valley of death between research and clinical development, accessing French innovation funding and angel networks, how click chemistry can produce therapies at a lower cost compared to antibody-drug conjugates (ADCs), and the potential use of drug combinations and umbrella trials for testing multiple cancer indications.Access this and hundreds of episodes of the Business of Biotech videocast under the Business of Biotech tab at lifescienceleader.com. Subscribe to our monthly Business of Biotech newsletter. Get in touch with guest and topic suggestions: ben.comer@lifescienceleader.comFind Ben Comer on LinkedIn: https://www.linkedin.com/in/bencomer/

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD information, and to apply for credit, please visit us at PeerView.com/DCA865. CME/NCPD credit will be available until July 30, 2026.Off-the-Shelf and on the Mark in NHL: Strategic Approaches With Bispecific Antibodies and ADCs In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and Genentech, a member of the Roche Group.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD information, and to apply for credit, please visit us at PeerView.com/DCA865. CME/NCPD credit will be available until July 30, 2026.Off-the-Shelf and on the Mark in NHL: Strategic Approaches With Bispecific Antibodies and ADCs In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and Genentech, a member of the Roche Group.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD information, and to apply for credit, please visit us at PeerView.com/DCA865. CME/NCPD credit will be available until July 30, 2026.Off-the-Shelf and on the Mark in NHL: Strategic Approaches With Bispecific Antibodies and ADCs In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and Genentech, a member of the Roche Group.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD information, and to apply for credit, please visit us at PeerView.com/DCA865. CME/NCPD credit will be available until July 30, 2026.Off-the-Shelf and on the Mark in NHL: Strategic Approaches With Bispecific Antibodies and ADCs In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and Genentech, a member of the Roche Group.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD information, and to apply for credit, please visit us at PeerView.com/DCA865. CME/NCPD credit will be available until July 30, 2026.Off-the-Shelf and on the Mark in NHL: Strategic Approaches With Bispecific Antibodies and ADCs In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and Genentech, a member of the Roche Group.Disclosure information is available at the beginning of the video presentation.

Featuring an interview with Dr Hope S Rugo, including the following topics: Pharmacologic features of antibody-drug conjugates (ADCs) and implications for their efficacy and toxicity in HR-positive breast cancer (0:00) Clinical and biological factors influencing the sequencing of approved ADCs for HR-positive and triple-negative metastatic breast cancer (4:03) Management of common toxicities with approved ADCs (10:48) Sacituzumab govitecan as first-line therapy for metastatic triple-negative breast cancer (18:17) Trastuzumab deruxtecan in combination with pertuzumab as first-line therapy for HER2-positive metastatic breast cancer (21:09) CME information and select publications

Microsoft has finally announced that it will offer an update to Active Directory Certificate Services (ADCS, formerly MSCA) to support post quantum cryptography. We discuss Microsoft's checkered support for ADCS and offer some questions users should be asking.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/XDB865. CME credit will be available until June 26, 2026.Tailwinds of Innovation in SCLC: Exploring the Therapeutic Potential of ADCs In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Daiichi Sankyo, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/XDB865. CME credit will be available until June 26, 2026.Tailwinds of Innovation in SCLC: Exploring the Therapeutic Potential of ADCs In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Daiichi Sankyo, Inc.Disclosure information is available at the beginning of the video presentation.

Join Sandra for a look at Dr. Jeffrey Mishlove's 1st prize winning Bigelow contest essay, loaded with NDEs, ADCs, ITC and reasons to believe in life after death. See omnystudio.com/listener for privacy information.

Join Sandra for a look at Dr. Jeffrey Mishlove's 1st prize winning Bigelow contest essay, loaded with NDEs, ADCs, ITC and reasons to believe in life after death. See omnystudio.com/listener for privacy information.