Lutetium (177 Lu) Vipivotide Tetraxetan

iStock, Shijo Jose Convergent Therapeutics’ Dr. Philip Kantoff and Plus Therapeutics’ Dr. Marc Hedrick discuss how unmet medical needs, maturing isotope supply chains and innovative delivery are positioning targeted radiation as oncology’s next big platform. Radiotherapeutics have evolved from early proofs-of-concept to oncology powerhouses, propelled by treatment gaps, Novartis’ Pluvicto and better supply chains and logistics. The field is ripe for exploration, with enormous potential due to the multiplicity of cancer surface targets to be addressed with different carriers, isotopes and formulation methods, said company executives in interviews with BioSpace . High Unmet Needs Dr. Philip Kantoff is the co-founder & CEO of Convergent Therapeutics. Prior to the company’s initiation, early Prostate-Specific Membrane Antigen (PSMA)-targeted radioantibody data from Cornell University in New York intrigued him. The data showed that Actinium-225, an alpha-emitting isotope, in a single-dose study showed responses in roughly 45% to 50% of heavily pretreated prostate cancer patients. The opportunity to further develop a therapy with an attractive safety pro in metastatic castration-resistant prostate cancer (mCRPC), where treatment options are very limited after hormonal therapy and chemotherapy, convinced Kantoff to move from academic medicines to biotech leadership. For Dr. Marc Hedrick, president and CEO of Plus Therapeutics, and a former academic surgeon and physician scientist, noted his motivation to join biotech leadership came from decades of largely flat survival outcomes for central nervous system (CNS) cancers. While Plus started as a targeted radiotherapy company, it came to recognize that diagnostics have not kept pace with disease complexity, especially in leptomeningeal cancer, primary brain cancers and brain metastases. The company’s wider strategy now combines therapeutics, diagnostic and data analytics to improve those survival metrics. Radiotherapeutic Roller Coaster Radioisotopes showed proven efficacy approximately 70 years ago with Iodine-131 (I-131) for treating thyroid diseases, Hedrick and Kantoff agreed. But GlaxoSmithKline Bexxar (tositumomab and I-131 tositumomab), a targeted radioimmunotherapy used to treat specific, relapsed or refractory CD20-positive, follicular NHL, didn’t fare as well commercially. The company pulled the asset from the market in 2014. The news elicited subsequent caution for radiotherapy development, Kantoff said. A major turning point in radiotherapy development arrived with the commercial success of Novartis’ Pluvicto, they agreed. It demonstrated both clinical benefit and commercial viability in a large tumor setting, Kantoff said. Pluvicto, approved by the FDA in 2022, is a targeted radioligand therapy for adult men with progressive, PSMA-positive mCRPC. The therapy combines a targeting compound (ligand) with a therapeutic radioactive isotope (Lutetium-177). Another advance in radiotherapies in prostate cancer is Bayer’s Xofigo (Radium-223 dichloride), Kantoff said. Xofigo is an injection is used to treat prostate cancer that no longer responds to hormonal or surgical treatment that lowers testosterone. It is the first targeted alpha-particle therapy that not only controls bone pain but also significantly lengthens survival for patients with mCRPC that has spread to the bones. Brain Cancer Differential Radiation to address brain cancer has a long history, particularly with external beam radiation, Hedrick said. Examples include X-rays, protons or electrons, directed at a tumor from outside the body. To overcome the complications of offsite toxicity, radiation oncologists will employ fractionation, where patients are given a specified maximum dose over multiple days to improve survival, Hedrick explained. Plus Therapeutics’ approach aims to carry much more radiation directly to the tumor, with minimal systemic and bone marrow toxicity, Hedrick said. The delivery technology, formulation and isotope together allow the company to intensify dose. Early phase data in glioblastoma suggest improved survival, he added. Supply Chain Solutions Back in 2021, industry concerns presented as to whether sufficient Actinium-225 could be produced for clinical and commercial use. Initial isotopes supply came from Department of Energy, and other material was derived from radioactive waste sources, Kantoff said. But the scenario has improved substantially, due to pharma development interest, and there are now accelerated generated methods enabling commercial-scale production of multiple isotopes, Kantoff said. Hedrick agreed the supply field has increased with a growing number of service providers, contract manufacturers and radiation specialists. Lutetium-177 and Actinium-225 remain the most requested isotopes, “reflecting their dominant position in clinical radiopharmaceutical pipelines,” said Denis R. Beckford-Vera, PhD, head of radiopharmacology at CRO Champions Oncology. For Plus Therapeutics, having both a primary and backup radiation service provider is important, especially because its isotope has a longer half-life, Hedrick said. Still, one of the biggest challenges in radiotherapeutics remains ensuring drug is sent to the patient on time, he added, due to isotopes often having short half-lives. However, as Plus Therapeutics has a drug with a 90-hour half-life, “we have some wiggle room in terms of if the patient is late to clinic or so forth,” Hedrick said. Bright Long-Term Therapy Prospects The field is bright for radiotherapy due to variable cancer surface targets that can be zeroed in by small molecules, peptides and antibodies, Kantoff said. The field is “still in its infancy” when it comes to matching isotopes, targets and delivery strategies, he added. There are multiples variables to optimize, creating considerable opportunity, Hedrick added. These include isotopes, formulations, linkers, delivery methods and dosing. While this can radiotherapy development complex, it also creates major opportunities, Hedrick concluded. You can hear more on this week’s Denatured  podcast episode .

— Inaugural Hästens-PCF Global Health Award will support expansion of STAMPEDE2 clinical trial in Nigeria — LOS ANGELES--(BUSINESS WIRE)--The Prostate Cancer Foundation (PCF) today announced the launch of the Hästens-PCF Global Health Award, a new initiative designed to advance equitable prostate cancer detection, diagnosis, and care in emerging countries. The award will support the expansion of STAMPEDE2 – a clinical trial testing new therapies in patients with advanced prostate cancer – in Nigeria. This program will be led by Dr. Omolara Aminat Fatiregun, MBBS, MSc, MPH, Lagos State University College of Medicine and Professor Nick James, MBBS, Ph.D. of The Institute of Cancer Research, London and The Royal Marsden NHS Foundation Trust, expanding access to high-quality prostate cancer research and clinical care in a region with significant unmet need. Through this partnership, Hästens has provided funding to directly support this research project as well as cover operational and administrative costs. The award is intended to serve as a foundational and recurring funding mechanism to support scalable, locally led prostate cancer initiatives worldwide. “The Hästens-PCF Global Health Award is a testament to our commitment to saving lives by accelerating the global impact of prostate cancer research and care,” said Gina Carithers, President and CEO of the Prostate Cancer Foundation. “Together, with the generous support of Hästens and our pioneering donors, we can achieve our ultimate vision of a future where a man’s chance of surviving prostate cancer is not determined by where he lives, but by access to timely, high-quality care grounded in global scientific excellence.” The inaugural project in Nigeria will focus on increasing community awareness and early detection, strengthening pathology and imaging capacity, standardizing risk-adapted clinical care pathways, and building sustainable local expertise through training and mentorship. The initiative will also generate high-quality data to inform continuous improvement of prostate cancer care and create models that can be replicated in other emerging-country settings. Beyond the initial award period, the Prostate Cancer Foundation and Hästens envision the program continuing through institutionalized training, policy integration, and regional networks of excellence. Lessons learned from the STAMPEDE2 expansion in Nigeria will inform future awards and strengthen global prostate cancer treatment efforts. “Much of my career has been dedicated to bridging the global disparity in prostate cancer research and treatment,” said Dr. Fatiregun. “It is with great honor and gratitude to the Prostate Cancer Foundation and Hästens that I can continue my life’s work and help bring world-class precision medicine to Nigerian patients.” STAMPEDE2 is a large, international, multi‑arm clinical trial designed to rapidly evaluate new treatment strategies for men with advanced prostate cancer. Building on the practice‑changing legacy of the original STAMPEDE trial, STAMPEDE2 tests the addition of novel therapies, including the targeted radioligand therapy 177 Lu‑PSMA‑617 (Pluvicto ® ), to standard‑of‑care treatment in patients with metastatic, hormone‑sensitive disease. Pluvicto ® targets PSMA, a protein highly expressed on prostate cancer cells, delivering radiation directly to tumors while minimizing damage to surrounding healthy tissue. By integrating comprehensive clinical, imaging, and tissue data, STAMPEDE2 aims to identify biomarkers of response, understand mechanisms of treatment resistance, and optimize patient selection. “The STAMPEDE2 clinical trial provides a powerful platform to translate scientific discovery into real‑world impact, which could profoundly transform prostate cancer treatment in underserved countries and communities,” said Dr. James. “The Hästens-PCF Global Health Award supports locally led solutions that will improve prostate cancer outcomes today while establishing models for lasting impact in the years ahead.” Globally, prostate cancer incidence is rising, yet mortality remains disproportionately high in low- and middle-income countries. Men often present with advanced disease because of limited awareness, stigma, inadequate screening infrastructure, and delayed referrals. Diagnostic bottlenecks – particularly shortages in pathology, imaging, and trained specialists – further compound inequities. In recognition of these gaps, which are most pronounced among rural populations and historically marginalized communities, the Hästens-PCF Global Health Award uniquely aligns with the urgent need to address these disparities by catalyzing innovative, collaborative, and sustainable solutions. “We are excited to be a part of the Prostate Cancer Foundation’s first-ever global health award to translate innovation into measurable benefit for men who currently face the greatest burden of this disease,” said Jacob Koo, owner of the largest network of Hästens stores worldwide. “Along our global journey to improve lives through incredible sleep, we are proud to support high quality science that will positively impact the lives of men in Nigeria and across the globe.” About the Prostate Cancer Foundation The Prostate Cancer Foundation (PCF) is the world’s leading philanthropic organization dedicated to funding life-saving prostate cancer research. Founded in 1993 by Mike Milken, PCF has raised more than $1 billion to fund cutting-edge research through more than 2,615 research projects at 312 leading cancer centers, with a global footprint spanning 29 countries. Since PCF’s inception, and through its efforts, patients around the world are living longer, suffering fewer complications, and enjoying better quality of life. PCF is committed to the mission of ending death and suffering from this disease. Learn more at pcf.org . About Hästens Founded in 1852, Hästens is dedicated to delivering extraordinary sleep to people worldwide so they can be their best and create the future they dream of upon waking. Hästens’ master craftsmen in Köping, Sweden, handcraft every detail of its bespoke beds using the finest natural materials. Hästens is a world-class, international, family-run business operating in more than 45 countries, is a Purveyor to the Royal Court of Sweden, and works with over 250 independent resellers across Europe, Asia, the Americas, and Africa. Contacts MEDIA CONTACT: Audra Friis Sam Brown Inc. audrafriis@sambrown.com