CAPhO Connections Podcast: Targeting Active RAS in Pancreatic Cancer: Daraxonrasib from Molecular Glue to Clinical Data
Pancreatic cancer has long remained one of the most challenging malignancies to treat. Could pan-RAS inhibition reshape the future treatment landscape for pancreatic cancer? In this episode, we explore daraxonrasib, a first-in-class oral pan-RAS inhibitor that uses a novel molecular glue mechanism to target active RAS signaling. We'll review the landmark RASolute 302 trial, unpacking the key efficacy and safety findings and discussing what they may mean for the future of pancreatic cancer treatment. The conversation also examines where daraxonrasib may fit within the evolving treatment paradigm, including patient selection, treatment sequencing, and practical considerations for safe use such as toxicity management, drug interactions, monitoring, administration, and patient counselling. Finally, we'll explore the opportunities and challenges of integrating this emerging therapy into multidisciplinary pancreatic cancer care, including feasibility, supportive care, access, reimbursement, and future directions. Join us as we unpack the science, evidence, and clinical questions surrounding one of the most closely watched emerging therapies in pancreatic cancer!
Learning Objectives:
- Describe the mechanism of action of Daraxonrasib as a first-in-class pan-RAS inhibitor and explain how it differs from conventional systemic therapies used in pancreatic cancer
- Review the landmark RASolute 302 trial, including its key efficacy and safety findings, and interpret the clinical significance of the study outcomes
- Discuss the evolving role of daraxonrasib within the pancreatic cancer treatment landscape, including potential patient selection and treatment sequencing across lines of therapy
- Recognize practical considerations for the safe use of daraxonrasib, including adverse event management, drug interactions, monitoring, administration, and patient counselling
- Explore the opportunities and challenges associated with integrating daraxonrasib into multidisciplinary pancreatic cancer care, including supportive care, access and reimbursement considerations, and future directions for clinical practice
About the Guest:
Ming-Hei Tai is currently an oncology pharmacist at William Beaumont University Hospital in Royal Oak, Michigan. He graduated from the University of Michigan Pharmacy School in 2019 and is a member of HOPA’s Publications and Resources Committee. As a pharmacist, he is involved in treating patients with both solid and liquid tumors, and has his own podcast, called PharmOncology.
Resources Used:
1. Wolpin, B. M., Wainberg, Z. A., Garrido-Laguna, I., Manji, G. A., Spira, A. I., Azad, N. S., ... & O'Reilly, E. M. (2025). Trial in progress: RASolute 302—A phase 3, multicenter, global, open-label, randomized study of daraxonrasib (RMC-6236), a RAS (ON) multi-selective inhibitor, versus standard of care chemotherapy in patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC).
2. Seufferlein, T., Hammel, P., Pietrantonio, F., Azad, N. S., Ko, A. H., Morizane, C., ... & Pant, S. Trial in Progress–RASolute 303: A Phase 3 Global, Open-Label, Randomized 3-Arm Study of Daraxonrasib Monotherapy or Daraxonrasib Plus Gemcitabine and Nab-paclitaxel Versus Gemcitabine and Nab-paclitaxel as a First Line Treatment for Patients With Metastatic Pancreatic Adenocarcinoma.
3. Honda, R. (2026). Daraxonrasib and Beyond: Pan‐RAS Inhibition, Resistance, and Next‐Generation Strategies. Cancer Science.