Revolution Medicines has announced the dosing of the first patient in the RASolute 302 Phase 3 clinical trial, evaluating RMC-6236 for the treatment of previously treated metastatic pancreatic ductal adenocarcinoma (PDAC). This global, randomized, open-label study aims to assess the safety and efficacy of RMC-6236 monotherapy compared to standard of care chemotherapy in patients with this aggressive cancer.
The RASolute 302 trial (NCT06625320) plans to enroll approximately 460 patients worldwide who have already undergone one prior line of therapy involving a 5-fluorouracil (5-FU)-based or gemcitabine-based regimen. The study will focus on a core patient population with PDAC harboring RAS mutations at position 12 (RAS G12X) and an expanded population including patients with RAS mutations at G12 (RAS G12X), G13 (RAS G13X) or Q61 (RAS Q61X), or those without any identified targetable mutation. The dual primary endpoints are progression-free survival (PFS) and overall survival (OS) in the core patient population, with key secondary endpoints including PFS and OS in the expanded patient population.
RMC-6236: Targeting RAS-Driven Cancers
RMC-6236 is an oral, direct RAS(ON) multi-selective inhibitor designed to address various cancers driven by oncogenic RAS mutations. It functions by suppressing RAS signaling through blocking the interaction of RAS(ON) with its downstream effectors, targeting mutations such as G12X, G13X, and Q61X found in PDAC, non-small cell lung cancer (NSCLC), and colorectal cancer (CRC).
Pancreatic Cancer: A Formidable Challenge
Pancreatic cancer is one of the most lethal malignancies, characterized by late-stage diagnosis, resistance to chemotherapy, and a high mortality rate. In the U.S., approximately 60,000 people are expected to be diagnosed with pancreatic cancer in 2024, with about 50,000 deaths. Pancreatic ductal adenocarcinoma (PDAC) accounts for approximately 92% of all pancreatic cancer cases. Approximately 80% of patients are diagnosed at an advanced or metastatic stage due to the lack of early symptoms and detection methods. More than 90% of patients with PDAC have tumors harboring RAS mutations. Metastatic PDAC has a five-year survival rate of approximately 3%.
Revolution Medicines' Perspective
"Treating the first patient in RASolute 302 is a significant milestone for Revolution Medicines as we seek to revolutionize treatment for patients with RAS-addicted cancers," said Mark A. Goldsmith M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. "RMC-6236 is designed to directly inhibit RAS(ON) signaling, which is the primary oncogenic driver of pancreatic cancer. Supported by the encouraging initial PFS and OS observations and safety profile reported from the Phase 1 RMC-6236 monotherapy trial, the randomized RASolute 302 trial will formally assess the potential for this bold investigational drug to make a meaningful difference for people living with metastatic PDAC, one of the most difficult-to-treat cancers."
