Revolution Medicines Begins Phase 3 Trial of RMC-6236 in Treated Metastatic Pancreatic Cancer Patients

Revolution Medicines, Inc. (Nasdaq: RVMD), an oncology company focused on developing therapies for patients with RAS-addicted cancers, recently announced the dosing of the first patient in its Phase 3 clinical trial, RASolute 302. This registrational study aims to evaluate RMC-6236, a RAS(ON) multi-selective inhibitor, in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) who have already undergone prior treatment.

The RASolute 302 trial is an international, randomized, open-label Phase 3 study that focuses on assessing the safety and efficacy of RMC-6236 as a monotherapy compared to the standard chemotherapy treatment. Approximately 460 patients from around the world will be enrolled in the study. These patients would have received one prior line of treatment that included either a 5-fluorouracil (5-FU)-based or gemcitabine-based regimen.

The design of the study targets a core group of patients with PDAC that have specific RAS mutations at position 12 (RAS G12X). It also includes an expanded group of patients with tumors that harbor mutations at RAS positions G12, G13, or Q61, or those without any identified targetable mutations. The primary endpoints of the study are progression-free survival (PFS) and overall survival (OS) in the core patient population, with secondary endpoints including PFS and OS in the expanded patient group.

Mark A. Goldsmith, M.D., Ph.D., the CEO and chairman of Revolution Medicines, emphasized the importance of this milestone for the company. He highlighted the potential of RMC-6236 to directly inhibit RAS(ON) signaling, which is a key driver of pancreatic cancer. The initiation of this trial follows encouraging preliminary results from the Phase 1 trial of RMC-6236, which demonstrated positive PFS and OS outcomes and a favorable safety profile. The RASolute 302 trial will further investigate the efficacy of this innovative drug in improving the prognosis for patients with metastatic PDAC.

Pancreatic cancer remains one of the deadliest forms of cancer, often diagnosed at an advanced stage and showing significant resistance to standard chemotherapy treatments. In the United States, it is estimated that around 60,000 people will be diagnosed with pancreatic cancer in 2024, and approximately 50,000 will die from the disease. The most prevalent type of pancreatic cancer, accounting for 92% of cases, is pancreatic ductal adenocarcinoma (PDAC). Due to the lack of early detection methods, the majority of PDAC patients are diagnosed at a late stage when the disease has metastasized. This form of cancer is heavily associated with RAS mutations, found in more than 90% of PDAC cases, making it particularly challenging to treat and contributing to a five-year survival rate of just 3%.

RMC-6236 is an oral, direct RAS(ON) multi-selective inhibitor that shows promise in treating various cancers driven by RAS mutations. It works by inhibiting RAS signaling across different oncogenic RAS mutations, including G12X, G13X, and Q61X, and is relevant for major cancers such as PDAC, non-small cell lung cancer (NSCLC), and colorectal cancer (CRC).

Revolution Medicines is a clinical-stage oncology company that is developing targeted therapies for cancers driven by RAS mutations. Their research and development pipeline includes a range of RAS(ON) inhibitors, such as RMC-6236, RMC-6291 (a G12C-selective inhibitor), and RMC-9805 (a G12D-selective inhibitor), all currently in clinical development. The company also focuses on developing mutant-selective inhibitors and companion inhibitors, broadening the scope of their therapeutic approaches for RAS-addicted cancers.