Revolution Medicines Doses First Patient in Clinical Trial Evaluating RMC-5127, a RAS(ON) G12V-Selective Inhibitor

On January 29, 2026 Revolution Medicines, a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers, reported the first patient was dosed in its first-in-human clinical trial evaluating RMC-5127, a RAS(ON) G12V-selective inhibitor.

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The first-in-human trial, RMC-5127-001 [NCT07349537], is an open-label trial evaluating the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of RMC-5127 as both a monotherapy and in combination settings. The trial will enroll patients with RAS G12V–mutated solid tumors, including pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC), and non–small cell lung cancer (NSCLC), who have progressed on or are intolerant to prior standard therapies, including targeted treatments.

"By bringing RMC-5127 to the clinic, we are building on our well-validated RAS(ON) inhibitor approach and extending it to RAS G12V, the second most common RAS mutation driving human cancers, where there are no approved targeted treatment options," said Alan Sandler, M.D., chief development officer of Revolution Medicines. "As our fifth disclosed mutant-selective RAS(ON) inhibitor and fourth clinical-stage program, RMC-5127 broadens the RAS variant coverage of our growing portfolio and opens a suite of development opportunities aimed at improving outcomes for patients with RAS-driven cancers."

RMC-5127 is an innovative inhibitor that binds to cyclophilin A, creating a complex that selectively recognizes and inhibits the oncogenic RAS(ON) form of the RAS G12V variant. RAS G12V is the second most common driver of RAS-addicted human cancers with approximately 48,000 patients diagnosed in the U.S.1 each year, predominantly among patients with PDAC, CRC, or NSCLC.

(Press release, Revolution Medicines, JAN 29, 2026, View Source [SID1234662355])