NEW YORK – Revolution Medicines on Tuesday said the first patient with a KRAS G12-mutant advanced solid tumor has received the firm's RAS inhibitor RMC-6236 in a Phase I/Ib trial.
The company aims to enroll around 140 patients with solid tumors such as colorectal, pancreatic, and non-small cell lung cancer. To participate in the study, patients must harbor a KRAS G12A, G12D, G12R, G12S, or G12V mutation in their tumors. The first dosed patient had pancreatic cancer driven by a KRAS G12D mutation.
In the trial, the main goal is to characterize the safety and tolerability of RMC-6236 and determine a recommended dose. Researchers will also evaluate response rate, duration or response, disease control rate, time to response, and progression-free survival.
"RMC-6236 is a compelling drug candidate with the potential to demonstrate broad utility across many RAS cancer variants, particularly those harboring KRAS G12 mutations," Steve Kelsey, Revolution's president of R&D, said in a statement. "We are enthusiastic about its potential both to display first-in-class single agent activity as an inhibitor of mutant RAS and to be deployed as a RAS companion inhibitor in combination with mutant-selective RAS(ON) Inhibitors we have in development."
Revolution describes RMC-6236 as a RAS(ON) inhibitor designed to block RAS proteins from turning on or becoming active. Revolution has three other RAS inhibitors in preclinical phase: the KRAS G12C inhibitor RMC-6291; the KRAS G12D inhibitor RMC-9805; and the KRAS G13C inhibitor RMC-8839.
The Redwood City, California-based firm is also advancing three RAS companion inhibitors, including the SHP2 inhibitor RMC-4630 under development in a Phase II trial with Sanofi; the mTORC1/4EBP1 inhibitor RMC-5552 in a Phase I trial; and the SOS1 inhibitor RMC-5845 in preclinical studies.