Revolution Medicines Announces Dosing of First Patient in Phase 1b Combination Study of RMC-4630 and AMG 510

Study Evaluates Combination Treatment with Investigational SHP2 and KRAS^G12C Inhibitors in Patients with KRAS^G12C Mutant Solid Tumors

REDWOOD CITY, Calif., June 09, 2020 (GLOBE NEWSWIRE) -- Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage oncology company focused on developing targeted therapies to inhibit frontier cancer targets, today announced dosing of the first patient in a Phase 1b clinical trial evaluating the combination of RMC-4630, the company’s investigational SHP2 inhibitor, and AMG 510, Amgen’s investigational KRAS^G12C inhibitor. The trial, which is being sponsored and conducted by Amgen with clinical supply of RMC-4630 provided by Revolution Medicines, is an open-label, dose-escalation and dose-expansion study evaluating the safety, tolerability, pharmacokinetics, and efficacy of the combination of RMC-4630 and AMG 510 in patients with advanced solid tumors harboring the KRAS^G12C mutation.

RMC-4630 is a potent and orally bioavailable small molecule that is designed to selectively inhibit the activity of SHP2, an upstream cellular protein that plays a central role in modulating cell survival and growth by transmitting signals from receptor tyrosine kinases to RAS. AMG 510 is a first-in-class investigational oral therapy designed to selectively and irreversibly target the KRAS^G12C protein, an oncogenic RAS mutant at the core of the RAS signaling cascade.

Preclinical and clinical research has shown that cancers caused by RAS pathway mutations exhibit “oncogene addiction,” in which tumor cells become highly dependent on signaling through the RAS pathway to survive. Suppressing KRAS^G12C activity, either directly with AMG 510 or indirectly by inhibiting SHP2 with RMC-4630, has shown anti-tumor activity against non-small cell lung tumors harboring KRAS^G12C in early clinical trials. In addition, adaptive resistance to inhibition of RAS signaling is common. SHP2 is an upstream RAS pathway node that often plays a key role in adaptive resistance, and inhibiting SHP2 with RMC-4630 has been shown preclinically to suppress adaptive resistance to KRAS^G12C inhibitors.

“Our strategy is to advance a broad clinical program to assess the therapeutic potential of RMC-4630 in both monotherapy and multiple combination treatment regimens. With our recent demonstration of encouraging monotherapy activity for RMC-4630 against KRAS^G12C lung cancers, it is compelling to pair this investigational drug with KRAS^G12C inhibitors such as AMG 510,” said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. “This collaborative trial sponsored by Amgen, a leader in the field, will help test our hypothesis that RMC-4630 may be useful as the backbone of targeted therapy combinations for the treatment of various RAS-dependent tumors.”