Amgen and Revolution Medicines Partner to Evaluate Combination Therapy of KRAS G12C Inhibitor AMG 510 and SHP2 Inhibitor RMC-4630 in Phase 1b Trial

Today, Amgen announced a collaboration agreement with Revolution Medicines to evaluate the efficacy and safety of a combination therapy comprising the KRAS G12C inhibitor AMG 510 and the SHP2 inhibitor RMC-4630 in patients with advanced solid tumors harboring KRAS G12C mutations, within a Phase 1b clinical study.

Revolution Medicines’ lead candidate, RMC-4630, is an orally bioavailable small molecule that selectively inhibits SHP2 activity. SHP2 is a well-validated oncogene and a convergence point for multiple signaling pathways that activate RAS. Given the critical role of RAS activation in cancer cell growth and survival, SHP2 has emerged as a compelling cancer therapeutic target. Amgen’s AMG 510 is a first-in-class covalent inhibitor of the KRAS G12C mutant. It irreversibly locks KRAS in its GDP-bound inactive state, thereby suppressing KRAS activity. Previously, AMG 510 demonstrated promising therapeutic potential by inducing responses in patients with non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and appendiceal cancer in clinical trials. Preclinical data indicate that combining KRAS G12C inhibitors with SHP2 inhibitors can enhance antitumor activity through complementary mechanisms of action.

▲SHP2 regulates the RAS signaling pathway (Image source: Revolution Medicines official website)

Under the terms of the agreement, Revolution Medicines, Inc. will provide Amgen with RMC-4630 for combination therapy research, while Amgen will primarily conduct this clinical trial.

“Our collaboration with Amgen provides us with a new opportunity to effectively leverage RMC-4630,” said Dr. Mark A. Goldsmith, President and Chief Executive Officer of Revolution Medicines, Inc. “Currently, our development program for RMC-4630 includes a Phase 1 monotherapy trial, a Phase 1b/2 trial of combination therapy with the MEK inhibitor cobimetinib, and a Phase 1b trial of combination therapy with AMG 510.”

References:

[1] Revolution Medicines and Amgen Partner on Phase 1b Study to Evaluate Combination of RMC-4630 and AMG 510, Retrieved November 4, 2019, from https://www.prnewswire.com/news-releases/revolution-medicines-and-amgen-partner-on-phase-1b-study-to-evaluate-combination-of-rmc-4630-and-amg-510-300950392.html

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