Revolution Medicines Reports Progress and Expansion of Combination Strategy with RMC-4630 as Therapeutic Backbone for RAS-Addicted Cancers - Seite 2

Expansion of Combination Program

Revolution Medicines also announced that it has signed an agreement with AstraZeneca (LSE/STO/Nasdaq: AZN) to enter a clinical collaboration to study RMC-4630 in combination with an emerging asset from AstraZeneca’s preclinical efforts targeting KRAS^G12C. Under the agreement, AstraZeneca will sponsor and conduct this combination study and Revolution Medicines will provide clinical supply of RMC-4630.

Separately, Revolution Medicines and Amgen are collaborators in an ongoing Amgen-sponsored clinical trial studying RMC-4630 in combination with AMG 510 (soratinib), an investigational KRAS^G12C(OFF) inhibitor.

“Drug combinations are likely to be critical for defeating inherent drug resistance mechanisms exploited by RAS-addicted cancers, and both the data presented at ENA 2020 and the new clinical collaboration announced today represent important steps forward in developing RMC-4630 as a backbone of such combination therapies. The ENA presentation focuses on cancers with RAS mutations lacking a mutant-selective inhibitor, and suggest that RMC-4630 and cobimetinib can be combined through an innovative dual intermittent dosing schedule to drive anti-tumor activity in advanced colorectal cancers,” said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. “We are currently refining a recommended Phase 2 dose and schedule to evaluate further for safety, tolerability and anti-tumor activity in dedicated expansion patient cohort(s).”

“We are also excited to collaborate with AstraZeneca to study RMC-4630 in combination with an emerging asset from AstraZeneca’s pipeline targeting KRAS^G12C(OFF) for tumors carrying a KRAS^G12C mutation, a planned study that represents an expansion of our commitment to RMC-4630 as a backbone for combinations with RAS-mutant inhibitors. We also continue growing our exciting pipeline of direct inhibitors of oncogenic RAS(ON) variants, including our direct inhibitors of KRAS^G12C(ON) and KRAS^G12D(ON) currently in lead optimization.”

RMC-4630 and cobimetinib are targeted inhibitors of oncogenic proteins at distinct positions within the RAS signaling cascade that is frequently exploited by human cancers and may develop adaptive resistance to single agent treatment. RMC-4630 is a potent and orally bioavailable small molecule designed to selectively inhibit the activity of SHP2, an upstream cellular protein that plays a key role in modulating cell growth by transmitting signals from receptor tyrosine kinases to RAS. Cobimetinib, marketed in the U.S. by Genentech, a member of the Roche group, inhibits the activity of MEK, a downstream effector of RAS that affects cell survival and growth. Cobimetinib is approved in the U.S. for the treatment of patients with BRAF^V600E or BRAF^V600K mutation-positive unresectable or metastatic melanoma in combination with vemurafenib (Zelboraf). Cobimetinib is provided by Genentech for the RMC-4630-02 study under a clinical collaboration agreement with Revolution Medicines.