Revolution Medicines Reports Progress and Expansion of Combination Strategy with RMC-4630 as Therapeutic Backbone for RAS-Addicted Cancers
Plenary Presentation at EORTC-NCI-AACR 32nd Symposium on Molecular Targets and Cancer Therapeutics Describes Encouraging Tolerability and Exposure Profiles for RMC-4630 Combined with Cobimetinib and Early Evidence of Clinical Activity in RASmut Colorectal Cancers
Company Also Announces New Clinical Collaboration with AstraZeneca to Study RMC-4630 in Combination with an Emerging AstraZeneca Asset Targeting KRASG12C
REDWOOD CITY, Calif., Oct. 24, 2020 (GLOBE NEWSWIRE) -- Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage precision oncology company developing targeted therapies to inhibit frontier targets in RAS-addicted cancers, today reported interim data from the company’s ongoing Phase 1b/2 clinical trial (RMC-4630-02) evaluating the combination of RMC-4630 and cobimetinib (Cotellic) in an oral presentation by Johanna C. Bendell, M.D., Sarah Cannon Research Institute, Nashville, TN in a plenary session at the EORTC-NCI-AACR 32nd Symposium on Molecular Targets and Cancer Therapeutics (ENA 2020). Interim results suggest that a dual intermittent dosing strategy for RMC-4630 and cobimetinib exceeds target plasma exposures for each drug based on preclinical models of RAS pathway-driven cancers that project potential clinical activity. The adverse event profile of the combination, which was consistent with expected on-pathway effects of both drugs, was tolerable under the dual intermittent dosing schedule.
The ongoing Phase 1b/2 RMC-4630-02 trial includes an open-label, dose-escalation and dose-expansion study arm designed to evaluate the safety, tolerability, pharmacokinetic, and pharmacodynamic proﬁles of RMC-4630 and cobimetinib in adult patients with relapsed/refractory solid tumors that harbor specific genomic RAS pathway mutations. The results of this study will inform Revolution Medicines’ pending selection of a recommended Phase 2 dose and schedule for the drug combination to be evaluated further in one or more expansion cohorts of patients selected by tumor genotype and histotype that are expected to initiate in 2020.
While evaluation of efficacy outcomes is not a primary objective of the dose escalation portion of the RMC-4630-02 study, investigators reported preliminary evidence of anti-tumor activity in patients with colorectal cancer driven by KRAS mutations. As of the data cut-off date, tumor volume reduction was observed in three of seven patients with colorectal cancers harboring KRAS mutations who were treated at the highest dose of RMC-4630, including one unconfirmed partial response in a patient carrying a KRASG12D mutation.