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Revolution Medicines Expands Development of SHP2 Inhibitor in KRAS-Mutated Cancers

NEW YORK – Revolution Medicines on Saturday presented data on the preliminary activity of RMC-4630 in combination with cobimetinib (Genentech/Exelixis' Cotellic) in KRAS-mutated colorectal cancer, and said that it will study its SHP2 inhibitor in combination with a drug being advanced by AstraZeneca.

At a virtual meeting this weekend hosted by the European Organization for Research and Treatment of Cancer, the National Cancer Institute, and the American Association for Cancer Research, researchers presented early data from the Phase Ib/II study of RMC-4630 and the MEK inhibitor cobimetinib. The dose escalation and expansion trial is investigating the combination in patients with relapsed or refractory solid tumors who harbor mutations in the RAS pathway.

Results of this study will inform the Phase II dose of RMC-4630 when paired with cobimetinib and select molecularly defined histologies for further study. The presentation at the meeting focused "on cancers with RAS mutations lacking a mutant-selective inhibitor, and suggested that RMC-4630 and cobimetinib can be combined through an innovative dual intermittent dosing schedule to drive anti-tumor activity in advanced colorectal cancers," Revolution Medicines CEO Mark Goldsmith said in a statement.

At the meeting, researchers reported that three out of seven colorectal cancer patients with KRAS mutations had reductions in tumor volume at the highest dose of RMC-4630, and one patient with a KRAS G12D mutation had an unconfirmed partial response. There were no unexpected safety issues.

Revolution Medicines also said it had signed an agreement with AstraZeneca to study RMC-4630 in combination with one of its "emerging assets" in KRAS G12C-mutated cancers. AstraZeneca will sponsor and conduct the study of the combination regimen, while Revolution Medicines will supply RMC-4630.

KRAS-mutated cancers, once considered undruggable, are now an active area of drug development. In addition to the latest collaboration with AstraZeneca, Revolution Medicines and Amgen are studying RMC-4630 in combination with Amgen's soratinib in the Phase Ib CodeBreak101 trial involving patients with KRAS G12C-mutated solid cancers.