Identifying KRAS G12C resistance mechanisms through genomic profiling; plus argenx, Revolution and Tenaya

A new paper in the New England Journal of Medicine shows how genomic profiling of tumor tissue and plasma circulating tumor DNA (ctDNA) could help characterize mechanisms of acquired resistance to KRAS G12C inhibitors. Dana-Farber Cancer Institute researchers and colleagues used tissue and plasma samples from 38 patients treated with Phase II KRAS G12C inhibitor adagrasib, in development by Mirati Therapeutics Inc. (NASDAQ:MRTX), to identify resistance mechanisms including secondary mutations, amplifications and fusions in KRAS and other genes. The study, which uses a liquid biopsy assay from the Foundation Medicine Inc. unit of Roche (SIX:ROG; OTCQX:RHHBY), could provide insights for companies exploring mechanisms to get around KRAS G12C resistance.

Revolution Medicines Inc. (NASDAQ:RVMD) demonstrated in Nature Chemical Biology that selectively blocking mTORC1 and its subsequent inactivation of the tumor suppressor eIF4EBP1 could treat breast cancer. In mice, two selective mTORC1 inhibitors reduced tumor growth and eIF4EBP1 inactivation, without inducing the glucose intolerance observed with pan-mTOR inhibitors. The findings make the case for mTORC1 inhibitor RMC-5552, which is part of the company’s pipeline of Ras companion inhibitors and began Phase I testing in April...