Assessing LY3537982 for KRAS G12C-Mutant Advanced Solid Tumors

Joshua K. Sabari, MD, assistant professor, Department of Medicine at NYU Grossman School of Medicine, and director of High Reliability Organization Initiatives at the Perlmutter Cancer Center, discusses LY3537982 for patients with KRAS G12C-mutant advanced solid tumors.

LY3537982 is a highly selective and potent KRAS G12C inhibitor currently being investigated in a first-in-human phase 1 study titled LOXO-RAS-20001 (NCT04956640). In the study, oral LY3537982 is being evaluated for the treatment of patients with KRAS G12C-mutated non–small cell lung cancer, colorectal cancer, pancreatic cancer, and other solid tumors.

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0:08 | LY3537982 is a potent, highly selective inhibitor of GTP bound KRAS G12C. It's one of the novel KRAS G12C inhibitors. We have seen FDA approvals of sotorasib [Lumakras] and adagrasib [Krazati]. This is a next in class KRAS G12C inhibitor, and I think what's unique about this agent is it has very unique pharmacological properties that permit a very high target occupancy at low exposures, which allow us to potentially combine this agent with other agents more safely.

0:44 | This was a classically designed phase 1a monotherapy escalation followed by a phase 1b expansion in patients with KRAS G12C mutation-positive lung cancer, I should say in general. This is the LOXO-RAS-20001 study. Patients were enrolled who had good performance status, who had a KRAS G12C mutation, and in the monotherapy escalation, we enrolled 84 patients starting at 50 milligrams BID [2 times a day], escalated all the way to 200 milligrams BID, and we included all patients with solid tumors. In the phase 1b expansion, we enrolled 2 different cohorts, including cohort part B4 which was specifically a non–small cell lung cancer population looking at LY3537982 in combination with pembrolizumab [Keytruda] and in part C2, we looked at a colorectal cancer population. This was LY3537982 in combination with cetuximab [Erbitux].