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The existence of two approved therapies, Lumakras (sotorasib, Amgen Inc.) and Karzati (adagrasib, Mirati Therapeutics Inc.), has been a triumphant success against KRAS, a protein that was once considered undruggable. KRAS is the most frequently mutated oncogene in solid tumors. KRAS driver mutations are found in about 30% of non-small-cell lung cancers (NSCLC), about half of colorectal cancers, and more than 90% of pancreatic cancers. Lumakras and Karzati both target the G12C mutation. Inhibitors that target other mutations, like G12D, are now making their way through preclinical and clinical development, while some companies are developing therapies that would target mutated KRAS more broadly, irrespective of the specific mutation that is activating the protein. ....
Kathryn C. Arbour, MD, discusses the unique mechanism of action of RMC-6236, the preliminary efficacy and safety findings for this agent in patients with KRAS-mutant NSCLC, and future directions for the RMC-6236-001 trial. ....
Ignacio Garrido-Laguna, MD, PhD, MBA, discusses preliminary safety and efficacy data with the use of RMC-6236 in patients with KRAS-mutated pancreatic ductal adenocarcinoma, highlighting the ongoing investigation of this agent. ....
Kathryn C. Arbour, MD, discusses preliminary safety and efficacy data with the RAS inhibitor RMC-6236 in patients with KRAS-mutated non–small cell lung cancer. ....