First-Ever KRAS Inhibitor Gets Accelerated Approval for Non-Small Cell Lung Cancer

Bob Li, MD, PhD, MPH

The U.S. Food and Drug Administration (FDA) has announced an accelerated approval of sotorasib (Lumakras™) for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC). Memorial Sloan Kettering’s Bob Li served as principal investigator of the CodeBreaK 100 trial, the largest clinical trial conducted to date exclusively for patients with the KRAS G12C mutation.

“This approval marks an important advance in targeted therapies and could change the treatment paradigm for patients with KRAS G12C-mutated non-small cell lung cancer,” explained Dr. Li. “Researchers and physicians at Memorial Sloan Kettering have had their sights set on this target for nearly 40 years and with this first-of-its-kind accelerated approval, we have taken an important first step in cracking KRAS and providing a new treatment option for patients.”

Approval was based on results from a subset of patients in the clinical trial. The trial demonstrated favorable efficacy and tolerability in 124 patients with KRAS G12C mutation-positive NSCLC who had disease progression after receiving an immunotherapy and/or chemotherapy. In the trial, 960 mg of sotorasib administered orally once-daily demonstrated an overall response rate of 36 percent with 81 percent of patients achieving disease control (percentage of patients who have achieved complete response, partial response and stable disease for more than three months). Earlier data from the CodeBreaK 100 trial was presented at the World Conference on Lung Cancer and published in the New England Journal of Medicine.

The cancer gene KRAS has been studied for almost 40 years and is responsible for many of the most common cancers, including about one-quarter of lung cancers and between one-third and one-half of colorectal cancers. However, until recently, the KRAS protein was considered an “undruggable” target.  In a paper published in Science in 2016, MSK physician-scientists Piro Lito and Neal Rosen showed how it was possible to target KRAS in cancer cells.