Dr. Iams on the Evaluation of Sotorasib in KRAS G12C–Mutant Solid Tumors

Wade T. Iams, MD, assistant professor of medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, discusses the evaluation of sotorasib (Lumakras) in KRAS G12C–mutant solid tumors, including non–small cell lung cancer (NSCLC).

The phase 1/2 CodeBreaK-100 trial (NCT03600883) is evaluating the safety, tolerability, and efficacy of sotorasib as a single agent and in combination with other agents in patients with solid tumors harboring KRAS G12C mutations. A cohort of patients with treatment-naïve advanced NSCLC is receiving sotorasib monotherapy.

Investigators are watching for hepatotoxicity, particularly in the combination approaches, and it was observed when pembrolizumab (Keytruda) was administered concurrently with sotorasib, Iams says. When sotorasib was given at higher doses in this cohort, grade 3 or higher hepatotoxicity occurred in more than75% of patients, Iams explains. However, when sotorasib was administered atdoses of 360 mg or less per day in combination with pembrolizumab, grade 3 or higher hepatotoxicity was observed in the range of 25% to 40% of patients, Iams adds.

Another method found to reduce the rates of hepatotoxicity in these patients was to conduct a 21- or 42-day lead-in with sotorasib at 360 mg or less before introducing pembrolizumab, Iams concludes.