Dr. Iams talks about the evaluation of sotorasib in KRAS G12C mutant solid tumors

Wade T. Iams, MD, discusses the evaluation of sotorasib in KRAS G12C mutant solid tumors, including non-small cell lung cancer.

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 monotherapy and in combination with other agents in patients with solid tumors harboring kras G12C mutations. A cohort of treatment-naïve patients with advanced NSCLC receive sotorasib as monotherapy.

Investigators watch for hepatotoxicity, especially in combination approaches, and this was seen when pembrolizumab (Keytruda) was given at the same time as sotorasib, Iams says. When sotorasib was given at higher doses in this cohort, grade 3 or higher hepatotoxicity occurred in more than 75% of patients, Iams says. However, when sotorasib was given at doses of 360 mg or less per day in combination with pembrolizumab, grade 3 or higher hepatotoxicity was seen in 25% to 40% of patients, adds Iams.

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

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