KRAS G12C Inhibition with Sotorasib for Advanced Solid Tumors

KRAS G12C mutations are associated with poor outcomes in patients with cancer, and they can occur in about 13% of non–small-cell lung cancers (NSCLCs) and 1% to 3% of colorectal cancers (CRCs) and other solid cancers.

Now, investigators have conducted an industry-funded, phase I study to evaluate the safety and activity of sotorasib, an oral KRAS G12C inhibitor, in 129 pretreated patients with advanced solid tumors (59 with NSCLC, 42 with CRC, and 28 with other tumors) harboring the KRAS G12C mutation.

Results were as follows:

• No dose-limiting toxicities or treatment-related deaths were reported.
• 12% of patients experienced grade 3–4 treatment-related toxicities, the most common of which were diarrhea (30%), fatigue (23%), and nausea (21%).
• In the NSCLC cohort, at a median follow-up of 11.7 months, the response rate was 32%, the disease control rate was 88%, and median progression-free survival (PFS) was 6.3 months.
• In the colorectal cohort, at a median follow-up of 12.8 months, the response rate was 7%, the disease control rate was 74%, and median PFS was 4.0 months.
• Responses were also seen in patients with pancreatic, endometrial, and appendiceal cancers and melanoma.