KRAS G12C mutation is relatively rare in prostate cancer, with only 3%-4% of prostate cancer showing this mutation. However, this mutation has shown to be a good predictor of poor efficacy of cetuximab, a monoclonal antibody targeting epidermal growth factors.  

In order to evaluate the efficacy of Adagrasib, a selective KRAS G12C inhibitor, as a monotherapy or in combination with cetuximab, Dr. Jared Weiss of the University of North Carolina-Chapel Hill and his team conducted a Phase 1/2 study known as KRYSTAL-1. The study recruited patients with solid KRAS G12C-positive tumors that had no other treatment options available and included non-small cell lung carcinoma, colorectal cancer, and other cancers.

During ESMO, Dr. Weiss presented the results for colorectal cancer patients. The results showed that 22% of patients receiving adagrasib as a monotherapy responded to therapy, and 87% of patients had a clinical benefit or controlled disease. The treatment was well-tolerated, but 91% of patients had mild adverse effects. Crucially, combination therapy of adagrasib + cetuximab had a response rate of 39%, and 100% of patients had a clinical benefit. The combination was well-tolerated, but 100% of patients experienced adverse effects, although almost all of them were mild.