Dr Sommerhalder on the Potential Utility of Single-Agent RMC-6291 in KRAS G12C–Mutant CRC

David Sommerhalder, MD, medical oncologist, hematologist, Texas Oncology, director, Clinical Research, NEXT Oncology, discusses the potential for RMC-6291 as a single agent in KRAS G12C–mutated advanced colorectal cancer (CRC).

The efficacy and tolerability of this KRAS G12C inhibitor was evaluated in a phase 1 trial (NCT05462717) in patients with advanced KRAS G12C–mutant solid tumors. The patient population included those with non–small cell lung cancer (NSCLC; n = -23), CRC (n = 33), and other tumors (n = 7). Preliminary data derived from the study demonstrated clinical activity with the agent in patients with KRAS G12C–mutant tumors who were previously exposed to a KRAS G12C inhibitor and in those who were not. The agent also had an acceptable safety profile and was tolerable across all dose levels.

Outcomes were particularly promising for patients with KRAS G12C–mutant CRC, Sommerhalder says. Efficacy evaluable patients with CRC who were naïve to a KRAS G12C inhibitor (n = 20) experienced an overall response rate of 40%, which was comprised entirely of partial responses. These patients also achieved a disease control rate of 80%. Responses were observed across various dose levels, and patients were still undergoing treatment, Sommerhalder notes. In these CRC patients with responses, the median time to response was 1.4 months (range, 1.2-4.1), and the median time on treatment was 2.4 months (range, 0.3-7.9).

Unlike other KRAS G12C inhibitors, which have shown lower response rates when used as single agents in patients with CRC, RMC-6921 monotherapy produced encouraging clinical activity in this population, Sommerhalder details. This indicates the potential for even deeper and longer-lasting responses with single-agent RMC-6291 in patients with CRC and supports the agent's continued development, he concludes.