Dr Desai on the Efficacy of Divarasib Plus Cetuximab in KRAS G12C–Mutant CRC

Jayesh Desai, MBBS, FRACP, medical oncologist, associate professor, head, Phase I/Early Drug Development Program, associate director, Clinical Research, Peter MacCallum Cancer Centre, chair, the Sir Peter MacCallum Department of Oncology, the University of Melbourne, discusses efficacy data for the combination of divarasib (formerly GDC-6036) plus cetuximab (Erbitux) in patients with colorectal cancer (CRC) harboring a KRAS G12C mutation from a phase 1B study (NCT04449874).

Findings presented at the 2023 AACR Annual Meeting showed that divarasib plus cetuximab elicited a confirmed objective response rate (ORR) of 62%. Notably, 5 of the 29 patients in the overall population received prior treatment with KRAS G12C inhibitor, and 3 of these 5 patients had a confirmed partial response with the divarasib-based combination, Desai says.

Previous data on divarasib monotherapy presented at the 2022 ESMO Congress showed that the KRAS G12C inhibitor had a good safety profile and was well managed in most patients, Desai says, adding that there was a low rate of patients requiring dose reductions or treatment discontinuation. In most instances, investigators were able to manage adverse effects with supportive care and other medications, Desai says.

Efficacy data with divarasib monotherapy showed that the ORR was 31% in patients who received the full 400-mg dose day within the CRC cohort (n = 39), and the ORR across all dose levels was 24%. Since those data were reported, the confirmed ORR in patients treated at 400 mg has risen to 36%, Desai says. Given the improved ORR for patients treated with the combination of divarasib plus cetuximab, these are exciting data for patients with KRAS G12C–mutant CRC, Desai concludes.