Dr Yaeger on the Background of the CodeBreaK 101 Trial in mCRC

Rona Yaeger, MD, associate attending physician, Memorial Sloan Kettering Cancer Center, discusses the rationale for launching an expansion cohort study based on findings from the phase 1b/2 CodeBreaK 101 trial (NCT04185883) of sotorasib (Lumakras) plus panitumumab (Vectibix) in patients with metastatic colorectal cancer (mCRC), highlights the characteristics of the specific patient population that was evaluated, and elucidates outcomes from the investigation.

This expansion cohort study extends the findings from the CodeBreaK 101 trial, which demonstrated promising activity with the combination of sotorasib and panitumumab in patients with mCRC, Yaeger begins. Focused on a defined second-line setting, the study enrolled 20 patients and assessed the safety and activity of this combination in a population that had not been heavily treated with later lines of therapy, she says. Most patients in this study had received no more than 1 prior treatment for metastatic disease, and the study focused on those with KRAS G12C–mutated mCRC, Yaeger explains. The combination elicited an observed overall response rate of 30% (95% CI, 11.9%-54.3%). All 6 responders achieved a partial response, she notes.

The median progression-free survival reached 11.0 months (95% CI, 4.3-14.3), and the safety profile was favorable, Yaeger expands. Although some patients required dose reductions of panitumumab, none had to discontinue treatment. The adverse effects associated with the combination in this cohort study aligned with those reported in prior studies of both agents, she highlights.

The study's emphasis on second-line patients provides valuable insights into the safety and efficacy of the sotorasib and panitumumab combination in a specific clinical setting, Yaeger continues. The overall tolerability of these targeted therapy combinations is encouraging, and the observed toxicities, primarily related to the EGFR antibody, are manageable with established strategies, such as prophylaxis for skin rash, as well as behavioral modifications, she explains. This study contributes to the ongoing exploration of targeted therapies in CRC, laying the groundwork for potential advancements in treatment strategies, Yaeger concludes.

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