CodeBreaK 300 OS results support sotoraxib 960mg and panitumumab as SOC for mCRC

A new update from the Phase 3 CodeBreaK 300 study was presented at the 2024 American Society of Clinical Oncology Annual Meeting, providing insights into the study's final overall survival (OS) analysis. CodeBreaK 300 studied the combination of sotorasiib (AMG510) and panitumumab in patients with KRAS G12C-mutated metastatic colorectal cancer (mCRC) that is refractory to chemotherapy. Although sotorasibr plus panitumumab was found to be superior in terms of progression-free survival (PFS), the study's primary endpoint, data on secondary endpoints, including OS and objective response rate (ORR), were still immature at the time.

A total of 160 patients participated in the study. They were randomly assigned to receive different treatment regimens: sotoracib 960 mg and panitumumab treatment group (n=53), sotoracib 240 mg and panitumumab treatment group, and the investigator's choice of trifluridine/tipiracil or regorafenib (n=54). As of December 2023, the median follow-up time was 13.6 months, and 82 patients had died, including 24, 28, and 30 deaths in the sotoracib 960 mg group, sotoracib 240 mg group, and the investigator's selection group, respectively. The median OS (95% confidence interval) for the sotoraxib 960 mg arm has not yet been reached. In the sotorasib 240 mg group and the investigator's choice group, the median OS was 11.9 months (7.5 to not estimable) and 10.3 months (7.0 to not estimable), respectively.

Compared with the investigator's choice of treatment, the hazard ratio was 0.70 (0.41-1.18) in the 960 mg group and 0.83 (0.49-1.39) in the 240 mg group. The objective response rates were 30.2% (18.3-44.3), 7.5% (2.1-18.2), and 1.9% (0.0-9.9) in the sotoraceib 960 mg, sotoraceib 240 mg, and investigator's choice groups, respectively. The findings revealed no new safety signals.

Results from the CodeBreaK 300 study showed that patients treated with sotoraxib 960mg and panitumumab showed a trend toward improved overall survival (OS). Taking into account the PFS and response rate of treatment, this study supports the use of sotoraxib 960 mg and panitumumab as a potential standard of care for patients with chemotherapy-refractory KRAS G12C mutant mCRC. These results provide important references for clinical practice. In future clinical practice, the conclusions of the CodeBreaK 300 study need to be further verified, and the treatment effect and safety of patients need to be closely monitored.