Sotorasib in KRAS G12C-Mutated Metastatic Colorectal Cancer: CodeBreaK 100 Trial

On December 14, 2021, Marwan G. Fakih and colleagues from the City of Hope Comprehensive Cancer Center published the results of the CodeBreaK 100 (NCT03600883) Phase 2 clinical trial in The Lancet Oncology. This study focused on the colorectal cancer (CRC) cohort of patients with KRAS G12C-mutated advanced solid tumors treated with Sotorasib.

Study Design: CodeBreaK 100 CRC Cohort

This open-label, multicenter Phase 2 trial enrolled 62 patients with KRAS G12C-mutated metastatic colorectal cancer who had progressed after prior standard therapies. All patients received Sotorasib at a dose of 960 mg orally once daily.

The primary endpoint was the objective response rate (ORR). Secondary endpoints included the disease control rate (DCR) and progression-free survival (PFS).

Key Efficacy Results

• Objective Response Rate (ORR): 9.7% (6 out of 62 patients).
  • All six responders achieved a partial response (PR).
• Disease Control Rate (DCR): 82.3%
• Median Progression-Free Survival (PFS): 4.0 months.

While the response rate was lower than that observed in KRAS G12C-mutated non-small cell lung cancer, the high disease control rate suggests some degree of clinical activity in this challenging population.

Safety Profile

Sotorasib was generally well-tolerated:

• Grade 3 Adverse Events: Occurred in 10% of patients, with diarrhea (3%) being the most common.
• Grade 4 Adverse Events: One patient (2%) experienced elevated blood creatine phosphokinase.
• No treatment-related deaths were reported.

Conclusion

The researchers concluded that while the ORR of 9.7% did not meet the predefined target for the monotherapy cohort, Sotorasib demonstrates a manageable safety profile and evidence of disease stability in heavily pretreated KRAS G12C-mutated metastatic CRC. Current research is exploring Sotorasib in combination with other agents (such as EGFR inhibitors) to enhance its efficacy in colorectal cancer.

Source: The Lancet Oncology - CodeBreaK 100 Colorectal Cancer Results

#ColorectalCancer #KRASG12C #Sotorasib #CodeBreaK100 #PrecisionMedicine #CancerResearch

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