Garsorasib, a KRAS G12C inhibitor, with or without cetuximab, an EGFR antibody, in colorectal cancer cohorts of a phase II trial in advanced solid tumors with KRAS G12C mutation

PMCID: PMC12170901

PMID: 40523897

DOI: 10.1038/s41392-025-02274-z

Journal: Signal transduction and targeted therapy

Publication Date: 2025-6-17

Authors: Ruan DY, Wu HX, Xu Y, Munster PN, Deng Y, et al.

Key Points

• First study with the highest proportion of Asian mCRC patients receiving a KRAS G12C inhibitor, demonstrating promising anti-tumor activity
• Combination therapy ORR of 45.2% (95% CI, 29.8–61.3) significantly outperformed historical standard-of-care treatments
• Garsorasib represents a potential new precision therapy option for KRAS G12C-mutated mCRC patients with limited treatment alternatives

Summary

This phase II clinical trial investigated garsorasib, a novel KRAS G12C inhibitor, in heavily pretreated metastatic colorectal cancer (mCRC) patients with KRAS G12C mutations. The study evaluated the drug's efficacy and safety in two cohorts: garsorasib monotherapy (n=26) and garsorasib plus cetuximab combination therapy (n=42), focusing on patients who had received multiple prior lines of treatment.

The combination therapy demonstrated superior clinical outcomes, with an objective response rate (ORR) of 45.2% compared to 19.2% in the monotherapy group. Notably, the combination cohort showed a median progression-free survival of 7.5 months and an unreached median overall survival, suggesting potential synergistic effects between the KRAS inhibitor and anti-EGFR antibody. Both treatment approaches exhibited manageable safety profiles, with most adverse events being reversible and grade 1-2 in severity.