Frontier Medicines Phase 1/2 Trial of FMC-376 in KRAS G12C-Mutant NSCLC at ESMO 2026

 

• FMC-376 is an equipotent ON+OFF KRAS G12C inhibitor designed with the Frontier™ Platform to address limitations of current KRAS G12C inhibitors, including resistance and tolerability
• Treatment with FMC-376 in the Phase 1A portion of the trial led to confirmed overall objective response rate of 56% in NSCLC patients, including 67% in KRAS G12C inhibitor-naïve patients and 44% in patients previously treated with OFF-state KRAS G12C inhibitors, with 90% of responders harboring at least one co-alteration associated with clinical resistance to KRAS inhibitors
• FMC-376 demonstrated 7.5 months median duration of response, with 60% of responders ongoing at time of data update
• FMC-376 was well tolerated, with low rates of gastrointestinal toxicities and hepatic transaminase elevations, which are known class effects of other KRAS G12C inhibitors 
• Phase 1/2 PROSPER trial is ongoing in NSCLC, evaluating: 1) FMC-376 in combination with pembrolizumab, 2) FMC-376 monotherapy in a randomized dose-optimization cohort in patients naïve to or previously treated with OFF-state KRAS G12C inhibitors, and 3) FMC-376 as first-line monotherapy

https://firstwordpharma.com/story/8267199