Multicenter phase 1-2a trial of glecirasib plus sitneprotafib for advanced KRAS-G12C-mutated non-small cell lung cancer
Glecirasib is an inhibitor of KRASG12C and sitneprotafib is an inhibitor of SHP2. The phase 1-2 JAB-21822-1006 trial at 26 centers in China evaluated the combination of glecirasib and sitneprotafib for KRASG12C-mutated advanced solid tumors. Among the 194 patients enrolled, 88% in phase 1 and 71% in phase 2a had NSCLC. At data cutoff, the median follow-up was 14.5 months (IQR 11.9-17.01). In phase 1, one dose-limiting toxicity was observed (grade 3 pneumonitis) at the highest dose level (glecirasib 800 mg plus sitneprotafib 3 mg once daily, 1 week on and 1 week off); no DLTs were observed at other dose levels. Across phase 1 and 2a, 98% of patients had at least one treatment-related adverse event. Three patients (2%) discontinued treatment due to TRAEs; there were no grade 5 TRAEs. The objective response rate was 71% (95% CI 61-79) in the subgroup with previously untreated NSCLC; 49% (32-65) in patients previously treated with systemic therapy but naïve to KRASG12C inhibitors, and 10% (2-27) in patients previously treated with KRASG12C inhibitor therapy. The authors conclude that the combination of glecirasib and sitneprotafib showed promising efficacy and manageable safety in patients with advanced KRASG12C-mutated NSCLC, particularly among those who had not received previous treatment.