Your Health, We Care
Release date: 2024-11-15 17:22:48 Recommended: 92
In a phase 1 study, sotorasib showed anticancer activity in patients with advanced solid tumors with KRAS p.G12C mutations, and particularly promising anticancer activity was observed in a subgroup of patients with non-small cell lung cancer (NSCLC).
In a single-arm phase 2 trial, the activity of sotorasib (960 mg dose orally once daily) was investigated in patients with advanced non-small cell lung cancer with KRAS p.G12C mutation who had previously received standard therapy. The primary endpoint is objective response (complete or partial response) according to independent central review. Key secondary endpoints include duration of response, disease control (defined as complete response, partial response, or stable disease), progression-free survival, overall survival, and safety. The correlation of exploratory biomarkers with treatment response to sotorasib was evaluated.
Of the 126 patients enrolled, the majority (81.0%) had received prior platinum-based chemotherapy and programmed death inhibitor 1 (PD-1) or programmed death-ligand 1 (PD-L1). According to the central review, 124 patients had measurable disease at baseline and remission was assessed. Objective response was observed in 46 patients (37.1%; 95% confidence interval [CI], 28.6 to 46.2), with 4 patients (3.2%) achieving a complete response and 42 patients (33.9%) achieving a partial response. Median duration of response was 11.1 months (95% CI, 6.9 to unevaluable). Disease was controlled in 100 patients (80.6%; 95% CI, 72.6 to 87.2). Median progression-free survival was 6.8 months (95% CI, 5.1 to 8.2) and median overall survival was 12.5 months (95% CI, 10.0 to unevaluable). Treatment-related adverse events occurred in 88 of 126 patients (69.8%), of which 25 patients (19.8%) had a grade 3 event and 1 patient (0.8%) had a grade 4 event. Reactions were observed in subgroups defined based on PD-L1 expression, tumor mutational burden, and concurrent mutations. STK11, KEAP1 or TP53.
In this Phase 2 trial, Sotorasib sortorasib therapy delivered a lasting clinical benefit in the absence of a new safety signal in patients previously treated with KRAS p.G12C-mutant non-small cell lung cancer.
