307?Atezolizumab plus vemurafenib and cobimetinib provides favorable survival outcomes in patients with high tumor mutation burden and proinflammatory gene signature in the phase 3 IMspire150 study

摘要

Background The phase 3 IMspire150 study ( NCT02908672 ) showed that first-line atezolizumab (A) combined with vemurafenib (V) cobimetinib (C) improved progression-free survival (PFS) vs placebo (P) V C in patients with BRAF V600 mutation–positive advanced melanoma (15.1 vs 10.6 months; hazard ratio [HR] 0.78; 95% CI 0.63–0.97; P=0.0249). Insights into the clinical benefit of the A V C triple combination in prognostic molecular subgroups of patients can inform treatment selection and future clinical research. Methods 514 patients were randomized 1:1 to A V C (n=256) or P V C (n=258). The efficacy endpoints analyzed included PFS and duration of response (DOR) estimated using the Kaplan-Meier method. Outcomes were based on investigator-assessed best overall response per Response Evaluation Criteria in Solid Tumors v1.1. Patients were primarily categorized into binary subgroups defined by tumor mutation burden (TMB; low or high: 10 mutations/Mb. Additional multivariate analyses are ongoing to delineate the PFS trends observed.