Phase 1b Study of Cobimetinib Plus Atezolizumab in Patients with Advanced BRAFV600 Wild-Type Melanoma Progressing on Prior Anti–Programmed Death-1 Therapy.

Objective: To evaluate the efficacy and safety of cobimetinib plus atezolizumab in the treatment of patients with advanced BRAFV600 wild-type melanoma who had progressed on prior anti‒programmed death-1 (PD-1) therapy.

Patients and Methods: This phase 1b, open-label, global, multicenter study enrolled 3 cohorts. Herein we report on patients in cohorts A and B who had progressed on prior anti‒PD-1 therapy. Cohort A patients received cobimetinib 60 mg once daily for 21 days followed by a 7-day break and concurrent intravenous atezolizumab 840 mg every 2 weeks. Cohort B patients received the same dosing regimen as cohort A except for cycle 1 in which patients received cobimetinib only for the first 14 days prior to initiation of atezolizumab on cycle 1 day 15. Coprimary endpoints were objective response rate (ORR) and disease control rate (DCR). Secondary endpoints were duration of response (DoR), progression free survival (PFS), and overall survival (OS).

Results: Between June 19, 2017, and December 12, 2018, 103 patients were enrolled. Median follow-up was 6.9 months (interquartile range, 4.8‒10.1 months); ORR was 14.6% and DCR was 38.8% (95% CI, 29.39–48.94). The median DoR, PFS, and OS was 12.7 months, 3.8 months, and 14.7 months, respectively. The most common adverse events were diarrhea (75/103; 72.8%), dermatitis acneiform (57/103; 55.3%), and nausea (52/103; 50.5%). Thirty-four patients (33.0%) died: 33 (91.7%) due to progressive disease and one (1%) due to treatment-related esophagitis.

Conclusions: Combination therapy with cobimetinib and atezolizumab in patients with advanced BRAFV600 wild-type melanoma with disease progression on or after prior anti‒PD-1 therapy demonstrated limited activity.