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

Sandhu S, Atkinson V, Cao MG, Medina T, Rivas AS, Menzies AM, Caro I, Roberts L, Song Y, Yan Y, Guo Y, Xue C, Long GV. European Journal of Cancer. 2022 Nov 02; doi: 10.1016/j.ejca.2022.10.019.


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.