Phase 1b study of cobimetinib plus atezolizumab in patients with advanced BRAFV600 wild-type melanoma progressing on prior anti-programmed death-1 therapy
- Author(s)
- 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;
- Journal Title
- European Journal of Cancer
- Publication Type
- Research article
- Abstract
- OBJECTIVE: To evaluate the efficacy and safety of cobimetinib plus atezolizumab in the treatment of patients with advanced BRAF(V600) wild-type melanoma who had progressed on prior anti‒programmed death-1 (PD-1) therapy. PATIENTS AND METHODS: This phase 1b, open-label, international multicentre study enrolled 3 cohorts. Herein, we report on patients in cohorts A and B who had progressed on prior anti‒PD-1 therapy. Patients in cohort A received cobimetinib 60 mg once daily for 21 days followed by a 7-day break and concurrent intravenous atezolizumab 840 mg every 2 weeks. Patients in cohort B 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 end-points were objective response rate and disease control rate. Secondary end-points were duration of response, progression free survival and overall survival. RESULTS: Between 19th June 2017 and 12th December 2018, 103 patients were enrolled. Median follow-up was 6.9 months (interquartile range, 4.8-10.1 months); objective response rate was 14.6% and disease control rate was 38.8% (95% confidence interval, 29.39-48.94). The median duration of response, progression-free survival and overall survival was 12.7 months, 3.8 months and 14.7 months, respectively. The most common adverse events were diarrhoea (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 oesophagitis. CONCLUSIONS: Combination therapy with cobimetinib and atezolizumab in patients with advanced BRAF(V600) wild-type melanoma with disease progression on or after prior anti‒PD-1 therapy demonstrated limited activity. CLINICAL TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov; NCT03178851.
- Publisher
- Elsevier
- Keywords
- Humans; *Proto-Oncogene Proteins B-raf/genetics; Antineoplastic Combined Chemotherapy Protocols/adverse effects; Mutation; *Melanoma/drug therapy/genetics; Drug therapy combination; Immunotherapy; Melanoma; Tumour biomarkers
- Department(s)
- Medical Oncology
- PubMed ID
- 36455412
- Publisher's Version
- https://doi.org/10.1016/j.ejca.2022.10.019
- Open Access at Publisher's Site
https://doi.org/10.1016/j.ejca.2022.10.019- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-06-13 07:55:25
Last Modified: 2023-06-13 07:56:08