Phase 1b study of cobimetinib plus atezolizumab in patients with advanced BRAFV600 wild-type melanoma progressing on prior anti-programmed death-1 therapy

Shahneen Sandhu; Victoria Atkinson; Maria González Cao; Theresa Medina; Ainara Soria Rivas; Alexander M Menzies; Ivor Caro; Louise Roberts; Yuyao Song; Yibing Yan; Yu Guo; Cloris Xue; Georgina V Long

doi:10.1016/j.ejca.2022.10.019

Phase 1b study of cobimetinib plus atezolizumab in patients with advanced BRAF^V600 wild-type melanoma progressing on prior anti-programmed death-1 therapy

Eur J Cancer. 2023 Jan:178:180-190. doi: 10.1016/j.ejca.2022.10.019. Epub 2022 Nov 2.

Authors

Affiliations

¹ Department of Medical Oncology, Peter MacCallum Cancer Centre and the University of Melbourne, Melbourne, Australia. Electronic address: shahneen.sandhu@petermac.org.
² Department of Medical Oncology, Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Greenslopes, and University of Queensland, Brisbane, Australia. Electronic address: Victoria.Atkinson@health.qld.gov.au.
³ Department of Oncology, Instituto Oncológico Dr. Rosell, Hospital Universitario Dexeus, Barcelona, Spain. Electronic address: mgonzalezcao@oncorosell.com.
⁴ Department of Medical Oncology, UC Health Cancer Care, University of Colorado Cancer Center, Aurora. Electronic address: theresa.medina@ucdenver.edu.
⁵ Department of Medical Oncology, University Hospital Ramón y Cajal, Madrid, Spain. Electronic address: ainarasoria@hotmail.com.
⁶ Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Department of Oncology, Royal North Shore and Mater Hospitals, Sydney, Australia. Electronic address: alexander.menzies@sydney.edu.au.
⁷ Department of Oncology, Roche Genentech, South San Francisco, CA, USA. Electronic address: caro.ivor@gene.com.
⁸ Department of Oncology, Roche Genentech, South San Francisco, CA, USA. Electronic address: robertl9@gene.com.
⁹ Department of Oncology, Roche Genentech, South San Francisco, CA, USA. Electronic address: yuyao.song@roche.com.
¹⁰ Department of Oncology, Roche Genentech, South San Francisco, CA, USA. Electronic address: yyan@gene.com.
¹¹ Department of Oncology, Roche Genentech, South San Francisco, CA, USA. Electronic address: guoy52@gene.com.
¹² Department of Oncology, Roche Genentech, South San Francisco, CA, USA. Electronic address: cloris.xue@roche.com.
¹³ Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Department of Oncology, Royal North Shore and Mater Hospitals, Sydney, Australia. Electronic address: Georgina.Long@sydney.edu.au.

PMID: 36455412
DOI: 10.1016/j.ejca.2022.10.019

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.

Keywords: Drug therapy combination; Immunotherapy; Melanoma; Tumour biomarkers.

Publication types

Multicenter Study
Clinical Trial, Phase I
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / adverse effects
Humans
Melanoma* / drug therapy
Melanoma* / genetics
Mutation
Proto-Oncogene Proteins B-raf* / genetics

Substances

cobimetinib
atezolizumab
Proto-Oncogene Proteins B-raf
BRAF protein, human

Associated data

ClinicalTrials.gov/NCT03178851