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

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

Free article

Clinical Trial

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

Shahneen Sandhu et al. Eur J Cancer. 2023 Jan.

Free article

. 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.

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Conflict of interest statement

Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SS reports personal fees and/or grants from AstraZeneca, Bristol Myers Squibb, Genentech, Merck Sharp & Dohme, Pfizer, and Novartis/Advanced Accelerator Applications directly to the institution. VA reports personal fees and/or nonfinancial support from Bristol Myers Squibb, Limbic, Merck, Merck Sharp & Dohme, Nektar, Novartis, Oncosec Medical, Pierre Fabre, QBiotics, and Roche. MGC reports personal fees and/or nonfinancial support from Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Roche, and Takeda. TM reports institutional funding from Alkermes, Array BioPharma, Checkmate Pharmaceuticals, Exicure, Immunocore, Iovance Biotherapeutics, Moderna, Nektar, Novartis, Oncosec Medical, Regeneron Pharmaceuticals, Replimune Group, Synlogic, and Taiga Biotechnologies. ASR reports no conflicts of interest. AMM reports personal fees from Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Roche, Pierre Fabre, and QBiotics. IC, LR, YS, YY, YG, and CX report employment and stock ownership with Roche. GVL reports personal fees from Amgen, Array BioPharma, Boehringer Ingelheim International, Bristol Myers Squibb, Hexal AG, Highlight Therapeutics, Merck Sharpe & Dohme, Novartis, Pierre Fabre, QBiotics, Regeneron Pharmaceuticals, SkylineDx BV, and Specialised Therapeutics Australia Pty Ltd.

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Publication types

MeSH terms

Substances

Associated data

LinkOut - more resources

Full Text Sources

Medical

Research Materials