Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2023 Apr;8(2):100877.
doi: 10.1016/j.esmoop.2023.100877. Epub 2023 Mar 21.

Safety and efficacy of cobimetinib plus atezolizumab in patients with solid tumors: a phase II, open-label, multicenter, multicohort study

E Sherman  1 , J L Lee  2 , P R Debruyne  3 , B Keam  4 , S J Shin  5 , A Gramza  6 , I Caro  7 , R Amin  7 , K Shah  7 , Y Yan  7 , R Huddart  8 , T Powles  9
Affiliations
Clinical Trial

Safety and efficacy of cobimetinib plus atezolizumab in patients with solid tumors: a phase II, open-label, multicenter, multicohort study

E Sherman et al. ESMO Open. 2023 Apr.

Abstract

Background: Although introduction of immune checkpoint inhibitors has revolutionized the treatment of cancer, their response rates are generally low. Preclinical and early phase clinical data suggest that MEK inhibition may sensitize tumors to immune checkpoint inhibitors by upregulating tumor antigen expression, programmed death-ligand 1 (PD-L1) expression, and tumor T-cell infiltration. We evaluated the efficacy and safety of cobimetinib plus atezolizumab in patients with advanced solid tumors in the open-label, multicohort phase II COTEST study.

Patients and methods: This analysis of the COTEST trial included patients from cohorts 1-4 [1-3: anti-programmed cell death protein 1 (PD-1)/PD-L1 treatment-naive patients; 4: patients with disease progression on anti-PD-1/anti-PD-L1 treatment] who received cobimetinib 60 mg once daily for the first 21 days and intravenous infusions of atezolizumab 840 mg on days 1 and 15 of each 28-day cycle. Efficacy endpoints included objective response rate, overall survival, progression-free survival (PFS), and disease control rate.

Results: Overall, 77 patients were enrolled in cohorts 1-4 (78% male; median age 62.8 years). Objective response rate was 20% in cohort 1 [squamous cell carcinoma of the head and neck (SCCHN)], 30% in cohort 2 (urothelial carcinoma), and 18% in cohort 3 (renal cell carcinoma); there were no responders among 20 patients in cohort 4 (SCCHN). The disease control rates in cohorts 1-4 were 50%, 40%, 24%, and 25%, respectively. The median PFS was 5.5, 3.4, 3.4, and 3.6 months in cohorts 1-4, respectively, and the median overall survival was 16.8, 18.7, 21.7, and 7.7 months, respectively. Most adverse events were of grade 1/2 and were manageable.

Conclusions: Cobimetinib plus atezolizumab had moderate activity in patients with anti-PD-1/PD-L1 treatment-naive SCCHN and urothelial carcinoma, and weak activity in anti-PD-1/PD-L1 treatment-naive renal cell carcinoma, and no activity in checkpoint inhibitor-treated patients.

Keywords: COTEST; atezolizumab; cobimetinib; phase II trial; solid tumors.

PubMed Disclaimer

Conflict of interest statement

Disclosure All authors report nonfinancial support from Roche for the preparation of the manuscript. ES has received grants from Regeneron and Eli Lilly and is an advisory board member for Eisai, Exelixis, Regeneron, Eli Lilly, and Roche/BluePrint outside the submitted work. JLL is an advisory board member for Pfizer Korea, Ipsen Korea, Sanofi Aventis, Astellas Korea, BMS Korea, MSD, and Merck; has received grants from Pfizer Korea, Ipsen Korea, BMS Korea, MSD, Merck, Esai, Roche, AstraZeneca, Exelixis, and Seagen; has received personal fees from Pfizer Korea, Ipsen Korea, Sanofi Aventis, Novartis Korea, Astellas Korea, BMS Korea, MSD, and AstraZeneca; and has stock ownership with Merck, Amgen, Myovant Sciences, and Johnson & Johnson outside the submitted work. PRD has received a grant from Pfizer; has received personal fees from BMS, Merck/Pfizer, MSD, Roche, and Bayer outside the submitted work; has received travel support from Janssen; and has stock ownership with Alkermes. BK has received grants from Ono Pharmaceuticals, MSD Oncology, and AstraZeneca and has received personal fees from MSD Oncology, AstraZeneca, Genexine, Handok, and CBS Bio outside the submitted work. IC, KS, RA, and YY are employees and stockholders of Genentech/Roche. RH reports grants from MSD and Roche and personal fees from MSD, Roche, Nektar Pharmaceuticals, Janssen, Bayer, Astellas, and Pfizer outside the submitted work. TP reports grants and personal fees from Roche, AstraZeneca, BMS, Exelixis, Ipsen, Merck, MSD, Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas, Johnson & Johnson, and Eisai; and personal fees from Incyte. Data sharing Qualified researchers may request access to individual patient-level data through the clinical study data request platform (https://vivli.org/). Further details on Roche’s criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche’s Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm). Ethics approval and consent to participate The study was carried out in accordance with Good Clinical Practice guidelines and the principles of the Declaration of Helsinki, and the study protocol was approved by the institutional review boards and/or an independent ethics committee at each study site. The institutional review boards of this study were Memorial Sloan Kettering Cancer Center Institutional Review Board (303071, 306949, 306974), Western Institutional Review Board (303115, 304982), Chesapeake IRB (303116), South Central – Oxford A Research Ethics Committee (303121, 303267, 311307), Seoul National Univ. Ethics Committee (303122), Asan Medical Center Ethics Committee (303124), EK an der Med. Fakultät d. (303129), AZ Groeninge Commissie voor Medische Ethiek (303132), Severance Hospital – Yonsei University (304256), and Medical Research Council, Ethics Committee for Clinical Pharmacology (304510, 304511, 304512). All patients provided written informed consent before participation in the study.

Figures

Figure 1
Figure 1
Kaplan–Meier curves for progression-free survival in (A) cohorts 1-3 (anti-PD-1/PD-L1 treatment naive) and (B) cohort 4 (following progression on anti-PD-1/PD-L1 treatment). PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; RCC, renal cell carcinoma, SCCHN, squamous cell carcinoma of the head and neck; UC, urothelial carcinoma.
Figure 2
Figure 2
Kaplan–Meier curves for overall survival in (A) cohorts 1-3 (anti-PD-1/PD-L1 treatment naive) and (B) cohort 4 (following progression on anti-PD-1/PD-L1 treatment). PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; RCC, renal cell carcinoma, SCCHN, squamous cell carcinoma of the head and neck; UC, urothelial carcinoma.
See this image and copyright information in PMC

References

    1. Ribas A., Wolchok J.D. Cancer immunotherapy using checkpoint blockade. Science (New York, NY) 2018;359:1350–1355. - PMC - PubMed
    1. Vaddepally R.K., Kharel P., Pandey R., et al. Review of indications of FDA-approved immune checkpoint inhibitors per NCCN guidelines with the level of evidence. Cancers (Basel) 2020;12(3):738. - PMC - PubMed
    1. Liu Y.T., Sun Z.J. Turning cold tumors into hot tumors by improving T-cell infiltration. Theranostics. 2021;11:5365–5386. - PMC - PubMed
    1. Tang T., Huang X., Zhang G., et al. Advantages of targeting the tumor immune microenvironment over blocking immune checkpoint in cancer immunotherapy. Signal Transduct Targeted Ther. 2021;6:72. - PMC - PubMed
    1. Ebert P.J.R., Cheung J., Yang Y., et al. MAP kinase inhibition promotes T cell and anti-tumor activity in combination with PD-L1 checkpoint blockade. Immunity. 2016;44:609–621. - PubMed

Publication types