Safety and efficacy of cobimetinib plus atezolizumab in patients with solid tumors: a phase II, open-label, multicenter, multicohort study.
Date
2023-04-01ICR Author
Author
Sherman, E
Lee, JL
Debruyne, PR
Keam, B
Shin, SJ
Gramza, A
Caro, I
Amin, R
Shah, K
Yan, Y
Huddart, R
Powles, T
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
COTEST
atezolizumab
cobimetinib
phase II trial
solid tumors
Humans
Male
Middle Aged
Female
Carcinoma, Renal Cell
Carcinoma, Transitional Cell
Immune Checkpoint Inhibitors
Urinary Bladder Neoplasms
Kidney Neoplasms
Research team
Clinic Acad RT Huddart
Language
eng
Date accepted
2023-01-16
License start date
2023-04-01
Citation
ESMO Open, 2023, 8 (2), pp. 100877 -
Publisher
ELSEVIER