A Study to Investigate Efficacy and Safety of Cobimetinib Plus Atezolizumab and Atezolizumab Monotherapy Versus Regorafenib in Participants With Metastatic Colorectal Adenocarcinoma (COTEZO IMblaze370)

Summary

This is a Phase III, multicenter, open-label, three-arm, randomized study in participants with unresectable locally advanced or metastatic colorectal cancer (CRC) who have received at least two prior regimens of cytotoxic chemotherapy for metastatic disease. The study compares regorafenib, a standard of care therapy in this setting, to cobimetinib plus atezolizumab and atezolizumab monotherapy.

Timeline

Start

2016-07-05

Primary completion

2018-03-09

Completion

2018-12-26

Outcome

Missed primary endpoint

paper IMblaze370 did not meet its primary endpoint of improved overall survival with atezolizumab plus cobimetinib or atezolizumab versus regorafenib. PMID 31003911 ↗

registry analysis (superiority test); Regorafenib vs Cobimetinib + Atezolizumab; p = 0.9871; Hazard Ratio (HR) 1.00 (95% CI 0.73 to 1.38); Stratified Log-Rank NCT02788279 ↗

registry analysis (superiority test); Regorafenib vs Atezolizumab; p = 0.3360; Hazard Ratio (HR) 1.19 (95% CI 0.83 to 1.71); Stratified Log-Rank NCT02788279 ↗

release “the Phase III IMblaze370 study evaluating the combination of Tecentriq® (atezolizumab) and Cotellic® (cobimetinib) did not meet its primary endpoint of overall survival (OS)” gene.com ↗

Publications

• Taraborrelli L, Senbabaoglu Y, Wang L, Lim J, Blake K, Kljavin N, Gierke S, Scherl A, Ziai J, McNamara E, Owyong M, Rao S, Calviello AK, Oreper D, Jhunjhunwala S, Argiles G, Bendell J, Kim TW, Ciardiello F, Wongchenko MJ, de Sauvage FJ, de Sousa E Melo F, Yan Y, West NR, Murthy A. Tumor-intrinsic expression of the autophagy gene Atg16l1 suppresses anti-tumor immunity in colorectal cancer. Nat Commun. 2023 Sep 23;14(1):5945. doi: 10.1038/s41467-023-41618-7.
• Barteselli G, Goodman GR, Patel Y, Caro I, Xue C, McCallum S. Characterization of Serous Retinopathy Associated with Cobimetinib: Integrated Safety Analysis of Four Studies. Drug Saf. 2022 Dec;45(12):1491-1499. doi: 10.1007/s40264-022-01248-2. Epub 2022 Oct 30.
• Eng C, Kim TW, Bendell J, Argiles G, Tebbutt NC, Di Bartolomeo M, Falcone A, Fakih M, Kozloff M, Segal NH, Sobrero A, Yan Y, Chang I, Uyei A, Roberts L, Ciardiello F; IMblaze370 Investigators. Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial. Lancet Oncol. 2019 Jun;20(6):849-861. doi: 10.1016/S1470-2045(19)30027-0. Epub 2019 Apr 16.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Atezolizumab	Monoclonal antibody	840 mg	Intravenous
Subject	Atezolizumab	Monoclonal antibody	1200 mg	Intravenous
Subject	Cobimetinib	Small molecule	60 mg	Oral
Comparator	Regorafenib	Small molecule	160 mg	Oral

Indications