# Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370)

Source: https://onco.cc/key-papers/paper-eng-imblaze370-atezolizumab-cobimetinib-colorectal-lancet-oncol-2019/  
OnCo record `paper-eng-imblaze370-atezolizumab-cobimetinib-colorectal-lancet-oncol-2019` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The phase 3 test of the idea that a MEK inhibitor could warm up an immunologically cold bowel cancer. It failed: neither immunotherapy alone nor the combination beat an existing pill.

## Summary

IMblaze370 was a multicentre, open-label, phase 3, randomised, controlled trial at 73 centres in 11 countries. Patients with unresectable locally advanced or metastatic colorectal cancer who had progressed on or were intolerant of at least two previous chemotherapy regimens were assigned 2:1:1 to atezolizumab plus cobimetinib, atezolizumab monotherapy or regorafenib, stratified by extended RAS status and time since first metastasis; recruitment of high microsatellite instability patients was capped at 5%. Between July 2016 and January 2017, 363 patients were enrolled. Median overall survival was 8.87 months with atezolizumab plus cobimetinib, 7.10 months with atezolizumab and 8.51 months with regorafenib, with hazard ratios against regorafenib of 1.00 for the combination and 1.19 for atezolizumab. Grade 3 to 4 adverse events were common in the combination arm.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Lancet Oncology
- Year: 2019
- DOI: 10.1016/S1470-2045(19)30027-0
- Authors: Eng C, Kim TW, Bendell J, et al.
- Findings: Median overall survival 8.87, 7.10 and 8.51 months for the combination, atezolizumab and regorafenib.; Hazard ratios against regorafenib 1.00 and 1.19; neither immunotherapy arm was better.; Trial capped microsatellite instability-high enrolment at 5%, so the result describes microsatellite-stable disease.
- What it means: It is the definitive negative result for unselected checkpoint blockade in microsatellite-stable colorectal cancer, and the reason later attempts have moved to Fc-enhanced CTLA-4 antibodies, TGF-beta blockade and vaccines rather than PD-L1 plus MEK.
- Caveats: Third-line population, so the biology may differ from earlier lines.; Regorafenib is a modest comparator, which makes the failure starker rather than softer.; Cobimetinib dosing may not have achieved the immune priming seen in mice.

## Sources

- Eng et al., Lancet Oncol 2019: IMblaze370, atezolizumab with or without cobimetinib versus regorafenib (363 patients): https://doi.org/10.1016/S1470-2045(19)30027-0
- PubMed: https://pubmed.ncbi.nlm.nih.gov/31003911/

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- targets: [PD-1](https://onco.cc/targets/pd1/)
- drugs: [Atezolizumab](https://onco.cc/drugs/atezolizumab/), [Regorafenib](https://onco.cc/drugs/regorafenib/)
- pathways: [Cold tumours: immune deserts and exclusion](https://onco.cc/pathways/immune-desert-exclusion/), [PD-1 / PD-L1 immune checkpoint & T-cell activation](https://onco.cc/pathways/pd1-checkpoint/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- terms: [Hot vs cold tumours](https://onco.cc/terms/cold-vs-hot/), [Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR)](https://onco.cc/terms/mss-pmmr/)
- journals: [The Lancet Oncology](https://onco.cc/journals/lancet-oncology/)

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