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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.
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.
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.
Shares Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR), Cold tumours: immune deserts and exclusion, Hot vs cold tumours, PD-1 / PD-L1 immune checkpoint & T-cell activation.
Shares Regorafenib, Hot vs cold tumours, Atezolizumab, PD-1.
Shares Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR), Hot vs cold tumours, PD-1 / PD-L1 immune checkpoint & T-cell activation, PD-1.
Shares Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR), Hot vs cold tumours, Atezolizumab, Immune checkpoint inhibitors.
Shares Atezolizumab, Immune checkpoint inhibitors, Colorectal cancer.
Shares Regorafenib, Atezolizumab, Immune checkpoint inhibitors, Colorectal cancer.
Shares Hot vs cold tumours, PD-1 / PD-L1 immune checkpoint & T-cell activation, PD-1.
Shares Cold tumours: immune deserts and exclusion, Hot vs cold tumours, PD-1 / PD-L1 immune checkpoint & T-cell activation.