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The trial that tried to make immunotherapy work in ordinary bowel cancer by adding a MEK inhibitor. It failed outright.
IMblaze370 randomised 363 patients 2:1:1 to atezolizumab with cobimetinib, atezolizumab alone, or regorafenib, after progression on at least two previous chemotherapy regimens. Median overall survival was 8.87 months with the combination, 7.10 months with atezolizumab alone and 8.51 months with regorafenib; the hazard ratio was 1.00 (95% CI 0.73 to 1.38, p=0.99) for the combination against regorafenib. Grade 3 to 4 adverse events affected 61 percent of the combination group. The preclinical rationale, that MEK inhibition raises MHC class I expression and drives T cells into tumours, did not translate. IMblaze370 is the reference failure for checkpoint inhibition in microsatellite-stable colorectal cancer and the reason later attempts focus on Fc-enhanced CTLA-4 blockade, on excluding patients with liver metastases, or on combining with targeted therapy.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
Shares Regorafenib, Hot vs cold tumours, Atezolizumab, PD-1.
Shares Regorafenib, Atezolizumab, Small-molecule kinase inhibitors, Immune checkpoint inhibitors.
Shares Atezolizumab, Small-molecule kinase inhibitors, Immune checkpoint inhibitors, Colorectal cancer.
Shares Hot vs cold tumours, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Immune checkpoint inhibitors, Colorectal cancer.
Shares Cobimetinib, Atezolizumab, Small-molecule kinase inhibitors, Immune checkpoint inhibitors.
Shares MEK1/2, Regorafenib, Colorectal cancer.
Shares Cobimetinib, Roche / Genentech, Atezolizumab.
Shares Roche / Genentech, Atezolizumab, Immune checkpoint inhibitors, Colorectal cancer.