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The trial that first showed checkpoint immunotherapy works in mismatch-repair deficient bowel cancer, and that adding a second antibody makes it work better.
CheckMate 142 is the multi-cohort phase 2 that established immunotherapy in mismatch-repair deficient metastatic colorectal cancer. In the nivolumab-with-ipilimumab dMMR cohort of 119 patients, 76 percent of whom had received two or more previous systemic therapies, the investigator-assessed objective response rate was 55 percent (95% CI 45.2 to 63.8) and disease control for at least twelve weeks 80 percent; median duration of response was not reached and 94 percent of responses were continuing at data cutoff. Progression-free survival was 76 percent at nine months and 71 percent at twelve, and overall survival 87 and 85 percent. Grade 3 to 4 treatment-related events affected 32 percent. The microsatellite-stable cohorts were the mirror image: a later report of nivolumab, ipilimumab and cobimetinib in 30 patients with MSS or proficient mismatch repair disease found an objective response rate of 3 percent and median overall survival 8.2 months, and concluded that the regimen should not be pursued. CheckMate 142 led to the 2017 and 2018 accelerated approvals and set up KEYNOTE-177 and CheckMate 8HW.
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.
385 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Objective response rate (dMMR, nivolumab plus ipilimumab)primary | Nivolumab plus ipilimumab | 119 | 55 percent | - | - | link |
| Objective response rate (MSS, nivolumab, ipilimumab and cobimetinib) | Nivolumab, ipilimumab and cobimetinib | 30 | 3 percent | - | - | link |
Shares CheckMate 8HW, CTLA-4, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Mismatch-repair deficient (MSI-high) colorectal cancer.
Shares KEYNOTE-177, CheckMate 8HW, CTLA-4, Mismatch-repair deficient (MSI-high) colorectal cancer.
Shares CheckMate 8HW, Mismatch-repair deficient (MSI-high) colorectal cancer, Ipilimumab, Nivolumab.
Shares CheckMate 8HW, CTLA-4, Mismatch-repair deficient (MSI-high) colorectal cancer, Ipilimumab.
Shares CTLA-4, Ipilimumab, Bristol Myers Squibb, PD-1.
Shares CTLA-4, Ipilimumab, PD-1, Nivolumab.
Shares CTLA-4, Ipilimumab, PD-1, Nivolumab.
Shares KEYNOTE-177, CheckMate 8HW, Hot vs cold tumours, CTLA-4.