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Showed that a two-drug immunotherapy combination controls mismatch-repair-deficient bowel cancer for over four years on average, and beats immunotherapy alone.
First-line nivolumab + ipilimumab vs chemotherapy: PFS HR 0.21 (NEJM 2024); at 47 months' follow-up median PFS 54.1 vs 5.9 months. Across all lines, nivolumab + ipilimumab beat nivolumab alone on PFS (Lancet 2025, HR 0.62), the first phase 3 to show the CTLA-4 add-on matters in this setting. FDA approved the combination first line in April 2025. Overall survival is not yet mature.
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.
839 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survival, first lineprimary | Nivolumab + ipilimumab | 202 | 54.1 months | 0.21 | - | link |
| Chemotherapy | 101 | 5.9 months | ||||
| Progression-free survival, all lines: combination vs nivolumab | Nivolumab + ipilimumab | 296 | - | 0.62 | - | link |
| Nivolumab | 286 | - |
Nivolumab-ipilimumab is a first-line standard for microsatellite-unstable metastatic colorectal cancer alongside pembrolizumab, with the trade-off of more immune toxicity for deeper and more durable control.
Combination checkpoint blockade became a first-line standard for mismatch repair-deficient metastatic colorectal cancer in 2025; the later all-lines comparison against nivolumab alone showed the CTLA-4 antibody adds to the PD-1 antibody, the first phase 3 to prove that in this disease.
This paper established a new regulatory paradigm: a drug approved for a molecular feature regardless of organ. It made MSI/MMR testing standard across advanced cancers and remains the clearest example of a biomarker that works across histologies. It also anchored the idea that mutation load, via neoantigens, is what makes tumours visible to T cells.
It gave the second PD-1 antibody a colorectal indication in mismatch repair deficient disease and, with the ipilimumab cohort that followed, set up CheckMate 8HW and the first-line combination.
This small trial explained why colorectal cancer had seemed immune-resistant (most is MMR-proficient) and established the principle that a genomic feature, not the tissue of origin, can predict immunotherapy response. It led directly to the 2017 tissue-agnostic approval of pembrolizumab and to routine MMR/MSI testing of many cancers. Every patient with advanced dMMR cancer should now be considered for checkpoint blockade.
Shares CheckMate 142, Thierry André, Making microsatellite-stable colorectal cancer immunotherapy-responsive, Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval.
Shares Heinz-Josef Lenz, Making microsatellite-stable colorectal cancer immunotherapy-responsive, Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR), Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ.
Shares Making microsatellite-stable colorectal cancer immunotherapy-responsive, Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, CTLA-4, Cold tumours and the immunosuppressive microenvironment.
Shares Study of Perioperative Dostarlimab in Participants With Untreated T4N0 or Stage III dMMR/MSI-H Resectable Colon Cancer, Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, Cold tumours and the immunosuppressive microenvironment, Mismatch-repair deficient (MSI-high) colorectal cancer.
Shares Nivolumab plus ipilimumab in microsatellite-instability-high metastatic colorectal cancer (CheckMate 8HW), Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval, CTLA-4, Mismatch-repair deficient (MSI-high) colorectal cancer.
Shares Nivolumab plus ipilimumab in microsatellite-instability-high metastatic colorectal cancer (CheckMate 8HW), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Ipilimumab, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation.
Shares Thierry André, Nivolumab plus ipilimumab in microsatellite-instability-high metastatic colorectal cancer (CheckMate 8HW), Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, Mismatch-repair deficient (MSI-high) colorectal cancer.
Shares Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval, Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation, PD-1.