In bowel (colorectal) cancer that has spread and has a "DNA repair defect" (MSI-H/dMMR), this study compared a combination of two immunotherapy drugs (nivolumab and ipilimumab) with chemotherapy. After two years, about 7 in 10 patients in the combined immunotherapy group still had no worsening of their disease, while in the chemotherapy group the figure was about 1 in 7. Serious side effects were also less common with immunotherapy. A second report from the same study showed that the two-drug combination controls the disease better than nivolumab alone, although it has slightly more side effects.
MSI-H/dMMR metastatic colorectal cancer; preferred option in ESMO 2026
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Phase 1: up to 4 doses, every 3 weeks | |||
| Nivolumab | 240 mg | IV | Day 1 |
| Ipilimumab | 1 mg/kg | IV (same day, after nivolumab) | Day 1 |
| Phase 2: maintenance | |||
| Nivolumab | 240 mg every 2 weeks or 480 mg every 4 weeks | IV | |
Doses from the FDA label for nivolumab; evidence: CheckMate 8HW.
On the page “Colorectal cancer” · MSI-H/dMMR metastatic colorectal cancer: first-line
Adults and children aged 12 and over; MSI-H/dMMR by an approved test
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Combination: up to 4 doses | |||
| Nivolumab | 240 mg (below 40 kg: 3 mg/kg) | IV, 30-minute infusion | Day 1 every 3 weeks (given first) |
| Ipilimumab | 1 mg/kg | IV, 30-minute infusion | Same day, after nivolumab |
| Maintenance | |||
| Nivolumab | 240 mg every 2 weeks or 480 mg every 4 weeks (below 40 kg: 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks) | IV, 30-minute infusion | After the combination doses |
On the page “Ipilimumab (Yervoy)” · Other cancers, with nivolumab (FDA label, revised 08/2026)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Nivolumab 240 mg + ipilimumab 1 mg/kg IV every 3 weeks for up to 4 doses; then nivolumab 480 mg IV every 4 weeks; until disease progression, unacceptable toxicity or a maximum of 2 years.
Nivolumab 240 mg IV every 2 weeks for 6 doses, then 480 mg every 4 weeks; maximum 2 years. (The comparison of this arm with the combination was published in a separate Lancet 2025 report.)
Every 2 weeks: mFOLFOX6 (oxaliplatin 85 mg/m², leucovorin 400 mg/m², fluorouracil 400 mg/m² bolus then 2400 mg/m² over 46 hours) or FOLFIRI (irinotecan 180 mg/m² with the same leucovorin and fluorouracil doses); with or without bevacizumab 5 mg/kg or cetuximab 500 mg/m² every 2 weeks. Patients could receive nivolumab + ipilimumab after disease progression.
Source of the regimen details: Doses from the FDA label for Opdivo (Clinical Studies section, CHECKMATE-8HW) and the abstract of the Lancet 2025 paper (DOI 10.1016/S0140-6736(24)02848-4)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Adults with unresectable or metastatic MSI-H or dMMR colorectal cancer by local testing who had not previously received immunotherapy. The comparison of nivolumab + ipilimumab with chemotherapy was made only in patients with no previous systemic treatment for metastatic disease. Patients with symptomatic brain metastases, active autoimmune disease or use of systemic corticosteroids were excluded.
Two independent primary endpoints (in patients with centrally confirmed MSI-H/dMMR): (1) progression-free survival by blinded independent central review with nivolumab + ipilimumab versus chemotherapy in the first line; (2) progression-free survival with nivolumab + ipilimumab versus nivolumab alone across all lines of therapy.
Secondary endpoints: response rate and duration, overall survival and safety.
In the first-line comparison, grade 3 or 4 treatment-related adverse events occurred in 23% of patients in the nivolumab + ipilimumab group and 48% of patients in the chemotherapy group. In the comparison with nivolumab alone (Lancet 2025), treatment-related adverse events of any grade were 81% versus 71% and grade 3 or 4 22% versus 14%, respectively; three treatment-related deaths were reported (myocarditis and pneumonitis in the combination group and one pneumonitis in the nivolumab group).
The FDA has approved nivolumab with ipilimumab for adults and children aged 12 years and older with unresectable or metastatic MSI-H/dMMR colorectal cancer (current Opdivo label: nivolumab 240 mg + ipilimumab 1 mg/kg every 3 weeks for up to 4 doses, then nivolumab alone for up to 2 years). Together with the report of the comparison with nivolumab alone (André T et al., Lancet 2025;405:383-395), the results made this combination one of the standard first-line options alongside pembrolizumab. Overall survival data were still immature at the time of these reports.
Open-label design; interim analysis and immature overall survival data; about 16% of patients randomised in the first line did not have centrally confirmed MSI-H/dMMR status (the importance of accurate testing); no direct comparison with pembrolizumab alone in the first line.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.
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