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CheckMate 067

The trial with the longest immunotherapy follow-up: about half of patients on the combination are alive at 10 years.

10-year OS 43% (combination), 37% (nivolumab), 19% (ipilimumab); melanoma-specific survival 52% for the combination. Established that immunotherapy can produce durable cures.

Setting
Untreated advanced melanoma: nivolumab + ipilimumab vs nivolumab vs ipilimumab
Phase
Phase 3
Sponsor
BMS
Registry
Headline result
10-year OS 43% vs 37% vs 19%.
Reported
2015
Enrolled
945
Replication
Replicated by CheckMate 069 (phase 2) and consistent with KEYNOTE-006 for single-agent PD-1; the longest immunotherapy follow-up in any solid tumour.

Outcomes

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In plain words
What these results mean for people, not percentages
945 people took part
Progression-free survival (co-primary)primarysurrogate endpoint
  • Median 11.5 vs 6.9 months with Nivolumab + ipilimumab compared with Nivolumab; about 4.6 months longer for half the group.
  • A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
  • Other groups: Ipilimumab 2.9 months.
  • Put another way, the treated group had about 58 percent lower chance of the event at any given time (hazard ratio 0.42).
  • This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
Overall survival at 10 yearssurvival endpoint
  • 43 vs 37 out of 100 alive at 10 years with Nivolumab + ipilimumab compared with Nivolumab; 6 more per 100.
  • Roughly one extra person helped for every 17 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
  • Other groups: Ipilimumab 19 of 100.
  • Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
Median overall survivalsurvival endpoint
  • Median 71.9 vs 36.9 months with Nivolumab + ipilimumab compared with Nivolumab; about 35 months longer for half the group.
  • A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
  • Other groups: Ipilimumab 19.9 months.
  • Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
Melanoma-specific survival at 10 yearssurvival endpoint
  • 52 vs 44 out of 100 alive at 10 years with Nivolumab + ipilimumab compared with Nivolumab; 8 more per 100.
  • Roughly one extra person helped for every 13 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
  • Other groups: Ipilimumab 23 of 100.
  • Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
Be careful
  • These results apply to the people the trial enrolled: Untreated advanced melanoma: nivolumab + ipilimumab vs nivolumab vs ipilimumab. People in a different situation may not see the same effect.

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.

945 participants enrolled.

Progression-free survival (co-primary)primary
HR 0.42
Nivolumab + ipilimumab
11.5 mo
Nivolumab
6.9 mo
Ipilimumab
2.9 mo

HR for combination vs ipilimumab

Source
Overall survival at 10 years
Nivolumab + ipilimumab43 of 100
n = 314
Nivolumab37 of 100
n = 316
Ipilimumab19 of 100
n = 315
Source
Median overall survival
Nivolumab + ipilimumab
71.9 mo
Nivolumab
36.9 mo
Ipilimumab
19.9 mo
Source
Melanoma-specific survival at 10 years
Nivolumab + ipilimumab52 of 100
Nivolumab44 of 100
Ipilimumab23 of 100
Source
EndpointArmnValueHR (95% CI)pSource
Overall survival at 10 yearsNivolumab + ipilimumab31443%link
Nivolumab31637%
Ipilimumab31519%
Median overall survivalNivolumab + ipilimumab71.9 monthslink
Nivolumab36.9 months
Ipilimumab19.9 months
Melanoma-specific survival at 10 yearsNivolumab + ipilimumab52%link
Nivolumab44%
Ipilimumab23%
Progression-free survival (co-primary)primaryNivolumab + ipilimumab11.5 months0.42link
Nivolumab6.9 months
Ipilimumab2.9 months
Replication
Replicated by CheckMate 069 (phase 2) and consistent with KEYNOTE-006 for single-agent PD-1; the longest immunotherapy follow-up in any solid tumour.

Key papers

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rctNew England Journal of Medicine 2025changed practice
CheckMate 067 at ten years: half of melanoma patients treated with nivolumab plus ipilimumab were alive a decade later

Before 2011 median survival in metastatic melanoma was under a year; this trial shows that roughly half of patients treated with combination checkpoint blockade are now long-term survivors, effectively cured. It anchors first-line treatment of advanced melanoma and sets the benchmark for every new regimen, including nivolumab-relatlimab. The combination's toxicity means nivolumab alone or newer doublets remain reasonable for some patients.

rctNew England Journal of Medicine 2025changed practice
CheckMate 067 at ten years: nivolumab plus ipilimumab produces long-term survival in half of patients with advanced melanoma

For patients with advanced melanoma, immunotherapy offers a realistic chance of long-term survival and probably cure, and the ten-year data show that patients who are alive and progression-free at three years rarely die of melanoma afterwards. Nivolumab plus ipilimumab gives the best long-term results but at a high price in serious side effects; nivolumab alone or nivolumab plus relatlimab are alternatives for patients at lower risk or with autoimmune concerns. The trial is also a caution about surrogate endpoints: the survival plateau took years to become visible.

rctNew England Journal of Medicine 2022changed practice
RELATIVITY-047: relatlimab plus nivolumab, the first LAG-3 checkpoint combination, in untreated advanced melanoma

Patients with newly diagnosed advanced melanoma have a dual-checkpoint option that improves on nivolumab alone with only a modest increase in serious side effects, making it attractive for those unable to tolerate or unwilling to risk the toxicity of ipilimumab. It did not prove superior survival, and it has not been compared with nivolumab plus ipilimumab, which remains preferred for patients with brain metastases or other high-risk features. LAG-3 is now an established target under study in many other cancers.

basicScience 1996
Leach, Krummel and Allison: releasing the CTLA-4 brake makes mice reject tumours

Every checkpoint inhibitor, from ipilimumab to pembrolizumab, rests on this idea: the immune system can already recognise cancer and just needs its brakes released. It changed the goal of immunotherapy from vaccinating against tumours to unleashing existing T cells.

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