# Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma

Source: https://onco.cc/key-papers/paper-nivolumab-melanoma-n-engl-j-med-2015/  
OnCo record `paper-nivolumab-melanoma-n-engl-j-med-2015` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Phase 2 or 3 results paper on Nivolumab in Melanoma, in New England Journal of Medicine (2015), one of the most cited Europe PMC records with Nivolumab in its title.

## Summary

Background: Nivolumab (a programmed death 1 [PD-1] checkpoint inhibitor) and ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] checkpoint inhibitor) have been shown to have complementary activity in metastatic melanoma. In this randomized, double-blind, phase 3 study, nivolumab alone or nivolumab plus ipilimumab was compared with ipilimumab alone in patients with metastatic melanoma.

Methods: We assigned, in a 1:1:1 ratio, 945 previously untreated patients with unresectable stage III or IV melanoma to nivolumab alone, nivolumab plus ipilimumab, or ipilimumab alone. Progression-free survival and overall survival were coprimary end points. Results regarding progression-free survival are presented here.

Results: The median progression-free survival was 11.5 months (95% confidence interval [CI], 8.9 to 16.7) with nivolumab plus ipilimumab, as compared with 2.9 months (95% CI, 2.8 to 3.4) with ipilimumab (hazard ratio for death or disease progression, 0.42; 99.5% CI, 0.31 to 0.57; P<0.001), and 6.9 months (95% CI, 4.3 to 9.5) with nivolumab (hazard ratio for the comparison with ipilimumab, 0.57; 99.5% CI, 0.43 to 0.76; P<0.001). In patients with tumors positive for the PD-1 ligand (PD-L1), the median progression-free survival was 14.0 months in the nivolumab-plus-ipilimumab group and in the nivolumab group, but in patients with PD-L1-negative tumors, progression-free survival was longer with the combination therapy than with nivolumab alone (11.2 months [95% CI, 8.0 to not reached] vs. 5.3 months [95% CI, 2.8 to 7.1]). Treatment-related adverse events of grade 3 or 4 occurred in 16.3% of the patients in the nivolumab group, 55.0% of those in the nivolumab-plus-ipilimumab group, and 27.3% of those in the ipilimumab group.

Conclusions: Among previously untreated patients with metastatic melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipilimumab alone. In patients with PD-L1-negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone. (Funded by Bristol-Myers Squibb; CheckMate 067 ClinicalTrials.gov number, NCT01844505.).

Indexed on Europe PMC as PubMed record 26027431 (DOI 10.1056/nejmoa1504030). Its title names Nivolumab and its text names Melanoma; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Comparative Study, Research Support, Non-U.S. Gov't, research-article, Randomized Controlled Trial). It was matched automatically to the idea "Treat the draining lymph node before removing it" and no figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: New England Journal of Medicine
- Year: 2015
- DOI: 10.1056/nejmoa1504030
- Authors: Larkin J, Chiarion-Sileni V, Gonzalez R, et al.
- What it means: One of the most cited trial reports Europe PMC returns for Nivolumab in Melanoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.
- Caveats: Matched by Nivolumab in the title and Melanoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.; Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper.

## Sources

- N Engl J Med 2015: https://doi.org/10.1056/nejmoa1504030
- PubMed: https://pubmed.ncbi.nlm.nih.gov/26027431/
- Europe PMC: https://europepmc.org/article/MED/26027431
- ClinicalTrials.gov NCT01844505: https://clinicaltrials.gov/study/NCT01844505

## Connected records

- trials: [CheckMate 067](https://onco.cc/trials/checkmate-067/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- ideas: [Treat the draining lymph node before removing it](https://onco.cc/ideas/idea-bio2-lymph-node-immune-priming/)

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