# CheckMate 648

Source: https://onco.cc/trials/checkmate-648/  
OnCo record `checkmate-648` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Showed two immunotherapy options for squamous oesophageal cancer, including one with no chemotherapy at all, both extending survival.

## Summary

CheckMate 648, trial NCT03143153 sponsored by Bristol Myers Squibb and reported in 2021, showed two immunotherapy options for first-line advanced oesophageal squamous cell carcinoma, nivolumab plus chemotherapy and a chemotherapy-free doublet of nivolumab plus ipilimumab, both extending survival. It randomised 970 patients across three arms and met its primary overall survival endpoint in PD-L1-positive patients for both regimens, with benefit in all randomised patients and durable separation confirmed at five-year follow-up in 2026, leading to FDA approval of both regimens in May 2022. OnCo links it to oesophageal cancer, PD-1 and CTLA-4 as targets, nivolumab, ipilimumab and Jaffer A. Ajani. Which patients are best served by avoiding chemotherapy altogether is the open question.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-07
- Registry id: NCT03143153
- Phase: 3
- Setting: First-line advanced oesophageal squamous cell carcinoma: nivolumab + chemotherapy, or nivolumab + ipilimumab (chemotherapy-free), vs chemotherapy
- Sponsor: BMS
- Enrolled: 970
- Result: PD-L1 ≥1%: OS 15.4 vs 9.1 months (nivo + chemo, HR 0.54); 13.7 vs 9.1 months (nivo + ipi, HR 0.64).
- Outcomes: Overall survival, PD-L1 ≥1% (nivolumab + chemotherapy): Nivolumab + chemotherapy 15.4 months vs Chemotherapy 9.1 months, HR 0.54; Overall survival, PD-L1 ≥1% (nivolumab + ipilimumab): Nivolumab + ipilimumab 13.7 months vs Chemotherapy 9.1 months, HR 0.64
- Replication: Consistent with KEYNOTE-590 and RATIONALE-306; the chemotherapy-free doublet is unique to this trial.

## Sources

- ClinicalTrials.gov NCT03143153: https://clinicaltrials.gov/study/NCT03143153
- 5-year follow-up: https://pubmed.ncbi.nlm.nih.gov/42575473/

## Connected records

- cancers: [Oesophageal cancer](https://onco.cc/cancers/esophageal/), [Oesophageal squamous cell carcinoma](https://onco.cc/cancers/oesophageal-squamous-cell-carcinoma/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- targets: [CTLA-4](https://onco.cc/targets/ctla4/), [PD-1](https://onco.cc/targets/pd1/)
- drugs: [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [Nivolumab](https://onco.cc/drugs/nivolumab/)
- people: [Jaffer A. Ajani](https://onco.cc/people/jaffer-ajani/)
- key papers: [CheckMate 648: nivolumab combination therapy in advanced oesophageal squamous cell carcinoma](https://onco.cc/key-papers/paper-checkmate-648-nejm-2022/)

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