# KEYNOTE-412

Source: https://onco.cc/trials/keynote-412/  
OnCo record `keynote-412` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

KEYNOTE-412 tested adding pembrolizumab to standard chemoradiotherapy for locally advanced head and neck cancer; the improvement in keeping patients free of disease fell short of statistical significance, so chemoradiotherapy alone remains the standard.

## Summary

KEYNOTE-412 randomised 804 patients with newly diagnosed locally advanced head and neck squamous cell carcinoma (oropharynx, larynx or hypopharynx, and oral cavity) to pembrolizumab or placebo given as a priming dose before, concurrently with and for a year after cisplatin-based chemoradiotherapy. The primary endpoint was event-free survival.

Event-free survival favoured pembrolizumab but the difference did not reach the prespecified threshold for statistical significance, with a larger effect in PD-L1-high tumours in exploratory analysis. Together with the negative JAVELIN Head and Neck 100 trial of avelumab, it showed that concurrent checkpoint blockade does not reliably add to definitive chemoradiotherapy, in contrast to the success of neoadjuvant and adjuvant pembrolizumab around surgery in KEYNOTE-689.

## Fields

- Kind: Trial
- Status: negative
- Last checked: 2026-09-17
- Tags: subtype-trials
- Registry id: NCT03040999
- Phase: 3
- Setting: Locally advanced head and neck squamous cell carcinoma: cisplatin chemoradiotherapy with pembrolizumab or placebo given before, during and after
- Sponsor: Merck & Co. (MSD)
- Enrolled: 804
- Result: Pembrolizumab added to chemoradiotherapy did not significantly improve event-free survival.
- Outcomes: Event-free survival: Pembrolizumab + chemoradiotherapy vs Placebo + chemoradiotherapy 46.6 months, HR 0.83; Grade 3 or worse adverse events: Pembrolizumab + chemoradiotherapy 92% vs Placebo + chemoradiotherapy 88%; Serious adverse events: Pembrolizumab + chemoradiotherapy 62% vs Placebo + chemoradiotherapy 49%

## Sources

- ClinicalTrials.gov NCT03040999: https://clinicaltrials.gov/study/NCT03040999

## Connected records

- cancers: [Head and neck squamous cell carcinoma](https://onco.cc/cancers/head-and-neck/), [HPV-negative head and neck squamous cell carcinoma (including HPV-negative oropharyngeal cancer)](https://onco.cc/cancers/hpv-negative-head-and-neck-cancer/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- drugs: [Cisplatin](https://onco.cc/drugs/cisplatin/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- companies: [Merck & Co. (MSD)](https://onco.cc/companies/merck/)
- people: [Jean-Pascal Machiels](https://onco.cc/people/jean-pascal-machiels/)
- ideas: [Photoimmunotherapy as an in situ vaccine with PD-1 blockade](https://onco.cc/ideas/idea-photoimmunotherapy-plus-pd1/), [Test one-tenth-dose immunotherapy where the full dose is unaffordable](https://onco.cc/ideas/idea-cost-low-dose-immunotherapy-trials/)

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