Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412

Future Oncol. 2020 Jun;16(18):1235-1243. doi: 10.2217/fon-2020-0184. Epub 2020 Jun 3.


Current treatment guidelines for patients with locally advanced head and neck squamous cell carcinoma (HNSCC) recommend multimodal treatment, including chemoradiation therapy (CRT) or surgery followed by radiation, with or without chemotherapy. The immune checkpoint inhibitor pembrolizumab has previously demonstrated antitumor activity in recurrent and/or metastatic HNSCC in large Phase III trials. For patients with locally advanced disease, Phase Ib data on the use of pembrolizumab in combination with chemoradiation have shown the approach to be safe and feasible. We describe here the design and rationale for KEYNOTE-412, a randomized, double-blind, Phase III trial investigating pembrolizumab or placebo administered concurrently with CRT and as maintenance treatment in patients with locally advanced HNSCC. Clinical Trial Registration: NCT03040999 (

Keywords: PD-1; PD-L1; chemoradiation; head and neck cancer; immune checkpoint blockade; pembrolizumab.

Publication types

  • Clinical Trial Protocol
  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Chemoradiotherapy
  • Combined Modality Therapy / adverse effects
  • Combined Modality Therapy / methods
  • Humans
  • Maintenance Chemotherapy
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Squamous Cell Carcinoma of Head and Neck / therapy*


  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • pembrolizumab

Associated data