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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

3285 - KEYNOTE-412: Phase 3 Study of Pembrolizumab Plus Chemoradiation vs Chemoradiation Alone for Locally Advanced Head and Neck Squamous Cell Carcinoma (HNSCC)


21 Oct 2018


Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology


Tumour Site

Head and Neck Cancers


Jean-Pascal Machiels


Annals of Oncology (2018) 29 (suppl_8): viii372-viii399. 10.1093/annonc/mdy287


J. Machiels1, L. Licitra2, Y.G. Tao3, C. Yen4, D. Rischin5, J.N. Waldron6, B.A. Burtness7, V. Gregoire8, S.S. Agarwala9, J. Yorio10, J. Delord11, S. Aksoy12, S. Ikeda13, R. Hong14, J.Y. Ge15, H. Brown15, B. Bidadi16, L.L. Siu17

Author affiliations

  • 1 Oncology, Cliniques Universitaires Saint-Luc, 1200 - Brussels/BE
  • 2 Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, University of Milan, Milan/IT
  • 3 Oncology, Gustave Roussy, Villejuif/FR
  • 4 Internal Medicine, National Cheng Kung University Hospital, 704 - Tainan/TW
  • 5 Oncology, Peter MacCallum Cancer Centre, 3002 - Melbourne/AU
  • 6 Medical Oncology And Hematology, UHN Princess Margaret Cancer Centre, Toronto/CA
  • 7 Medicine, Yale University School of Medicine, New Haven/US
  • 8 Oncology, Cliniques Universitaires Saint-Luc, Brussels/BE
  • 9 Oncology, St. Luke's Cancer Center, 18015 - Bethlehem/US
  • 10 Oncology, Texas Oncology–Austin Central, Austin/US
  • 11 Oncology, Institut Claudius Régaud, Toulouse/FR
  • 12 Oncology, Hacettepe University, 6100 - Ankara/TR
  • 13 Oncology, Medical Hospital, Tokyo Medical and Dental University, 113-8519 - Tokyo/JP
  • 14 Oncology, National Taiwan University Hospital, Taipei/TW
  • 15 Medical Oncology, Merck & Co., Inc., Kenilworth/US
  • 16 Medical Oncology, Merck & Co., Inc., 07033 - Kenilworth/US
  • 17 Medical Oncology And Hematology, Princess Margaret Cancer Center, M5G 2M9 - Toronto/CA

Abstract 3285


Preclinical data suggest improved tumor growth control and survival when radiation therapy (RT) is combined with a PD-1 inhibitor. Pembrolizumab is effective for treatment of recurrent/metastatic HNSCC, and initial results from a phase 1b study suggest that pembrolizumab plus chemoradiation therapy (CRT) is tolerable in patients with locally advanced (LA) HNSCC. KEYNOTE-412 (NCT03040999) is a phase 3, randomized, placebo-controlled, double-blind trial to determine efficacy and safety of pembrolizumab plus CRT and as maintenance therapy vs placebo plus CRT in LA-HNSCC.

Trial design

Eligibility criteria are age ≥18 years; newly diagnosed, treatment-naive, oropharyngeal p16–positive (any T4 or N3), oropharyngeal p16–negative (any T3-T4 or N2a-N3), or larynx/hypopharynx/oral cavity (any T3-T4 or N2a-N3) SCC; evaluable tumor burden (RECIST v1.1); and ECOG performance status 0/1. Patients will be randomly assigned (1:1) to receive pembrolizumab 200 mg every 3 weeks plus cisplatin-based CRT or placebo plus cisplatin-based CRT. Treatment will be stratified by RT regimen (accelerated RT [56-70 Gy, 6 fractions/week for 6 weeks] or standard RT [56-70 Gy, 5 fractions/week for 7 weeks]), tumor site/p16 status (oropharynx p16 positive vs p16 negative or larynx/hypopharynx/oral cavity), and disease stage (III vs IV). Priming dose of pembrolizumab or placebo will be given 1 week before CRT, followed by 2 doses during CRT, and an additional 14 doses after CRT, for a total of 17 pembrolizumab or placebo infusions. Response will be assessed by MRI and CT 12 weeks after CRT, every 3 months for 3 years, then every 6 months for years 4 and 5. Treatment will be discontinued at time of centrally confirmed disease progression, unacceptable toxicity, or patient/physician decision to withdraw. Patients will be evaluated to determine necessity of neck dissection 12 weeks after completion of CRT. Primary end point is event-free survival and secondary end points are overall survival, safety, and patient-reported outcomes. Biomarkers will be an exploratory end point. Recruitment is ongoing in 21 countries and will continue until ∼780 patients are enrolled.

Clinical trial identification

NCT03040999, trial initiation date: 2/2/17.

Legal entity responsible for the study

Merck & Co, Inc.


Merck & Co, Inc.

Editorial Acknowledgement

Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck & Co, Inc, Kenilworth, NJ, USA.


J.-P. Machiels: Consultant: Boehringer Ingelheim, Pfizer, Merck, Debiopharm Group, Nanobiotix, Innate Pharma; Research funding: Novartis, Sanofi, Bayer, Janssen. L. Licitra: Consultant: Eisai, Amgen, Boehringer Ingelheim, Debiopharm Group, AstraZeneca, Novartis, Bayer, Merck, Merck Serono, Roche, Bristol-Myers Squibb; Research funding: Eisai, Amgen, Merck Serono, Boehringer Ingelheim, AstraZeneca, Novartis, Roche, Merck. D. Rischin: Research funding: Genentech/Roche, Merck, Amgen, Regeneron, BMS. B.A. Burtness: Consultant: Merck, MedImmune, Boehringer Ingelheim, Amgen, Bayer, Debiopharm Group, VentiRx, AstraZeneca; Research funding: Merck, Advaxis. S. Aksoy: Honararia: Novartis, Roche, Merck, Abdi Ibrahim AS, Astellas Oncology; Consultant: Pfizer, Abdi Ibrahim AS. J.Y. Ge, H. Brown, B. Bidadi: Employment and stock: Merck. L.L. Siu: Consultant: Merck, AstraZeneca, MorphoSys, Symphogen; Research funding: Bristol-Myers Squibb, Genentech/Roche, GlaxoSmithKline, Merck, Novartis, Pfizer, Medimmune, AstraZeneca, Boehringer Ingelheim, Bayer, Amgen, Syhphogen, Astellas Pharma. All other authors have declared no conflicts of interest.

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