96TiP - Phase 3 KEYNOTE-412 Trial: Pembrolizumab Plus Chemoradiation (CRT) vs CRT Alone for Locally Advanced Head and Neck Squamous Cell Carcinoma (LA-HNSC...

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Lunch & Poster Display session
Topics Breast Cancer
Presenter Jean-Pascal Machiels
Citation Annals of Oncology (2017) 28 (suppl_11): xi6-xi29. 10.1093/annonc/mdx711
Authors J. Machiels1, C. Yen2, L. Licitra3, D. Rischin4, J. Waldron5, B. Burtness6, V. Gregoire1, Y.G. Tao7, J. Yorio8, S. Aksoy9, S. Ikeda10, R. Hong11, J.Y. Ge12, H. Brown12, B. Bidadi12, L. Siu13
  • 1Oncology, Cliniques Universitaires St-Luc, 1200 - Brussels/BE
  • 2Department Of Internal Medicine And Division Of Hematology And Oncology, National Cheng Kung University Hospital, Tainan/TW
  • 3Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 4Oncology, Peter MacCallum Cancer Center, 3002 - East Melbourne/AU
  • 5Oncology, Princess Margaret Cancer Centre, Toronto/CA
  • 6Medicine, Yale University School of Medicine, New Haven/US
  • 7Oncology, Institut Gustave Roussy, Villejuif/FR
  • 8Oncology, Texas Oncology–Austin Central, Austin/US
  • 9Oncology, Hacettepe Universitesi Tip Fakultesi, Ankara/TR
  • 10Oncology, Medical Hospital, Tokyo Medical and Dental University, Tokyo/JP
  • 11Oncology, National Taiwan University Hospital, 100 - Taipei/TW
  • 12Oncology, Merck & Co., Inc., Kenilworth/US
  • 13Medical Oncology And Hematology, Princess Margaret Hospital, M5G 2M9 - Toronto/CA



CRT with cisplatin is the standard of care for patients with LA-HNSCC not treated by surgery. Preclinical data in murine cancer models show improved tumor growth control and survival when RT is combined with a PD-1 inhibitor. Pembrolizumab has proven effective for the treatment of recurrent/metastatic HNSCC, and initial results from a phase 1b study suggest that pembrolizumab plus CRT is tolerable in patients with LA-HNSCC. KEYNOTE-412 (NCT03040999) is a phase 3, randomized, placebo-controlled, double-blind trial to determine the efficacy and safety of pembrolizumab given concomitantly with CRT and as maintenance therapy versus placebo plus CRT in LA-HNSCC.

Trial design

Eligibility includes 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 PS 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). A 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. Treatment will be discontinued at centrally confirmed disease progression, unacceptable toxicity, or patient/physician decision to withdrawal. Response will be assessed by computed tomography or magnetic resonance imaging 12 weeks after CRT, every 3 months for 3 years, then every 6 months for years 4 and 5. Safety will be monitored throughout the study and for 30 days after treatment end. The primary end point is event-free survival. Secondary end points include overall survival, safety, and patient-reported outcomes. Recruitment will continue until ∼780 patients are enrolled.

Clinical trial identification


Legal entity responsible for the study

Merck & Co., Inc.


Merck & Co., Inc.


J-P. Machiels: Advisory board: MSD (uncompensated), INNATE, AstraZeneca, Nanobiotix, DEBIO Research funding: Bayer, Janssen, Novartis. L. Licitra: Travel expenses, including accommodations: Merck-Serono, Debiopharm, Jobi, Bayer, Amgen Consulting or Advisory Role: Eisai, BMS, MSA, Merck-Serono, BMS, Debiopharm, Jobi, Novartis, AstraZeneca, Bayer, Roche, Amgen. D. Rischin: Research funding: Genentech/Roche, Merck, Threshold Pharmaceuticals. B. Burtness: Advisory board: Merck, Boehringer Ingelheim, Celgene, Astra Zeneca, BMS, Amgen Research funding: Merck, Advaxis, Innate. S. Aksoy: Advisory board: Pfizer, Abdi İbrahim AŞ, MSD, Honoraria: Novartis, Roche, MSD, Abdi İbrahim AŞ, Astellas. J.Y. Ge: Employment and stock ownership: Merck Sharp & Dohme. H. Brown, B. Bidadi: Employment and Stock Ownership: Merck. L. Siu: Advisory board: Merck, AstraZeneca/MedImmune, Boehringer Ingelheim, Celgene, and Pfizer Research funding: AstraZeneca/MedImmune, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Genentech/Roche, GlaxoSmithKline, Merck, Novartis, and Pfizer. O. Peeters: MSD Employee.

All other authors have declared no conflicts of interest.