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

Jean-Pascal Machiels

*Author for correspondence: Tel.: +322 764 5457; Fax: +322 764 5428;

E-mail Address: jean-pascal.machiels@uclouvain.be

https://orcid.org/0000-0001-6369-9742

Department of Medical Oncology, Institut Roi Albert II, Cliniques Universitaires Saint-Luc & Institut de Recherche Clinique et Expérimentale, Université Catholique de Louvain (UCLouvain), Avenue Hippocrate 10, Brussels, Belgium

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Yungan Tao

Department of Radiation Oncology, Gustave Roussy Cancer Campus, 114 Rue Edouard Vaillant, 94800, Villejuif, France

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Barbara Burtness

Department of Medicine, Yale University School of Medicine & Yale Cancer Center, 333 Cedar Street, New Haven, CT 06510, USA

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Makoto Tahara

Department of Head & Neck Medical Oncology, National Cancer Center Hospital East, 6-Chome-5-1 Kashiwanoha, Kashiwa, Chiba, 27-8577, Japan

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Lisa Licitra

Department of Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori and University of Milan, Via Giacomo Venezian 1, 20133, Milan, Italy

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Danny Rischin

Department of Medical Oncology, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC, 3000, Australia

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John Waldron

Department of Radiation Oncology University of Toronto, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, ON, M5G 2M9, Canada

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Christian Simon

Department of Otorhinolaryngology, University Hospital CHUV, Rue du Bugnon 21, 1011, Lausanne, Switzerland

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Vincent Gregoire

Department of Radiation Oncology, Centre Leon Berard, 28 Prom. Lea et Napoleon Bullukian, 69008, Lyon, France

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Kevin Harrington

Division of Radiotherapy & Imaging, The Institute of Cancer Research, London, SW3 6JB, UK

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Gustavo Vasconcelos Alves

Centro Integardo de Pesquisa em Oncologia, Hospital Nossa Senhora da Conceição, Avenida Francisco Trein, 596 – Cristo Redentor Porto Alegre – RS, 91350-200, Brazil

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Iane Pinto Figueiredo Lima

Crio Centro Regional Integrado de Oncologia, R. Francisco Calaca, 1300 – Alvaro Weyne, Fortaleza – CE, 60335-480, Brazil

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Yoann Pointreau

Department of Radiation Oncology, Institut Inter-Regional de Cancerologie-Centre Jean Bernard/Clinique Victor Hugo, 72000, Le Mans, France

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Brett G M Hughes

Cancer Care Services, Royal Brisbane & Women's Hospital, Butterfield Street, Herston QLD 4029, Australia & School of Medicine, University of Queensland, 20 Weightman Street, Herston, QLD, 4006, Australia

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Sercan Aksoy

Hacettepe University, Cancer Institute, Department of Medical Oncology, 06100, Ankara, Turkey

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Marcin Hetnal

Faculty of Medicine & Health Sciences, Andrzej Frycz Modrzewski Krakow University, Amethyst Radiotherapy Centre, Rydygier Hospital, Krakow, Poland, Złotej Jesieni 1, Krakow, Poland

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Joy Y Ge

Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA

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Holly Brown

Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA

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Jonathan Cheng

Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA

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Behzad Bidadi

Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA

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Lillian L Siu

Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, ON, M5G 2M9, Canada

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Published Online:3 Jun 2020https://doi.org/10.2217/fon-2020-0184

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Abstract

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 (ClinicalTrials.gov).

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 16, No. 18

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History

Received 2 March 2020

Accepted 17 April 2020

Published online 3 June 2020

Published in print June 2020

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Keywords

Author contributions

JP Machiels, B Burtness, L Licitra, J Waldron, JY Ge, H Brown, J Cheng, B Bidadi, and LL Siu conceived, designed, or planned the study. Drafting of the manuscript: Y Tao and L Licitra. JP Machiels, Y Tao, B Burtness, M Tahara, L Licitra, J Waldron, C Simon, V Gregoire, Y Pointreau, BGM Hughes, M Hetnal, S Aksoy, JY Ge, H Brown, J Cheng, B Bidadi, and LL Siu critically reviewed or revised the manuscript for important intellectual content. All authors reviewed the final version and are in agreement with the content and approved of the decision to submit.

Acknowledgments

The authors thank the patients and their families and caregivers and all investigators and site personnel.

Financial & competing interests disclosure

Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. JP Machiels reports advisory board fees from Roche, AstraZeneca, Bayer, Innate, Merck Serono, Boehringer Ingelheim, Bristol-Myers Squibb, Novartis, Janssen, Incyte, Cue Biopharma, ALX Oncology, and Pfizer; travel expenses from Bristol-Myers Squibb, Amgen, and Pfizer; uncompensated advisory board for Merck Sharp & Dohme; and safety monitoring committee for PsiOxus, Debiopharm, and Nanobiotix. Y Tao reports research funding from Debiopharm, Merck Sharp & Dohme, and Pfizer; and travel/accommodation expenses from Merck Sharp & Dohme and Merck Serono. B Burtness reports consulting/advisory fees from Merck Sharp & Dohme, Celgene, CueBioPharma, Aduro, Glaxo Smith Kline, Genentech, AstraZeneca, Bristol-Myers Squibb, Debiopharm, Macrogenics, and IOBiotech; speaker fees from Physician's Education Resource, CCO Pharma, and OncLive; and travel/gifts/in-kind payments from Merck Sharp & Dohme and Aduro. M Tahara reports grants and personal fees from Merck Sharp & Dohme, Bayer, AstraZeneca, Eisai, Bristol-Myers Squibb, Ono Pharmaceutical, Pfizer, Rakuten Medical; personal fees from Merck Serono, Celgene, and Amgen; and grants from Novartis. L Licitra reports research funding to her institution from AstraZeneca, Boehringer Ingelheim, Eisai, Merck Serono, Merck Sharp & Dohme, Novartis, and Roche; consulting fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Debiopharm, Eisai, Merck Serono, Merck Sharp & Dohme, Novartis, Roche, and Sobi; speaker fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Debiopharm, Eisai, Merck Serono, Merck Sharpe & Dohme, Novartis, Roche, and Sobi; advisory board fees from Ipsen, GlaxoSmithKline, Health & Life SRL, and Doxapharma; personal fees for public speaking/teaching in medical meetings from Immuno-Oncology hubXchange, Incyte Biosciences Italy SRL, Amgen, and Nanobiotix. D Rischin reports research funding from Merck Sharp & Dohme, Regeneron, GlaxoSmithKline, Sanofi, Roche, and Bristol-Myers Squibb. K Harrington reports research funding to his institution from AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme, and Replimune; and honoraria and advisory/consulting fees from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Merck Serono, Merck Sharp & Dohme, Oncolys BioPharma, Pfizer, and Replimune. G Alves reports research funding from Merck Sharp & Dohme, Roche, AstraZeneca, Merck Serono, Bristol-Myers Squibb, BeiGene, and Pfizer; and personal fees from Roche, Merck Serono, and Pfizer. BGM Hughes reports consulting/advisory fees from Merck Sharp & Dohme, Bristol-Myers Squibb, Roche, AstraZeneca, Pfizer, Eisai, and Boehringer Ingelheim. Y Pointreau: advisory board fees from Merck Serono, Bristol-MyersSquib, Merck Sharp & Dohme. S Aksoy reports honoraria from Roche, Novartis, Astellas, Pfizer, and Abdi Ibrahim Pharmaceuticals; and advisory board fees from Roche, Novartis, Eli Lilly, Abdi Ibrahim Pharmaceuticals, Bristol-Myers Squibb, and Merck Sharp & Dohme. JY Ge, J Cheng, and B Bidadi report employment with and stock options from Merck & Co., Inc. LL Siu reports research funding to her institution from Merck Sharp & Dohme, Novartis, Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim, GlaxoSmithKline, Roche/Genentech, Karyopharm, AstraZeneca/Medimmune, Celgene, Astellas, Bayer, AbbVie, Amgen, Symphogen, Intensity Therapeutics, Mirati Therapeutics, Shattuck Labs, Avid Radiopharmaceuticals; advisory board fees from Merck Sharp & Dohme, AstraZeneca/Medimmune, Pfizer, Celgene, MorphoSys, Roche/Genentech, Geneseeq Technology, Loxo, Oncorus, Symphogen, Seattle Genetics, GlaxoSmithKline, Voronoi, Treadwell Therapeutics, Arvinas, Tessa Therapeutics, and Navire Pharma; spouse stock ownership in Agios; and spouse leadership at Treadwell Therapeutics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Medical writing and/or editorial assistance was provided by HC Cappelli and D Mitra of the ApotheCom pembrolizumab team (PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., NJ, USA.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval and have followed the principles outlined in the Declaration of Helsinki for all human experimental investigations. In addition, informed consent has been obtained from the participants involved.

Open access

This work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/

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