Despite significant advancements in oncologic treatment, the outcome for patients with advanced or recurrent HNSCC is poor. Identification of abscopal effects by use of radiotherapy (RT) in combination with immunotherapy in a patient with metastatic melanoma has prompted interest in the use of combination regimens. The objective of the KEYNOTE-412 trial (NCT03040999) is to assess efficacy and safety of pembrolizumab in combination with CRT as maintenance therapy for subjects with LA-HNSCC.
KEYNOTE-412 is a phase 3, randomized, placebo-controlled, double-blind trial enrolling subjects with newly diagnosed, treatment-naive, oropharyngeal p16 positive (any T4 or any N3), oropharyngeal p16 negative (any T3-T4, or N2a-N3), or larynx/hypopharynx/oral cavity (any T3-T4, any N2a-N3) SCC. Approximately 780 subjects will be randomly assigned (1:1) to receive pembrolizumab plus cisplatin-based CRT or placebo plus cisplatin-based CRT. Subjects will be stratified by RT regimen, tumor site/p16 status, and disease stage. Treatment will include a priming dose of pembrolizumab 200 mg or placebo 1 week before initiation of CRT, followed by 7 weeks’ CRT (cisplatin 100 mg/m2 every 3 weeks [Q3W] [3 doses]; accelerated RT [70 Gy, 6 fractions/week] or standard RT [70 Gy, 5 fractions/week]) plus pembrolizumab 200 mg Q3W or placebo Q3W. Treatment with pembrolizumab 200 mg Q3W or placebo Q3W will continue up to 1 year (maximum 17 doses). Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision to withdraw the patient. Response will be assessed by computed topography or magnetic resonance imaging 12 weeks after completion of CRT, every 4 months for a subsequent 2 years, and every 6 months thereafter up to year 5. Safety will be monitored throughout the study. The primary end point is event-free survival by blinded independent central review per RECIST v1.1. Secondary end points include overall survival, safety, and quality of life. Exploratory biomarker analyses will be conducted.
Clinical trial identification
NCT03040999, February 1, 2017
Legal entity responsible for the study
Merck & Co., Inc., Kenilworth, NJ, USA
Merck & Co., Inc., Kenilworth, NJ, USA Disclosure: J-P. Machiels: Advisory board member: MSD (uncompensated), Innate, AstraZeneca, Nanobiotix, Debio; Research funding: Bayer, Janssen, Novartis. L. Licitra: Travel expenses, including accommodations: Merck-Serono, Debiopharm, Jobi, Bayer, Amger; Consulting or Advisory Role: Eisai, Bristol-Myers Squibb, MSA, Merck-Serono, Debiopharm, Jobi, Novartis, AstraZeneca, Bayer, Roche, Amgen. D. Rischin: Research funding: Genentech/Roche, Merck, Threshold Pharmaceuticals. B. Burtness: Advisory board member: Merck, Boehringer Ingelheim, Celgene, AstraZeneca, Bristol-Myers Squibb, Amgen; Research funding: Merck, Advaxis, Innate. T. Shekar, H.M. Brown: Employment and Stock ownership: Merck. J. Cheng: Employment and Stock ownership: Merck MSD. L.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. All other authors have declared no conflicts of interest.