Abstract 3285
Background
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.
Funding
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.
Disclosure
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.