Phase I expansion cohort results of cemiplimab, a human PD-1 monoclonal antibody, in combination with radiotherapy (RT), cyclophosphamide and GM-CSF, in patients (pts) with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC)
Authors: H.M. Babiker, I. Brana, D. Mahadevan, T.K. Owonikoko, E. Calvo, D. Rischin, V. Moreno, K.P. Papadopoulos, M. Crittenden, S. Formenti, J. Giralt, P. Garrido, A. Hervás Morón, K.K. Mohan, M.G. Fury, I. Lowy, E. Stankevich, M. Feng, J. Li, M. Mathias
Journal: Annals of Oncology (2018)

Background: Most pts with R/M HNSCC do not respond to PD-1 inhibitor monotherapy. Cemiplimab is a human monoclonal anti-PD-1. An expansion cohort in the phase 1 study (NCT02383212) combined cemiplimab with other potential immune-supportive treatments for pts with R/M HNSCC. Methods: Pts with R/M HNSCC who were refractory to at least first-line therapy and for whom palliative RT is clinically indicated received cemiplimab 3 mg/kg Q2W IV for up to 48 weeks plus RT (9 Gy × 3 times/week beginning 6–8 days after first dose of cemiplimab), cyclophosphamide (200 mg/m2 every 14 days for 4 doses), and GM-CSF (200 μg daily for 7-days after each of the first 4 doses of cemiplimab). The co-primary objectives were to characterise the safety, tolerability, and efficacy of cemiplimab in combination with RT, cyclophosphamide and GM-CSF in 15 pts with R/M HNSCC. Tumour assessments were performed by RECIST 1.1 Q8W. Results: As of 1 Sept, 2017, 15 pts (9 M/6 F) had been enrolled. Median (range) age was 62.0 (45–78) years; ECOG performance status was 1 in 12 pts (80%), and 0 in 3 (20%); and 14 (93.3%) had received prior RT. The primary site of cancer was upper aerodigestive tract of head and neck. With a median (range) duration of follow-up of 3.3 (0.5–10.2) months, treatment is ongoing in 3 pts (20.0%) and 12 (80%) had discontinued, mainly due to disease progression/recurrence (53.3%). The most common treatment-emergent adverse events (TEAEs) of any grade were fatigue (40.0%), constipation (26.7%), asthenia, dyspnoea, maculo-papular rash and pneumonia (each 20%). The only grade ≥3 TEAE that occurred in > 1 pts was pneumonia (13.3%). By investigator-assessment, there was 1 partial response (6.7%); disease control rate was 40.0% (95% CI: 16.3–67.7; 5 stable disease), 7 pts had progressive disease and 2 were not evaluable. Median progression-free survival by investigator-assessment was 1.8 months (95% CI: 1.7–4.7). Conclusions: The combination therapy regimen did not demonstrate efficacy above that which can be achieved with PD-1 inhibitor monotherapy for R/M HNSCC. Editorial acknowledgement: Medical writing support under the direction of the authors was provided by Emmanuel Ogunnowo, PhD, of Prime (Knutsford, UK) and funded by Regeneron Pharmaceuticals, Inc. and Sanofi according to Good Publication Practice guidelines. Clinical trial identification: NCT02383212. Legal entity responsible for the study: Regeneron Pharmaceutical Inc. and Sanofi. Funding: Regeneron Pharmaceutical Inc. and Sanofi. Disclosure: H.M. Babiker: Honoraria: Bayer, Sirtex; Consulting or advisory role: Celgene, Endocyte. D. Mahadevan: Speakers' bureau, travel, accommodation expenses: Abbvie. T.K. Owonikoko: Fees for consulting or advisory role: Novartis, Celgene, Lilly, Sandoz, Abbvie, Eisai, G1 Therapeutics, Takeda, Seattle Genetics, Bristol-Myers Squibb, MedImmune. E. Calvo: Research funding: Boehringer Ingelheim, Roche/Genentech, BMS, Novartis, PsiOxus, Nanobiotix, Janssen, Abbvie, PharmaMar, PUMA, Sanofi, Lilly, Pfizer, Merck, Nektar, Amcure, Amgen, AstraZeneca, Principia, Bayer, CytomX, H3, Incyte, Kura, Loxo, Macrogenics, Menarini, Merck, Serono, Merus, Millenium, Rigontec, Tahio, TesaroReceipt; Honoraria/consultation fees: Novartis, Nanobiotix, Janssen-Cilag, PsiOxus Therapeutics, Seattle Genetics, Pierre Fabre, Boehringer Ingelheim, Cerulean Pharma, EUSA, Abbvie, Celgene; Speaker's bureau fees: Novartis. D. Rischin: Research funding: Genentech/Roche, Merck, Amgen, Regeneron, Bristol-Myers Squibb. M. Crittenden: Research funding: Jounce, Nanobiotix. P. Garrido: Personal fees: Roche, BMS, MSD, Pfizer, Lilly, Abbvie, Regeneron, AstraZeneca, Novartis, Boerinhger-Ingelheim, outside the submitted work. K.K. Mohan, J. Li, M. Mathias: Employee and shareholder: Regeneron Pharmaceuticals, Inc. M.G. Fury: Shareholder, employee, patents, royalties, other intellectual property: Regeneron Pharmaceuticals, Inc. I. Lowy: Shareholder, employee, fees for travel and accommodation expenses, leadership: Regeneron Pharmaceuticals, Inc. E. Stankevich: Shareholder, employee: Regeneron Pharmaceuticals, Inc.; Shareholder: Celgene, Bristol-Myers Squibb, Merck. M. Feng: Shareholder, employee: Regeneron Pharmaceuticals, Inc.; Shareholder: Bayer. All other authors have declared no conflicts of interest.