Cemiplimab, a human monoclonal anti-PD-1, plus radiotherapy (RT) in advanced non-small cell lung cancer (NSCLC): Results from a phase I expansion cohort (EC 2)
Authors: V. Moreno, M. Gil-Martin, M.L. Johnson, R. Aljumaily, P. Lopez Criado, D.W. Northfelt, M. Crittenden, S. Jabbour, L. Rosen, P. Garrido, A. Hervás Morón, P. Rietschel, K.K. Mohan, J. Li, E. Stankevich, M. Feng, I. Lowy, M.G. Fury
Journal: Annals of Oncology (2018)

Background: Cemiplimab (REGN2810), a human monoclonal antibody to PD-1, has exhibited substantial antitumour activities in patients (pts) with advanced malignancies in a Phase 1 study. Most patients with advanced NSCLC do not respond to PD-1 inhibitor monotherapy. Here we report results of the Phase 1 EC 2, a combination regimen of cemiplimab plus RT in advanced NSCLC (NCT02383212). Methods: Pts with advanced NSCLC who had relapsed after, or were refractory to at least first-line therapy and for whom palliative RT was clinically indicated, received cemiplimab 3 mg/kg every 2 weeks intravenously for up to 48 weeks plus RT (9 Gy × 3 times/week given 1 week after first dose of cemiplimab) to a single lesion. The co-primary objectives were to evaluate the safety, tolerability, and efficacy of cemiplimab plus RT. Tumour measurements (of non-irradiated target lesions) were performed by RECIST 1.1 every 8 weeks. Results: As of 1 Sept, 2017, 33 pts (22 M/11 F; median age 67.0 years [range, 47–82]) were enrolled; 66.7% and 30.3% had an ECOG performance status of 1 and 0, respectively; the status of one pt was unknown. Overall response rate (ORR; complete response [CR] + partial response [PR]) was 18.2% (0 CR and 6 PRs) with a median duration of response of 14.9 months (95% CI: 5.5–14.9). Disease control rate (ORR + stable disease [SD]) was 72.7% (6 PRs + 18 SDs). The most common treatment-emergent adverse events (TEAEs) of any grade were decreased appetite (30.3%), fatigue (27.3%), and cough (24.2%). Grade ≥3 TEAEs occurring in ≥ 2 patients include anaemia (12.1%), hypophosphataemia, and urinary tract infection (each 6.1%). One patient had a TEAE of pneumonitis, considered related to study drug, with an outcome of death. Conclusions: Cemiplimab plus RT demonstrated antitumour activity in pretreated pts with NSCLC. The safety profile is comparable with other anti-PD-1 agents and RT. The combination therapy regimen did not produce greater efficacy above that which can be achieved with PD-1 inhibitor monotherapy for advanced NSCLC. 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: M.L. Johnson: Consulting or advisory role: Astellas Pharma, Otsuka. M. Crittenden: Research funding: Jounce, Nanobiotix. S. Jabbour: Research funding grants: Merck, Nestle, outside the submitted work. L. Rosen: Research funding: Regeneron Pharmaceuticals, Inc. P. Garrido: Personal fees: Roche, BMS, MSD, Pfizer, Lilly, Abbvie, Regeneron, AstraZeneca, Novartis, Boerinhger-Ingelheim, outside the submitted work. P. Rietschel: Shareholder and employee, honoraria: Regeneron Pharmaceuticals, Inc. K.K. Mohan, J. Li: Shareholder and employee: Regeneron Pharmaceuticals, Inc. E. Stankevich: Shareholder and employee: Regeneron Pharmaceuticals, Inc.; Shareholder: Celgene, Bristol-Myers Squibb, Merck. M. Feng: Shareholder and employee: Regeneron Pharmaceuticals, Inc.; Shareholder: Bayer. I. Lowy: Shareholder and employee, fees for travel and accommodation expenses, leadership: Regeneron Pharmaceuticals, Inc. M.G. Fury: Shareholder and employee, patents, royalties, other intellectual property: Regeneron Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.