2873 - Cemiplimab, a human monoclonal anti-PD-1, plus radiotherapy (RT) in advanced non-small-cell lung cancer (NSCLC): Results from a Phase 1 expansion cohort (EC 2)

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 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.

Clinical trial identification

NCT02383212.

Legal entity responsible for the study

Regeneron Pharmaceutical Inc.; Sanofi.

Funding

Regeneron Pharmaceutical Inc.; Sanofi.

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 (http://annals.org/aim/article/2424869/good-publication-practice-communicating-company-sponsored-medical-research-gpp3).

Disclosure

M. 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 an employee of, and has received honoraria: Regeneron Pharmaceuticals, Inc. K.K. Mohan, J. Li, T. Rowlands: Shareholder and employee of 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 of, and gained fees for travel and accommodation expenses as well as leadership: Regeneron Pharmaceuticals, Inc. M.G. Fury: Shareholder and an employee of, and holds patents, royalties, other intellectual property: Regeneron Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.