4037 - Cemiplimab, a human PD-1 monoclonal antibody, in patients (pts) with recurrent or metastatic cervical cancer: Interim data from Phase 1 cohorts

Background

For pts who progress after first–line platinum based therapy for recurrent/metastatic cervical cancer, there are no therapies available that have been demonstrated to improve survival or quality of life. Cemiplimab (REGN2810), a human monoclonal antibody to PD-1, exhibited encouraging efficacy and acceptable tolerability in a phase 1 dose escalation study. The present report focuses on interim data from the phase 1 cervical cancer expansion cohorts (ECs) of cemiplimab as a monotherapy (EC 23) or in combination with hypofractionated radiotherapy (hfRT) (EC 24) (NCT02383212).

Methods

Pts with recurrent or metastatic cervical cancer resistant to or intolerant of platinum and taxane doublet therapy received cemiplimab 3 mg/kg Q2W for up to 48 weeks, in ECs 23 and 24, and hfRT (9 Gy x 3 times/week given 1 week after first dose of cemiplimab) in EC 24. The co-primary objectives were to evaluate the safety, tolerability, and efficacy of cemiplimab monotherapy or in combination with hfRT. Tumour response assessments (in non-irradiated target lesions) were performed by RECIST 1.1 Q8W.

Results

As of 1 Sept, 2017, these ECs were fully enrolled with 20 pts (EC 23, n = 10, EC 24, n = 10). Median (range) age was 55.0 (31–76) years (EC 23) and 51.5 (29–65) years (EC 24). ECOG performance status 1 vs. 0 was 60% vs. 40% and 80% vs. 20%, respectively, for EC 23 and EC 24. Investigator-assessed overall response rate (ORR; complete response [CR] + partial response [PR]) was 10.0% (0 CR and 1 PR) in each of EC 23 and EC 24. At the time of data cut-off, both responses were ongoing with durations of 3.7+ months. The most common treatment-emergent adverse events (TEAEs) of any grade were diarrhoea (40.0%), fatigue, hypokalaemia and pain in extremity (each 30.0%) in EC 23, and diarrhoea and urinary tract infection (each 30.0%) in EC 24. There was no grade ≥3 TEAE reported in > 1 patient in either cohort.

Conclusions

Cemiplimab as monotherapy and in combination with hfRT demonstrated antitumour activity with an acceptable safety profile in pts with metastatic or recurrent cervical cancer. Cemiplimab monotherapy vs. chemotherapy in ≥ 2^nd line cervical cancer is currently being evaluated in a global randomised phase 3 study (NCT03257267).

Clinical trial identification

NCT02383212.

Legal entity responsible for the study

Regeneron Pharmaceutical, Inc. and Sanofi.

Funding

Regeneron Pharmaceutical, Inc. and 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.

Disclosure

D. Rischin: Research funding: Genentech/Roche, Merck, Amgen, Regeneron, Bristol-Myers Squibb. A. González-Martín: Consulting, Advisory, Speakers’ bureau and Travel accommodation expenses: AstraZeneca, Tesaro, Roche, Pharmamar. J.Y. Hou: Consultant and receives fees: Foundation Medicine, Massive Bio, Inc. D. Cho: Consulting fees: Pfizer, BMS, Exelixis, Genentech, Prometheus. G.S. Falchook: Funding: Regeneron Pharmaceuticals for trial for submitted work. S. Jabbour: Research funding grants: Merck, Nestle outside of the submitted work. K. Moore: Institutional consultancy (honorarium and ad board) fees: Tesaro, Genentech Roche, Clovis, AstraZeneca (for agents not involved in the SOLO-1 study), Immunogen, VBL Therapeutics, Janssen. M.G. Fury: Employee of and shareholder: Regeneron Pharmaceuticals, Inc.; Patents, royalties, other intellectual property: Regeneron Pharmaceuticals, Inc. M. Feng: Employee and shareholder: Regeneron Pharmaceuticals, Inc., Bayer. J. Li: Employee and shareholder: Regeneron Pharmaceuticals, Inc., Novartis. I. Lowy: Employee of, shareholder of, and fees for travel and accommodation expenses as well as leadership: Regeneron Pharmaceuticals, Inc. M. Mathias: Employee and shareholder: Regeneron Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.