Blockade of the programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) T-cell checkpoint pathway has been shown to be an effective and tolerable approach to stimulate the immune response against cancer cells. Cemiplimab (REGN2810), a high-affinity, highly potent human monoclonal antibody to PD-1, has demonstrated substantial antitumor activity and an acceptable safety profile in a variety of solid tumours including cutaneous squamous cell carcinoma, cervical cancer, and non-small-cell lung cancer (NSCLC), including in some NSCLC patients with PD-L1 expression <50% (PD-L1lo). Studies with other PD-1/PD-L1 inhibitors in NSCLC suggest that more benefit may be obtained from monotherapy in patients whose tumours have PD-L1 expression in ≥ 50% cells (PD-L1hi), and that patients with PD-L1lo may derive more benefit from a combination therapy approach.
This is a multicentre, open-label, two-part, phase 1 study of cemiplimab in Japanese patients (NCT03233139). In Part 1, patients with advanced malignancies will receive cemiplimab every 3 weeks (Q3W). Part 2 consists of two expansion cohorts of treatment-naïve patients with squamous or nonsquamous NSCLC. In Cohort A, PD-L1hi patients will receive cemiplimab Q3W; in Cohort B, PD-L1lo patients will receive cemiplimab Q3W in combination with ipilimumab 50 mg every 6 weeks (for up to four doses) and two cycles of investigators’ choice chemotherapy Q3W (i.e. gemcitabine, paclitaxel, or pemetrexed, combined with carboplatin or cisplatin, per local guidelines). All patients will receive cemiplimab for up to 108 weeks. The primary objective is to evaluate the safety, tolerability and pharmacokinetics (PK) of cemiplimab in Japanese patients with advanced malignancies. For Part 2 (Cohort A), an additional objective is to assess overall response rate (ORR) and duration of response to cemiplimab in the first-line treatment of Japanese patients with advanced PD-L1hi NSCLC. Part 1 has completed enrolment and Part 2 (first-line NSCLC) is opening for enrolment.
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).
Clinical trial identification
Legal entity responsible for the study
Regeneron Pharmaceutical, Inc. and Sanofi.
Regeneron Pharmaceutical, Inc. and Sanofi.
S. Kitano: Research grants: Regeneron Pharmaceutical, Inc., during the conduct of the study; Personal lecture fees: Sanofi, Nippon Kayaku, Meiji Seika Pharma, Taiho, Celgene, Sumitomo Dainippon Pharma; Personal lecture, advisory board fees: AstraZeneca, Chugai, Pfizer, Boehringer Ingelheim, Novartis, Daiichi-Sankyo, MSD, Kyowa Hakko Kirin, Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb; Research grants, personal lecture, advisory board fees: Eisai; Research grants: Astellas, Gilead Sciences, AMED (Japan Agency for Medical Research and Development), JSPS (Japan Society for the Promotion of Science). T. Shimizu: Institutional research expenses: Regeneron Pharmaceuticals, Inc., during the conduct of the study; Institutional research expenses: Bristol-Myers Squibb, Daiichi-Sankyo, Milleniam-Takeda, PharmaMar, FivePrime, 3D-Medicine, Symbio-Pharma; Advisory role personal fees: Milleniam-Takeda; Personal lecture fees: Boehringer Ingelheim, Taiho Pharma, Chugai Pharmaceutical, Co., Ltd, Ono Pharmaceuticals Co., Ltd, Ono Pharma Taiwan Co., Ltd, outside the submitted work. Y. Fujiwara: Research funding grants: Abbie, AstraZeneca, BMS, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Incyte, Merck Serono, MSD, Novartis; Advisory role personal fees: AstraZeneca, BMS, Novartis, Ono; Speakers’ bureau personal fees: BMS, Ono, Taiho, all outside of the submitted work. N. Yamamoto: Research grants: Chugai, Taiho, Eisai, Lilly, Quintiles, Astellas, BMS, Novartis, Daiichi-Sankyo, Pfizer, Boehringer Ingelheim, Kyowa-Hakko Kirin, Bayer, Ono Pharmaceuticals Co., Ltd, Takeda; Honoraria: Ono Pharmaceuticals Co., Ltd, Chugai, AstraZeneca, Pfizer, Lilly, BMS; Consulting fees: Eisai, Otsuka, Takeda, Boehringer Ingelheim, outside the submitted work. C. Baum, S. Li, T. Sims: Employee and shareholder of Regeneron Pharmaceuticals, Inc. P. Rietschel: Employee, shareholder, honoraria: Regeneron Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.