Phase I study of cemiplimab, a human monoclonal anti-PD-1, in patients with unresectable locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC): Longer follow-up efficacy and safety data

Background: Cemiplimab (REGN2810) demonstrated a positive risk/benefit profile and produced antitumour activity in patients (pts) with advanced CSCC in the primary analysis, by independent central review, of a phase 1 CSCC expansion cohorts (ECs). We now report longer follow-up data from the CSCC ECs of the phase 1 study (NCT02383212). Methods: Pts with distantly metastatic or locally/regionally advanced CSCC who were not candidates for surgery were enrolled in ECs 7 and 8, respectively. All pts received cemiplimab 3 mg/kg by intravenous infusion over 30 minutes every 2 weeks for up to 48 weeks. Tumour measurements were performed every 8 weeks by RECIST 1.1 to determine overall response rate (ORR; complete response [CR] + partial response [PR]) according to intention to treat. The data cut-off date was Jan 20, 2018. Tumour response in this report was by investigator assessment. Results: A total of 26 pts were enrolled (21 M/5 F; 10 in EC 7, 16 in EC 8; median age: 72.5 years [range: 55–88]; ECOG performance status was 1 in 16 pts and 0 in 10 pts). Median duration of follow-up was 11.9 months (range: 1.1–18.2). Median duration of cemiplimab exposure was 36.0 weeks. The most common treatment-emergent adverse event (TEAE) of any grade was fatigue (26.9%). The only TEAEs of grade ≥3 that occurred in more than one pt were hypercalcaemia and skin infection (each 7.7%). ORR was 50.0% (95% CI: 29.9–70.1), with 2 CRs and 11 PRs; 5 patients had stable disease (SD), 6 had progressive disease, and 2 were not evaluable for response. Durable disease control rate (SD or response for ≥105 days) was 57.7% (95% CI: 36.9–76.6). The median time to response was 1.9 months (range: 1.7–7.5). The median duration of response has not been reached, and as of the data cut-off date, for pts with CR or PR, the observed duration of response exceeded 6 months in 9 pts and 12 months in 5 pts. Conclusions: The increasing duration of response in this analysis provides further evidence of a positive risk/benefit profile for cemiplimab in pts with advanced CSCC. 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: T.K. Owonikoko: Fees for consulting or advisory role: Novartis, Celgene, Lilly, Sandoz, Abbvie, Eisai, G1 Therapeutics, Takeda, Seattle Genetics, Bristol-Myers Squibb, MedImmune. A.K. Salama: Fees for consulting or advisory and speakers’ bureau roles: Bristol-Myers. 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 or consultation fees: Novartis, Nanobiotix, Janssen-Cilag, PsiOxus Therapeutics, Seattle Genetics, Pierre Fabre, Boehringer Ingelheim, Cerulean Pharma, EUSA, Abbvie, Celgene; Speaker’s bureau fees: Novartis. N.S. Yee: Institutional research funding: Boston Biomedical Inc., Merck and Co. Inc., Pharmacyclics, Regeneron Pharmaceuticals Inc; Travel/accommodation expenses: Daiichi Sankyo, Foundation Medicine, Caris Life Sciences. D. Mahadevan: Speakers’ bureau and travel, accommodation expenses: Abbvie. J. Niu: Consulting or advisory role fees: Genentech, Biodesix, Paradigm, Ignyta, AstraZeneca and Teueda. K. Kal Mohan: Employee and shareholder of Regeneron Pharmaceuticals, Inc. J. Li: Employee and shareholder of Regeneron Pharmaceuticals, Inc. and Novartis. E. Stankevich: Employee of Regeneron Pharmaceuticals, Inc., a shareholder of Regeneron Pharmaceuticals, Inc., Celgene, Bristol-Myers Squibb, and Merck. M. Mathias: Shareholder and an employee of Regeneron Pharmaceuticals, Inc. I. Lowy: Employee, shareholder, fees for travel and accommodation expenses, leadership: Regeneron Pharmaceuticals, Inc. M.G. Fury: Employee and shareholder of Regeneron Pharmaceuticals, INC.; patents, royalties, other intellectual property: Regeneron Pharmaceuticals, Inc. H.M. Babiker: Honoraria: Bayer, Sirtex; Consulting or advisory role fees: Celgene, Endocyte. All other authors have declared no conflicts of interest.