Cemiplimab, a human monoclonal anti-PD-1, in patients (pts) with advanced or metastatic hepatocellular carcinoma (HCC): Data from an expansion cohort (EC) in a phase I study
Authors: A.R. He, G.J. Weiss, G. Falchook, N.S. Yee, M. Gil-Martin, S. Shahda, V. Moreno, I. Brana, M. Crittenden, S. Formenti, R. Al-Rajabi, K.P. Papadopoulos, M.J. Pishvaian, E. Stankevich, M. Feng, J. Li, M. Mathias, G. Kroog, I. Lowy, M.G. Fury
Journal: Annals of Oncology (2018)

Background: For pts with unresectable HCC, systemic therapy options are limited. Sorafenib and lenvatinib are approved in the US and Europe for HCC treatment. For pts who progress on sorafenib, regorafenib and nivolumab are approved as second-line therapy. Cemiplimab (REGN2810) has demonstrated encouraging efficacy and safety profile in a Phase 1 dose escalation study in pts with advanced malignancies (NCT02383212). We present results of the Phase 1 HCC EC. Methods: HCC pts who are not candidates for surgery and had progressed on, could not tolerate, or refused first-line systemic therapy received cemiplimab 3 mg/kg Q2W IV for up to 48 weeks. The objectives were to evaluate the safety and tolerability (primary) and antitumour activity (secondary) of cemiplimab. Results: As of 1 Sept 2017, 26 pts were enrolled (25 M/1 F; median age: 65 [range: 40–78] years; ≥1 prior systemic therapy: 24 pts [92.3%]; ECOG PS: 1 in 19 pts [73.1%], 0 in 6 [23.1%], and missing in 1). Median duration of follow-up was 7.2 (range: 1.8–15.5) months. By investigator assessment, 5 pts (19.2%) had partial response, 14 (53.8%) had stable disease, 6 (23.1%) had progressive disease and 1 was not evaluable. Median progression-free survival was 3.7 months (95% CI: 2.3–9.1). Five pts (19.2%) completed the planned 48-week treatment, and 21 (80.8%) discontinued prematurely, primarily due to disease progression (65.4%). Three of the 5 pts who completed planned treatment remain without disease progression at the last response assessment. The most common treatment-emergent adverse events (TEAEs) of any grade were fatigue (26.9%), decreased appetite, increased aspartate aminotransferase (AST), abdominal pain, pruritus, and dyspnoea (each 23.1%). Grade ≥3 TEAEs occurring in ≥ 2 pts were hyponatraemia (3 pts), autoimmune hepatitis (2 pts) and increased AST (2 pts). Two pts (7.7%) had a TEAE resulting in death: 1 with pulmonary embolism that was considered unrelated to treatment and another with hepatic failure considered possibly related to treatment. Conclusions: Cemiplimab demonstrated evidence of antitumour activity in pts with advanced or metastatic HCC. The safety profile is comparable with that of other anti-PD-1 inhibitors. 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: G.J. Weiss: Personal fees and ownership interest: Circulogene; Ownership interest: Angiex; Personal fees: Paradigm, Igynta, IDEA Pharma, GLG Council, Guidepoint Global; Travel/lodging fees: Cambridge Health tech Institute, Tesaro; Patent PCT/US2011/020612 issued. G. Falchook: Funding for trial for submitted work. N.S. Yee: Research, travel, accommodation and expenses: Daiichi Sankyo, Foundation Medicine, Caris Life Sciences. S. Shahda: Advisory board fees: Ipsen, Bayer; Research grants: Incyte, Apexian. M. Crittenden: Research funding: Jounce, Nanobiotix. R. Al-Rajabi: Grants: Regeneron Pharmaceuticals Inc., during the conduct of the study. E. Stankevich: Shareholder and employee: Regeneron Pharmaceuticals, Inc.; Shareholder: Celgene, Bristol-Myers Squibb, Merck. M. Feng: Shareholder and employee of Regeneron Pharmaceuticals, Inc.; Shareholder: Bayer. J. Li, M. Mathias, G. Kroog: Shareholder and employee: Regeneron Pharmaceuticals, Inc. I. Lowy: Shareholder and employee, fees for travel and accommodation expenses, leadership: Regeneron Pharmaceuticals, Inc. M.G. Fury: Shareholder, employee, patents, royalties, other intellectual property: Regeneron Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.