Dose exploration results from Phase 1 study of cemiplimab, a human monoclonal programmed death (PD)-1 antibody, in Japanese patients with advanced malignancies

Purpose Part 1 of this two-part, open-label, Phase 1 study (NCT03233139) assessed the safety, tolerability, pharmacokinetics, immunogenicity, and clinical activity of cemiplimab in Japanese patients with advanced malignancies. Methods Patients received cemiplimab 250 mg ( n = 6) or 350 mg ( n = 7) every 3 weeks intravenously for up to 108 weeks in Part 1. Tumor responses were assessed by investigators every 9 weeks using the Response Evaluation Criteria in Solid Tumors version 1.1. Results Of 13 patients enrolled, median age was 62 years (range 33–75) and eight patients were female. Median duration of cemiplimab exposure was 13.1 weeks (range 3.0‒113.6). At the time of data cut-off, 11 patients (84.6%) had discontinued treatment (majority due to disease progression: n = 8, 61.5%). The most common treatment-emergent adverse events (TEAEs) of any grade were contact dermatitis, rash, and viral upper respiratory tract infection (each n = 3, 23.1%). Five grade ≥ 3 TEAEs were reported in four patients: autoimmune colitis, dehydration, hyponatremia, hypophosphatemia, and muscular weakness. No dose-limiting toxicities were reported and no TEAEs led to death. Cemiplimab concentrations in serum were consistent with previously reported pharmacokinetic characteristics of cemiplimab. No anti-drug antibodies were detected in serum. Objective response rate [ORR; complete response + partial response (PR)] was 30.8% (four PR) and disease control rate [ORR + stable disease (SD)] was 46.2% (6/13; two SD). Conclusion Cemiplimab exhibited antitumor activity in Japanese patients with advanced malignancies. The safety profile was comparable to those previously reported for cemiplimab and other PD-1 inhibitors. Trial registration NCT03233139 at ClinicalTrials.gov. Graphic abstract