First-In-Human Study of Cemiplimab Alone or In Combination with Radiotherapy and/or Low Dose Cyclophosphamide in Patients with Advanced Malignancies.

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Clinical cancer research : an official journal of the American Association for Cancer Research


PURPOSE: This first-in-human study assessed the safety, tolerability, dose-limiting toxicities (DLTs), antitumor activity, and pharmacokinetics of cemiplimab, a monoclonal anti-programmed cell death-1 (PD-1), as monotherapy and in combination with hypofractionated radiotherapy (hfRT) and/or cyclophosphamide (CPA) in patients with advanced solid tumors.

EXPERIMENTAL DESIGN: Patients were enrolled in 1 of 10 dose escalation cohorts and received cemiplimab 1, 3, or 10 mg/kg every 2 weeks intravenously for up to 48 weeks. Depending on the cohort, patients received hfRT and/or low-dose (200 mg/m

RESULTS: Sixty patients were enrolled. The median duration of follow-up was 19.3 weeks (range 2.3-84.3). There were no DLTs. The most common treatment-emergent adverse events (TEAEs) of any grade were fatigue (45.0%), nausea (36.7%), and vomiting (25.0%). The most common immune-related adverse events (irAEs) of any grade were arthralgia (10.0%), hypothyroidism (8.3%), and maculo-papular rash (8.3%). Cemiplimab pharmacokinetic parameters increased in a close to dose-proportional manner and were similar regardless of combination therapy regimen. Two patients (one with cutaneous squamous cell carcinoma and one with cervical cancer) experienced a complete response; seven had a partial response. Observed duration of response was ≥12 months in six patients.

CONCLUSIONS: The safety profile of cemiplimab was comparable with other anti-PD-1 agents. Addition of hfRT and/or CPA did not appear to increase grade ≥3 irAEs. Cemiplimab exhibited encouraging antitumor activity and durable responses.

Clinical Institute





Earle A. Chiles Research Institute