First-In-Human Study of Cemiplimab Alone or In Combination with Radiotherapy and/or Low-dose Cyclophosphamide in...

Area of Science:

• Oncology
• Immunotherapy
• Clinical Trials

Background:

• Advanced solid tumors represent a significant unmet medical need.
• Programmed cell death-1 (PD-1) inhibitors have emerged as a promising therapeutic strategy.
• Combination therapies are being explored to enhance treatment efficacy.

Purpose of the Study:

• To evaluate the safety, tolerability, and efficacy of cemiplimab, a PD-1 inhibitor.
• To assess cemiplimab as monotherapy and in combination with hypofractionated radiotherapy (hfRT) and cyclophosphamide (CPA).
• To determine dose-limiting toxicities (DLTs) and pharmacokinetic profiles of cemiplimab.

Main Methods:

• A first-in-human, dose-escalation study.
• Patients received cemiplimab (1, 3, or 10 mg/kg IV every 2 weeks) with or without hfRT and/or CPA.
• Safety, antitumor activity (RECIST v1.1), and pharmacokinetics were assessed.

Main Results:

• No DLTs were observed in 60 enrolled patients.
• Common treatment-emergent adverse events included fatigue, nausea, and vomiting.
• Two complete responses and seven partial responses were observed, with durable responses in some patients.
• Cemiplimab pharmacokinetics were dose-proportional and unaffected by combination therapy.

Conclusions:

• Cemiplimab demonstrated a favorable safety profile, comparable to other anti-PD-1 agents.
• Combination of cemiplimab with hfRT and/or CPA did not increase grade ≥3 immune-related adverse events.
• Cemiplimab showed encouraging and durable antitumor activity in patients with advanced solid tumors.