189: Pharmacokinetics of Cemiplimab in Patients With Advanced Non-Small Cell Lung Cancer

Statement of Purpose: In the first-in-human study of cemiplimab (NCT02383212) in patients with advanced solid tumors, including advanced non-small cell lung cancer (NSCLC), cemiplimab was administered intravenously every 2 weeks (Q2W) as a 30-minute infusion in monotherapy and in combination with radiotherapy and/or chemotherapy. Cemiplimab pharmacokinetics were linear and increased dose-proportionally over a dosing range of 1–10 mg/kg Q2W. In this first-in-human study, cemiplimab pharmacokinetics were similar across solid tumor types and irrespective of monotherapy or combination therapy. Based on the pivotal Phase 3 trials of cemiplimab (EMPOWER-Lung 1, NCT03088540; EMPOWER-Lung 3, NCT03409614), cemiplimab 350 mg every 3 weeks (Q3W) intravenous was approved for first-line treatment of advanced NSCLC as monotherapy and in combination with chemotherapy. Here we characterize the pharmacokinetics of cemiplimab from these Phase 3 trials.

Description of Methods & Materials: Cemiplimab pharmacokinetics were assessed in patients with advanced NSCLC who received (1) cemiplimab 350 mg Q3W as monotherapy in EMPOWER-Lung 1, (2) cemiplimab 350 mg Q3W + platinum-doublet chemotherapy for four 3-week cycles in EMPOWER-Lung 3 Part 2 and (3) cemiplimab 350 mg Q3W + platinum-doublet chemotherapy for 4 cycles, or cemiplimab 350 mg Q3W + platinum-doublet chemotherapy for 2 cycles + ipilimumab 50 mg every 6 weeks for four 3-week cycles in EMPOWER-Lung 3 Part 1. Blood samples for pharmacokinetic assessment were collected pre-dose and at various times throughout the treatment and follow-up periods. Cemiplimab concentrations in serum were measured as functional cemiplimab and assessed using a validated enzyme-linked immunosorbent assay with a lower limit of quantitation of 0.078 mg/L. In addition, immunogenicity against cemiplimab was assessed using a validated electrochemiluminescence bridging immunoassay for antidrug antibodies (ADAs).

Data & Results: Mean cemiplimab maximum concentration (C_max) and trough concentration (Ctrough) values at steady-state (after approximately 18–24 weeks) were similar in monotherapy in EMPOWER-Lung 1 and combination therapy in EMPOWER-Lung 3 (Table 1). In EMPOWER-Lung 3, cemiplimab exposure was similar regardless of histology type (squamous or non-squamous) and PD-L1 expression level (Part 1: < 1%, 1–24% and 25–50%; Part 2: < 1%, 1–49% and ≥50%). Occurrence of ADAs against cemiplimab was low and did not affect cemiplimab concentrations in serum.

Interpretation, Conclusion or Significance: Cemiplimab pharmacokinetics were similar in patients with advanced NSCLC receiving cemiplimab as monotherapy or combination treatment, irrespective of tumor histology or PD-L1 expression level.

Disclosures: Apostolos Papachristos, Sheila Masinde, Xiao Meng, Jenny Valentine, Hong Yan, John D Davis and Anne Paccaly are employees and shareholders of Regeneron Pharmaceuticals Inc. The study was funded by Regeneron Pharmaceuticals Inc. Medical writing support was provided by Atif Riaz, PhD, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals Inc.