First-in-human, open-label, phase 1/2 study of the monoclonal antibody programmed cell death protein-1 (PD-1) inhibitor cetrelimab (JNJ-63723283) in patients with advanced cancers

Enriqueta Felip, Victor Moreno, Daniel Morgensztern, Giuseppe Curigliano, Piotr Rutkowski, José Manuel Trigo, Aitana Calvo, Dariusz Kowalski, Diego Cortinovis, Ruth Plummer, Michele Maio, Paolo A. Ascierto, Vladimir I. Vladimirov, Andres Cervantes, Enrique Zudaire, Anasuya Hazra, Huybrecht T’jollyn, Nibedita Bandyopadhyay, James G. Greger, Edward AttiyehHong Xie, Emiliano Calvo

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: To assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of cetrelimab (JNJ-63723283), a monoclonal antibody programmed cell death protein-1 (PD-1) inhibitor, in patients with advanced/refractory solid tumors in the phase 1/2 LUC1001 study. Methods: In phase 1, patients with advanced solid tumors received intravenous cetrelimab 80, 240, 460, or 800 mg every 2 weeks (Q2W) or 480 mg Q4W. In phase 2, patients with melanoma, non-small-cell lung cancer (NSCLC), and microsatellite instability–high (MSI-H)/DNA mismatch repair-deficient colorectal cancer (CRC) received cetrelimab 240 mg Q2W. Response was assessed Q8W until Week 24 and Q12W thereafter. Results: In phase 1, 58 patients received cetrelimab. Two dose-limiting toxicities were reported and two recommended phase 2 doses (RP2D) were defined (240 mg Q2W or 480 mg Q4W). After a first dose, mean maximum serum concentrations (Cmax) ranged from 24.7 to 227.0 µg/mL; median time to Cmax ranged from 2.0 to 3.2 h. Pharmacodynamic effect was maintained throughout the dosing period across doses. In phase 2, 146 patients received cetrelimab 240 mg Q2W. Grade ≥ 3 adverse events (AEs) occurred in 53.9% of patients. Immune-related AEs (any grade) occurred in 35.3% of patients (grade ≥ 3 in 6.9%). Overall response rate was 18.6% across tumor types, 34.3% in NSCLC, 52.6% in programmed death ligand 1–high (≥ 50% by immunohistochemistry) NSCLC, 28.0% in melanoma, and 23.8% in centrally confirmed MSI-H CRC. Conclusions: The RP2D for cetrelimab was established. Pharmacokinetic/pharmacodynamic characteristics, safety profile, and clinical activity of cetrelimab in immune-sensitive advanced cancers were consistent with known PD-1 inhibitors. Trial registrations: NCT02908906 at ClinicalTrials.gov, September 21, 2016; EudraCT 2016–002,017-22 at clinicaltrialsregister.eu, Jan 11, 2017.

Original languageEnglish
Pages (from-to)499-514
Number of pages16
JournalCancer Chemotherapy and Pharmacology
Volume89
Issue number4
DOIs
StatePublished - Apr 2022

Keywords

  • Colorectal cancer
  • Melanoma
  • Microsatellite instability–high
  • Monoclonal antibody PD-1 inhibitor efficacy
  • Non-small-cell lung cancer
  • Pharmacokinetics/pharmacodynamics

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