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.
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: 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.
|
Authors | 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 Attiyeh, Hong Xie, Emiliano Calvo |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 89
Issue 4
Pg. 499-514
(04 2022)
ISSN: 1432-0843 [Electronic] Germany |
PMID | 35298698
(Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | © 2022. The Author(s). |
Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Apoptosis Regulatory Proteins
- Immune Checkpoint Inhibitors
- Programmed Cell Death 1 Receptor
|
Topics |
- Antibodies, Monoclonal
(adverse effects)
- Antibodies, Monoclonal, Humanized
(adverse effects)
- Apoptosis Regulatory Proteins
- Carcinoma, Non-Small-Cell Lung
(drug therapy)
- Humans
- Immune Checkpoint Inhibitors
- Lung Neoplasms
(drug therapy)
- Melanoma
(drug therapy)
- Neoplasms
(drug therapy, pathology)
- Programmed Cell Death 1 Receptor
|
|
Join CureHunter, for free Research Interface BASIC access!
Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease.
Find out why thousands of doctors, pharma researchers and patient activists
around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!
|