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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.
- Source :
-
Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2022 Apr; Vol. 89 (4), pp. 499-514. Date of Electronic Publication: 2022 Mar 17. - Publication Year :
- 2022
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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.<br />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.<br />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 (C <subscript>max</subscript> ) ranged from 24.7 to 227.0 µg/mL; median time to C <subscript>max</subscript> 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.<br />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.<br />Trial Registrations: NCT02908906 at ClinicalTrials.gov, September 21, 2016; EudraCT 2016-002,017-22 at clinicaltrialsregister.eu, Jan 11, 2017.<br /> (© 2022. The Author(s).)
- Subjects :
- Antibodies, Monoclonal adverse effects
Antibodies, Monoclonal, Humanized adverse effects
Apoptosis Regulatory Proteins
Humans
Immune Checkpoint Inhibitors
Programmed Cell Death 1 Receptor
Carcinoma, Non-Small-Cell Lung drug therapy
Lung Neoplasms drug therapy
Melanoma drug therapy
Neoplasms drug therapy
Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0843
- Volume :
- 89
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cancer chemotherapy and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 35298698
- Full Text :
- https://doi.org/10.1007/s00280-022-04414-6