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.
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
Programmed Cell Death 1 Receptor
Colorectal cancer
Melanoma
Microsatellite instability–high
Monoclonal antibody PD-1 inhibitor efficacy
Non-small-cell lung cancer
Pharmacokinetics/pharmacodynamics
Journal
Cancer chemotherapy and pharmacology
ISSN: 1432-0843
Titre abrégé: Cancer Chemother Pharmacol
Pays: Germany
ID NLM: 7806519
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
21
09
2021
accepted:
16
02
2022
pubmed:
18
3
2022
medline:
12
4
2022
entrez:
17
3
2022
Statut:
ppublish
Résumé
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. 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. 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 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. NCT02908906 at ClinicalTrials.gov, September 21, 2016; EudraCT 2016-002,017-22 at clinicaltrialsregister.eu, Jan 11, 2017.
Identifiants
pubmed: 35298698
doi: 10.1007/s00280-022-04414-6
pii: 10.1007/s00280-022-04414-6
pmc: PMC8956549
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Monoclonal, Humanized
0
Apoptosis Regulatory Proteins
0
Immune Checkpoint Inhibitors
0
Programmed Cell Death 1 Receptor
0
Banques de données
ClinicalTrials.gov
['NCT02908906']
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
499-514Informations de copyright
© 2022. The Author(s).
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