RT Journal Article
T1 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.
A1 Felip, Enriqueta
A1 Moreno, Victor
A1 Morgensztern, Daniel
A1 Curigliano, Giuseppe
A1 Rutkowski, Piotr
A1 Trigo, José Manuel
A1 Calvo, Aitana
A1 Kowalski, Dariusz
A1 Cortinovis, Diego
A1 Plummer, Ruth
A1 Maio, Michele
A1 Ascierto, Paolo A
A1 Vladimirov, Vladimir I
A1 Cervantes, Andres
A1 Zudaire, Enrique
A1 Hazra, Anasuya
A1 T'jollyn, Huybrecht
A1 Bandyopadhyay, Nibedita
A1 Greger, James G
A1 Attiyeh, Edward
A1 Xie, Hong
A1 Calvo, Emiliano
K1 Colorectal cancer
K1 Melanoma
K1 Microsatellite instability–high
K1 Monoclonal antibody PD-1 inhibitor efficacy
K1 Non-small-cell lung cancer
K1 Pharmacokinetics/pharmacodynamics
AB 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 (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. 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.
YR 2022
FD 2022-03-17
LK http://hdl.handle.net/10668/19753
UL http://hdl.handle.net/10668/19753
LA en
DS RISalud
RD Apr 5, 2025