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oai:recercat.cat:11351/79732025-10-04T05:19:55Zcom_2072_378070com_2072_378040col_2072_378092

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 Morgensztern, Daniel Trigo, José Manuel Curigliano, Giuseppe Rutkowski, Piotr Moreno, Victor Felip Font, Enriqueta Institut Català de la Salut [Felip E] Unitat de Càncer Toràcic, Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Moreno V] Phase 1 Trials Unit, START MADRID-FJD, Hospital Fundación Jiménez Díaz Medical Oncology Division, Madrid, Spain. [Morgensztern D] Division of Oncology, Section of Medical Oncology, Washington University School of Medicine, St. Louis, MO, USA. [Curigliano G] Division of Early Drug Development, European Institute of Oncology, IRCCS and University of Milano, Milan, Italy. [Rutkowski P] Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland. [Trigo JM] Department of Medical Oncology, Hospital Universitario Virgen de La Victoria y Regional, Málaga, Spain Vall d'Hebron Barcelona Hospital Campus Càncer - Tractament Anticossos monoclonals - Ús terapèutic - Eficàcia DISEASES::Neoplasms Other subheadings::Other subheadings::Other subheadings::/drug therapy ENFERMEDADES::neoplasias Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia Melanoma; Monoclonal antibody PD-1 inhibitor efficacy; Pharmacokinetics/pharmacodynamics Melanoma; Eficacia del inhibidor del anticuerpo monoclonal PD-1; Farmacocinética/farmacodinamia Melanoma; Eficàcia de l'inhibidor de l'anticòs monoclonal PD-1; Farmacocinètica/farmacodinàmica 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. This study was funded by Janssen Research & Development. 2022-08-10T06:25:51Z 2022-08-10T06:25:51Z 2022-04 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Felip E, Moreno V, Morgensztern D, Curigliano G, Rutkowski P, Trigo JM, et al. 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. Cancer Chemother Pharmacol. 2022 Apr;89:499–514. 1432-0843 https://hdl.handle.net/11351/7973 10.1007/s00280-022-04414-6 35298698 000770203700002 eng Cancer Chemotherapy and Pharmacology;89 https://doi.org/10.1007/s00280-022-04414-6 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess application/pdf Springer Scientia