Reference Detail

Ref Type

Journal Article

PMID

(35298698)

Authors

Felip E, Moreno V, Morgensztern D, Curigliano G, Rutkowski P, Trigo JM, Calvo A, Kowalski D, Cortinovis D, Plummer R, Maio M, Ascierto PA, Vladimirov VI, Cervantes A, Zudaire E, Hazra A, T'jollyn H, Bandyopadhyay N, Greger JG, Attiyeh E, Xie H, Calvo E

Title

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.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Cancer chemotherapy and pharmacology	89	4	2022 04	499-514	Cancer Chemother Pharmacol

URL

Abstract Text

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.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
CD274 positive	melanoma	predicted - sensitive	Cetrelimab	Phase Ib/II	Actionable	In a Phase I/II trial, Cetrelimab (JNJ-63723283) treatment demonstrated safety, and resulted in an overall response rate (ORR) of 18.6% (38/204), clinical benefit rate (CBR) of 31.3% (64/204), median progression-free survival (mPFS) of 2.8 mo, and median overall survival (mOS) of 17.8 mo in advanced solid tumor patients, with an ORR of 50% (4/8, 1 complete and 3 partial responses), and CBR of 75% (6/8) in CD274 (PD-L1)-positive melanoma patients (PMID: 35298698; NCT02908906).	35298698
CD274 over exp	lung non-small cell carcinoma	predicted - sensitive	Cetrelimab	Phase Ib/II	Actionable	In a Phase I/II trial, Cetrelimab (JNJ-63723283) treatment demonstrated safety and resulted in an overall response rate (ORR) of 18.6% (38/204), clinical benefit rate (CBR) of 31.3% (64/204), median progression-free survival (mPFS) of 2.8 mo, and median overall survival (mOS) of 17.8 mo in patients with advanced solid tumors, with an ORR of 52.6% (10/19, all partial responses) and CBR of 73.7% (14/50) in non-small cell lung cancer patients with high CD274 (PD-L1) expression (PMID: 35298698; NCT02908906).	35298698