Sistema de Salut de Catalunya
Institut Català de la Salut
[Calvo E] START Madrid-CIOCC, Centro Integral Oncológico Clara Campal, Madrid, Spain. [Doger B] START Madrid-FJD, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain. [Carles J] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Peer A] Rambam Health Care Campus, Haifa, Israel. [Sarid D] Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. [Eigl BJ] BC Cancer – Vancouver, Vancouver, Canada
Vall d'Hebron Barcelona Hospital Campus
2025-03-14T13:21:22Z
2025-03-14T13:21:22Z
2025-01-20
T-lymphocytes; Castration-resistant prostate cancer; Immunotherapy
Linfocitos T; Cáncer de próstata resistente a la castración; Inmunoterapia
Limfòcits T; Càncer de pròstata resistent a la castració; Immunoteràpia
Background: Metastatic castration-resistant prostate cancer (mCRPC) has a poor prognosis, necessitating the investigation of novel treatments and targets. This study evaluated JNJ-70218902 (JNJ-902), a T-cell redirector targeting transmembrane protein with epidermal growth factor-like and 2 follistatin-like domains 2 (TMEFF2) and cluster of differentiation 3, in mCRPC. Patients and methods: Patients who had measurable/evaluable mCRPC after at least one novel androgen receptor-targeted therapy or chemotherapy were eligible. Participants received subcutaneous JNJ-902 0.3, 1.0, 1.5, 3.0, or 6.0 mg once weekly (QW) or 2.0, 3.0, 4.0, or 6.0 mg biweekly (Q2W). Study objectives included assessment of safety, pharmacokinetics, immunogenicity, and preliminary efficacy. Results: Eighty-two participants were enrolled to receive at least one dose of JNJ-902 (QW; n = 38; Q2W; n = 44). Median duration of treatment was 1.91 (0.0-19.4) months across dosing groups. All participants experienced at least one treatment-emergent adverse event (TEAE) and 76 (92.7%) experienced treatment-related TEAEs. Fourteen participants (17.1%) experienced a TEAE that led to study discontinuation, of which 3 (3.7%) were related to JNJ-902. Dose-limiting toxicities were observed in 2 participants (2.4%). Five participants (15.2%) with measurable disease had a confirmed partial response and 10 participants (12.2%) had ≥50% decrease from baseline prostate-specific antigen levels. Clinical activity was not dose related and no clear exposure-response relationship was observed. Conclusions: In this study, dose escalation was limited by emerging dose-limiting toxicities. Although a recommended phase II dose was not determined, findings indicate TMEFF2 to be a potential target in mCRPC that warrants further investigation.
This study was funded by Janssen Research & Development, LLC.
Article
Published version
English
Metàstasi; Anticossos monoclonals - Ús terapèutic; Posologia; Pròstata - Càncer - Immunoteràpia; CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Bispecific; Other subheadings::Other subheadings::Other subheadings::/administration & dosage; DISEASES::Neoplasms::Neoplastic Processes::Neoplasm Metastasis; DISEASES::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms::Prostatic Neoplasms, Castration-Resistant; Other subheadings::Other subheadings::Other subheadings::/drug therapy; COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos biespecíficos; Otros calificadores::Otros calificadores::Otros calificadores::/administración & dosificación; ENFERMEDADES::neoplasias::procesos neoplásicos::metástasis neoplásica; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales masculinos::neoplasias de la próstata::neoplasias prostáticas resistentes a la castración; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
Oxford University Press
The Oncologist;30(1)
https://doi.org/10.1093/oncolo/oyae313
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
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