2026-04-13T01:28:10Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/127622025-05-04T02:55:27Zcom_2072_378070com_2072_378040col_2072_378092

A first-in-human study of JNJ-70218902, a bispecific T-cell-redirecting antibody against TMEFF2 in metastatic castration-resistant prostate cancer Doger, Bernard Peer, Avivit Sarid, David Eigl, Bernhard Calvo, Emiliano Carles, Joan 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 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. 2025-03-14T13:21:22Z 2025-03-14T13:21:22Z 2025-01-20 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion The Oncologist;30(1) https://doi.org/10.1093/oncolo/oyae313 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Oxford University Press Scientia