Type: Oral
Session: 651. Multiple Myeloma and Plasma Cell Dyscrasias: Basic and Translational: Characterizing Response and Resistance to CAR-T and TCEs
Hematology Disease Topics & Pathways:
Research, Diseases, Therapies
Methods: JNJ-79635322 is a trispecific antibody composed of an anti-CD3 binding domain an anti-BCMA binding domain, and an anti-GPRC5D binding domain. It was selected based on biophysical assessment and showed activity in multiple myeloma models.
Results: JNJ-79635322 induced potent cytotoxicity in various myeloma cell lines in vitro with concomitant T-cell activation. Importantly, JNJ-79635322 was able to deplete both dual (BCMA and GPRC5D) and single (BCMA or GPRC5D) target expressing cells efficiently. In addition, dose dependent depletion of H929 myeloma cells was observed in a more physiological healthy fresh whole blood co-culture assay. In vivo, JNJ-79635322 exhibited potent antitumor activity compared to vehicle and antibody controls in a murine MM xenograft prevention model (single target expressing clonal H929 cells) and two tumor regression models (RPMI 8226 and MM.1S cells).
Conclusion: JNJ-79635322 is a potential first-in-class trispecific antibody targeting BCMA and GPRC5D with the ability to deplete dual and single target expressing MM clones in preclinical studies vitro and in vivo. A Phase 1 dose-escalating study of JNJ-79635322 in myeloma patients is ongoing (NCT05652335).
Disclosures: Pillarisetti: Janssen Pharamceuticals: Current Employment, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company. Yang: Janssen Pharmaceuticals: Ended employment in the past 24 months. Yao: Janssen Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Smith: Janssen Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Luistro: Janssen Pharmaceuticals: Current Employment, Current holder of stock options in a privately-held company. Vulfson: Janssen Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Testa: Janssen Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Packman: Janssen: Current Employment, Current equity holder in publicly-traded company. Brodeur: Janssen Pharmaceuticals: Ended employment in the past 24 months. Attar: Janssen Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Elsayed: Janssen: Current Employment, Current equity holder in publicly-traded company. Philippar: Janssen: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties.
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