Phase 1b JNJ-79635322 BCMA×GPRC5D×CD3 T‑cell–redirecting trispecific antibody combos in multiple myeloma

This Janssen Research & Development (Johnson & Johnson) Phase 1b, open-label, multi-part dose-escalation/expansion study is designed to define recommended Phase 2 dose(s) and schedules for JNJ-79635322 (a BCMA×GPRC5D×CD3 trispecific antibody that redirects T cells to kill myeloma cells) when combined with daratumumab (a CD38 monoclonal antibody; from Janssen/Genmab) with or without lenalidomide, or combined with pomalidomide (both IMiDs that enhance anti-myeloma immune activity and have direct tumor effects). It enrolls both newly diagnosed/treatment-naïve multiple myeloma (NDMM) cohorts (including triplet regimens adding lenalidomide) and relapsed/refractory cohorts with prior proteasome inhibitor + IMiD exposure, including lenalidomide-refractory disease (pomalidomide combination). The key scientific angle is “dual tumor-antigen” targeting (BCMA and GPRC5D) in one molecule, intended to reduce antigen-escape risk versus single-antigen T-cell engagers, while leveraging daratumumab/IMiDs as immune-priming backbones. Today’s care for NDMM is typically anti-CD38–based induction (often daratumumab + bortezomib + lenalidomide + dexamethasone in eligible patients) followed by transplant/maintenance when appropriate, while relapsed disease is treated with sequential triplets and—later—BCMA- or GPRC5D-directed bispecifics or CAR-T; this trial explores whether a next-generation trispecific can be safely layered earlier and across lines.