JNJ-5322 Trispecific BCMA/GPRC5D/CD3 Antibody Delivers 100% ORR in Target-Naïve R/R Myeloma

JNJ-79635322 (JNJ-5322) is an off-the-shelf trispecific antibody that co-engages BCMA and GPRC5D on myeloma cells while recruiting CD3⁺ T cells. In the first-in-human phase 1 dose-escalation/optimization trial (NCT05652335), 147 adults with heavily pre-treated relapsed/refractory multiple myeloma received subcutaneous doses every 4 weeks with a recommended phase 2 dose (RP2D) is 100 mg. Among BCMA/GPRC5D inhibitor-naïve patients at the RP2D (n = 27, median five prior lines), investigator-assessed ORR hit 100%, with 70% achieving CR/ sCR and an estimated 95% 1-year PFS. Prior-exposed patients (n = 20) showed 55% ORR. Grade 1-2 CRS occurred in 59% of the overall patient populations, with 69% of patients with prophylactic tocilizumab and 20% without prophylactic tocilizumab experiencing grade 1-2 CRS. Grade ≥3 infections were 33%, with one infection-related death and no ICANS. For context, the GPRC5D bispecific talquetamab posts ~73% ORR, while BCMA CAR-T cilta-cel reaches 98% ORR but requires bespoke manufacturing.