First-in-human study of JNJ-79635322 (JNJ-5322), a novel, next-generation trispecific antibody (TsAb), in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Initial phase 1 results.
As of Jan 15, 2025, 126 pts received JNJ-5322 (36 at 100 mg Q4W); median follow-up (mFU) 8.2 mo. Median age 64 yrs; median 4 prior lines of therapy; 100% triple-class exposed (56% refractory); 31% high-risk cytogenetics; 23% had prior anti-BCMA/-GPRC5D therapy (77% naïve). The putative RP2D was identified as 100 mg Q4W. Overall, 99% of pts had ≥1 AE, most commonly CRS (59%; all grade [gr] 1 [45%]/2 [14%]; no gr ≥3), nail AEs (gr 1/2 56%), taste AEs (gr 1/2 56%), neutropenia (48%; gr 3/4 41%), and non-rash skin AEs (47%; gr 3/4 1%). Overall, 16% had weight decreases (no gr ≥3), 16% had rashes (no gr ≥3), 2% had ICANS (all gr 1), and 75% had infections (gr 3/4 28%). 5 pts had dose-limiting toxicities. 4 pts died due to AEs. In response-evaluable pts, ORR was 86% (75% ≥VGPR) at the RP2D (n=36), and 73% (66% ≥VGPR) overall (n=124). ORR was 100% (89% ≥VGPR) at the RP2D among pts naïve to anti-BCMA/-GPRC5D therapies (n=27), and all patients remain in response (mFU 8.5 mo). Median time to first response was 1.2 mo.