An ongoing phase 1 study observed an 86% overall response rate (ORR) in patients with multiple myeloma (MM) treated with the novel trispecific antibody JNJ-5322.
The study was presented by Hans Lee, MD, director of myeloma research at the Sarah Cannon Research Institute in Nashville, Tennessee, as part of the SOHO 2025 Annual Meeting.
JNJ-5322 is a trispecific antibody targeting B-cell maturation antigen (BCMA) and GPRC5D via T-cell redirection.
As of January 15, 2025, 126 patients (median age, 65 years) received JNJ-5322. Patients had received a median of four prior lines of therapy, and all were triple-class-exposed; 23% received prior anti-BCMA and/or -GPRC5D therapy.
Patients received escalating fixed doses of JNJ-5322 ranging from 0.4 mg to 300 mg subcutaneously every two or four weeks. Patients received one step-up dose of 5 mg prior to the recommended phase 2 dose (RP2D).
Researchers determined the RP2D was 100 mg every four weeks. Almost all patients (99%) experienced one or more adverse events, the most common of which were:
- Cytokine release syndrome (59%)
- Nail-related adverse events (56%)
- Taste-related adverse events (56%)
- Neutropenia (48%)
- Nonrash skin-related adverse events (47%)
Most patients (75%) experienced infections, and 2% experienced immune effector cell-associated neurotoxicity syndrome. Four adverse event-related deaths occurred.
The ORR was 100% among patients treated with the RP2D who had not previously received an anti-BCMA and/or -GPRC5D therapy (n=27); response was ongoing in all of these patients at a median follow-up of 8.5 months. The median time to first response was 1.2 months.
“J&J-5322 may represent a potential paradigm shift with an overall response rate comparable to CAR-T, with manageable safety and tolerability with a convenient, off-the-shelf, every four-week dosing, with a single step-up dose to facilitate outpatient dosing,” Dr. Lee said during the presentation.
Reference
Lee H, Popat R, Touzeau C, et al. First-in-human study of JNJ-79635322 (JNJ-5322), a novel, next-generation trispecific antibody, in patients with relapsed/refractory multiple myeloma: initial phase 1 results. Presented at the Society of Hematologic Oncology 2025 Annual Meeting; September 3-6, 2025; Houston, Texas.
Visit the SOHO 2025 meeting news page for more coverage from the meeting.
