Johnson & Johnson's JNJ-5322 Trispecific Antibody Shows Promising Response in Multiple Myeloma Patients with 86.1% Overall Response Rate

Johnson & Johnson's trispecific antibody JNJ-5322 has shown a promising 86.1% overall response rate in a Phase 1 trial for multiple myeloma. The antibody simultaneously targets three proteins: BCMA and GPRC5D on myeloma cells and CD3 on T-cells. However, safety concerns were noted, with cytokine release syndrome in 59% of patients and 28% experiencing serious infections.

Johnson & Johnson (J&J) announced initial Phase 1 results of JNJ-79635322 (JNJ-5322), a novel trispecific antibody (TsAb) for patients with relapsed or refractory multiple myeloma. The study, presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and featured as one of the six best abstracts at the 2025 European Hematology Association (EHA) Congress, showed an overall response rate (ORR) of 86.1% among 36 patients who received the recommended phase 2 dose (RP2D) [1].

JNJ-5322 uniquely targets three proteins: BCMA and GPRC5D on myeloma cells and CD3 on T-cells. This approach aims to overcome tumor heterogeneity and prevent resistance, building upon the success of two approved first-in-class bispecific antibodies, teclistamab and talquetamab [1].

The Phase 1, first-in-human study (NCT05652335) involved 126 heavily pretreated patients with a median follow-up of 8.2 months. The RP2D of 100 mg Q4W consisted of one step-up dose of 5 mg and monthly dosing with 100 mg thereafter [1].

While the study demonstrated encouraging efficacy, safety concerns were noted. Cytokine release syndrome (CRS) occurred in 59% of patients, with no events reaching Grade 3 or higher. Serious infections were reported in 28% of patients, and five patients had dose-limiting toxicities. Four treatment-related deaths were reported, including one caused by adenoviral encephalitis related to the drug [1].

Common adverse events included taste-related AEs in 58% of patients, with most being Grade 1. GPRC5D-related oral AEs, such as dry mouth and dysphagia, were reported in 17% and less than 4% of patients, respectively. Weight loss was also noted, with 6% (RP2D) and 12% (all doses) of patients experiencing Grade 1/2 weight loss [1].

References:
[1] https://www.jnj.com/media-center/press-releases/early-results-from-johnson-johnsons-trispecific-antibody-show-promising-response-in-heavily-pretreated-multiple-myeloma-patients
[2] https://www.marketscreener.com/quote/stock/JOHNSON-JOHNSON-4832/news/Johnson-Johnson-Announces-Initial-Phase-1-Results-of-JNJ-79635322-in-Patients-with-Relapsed-or-Ref-50144632/