Johnson & Johnson announces clinical data from Phase 1b study of JNJ-4496

Johnson & Johnson announced clinical data from an ongoing Phase 1b study for JNJ-90014496, an investigational dual-targeting anti-CD19/CD20 bispecific autologous chimeric antigen receptor T-cell therapy, being studied in patients with relapsed or refractory large B-cell lymphoma who have not been previously treated with CAR T-cell therapy. Findings demonstrate the potential of JNJ-4496 in the treatment of patients with R/R LBCL, including R/R diffuse large B-cell lymphoma, the most common type of aggressive lymphoma, a blood cancer that originates in the lymphatic system. These data were presented as an oral presentation at the 2025 European Hematology Association Congress. JNJ-4496, formerly known as C-CAR039, is a dual-targeting CAR T designed to bind to both CD19 and CD20 antigens, two cell surface proteins commonly expressed on malignant B-cells. This design, including a 4-1BB costimulatory domain, is intended to enhance binding strength and persistence, also potentially addressing common mechanisms of resistance in relapsed or refractory disease. In the Phase 1b dose confirmation study in patients with R/R LBCL, data at the recommended Phase 2 dose were reported in patients with a median follow-up of 4 months. Results informed a RP2D of JNJ-4496 at 75 million CAR+ T-cells. Among the 22 patients in the RP2D group where efficacy was assessed, those who received one prior line of therapy had an objective response rate of 100 percent and a complete response rate of 80 percent. In the patients who had received two or more prior lines of therapy, the ORR was 92 percent and the CRR was 75 percent. Within the RP2D safety group, 52 percent of patients received two or more prior lines of therapy, and 56 percent received bridging therapy. In the RP2D cohort studied, no cases of Grade 3 or 4 cytokine release syndrome were observed. Two patients had immune effector cell-associated neurotoxicity syndrome, one Grade 1 and one Grade 3. The Grade 3 event occurred in a patient with central nervous system lymphoma. Overall, 84 percent of patients had Grade 3/4 treatment-emergent adverse events, and 28 percent reported serious TEAEs. The most common Grade 3/4 TEAE was neutropenia, a reduction in white blood cells. One patient experienced a Grade 3 infection.