JNJ-4496/JNJ-90014496 (formerly C-CAR039) is a dual-targeting CAR-T cell therapy engineered to recognize both CD19 and CD20, two antigens commonly expressed on malignant B cells. Featuring a 4-1BB costimulatory domain, it is designed to enhance cellular persistence and efficacy in relapsed or refractory large B-cell lymphoma (R/R LBCL).  

The company presented the results of the trial in EHA 2025. As per the results, JNJ-4496 showed strong safety and efficacy in relapsed/refractory LBCL. At the recommended Phase II dose (RP2D, n = 25), cytokine release syndrome (CRS) occurred in 88% of patients—mostly Grade 1 (68%) and Grade 2 (20%), with no Grade 3/4 events. Across all doses (n = 51), CRS was seen in 80% of patients, including two Grade 3 events (4%). CRS had a median onset of 3 days and lasted 6 days at RP2D, managed with tocilizumab (84%) and corticosteroids (40%), without prophylactic use. Immune effector cell-associated neurotoxicity syndrome (ICANS) was infrequent—only two cases (8%) at RP2D, including one Grade 1 and one Grade 3, both resolved; overall, ICANS occurred in 16% (four Grade 1, four Grade 3). 

It was managed with corticosteroids, anakinra, and levetiracetam. In terms of efficacy, JNJ-4496 demonstrated a 96% objective response rate (ORR) at RP2D, composed of 77% complete response (CR) and 18% partial response (PR). Across all doses (n=44), the ORR was 91% (75% CR, 16% PR). The therapy showed consistent efficacy regardless of prior lines of therapy—100% ORR (80% CR, 20% PR) with 1 prior line, and 92% ORR (75% CR, 17% PR) with ≥2 prior lines. These data support JNJ-4496 as a highly effective and tolerable treatment option for R/R LBCL.

KOL insights

“Safety, efficacy, and the pharmacokinetic profile support 75M CAR-positive T cells as the RP2D of the CD19/CD20 CAR-T therapy, JNJ’4496, in a broad population of patients with relapsed or refractory LBCL.” – Expert Opinion

Conclusion

JNJ-4496 enters a highly competitive CAR T-cell therapy landscape dominated by established products like YESCARTA, which has demonstrated strong commercial success and sustained efficacy in R/R B-cell lymphomas. However, limitations such as antigen escape have spurred the development of next-generation therapies. Emerging competitors like KITE-363, with its dual-targeting of CD19 and CD20, offer similar mechanisms and aim to overcome resistance seen in single-antigen therapies. These innovations pose significant competitive pressure, positioning JNJ-4496 against both proven market leaders and promising pipeline candidates that may set new benchmarks for durability and depth of response in the evolving CAR-T space.