JNJ-4496 Prevents Antigen Escape, May Work as Salvage Therapy in R/R LBCL

Patients who have progressed following treatment with CD19 chimeric antigen receptor (CAR) T-cell therapy may benefit from subsequent treatment with JNJ-90014496 (JNJ-4496), an investigational CD19/CD20-targeted CAR T-cell therapy, according to Matthew Ku, MBBS, PhD, FRACP, RACP, FRCPA/RCPA.

Ku, a clinical and laboratory hematologist and lymphoma stream lead at St Vincent’s Private Hospital, Fitzroy in Australia, spoke with CancerNetwork® about how JNJ-4496 may improve clinical outcomes vs other CAR T-cell therapies used to manage relapsed/refractory large B-cell lymphoma (LBCL).

He initially suggested that despite CD19 CAR T-cell therapy enhancing outcomes for patients with the disease, the long-term remission rate is still wanting, with less than 50% achieving it. Highlighting antigen escape via loss of CD19 on the lymphoma cell surface as a primary concern, he explained that JNJ-4496 was specifically designed to prevent antigen escape with the potential to serve as a salvage therapy. Furthermore, he concluded by expressing the potential for the investigational agent to replace CD19 CAR T-cell therapy as a second-line option altogether, given the potential for enhanced efficacy outcomes.

Results from a small cohort of patients (n = 25) enrolled in a phase 1b study (NCT05421663) he presented at the European Hematology Association 2025 Congress revealed that for patients treated with the recommended phase 2 dose (RP2D) of 75 million CAR T cells, the objective response rate (ORR) was 96% (95% CI, 77%-100%), with 77% of patients achieving a complete response (CR).

Among patients given the RP2D previously treated with 1 prior line of therapy, the ORR was 100% (95% CI, 69%-100%), with 80% of patients achieving a CR. In the same patient group previously treated with 2 or more prior lines of therapy, the ORR was 92% (95% CI, 62%-100%), with 75% of patients attaining a CR.

Transcript:

CD19 CAR [T-cell] therapy has been good at transforming the treatment landscape for patients with relapsed/refractory large B-cell lymphoma. Despite that, less than 50% of patients achieve long-term remission. Antigen escape with the loss of CD19 on the lymphoma cell surface is one of the major issues. With a CD19/CD20 bispecific CAR T, it is designed to prevent antigen escape as a mechanism for resistance and possibly [work as] a salvage therapy.

If you have a patient who has had CD19 CAR [T-cell therapy] and progressed from that, then this could be a salvage option after that. In the future, perhaps this would be shown to be superior [vs] the CD19 CAR [T-cell therapy] and therefore even replace single CD19 CAR T as a second-line therapy in the future.

Reference

Patel K, Rhodes JM, Mountjoy L, et al. A global phase 1b study of JNJ-90014496, a CD19/CD20 bi-specific chimeric antigen receptor (CAR) T-cell therapy, in patients (pts) with relapsed/refractory (R/R) large B-cell lymphoma. Abstract presented at: European Hematology Association 2025 Congress; June 12-15, 2025; Milan, Italy. Abstract S239.