J&J's Dual-Targeting CAR-T Therapy Shows Promising Results in Lymphoma Study

Johnson & Johnson's investigational CAR-T therapy, JNJ-4496, has demonstrated impressive efficacy in a Phase Ib trial for large B cell lymphoma, potentially challenging the current standard of care. The study results, presented at the 2025 European Hematology Association congress, reveal high response rates and a favorable safety profile, positioning the therapy as a strong competitor in the CAR-T space.

Efficacy Data Surpasses Current Standard

JNJ-4496 showed remarkable results across different patient populations. In patients who had undergone one prior line of therapy, the objective response rate (ORR) reached 100%, with an 80% complete response (CR) rate. For those who had received two or more treatments, the therapy maintained high efficacy with a 92% ORR and 75% CR rate.

These figures represent a significant improvement over the current standard of care, Gilead's Yescarta. Analysts at Truist Securities noted that Yescarta demonstrated a 65% CR rate in the second-line setting, dropping to 36% in the third-line. The compelling efficacy of JNJ-4496 across different treatment lines suggests its potential to reshape the treatment landscape for large B cell lymphoma.

Safety Profile Shows Promise

One of the most notable aspects of JNJ-4496's performance was its safety profile. The Phase Ib study reported no cases of grade 3 or 4 cytokine release syndrome, a common and serious adverse effect associated with CAR-T therapies. While 84% of patients developed grade 3 or 4 treatment-emergent serious adverse events, with neutropenia being the most common, analysts at Truist Securities characterized the overall safety profile as "superior" to Yescarta.

The improved safety at the recommended Phase II dose represents a significant advancement over first-generation CAR-T therapies, potentially offering patients a more tolerable treatment option without compromising efficacy.

Mechanism of Action and Development

JNJ-4496 employs a dual-targeting approach, binding to both CD19 and CD20 proteins commonly found on malignant B cells. This mechanism is designed to enhance the therapy's ability to identify and destroy cancer cells. Additionally, the therapy incorporates a 4-1BB costimulatory domain, which aims to improve binding strength and persistence while overcoming common pathways of treatment resistance.

The development of JNJ-4496 stems from a partnership between Johnson & Johnson and AbelZeta Pharma (formerly Cellular Biomedicine Group), established in May 2023 through a $245 million upfront payment. This collaboration underscores J&J's commitment to maintaining its leadership in the CAR-T space, particularly as competition intensifies with rivals like Gilead advancing their own cell therapy candidates.