Johnson & Johnson's Dual-Targeting CAR-T Therapy Achieves 80% Complete Response Rate in Lymphoma Trial
核心洞察
Johnson & Johnson's investigational dual-targeting CAR-T therapy JNJ-4496 demonstrated 75-80% complete response rates in patients with relapsed or refractory large B-cell lymphoma (搜索) at the recommended Phase 2 dose.
The therapy targets both CD19 (搜索) and CD20 (搜索) antigens on malignant B-cells, potentially addressing resistance mechanisms that limit current single-antigen CAR-T treatments to 40% long-term remission rates.
Safety data showed no Grade 3 or 4 cytokine release syndrome (搜索) cases, with neutropenia (搜索) being the most common severe adverse event affecting 72% of patients.
Johnson & Johnson announced promising first clinical results for its investigational dual-targeting CAR-T cell therapy JNJ-90014496 (JNJ-4496) in patients with relapsed or refractory large B-cell lymphoma (搜索), demonstrating complete response rates of 75-80% at the recommended Phase 2 dose. The data, presented at the 2025 European Hematology Association Congress, represents a potential breakthrough in treating the most common type of aggressive lymphoma.
Novel Dual-Targeting Approach Shows Superior Efficacy
The Phase 1b dose confirmation study (NCT05421663) evaluated JNJ-4496, a dual-targeting CAR-T therapy designed to bind both CD19 (搜索) and CD20 (搜索) antigens on malignant B-cells. This approach differs from current single-antigen-targeting CD19 CAR-T therapies, which achieve long-term remissions in only about 40% of patients with relapsed or refractory diffuse large B-cell lymphoma (搜索).
Among 22 patients evaluated for efficacy at the recommended Phase 2 dose of 75 million CAR+ T-cells, those who received one prior line of therapy (n=10) achieved a 100% objective response rate and 80% complete response rate (95% CI, 69-100). Patients with two or more prior lines of therapy (n=12) demonstrated a 92% objective response rate and 75% complete response rate (95% CI, 62-100).
"There is a pressing need to continue advancing therapies for patients with relapsed or refractory diffuse large B-cell lymphoma (搜索)," said Dr. Krish Patel, Director of Lymphoma Research at Sarah Cannon Research Institute (搜索) and principal study investigator. "The data presented today show encouraging clinical activity and promising safety, and represent a step forward in delivering a potential new treatment option to patients living with the most common type of aggressive lymphoma."
Favorable Safety Profile Observed
The safety analysis included 25 patients at the recommended Phase 2 dose, with 52% having received two or more prior lines of therapy and 56% receiving bridging therapy. Notably, no cases of Grade 3 or 4 cytokine release syndrome (搜索) were observed, a significant safety advantage given this is a common serious complication of CAR-T therapies.
Two patients experienced immune effector cell-associated neurotoxicity syndrome (ICANS), one Grade 1 and one Grade 3, with the Grade 3 event occurring in a patient with central nervous system lymphoma. Overall, 84% of patients experienced Grade 3/4 treatment-emergent adverse events, with neutropenia (搜索) being the most common severe side effect, affecting 72% of patients. Twenty-eight percent of patients reported serious treatment-emergent adverse events, and one patient experienced a Grade 3 infection.
Addressing Unmet Medical Need
Large B-cell lymphoma (搜索) represents a significant clinical challenge, with diffuse large B-cell lymphoma (搜索) accounting for approximately 40% of all non-Hodgkin lymphoma (搜索) cases globally and an estimated 150,000 new cases diagnosed annually. Up to 40% of patients can relapse or become refractory to initial therapy, often facing limited treatment options and poor prognosis.
JNJ-4496 incorporates a 4-1BB (搜索) costimulatory domain and is designed to enhance binding strength and persistence while potentially addressing common resistance mechanisms in relapsed or refractory disease. The therapy was formerly known as C-CAR039 and represents an extension of Johnson & Johnson's collaboration with AbelZeta Inc., initiated in 2023 to develop next-generation CAR-T cell therapies.
Clinical Development Progress
"We're really excited to share the first results for our dual-targeting anti-CD19 (搜索)/CD20 (搜索) CAR T-cell therapy in relapsed or refractory large B-cell lymphoma (搜索), underscoring our more than decade-long commitment to addressing unmet needs for patients with B-cell malignancies," said Dr. Jeffrey Infante, Vice President of Early Clinical Development and Translational Research at Johnson & Johnson Innovative Medicine.
The current Phase 1b study data were based on a median follow-up of 4 months. Johnson & Johnson is conducting separate studies to evaluate the therapy's safety and efficacy in global patient populations, with additional data presentations scheduled for the 2025 International Conference on Malignant Lymphoma from June 17-21.