Anti-CD20 CART-transduced T cells(Chinese People's Liberation Army General Hospital)

Johnson & Johnson is scrapping two CAR-T cell programs for B cell lymphoma amid a wave of approvals in recent years for cell therapies and antibody-based drugs addressing the disease. The drugmaker said Thursday it will no longer develop two candidates, called JNJ-9530 and JNJ-4496. The former is a CD20-directed therapy, while the latter is a bispecific candidate that targets both CD20 and CD19. Both treatments are being tested in separate Phase 1 trials. J&J said its decision was based on “an assessment of the evolving large B-cell lymphoma treatment landscape.” It added it will continue to support patients enrolled in the studies. The company shared positive Phase 1 results from the bispecific program in June 2025. That trial enrolled patients with relapsed or refractory B cell non-Hodgkin lymphoma (B-NHL) or frontline high-risk diffuse large B cell lymphoma (DLBCL). J&J said that 10 patients who had received one prior line of therapy had an objective response rate of 100% and a complete response rate of 80% when given JNJ-4496. In 12 patients who had two or more prior treatments, the ORR was 92% and the CRR was 75%. The Phase 1 test for JNJ-9530 is looking at patients with relapsed or refractory B-NHL. There have been major shifts in standard of care for both first- and second-line lymphomas. CAR-T therapies have moved from the third-line to the second-line in large B cell lymphoma, following label expansions for Bristol Myers Squibb’s Breyanzi in 2021 and Kite’s Yescarta in 2022. Yescarta and Breyanzi are now considered standard of care in this setting, meaning newer candidates could have to go head-to-head with one or the other in a clinical trial to have a chance of contesting this market. Kite is aiming to bring Yescarta to the front line, and is running a Phase 3 study called ZUMA-23 in patients with untreated high-risk large B cell lymphoma. Meanwhile, Roche’s CD79b-directed ADC Polivy has already made a splash in the frontline setting. Back in 2021, that drug — combined with R-CHOP chemotherapy — led to a 27% reduction in the risk of disease progression, relapse or death versus R-CHOP alone in a Phase 3 DLBCL study. Roche won approval for the regimen in 2023. But there is some debate about the extent to which Polivy benefits different DLBCL patient subgroups. J&J did not immediately respond to a request for comment.

Johnson & Johnson is pulling the plug on two investigational CAR-T cell therapies for large B-cell lymphoma, stepping back from a crowding treatment space even though one of the programmes generated encouraging early clinical data. The company said the move reflects portfolio prioritisation and "an assessment of the evolving large B-cell lymphoma (LBCL) treatment landscape."The decision affects JNJ-4496, a dual-targeting CAR-T designed to bind both CD19 and CD20 antigens on malignant B cells, and JNJ-9530, a CD20-directed autologous CAR-T therapy. Both were in Phase I testing in patients with relapsed or refractory B-cell non-Hodgkin lymphoma.The retreat comes less than a year after J&J reported Phase Ib data at the European Hematology Association (EHA) congress showing near-universal responses with JNJ-4496.According to data from 22 patients with relapsed or refractory LBCL, the therapy produced objective response rates of 100% in patients who had received one prior line of therapy and 92% in those more heavily pretreated. Complete response rates reached 80% and 75%, respectively, at a median follow-up of four months. Safety findings showed no grade 3 or 4 cytokine release syndrome, though cases of neurotoxicity were observed.Meanwhile, JNJ-9530's Phase I study began in late 2023 and was exploring safety and preliminary efficacy in a cohort of 21 patients, according to ClinicalTrials.gov.Despite the early promise, the commercial and clinical bar for new CAR-T entrants is getting higher. CAR-Ts, particularly Gilead Sciences' Yescarta (axicabtagene ciloleucel) and Bristol Myers Squibb's Breyanzi (lisocabtagene maraleucel), have been playing an established role in treating relapsed or refractory LBCL, while a number of next-generation CAR T-cell therapies offering allogeneic products or faster manufacturing have been capturing the interest of key opinion leaders (see – KOL Insight - Non-Hodgkin Lymphoma).J&J currently markets the CAR-T therapy Carvykti (ciltacabtagene autoleucel) for relapsed or refractory multiple myeloma.