WU-CART-007, a CD7-directed allogeneic CAR-T cell therapy for R/R T-cell acute lymphoblastic leukemia/lymphoma: Phase 1/2 correlative data and long-term follow-up update

Abstract Background: WU-CART-007 (WU-007), an allogeneic CD7-targeted CAR-T cell therapy, is under evaluation for relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (R/R T-ALL/LBL). CD7 and T-cell receptor alpha constant are deleted to mitigate fratricide and graft-versus-host disease, respectively (Leedom, et al. ASH 2021). A Phase 1/2 study, which evaluated safety, response, and determined the recommended phase 2 dose (RP2D) of WU-007 in patients with R/R T-ALL/LBL, demonstrated promising efficacy (Ghobadi, et al. Blood 2025). Patients from the completed Phase 1/2 study were subsequently enrolled in a long-term follow-up (LTFU) study. Herein, we report translational data from the Phase 1/2 study and a clinical update from the LTFU study. Methods: In the Phase 1/2 study, translational methods included cellular pharmacokinetics (cPK) by droplet digital polymerase chain reaction (ddPCR), minimal residual disease (MRD) by flow cytometry at a central lab, and serum cytokine analysis by Luminex and nELISA. Disease response was determined at Day 28 by bone marrow assessment and PET-CT, if applicable. Objective response rate was defined as complete remission (CR), CR with incomplete hematologic recovery (CRi), and partial response. Duration of response (DOR) was measured from initial response to relapse or death. In the LTFU study patients are followed for 15 years after WU-007 infusion. LTFU evaluation includes survival, late adverse events (AEs) of special interest (AESIs; new malignancies, new incidence or exacerbation of a pre-existing neurologic, rheumatologic or autoimmune disorder, and new incidence of other hematologic disorders), AEs related to WU-007, anticancer therapies, and replication competent lentivirus (RCL) testing. Results: In the Phase 1/2 study, 28 patients received WU-007, 13 at the RP2D. The mean baseline CD7 expression on bone marrow blasts was 98.8% (88.8%-100%). WU-007 exhibited rapid multi-log expansion with peak levels at 10-14 days post infusion (mean maximum concentration [Cmax] = 232,985 copies/µg gDNA; mean area under the curve [AUC]Day 0-28 = 2,651,335 copies/µg gDNA x days), persisting up to 3 months at the RP2D. There was a strong correlation between WU-007 Cmax and AUCDay 0-28 (r=0.92). Patients who responded to WU-007 exhibited significantly higher mean Cmax (184,819 vs. 37,169 copies/µg gDNA; p<0.01) and AUCDay 0-28 (2,249,227 vs. 153,069 copies/µg gDNA x days; p<0.0001),compared to those with no response. In addition, WU-007 cPK correlated with the MRD status on Day 28 with higher AUCDay 0-28 observed in patients with MRD-negative (< 0.01%) vs. MRD-positive (≥ 0.01%) bone marrow blasts (p<0.05). There was no significant correlation between cPK and the DOR, with or without censoring for hematopoietic stem cell transplantation (HSCT). WU-007 cPK and response were not affected by the degree of shared HLA alleles with the allogeneic donor. Serum cytokine analysis demonstrated peak levels approximately 48 hours post WU-007 infusion, coinciding with the onset of cytokine release syndrome (CRS), and declined thereafter. Patients with Grade ≥3 CRS had significantly higher IL-15, IFNγ, IL-2, IP10, IL-3, MCP-1, CXCL9, and TNFα than those with Grade ≤2 CRS. Nine patients with T-ALL/LBL transitioned to the LTFU study. The LTFU study patients included 4 adolescents (3 T-ALL and 1 T-LBL) and 5 adults (4 T-ALL and 1 T-LBL). Six patients in the LTFU study expired, 5 from disease progression and 1 from infection unrelated to WU-007. As of 1 Aug 2025, there were no reported late AESIs, related serious AEs, or positive RCL. The median (m)DORof the Phase 1/2 study was6.7 months; at the RP2D, mDOR was not reached. Across all dose levels, the median overall survival (mOS) was 3.5 months (0.1-22.8) and for patients that achieved CR/CRi at Day 28, the mOS was 8.8 months (1.4-22.8). For the LTFU patients, the mOS was 16.3 months (1.7-22.8). The 3 surviving LTFU study patients (2 adolescents and 1 adult) had CR as best overall response, underwent HSCT 2.6-5.4 months post WU-007 infusion, and had a mOS of 18.0 months (18.0-20.0).Conclusions: WU-007 demonstrated robust expansion and manageable long-term safety in heavily pretreated patients with R/R T-ALL/LBL. A pivotal Phase 2 trial (T-RRex) is enrolling patients ≥ 1 year old with R/R T-ALL/LBL (NCT06514794).