WU-CART-007 Is an Effective Treatment for Adolescent Patients with Relapsed or Refractory (R/R) T-Cell Acute Lymphoblastic Leukemia/ Lymphoblastic Lymphoma (T-ALL/LBL) – Subgroup Analysis of WU-CART-007 1001

T-ALL/LBL are challenging hematologic cancers with high rates of relapse and mortality in children and adults. Autologous CAR T-cell therapy for T-cell malignancies faces challenges including of malignant cell contamination and fratricide. WU-CART-007 is an allogeneic, off-the-shelf, CD7-targeted CAR T-cell product with CRISPR/Cas9 deletion of CD7 to prevent fratricide and TRAC deletion to enable the use of healthy donor allogeneic T-cells (Leedom et al. ASH 2021). WU-CART-007 1001 (NCT04984356) previously reported an acceptable safety profile and efficacy in R/R T-ALL/LBL pts (Aldoss et al , EHA 2024). Here, we present data on the adolescent subgroup. Adolescent patients 12-18 years old were enrolled in Phase 2 and received 900M WU-CART-007 cells on Day 1 following lymphodepleting chemotherapy (fludarabine 30 mg/m2/day x 4 days and cyclophosphamide 1000 mg/m2/day x 3 days). Disease response was assessed by a Day 28 bone marrow (BM) assessment and CT/PET, as needed. Composite complete remission (CRc) included CR (BM blasts <5%, absolute neutrophil count ≥1,000/μL, and platelets ≥100,000/μL) and CRi (CR with incomplete hematologic recovery), and SUV uptake less than background for extramedullary disease (EMD). Objective response rate (ORR) was defined as CRc plus partial response (reduced EMD uptake). As of 24 July 2024, 5 adolescent patients were treated in Phase 2. The median age was 16 years (range 14-17) with a median of 4 prior therapies (range 2-7), including 2 with previous allogeneic HSCT. Baseline disease burden included median bone marrow blasts of 49.3% (range 5-95%) and one patient with EMD only. WU-CART-007 showed a manageable safety profile; all patients experienced cytokine release syndrome—two Grade 2 or less, one Grade 3 and two Grade 4—all resolved with supportive care. One patient had Grade 1 ICANS. No Graft-versus-Host disease or hemophagocytic lymphohistiocytosis was reported. One patient experienced a Grade 5 multi-organ failure in the context of rapid disease progression and was not efficacy evaluable. WU-CART-007 demonstrated anti-leukemic activity with a CRc of 75% and ORR of 100% in evaluable patients. Minimal residual disease was undetected in 67% of CRc patients. All three CRc patients transitioned to HSCT, including two with prior transplants. With a median follow up of 276 days (range 234-302 days), the median duration of response has not yet been reached. WU-CART-007 has shown efficacy and an acceptable safety profile in adolescent patients with R/R T-ALL/LBL. These promising results support the follow up Phase 2 trial to include children aged 1 year and above, with a potential exploratory cohort for patients with MRD positive disease after induction and consolidation chemotherapy. This study, NCT06514794, will begin enrolling in late 2024.