R/R T-ALL/LBL are challenging hematologic cancers with high rates of relapse and mortality in both children and adults. Development of autologous chimeric antigen receptor (CAR) T-cell therapy for T-cell malignancies is complicated by potential for risk of malignant cell contamination and fratricide. WT-7 is an allogeneic CD7-targeted CAR T-cell product with CRISPR/Cas9 deletion of CD7 and T-cell receptor alpha constant (TRAC), to prevent fratricide and enable the use of healthy donor allogeneic T-cells, respectively (Leedom et al. ASH 2021). This off-the-shelf CAR T-cell product is being developed for the treatment of CD7-positive malignancies. WU-CART-007 1001 (NCT04984356) has demonstrated an acceptable safety profile and efficacy in heavily pre-treated R/R T-ALL/LBL pts (Aldoss et al, EHA 2024). Herein, we report data on the adolescent population. Adolescent patients 12-18 years old were eligible. In the Phase 2 portion, pts received 900M WT-7 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 a CT/PET, if applicable. Composite complete remission (CRc) rate was defined as the combination of CR (BM blasts <5% with absolute neutrophil count ≥1,000/μL and platelet count ≥100,000/μL) and CRi (CR with incomplete hematologic recovery), and SUV uptake < than liver/mediastinum for those with extramedullary disease (EMD). Objective response rate (ORR) was defined as CRc plus partial response (PR; reduced uptake compared to baseline in EMD). Pharmacokinetics were measured by ddPCR and immunophenotyping. As of 24 July 2024, 5 adolescent patients were treated in Phase 2. The median age was 16 years (range 14-17), patients were heavily pre-treated with median of 4 prior lines of therapy (range 2-7), including 2/5 with a history of previous allogeneic hematopoietic stem cell transplantation (HSCT). Disease burden at baseline included median bone marrow blasts of 49.3% (range 5-95%) and one patient with extramedullary disease only. Cytokine release syndrome (CRS) was reported in all patients (Grade [G] 1-2 in 40%, G3 in 20%, and G4 in 40%) and fully resolved with supportive care in all but 1 patient. One patient had a G1 ICANS event. No Graft-versus-Host-Disease or hemophagocytic lymphohistiocytosis were reported. A single G5 event of multi-organ failure occurred in the setting of fulminant disease progression; per protocol, this patient was not evaluable for efficacy. WT-7 demonstrated significant anti-leukemic activity with a CR/CRi rate of 75% and 1 PR with CD7-negative residual EMD, for an ORR of 100% in evaluable patients (4/4). Minimal residual disease was undetected in 2/3 of CRc patients. All three of the patients who achieved a CR/CRi transitioned to HSCT, two with history of prior transplant, and all remain in complete remission at 9, 8.1, and 6.1 months. WT-7 has shown preliminary evidence of efficacy and an acceptable safety profile in adolescent patients with R/R T-ALL/LBL. Given these promising results, the follow up Phase 2 trial will expand enrollment to include children 1 year of age and above, with the potential to open an exploratory cohort with patients with MRD positive disease following induction and consolidation chemotherapy will be initiated after additional safety data is collected in the R/R population. This study, NCT06514794, will begin enrolling in late 2024.
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