Phase 1/2 trial of anti-CD7 allogeneic WU-CART-007 for patients with relapsed/refractory T-cell malignancies

Relapsed/refractory T-cell acute lymphoblastic leukemia (ALL; T-ALL)/lymphoma (LBL) represent a significant unmet medical need. WU-CART-007 is a CD7-targeting, allogeneic, fratricide-resistant chimeric antigen receptor T-cell product generated from healthy donor T cells. WU-CART-007 was evaluated in a phase 1/2 study with a 3+3 dose-escalation design followed by cohort expansion in relapsed/refractory T-ALL/LBL. Patients received 1 infusion of WU-CART-007 after standard or enhanced lymphodepleting chemotherapy. The primary objectives, to characterize safety and assess the composite complete remission rate, were met. Of 28 patients enrolled, 13 received the recommended phase 2 dose (RP2D) of 900 × 106 cells of WU-CART-007 with enhanced lymphodepletion. The most common treatment-related adverse event was cytokine release syndrome (88.5%; 19.2% grade 3-4). Two grade 1 immune effector cell-associated neurotoxicity syndrome events (7.7%) and 1 grade 2 acute graft-versus-host disease event occurred (3.8%). One grade 2 immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome was observed. Among the 11 patients evaluable for response at the RP2D who received enhanced lymphodepleting chemotherapy, the overall response rate was 90.9%, and the composite complete remission rate was 72.7%. WU-CART-007 at the RP2D demonstrated a high response rate in patients with relapsed/refractory T-ALL/LBL and has the potential to provide a new treatment option. This trial was registered at www.ClinicalTrials.gov as #NCT04984356.