An ongoing Phase 1/2 trial of WU-CART-007 (W-T7), an off-the-shelf, allogeneic, CD7-targeted chimeric antigen receptor (CAR) T-cell therapy, has demonstrated promising results in patients with relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL). The Phase 2 expansion cohort of the 1001 study, using W-T7 at the recommended Phase 2 dosing after enhanced lymphodepletion, showed high efficacy and a manageable safety profile in this heavily pretreated patient population. These findings were presented at the European Hematology Association (EHA) 2024 Congress by Dr. Ibrahim Aldoss from City of Hope.
Key Findings from the Phase 2 Trial
The trial's results indicate a significant potential for W-T7 in treating patients with limited options. The overall response rate was reported at 91%, with a composite complete remission rate of 73%. The median duration of remission was 6.2 months. Notably, seven patients who responded to W-T7 were able to proceed to allogeneic stem cell transplant, including five treated at the recommended Phase 2 dose.
"We observed that W-T7 showed a manageable safety profile. Treatment-related adverse events grade 3 or higher were observed in 61.5% of all patients," said Dr. Aldoss. The majority of these adverse events were cytokine release syndrome (CRS), primarily grade 1 and 2, with grade 3 observed in three patients and grade 4 in two patients. All cases were manageable with supportive care and resolved completely. Additionally, grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS) was seen in two patients, grade 2 hemophagocytic lymphohistiocytosis (HLH) in two patients, and grade 2 graft-versus-host disease in one patient.
Patient Population and Prior Treatments
The patients enrolled in the trial were heavily pretreated, with a median of four prior lines of therapy in the Phase 1 cohort and three lines in the Phase 2 cohort. Over a third of the patients had undergone prior allogeneic stem cell transplants, highlighting the advanced stage of their disease and the limited treatment alternatives available.
Future Directions
Based on these encouraging outcomes, plans are underway to initiate a registration study with two arms. One arm will focus on patients with relapsed/refractory disease, while the other will include patients with minimal residual disease (MRD) relapsed/refractory disease. The study will enroll patients as young as one year old with relapsed/refractory T-cell ALL and lymphoblastic lymphoma. The goal is to secure FDA approval for W-T7, providing a new treatment option for this challenging patient population.
