W-T7 Shows Encouraging Response Rate, Manageable Safety in Relapsed/Refractory T-ALL/LBL

Ibrahim Aldoss, MD, of the department of hematology and stem cell transplant at City of Hope, discusses the promising phase 2 results of the phase 1/2 WU-CART-007 (W-T7) 1001 trial, which demonstrated high efficacy and a manageable safety profile for W-T7, an off-the-shelf, allogeneic, CD7-targeted chimeric antigen receptor (CAR) T-cell therapy, in patients with relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL).

Aldoss presented this data last month at the European Hematology Association (EHA) 2024 Congress.

This transcript has been lightly edited for clarity.

Transcript

Could you discuss the design and objectives of the Phase 2 WU-CART-007 trial?

So, W-T7 1001 clinical trial is a global first in human phase 1/2 single agent studies of W-T7 in patients with relapsed/refractory T-cell ALL and lymphoblastic lymphoma [LBL]. There was a phase 1 part of the study, using dose escalation for single infusion of the W-T7. There were 4 dose levels that were completed and presented last year at ASH [American Society of Hematology annual meeting]. Here [at EHA 2024 Congress], I'm presenting the expansion cohort for the 1001 study that uses W-T7 at the recommended phase 2 dosing after an enhanced lymphodepletion regimen.

Could you summarize the key findings?

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. Now, the majority of these treatment-related adverse events were CRS [cytokine release symdrome], but the majority were grade 1 and grade 2. Grade 3 was only observed in 3 patients and grade 4 in 2 patients; both grade 3 and 4 were manageable with supportive care and completely resolved. We have seen grade 1 ICANS [immune effector cell-associated neurotoxicity syndrome] in 2 patients, grade 2 HLH [hemophagocytic lymphohistiocytosis] in 2 patients, and grade 2 graft-versus-host disease in 1 patient.

Now, more important is the activity of the W-T7 at the recommended phase 2 dosing. The overall response rate was 91%, very encouraging. The composite complete remission was 73%, and the median duration of remission was 6.2 months. We had 7 patients after response who were able to receive consolidation with allogeneic stem cell transplant, including 5 patients treated on the recommended phase 2 dosing.

These patients were heavily pretreated. The median number of prior lines of therapy was 4 lines of therapy in patients treated in phase 1, and it was 3 lines of therapy in patients treated in the phase 2 portion of the study. Over a third of the patients had prior allogeneic stem cell transplants, so these are heavily pretreated patients with very limited options. We're seeing a very encouraging response rate with a manageable safety profile.

How could future studies build on these findings to enhance treatment outcomes for patients with R/R T-ALL/LBL?

With these encouraging outcomes, they are actually actively designing a registration study that will have 2 arms: 1 arm for relapsed/refractory disease and a second arm for patients with only MRD [minimal residual disease] relapsed/refractory disease.

The study will enroll patients as young as 1 year old with relapsed/refractory T-cell ALL, as well as lymphoblastic lymphoma [LBL]. The hope is, if these trials are successful, that it will lead to the FDA approval of the W-T7.