WU-CART-007 (WT-7), an investigational allogeneic CAR T-cell therapy targeting CD7, has demonstrated significant anti-leukemic activity and a manageable safety profile in patients with relapsed/refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (LBL). The Phase 2 results of the Phase 1/2 study (NCT04984356) were presented at the 2024 ASH Annual Meeting, showcasing the potential of this off-the-shelf therapy in a challenging patient population.
High Response Rates in Heavily Pretreated Patients
The study included heavily pretreated patients with a median of 5 prior lines of therapy. The data cutoff was July 24, 2024, with 13 patients dosed. The overall response rate (ORR) among evaluable patients was 91% (10/11), with a composite complete remission (CRc) rate of 73% (8/11; 6 CR, 2 CRi). Notably, 83% (5/6) of patients who achieved CRc also attained minimal residual disease-negative (MRDneg) status. Five patients proceeded to consolidating allogeneic hematopoietic stem cell transplant (allo-HSCT).
With a median follow-up of up to 9.9 months, the median duration of response (DOR) has not been reached (95% CI: 0.5, NE; range 0.5-9.1 months), and 4 patients remain in continuous CR at 9.1, 8.2, 6.7, and 6.7 months. In the subgroup of patients with extramedullary disease (EMD), the ORR was 80% (4/5; 2CR/2PR), indicating the therapy's effectiveness even in more challenging cases.
Safety Profile and Adverse Events
Treatment-related adverse events of Grade ≥3 were observed in 77% (10/13) of patients. Cytokine Release Syndrome (CRS) occurred in all patients (13/13), with most cases being Grade 1-2 (69%; 9/13). Grade ≥3 CRS occurred in 31% (4/13) of patients and was effectively managed with steroids (75%), tocilizumab (100%), and anakinra (25%). A single event of Grade 1 immune effector cell-associated neurotoxicity (ICANS) was reported in one patient (8%). Severe infections (≥G3) were observed in 46% (6/13), including sepsis (31%; 4/13). One case of Grade 2 graft vs. host disease was reported. Two Grade 5 events occurred: sepsis due to fungal infection on day 13, and multi-organ failure in the setting of Grade 3 CRS and fulminant disease progression on Day 7 post infusion.
Impact of MRD Response on Outcomes
Further analysis revealed the impact of MRD response on patient outcomes. The median duration of response for patients with MRDneg CR/CRi (n=7) was 6.6 months (95%CI: 1.8, NE) compared to 3.7 months (95%CI: 0.5, NE) for those with CR/CRi MRDpos (n=3). Similar findings were observed for overall survival (OS), with MRDneg patients achieving a median OS of 11.5 months (95%CI: 2.7, NE) versus 6.1 months (95%CI: 1.4, NE) for MRDpos patients.
Future Directions
The promising results from this study have paved the way for a pivotal Phase 2 trial (NCT06514794) set to begin in late 2024. This global, single-arm, multicenter study will evaluate WU-CART-007 in both pediatric and adult patients with relapsed or primary refractory T-ALL and LBL. The trial will include an exploratory cohort of patients with minimal residual disease (MRD)-positive status. According to Kumar Srinivasan, PhD, President and Chief Executive Officer of Wugen, this trial marks the first pivotal study of an off-the-shelf, allogeneic CD7-targeted CAR T-cell therapy for this patient population.
Armin Ghobadi, MD, Professor of Medicine, Oncology, Section of Bone Marrow Transplant, and Clinical Director of the Center for Gene and Cellular Immunotherapy at Washington University’s Siteman Cancer Center, noted that WU-CART-007 has also shown good responses in other CD7-positive malignancies, including T-cell lymphoma and T-cell prolymphocytic leukemia, expressing hope that it will change the treatment landscape for these patients.
