CAR-T WU-CART-007 Shows Evidence of Antileukemic Activity Among Patients With T-ALL/LBL

Article

The objective response rate among patients treated at DL2 and DL3 who were evaluable for efficacy was 57%.

Wugen’s WU-CART-007, an investigational allogeneic CD7-directed chimeric antigen receptor T-cell (CAR-T) therapy intended to treat relapsed/refractory (r/r) T-cell acute lymphoblastic leukemia (T-ALL) and r/r T-cell lymphoblastic lymphoma (LBL), has shown the ability to produce responses in some patients treated at higher dose levels in a phase 1/2 clinical trial (NCT04984356).1,2 Data from the trial were presented in a poster at the European Hematology Association (EHA) 2023 Congress, held June 8-11, both virtually and in Frankfurt, Germany.

Among 7 patients in the trial who were treated at dose level 2 (DL2; 3x108 cells) or DL3 (6x108 cells) and evaluable for efficacy as of the January 30, 2023, data cut-off date, the objective response rate was 57% (n = 4). Two of the 4 patients who responded achieved a complete response (CR), 1 patient achieved a partial response, and 1 patient achieved a morphological leukemia-free state. First author Armin Ghobadi, MD, of Washington University School of Medicine, and colleagues noted that the median duration of response was 12.2 weeks (range, 1 to 17.2 weeks) and that 2 patients remain in remission. They also stated that 1 patient treated at DL3, who achieved a CR, received a successful allogeneic hematopoietic stem cell transplant with full engraftment. None of the 3 patients treated at DL1 (1x108 cells) achieved a response.

In terms of safety, WU-CART-007 was reported to be well-tolerated and to have manageable toxicity. Among 12 patients evaluable for safety, 8 patients experienced cases of cytokine release syndrome (CRS); 1 of the patients experienced a grade 3 case of CRS and all other cases were grade 1 to grade 2. The patient who experienced the grade 3 CRS case recovered within 72 hours of receiving tocilizumab, dexamethasone, and low-dose vasopressors. A single case of grade 1 immune effector cell-associated neurotoxicity syndrome was observed in 1 patient who was treated at DL3; the case was reported to have resolved spontaneously. Other treatment-related adverse events (AEs) of grade 3 or higher included decreases in neutrophil count or neutropenia in 3 patients (25%), hemophagocytic lymphohistiocytosis in 2 patients (17%), anemia in 1 patient (8%), and decreased appetite in 1 patient (8%). None of the patients experienced graft versus host disease, prolonged T-cell aplasia, or pancytopenia in the absence of disease. Ghobadi and colleagues noted that 1 patient experienced a case of encephalopathy secondary to intracranial bleeding associated with a Rhizomucor infection. This event was deemed to be an unrelated dose-limited toxicity.

“We are very encouraged by these initial safety and efficacy data from our ongoing phase 1/2 trial of WU-CART-007 in patients with r/r T-ALL/LBL,” Jan Davidson-Moncada, MD, PhD, the chief medical officer of Wugen, said in a statement.2 “T-ALL/LBL are very challenging hematologic cancers. Many children and adults relapse after first line therapy and are left with very limited treatment options thereafter, often leading to high mortality. We are hopeful today’s data can be an early step to advance our goal of harnessing the power of innovative CAR-T cell therapies to address this stark unmet need.”

The group of 12 patients treated as of the cut-off date included 9 patients with r/r T-ALL and 3 patients with r/r T-LBL. Three of the 12 patients were treated at DL1, 3 were treated at DL2, and 6 were treated at DL3.1 The ages of the patients ranged from 21 years to 61 years (median, 32.5) and the group included 4 women and 8 men. The number of prior lines of treatment for the patients ranged from 2 to 8 (median, 5); 4 (33%) of the patients had previously received treatment with allogeneic stem cell transplant. Baseline bone marrow (BM) blast count ranged from 43% to 85% (median, 61.5%) in patients with BM disease.1,2 Eight patients (67%) had extramedullary disease at baseline.

Ghobadi and colleagues concluded that in a subset of the treated patients WU-CART-007 demonstrated preliminary evidence of antileukemic activity and deemed the CAR-T's safety profile “acceptable”. They noted that enrollment in the trial remains ongoing. WU-CART-007 has previously been granted FDA fast track designation, orphan drug designation, and rare pediatric disease designation.

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REFERENCES
1. Ghobadi A, Aldoss I, Maude S, et al. P356 Phase 1/2 dose-escalation study of anti-CD7 allogenic CAR-T cell in relapsed or refractory(r/r) T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma(T-ALL/LBL). Presented at: the European Hematology Association (EHA) 2023 Congress, June 8-11, held both virtually and in Frankfurt, Germany. Abstract #P3562.
2. Wugen presents initial data from first-in-human phase 1/2 trial of WU-CART-007 at the European Hematology Association (EHA) 2023 congress. News release. Wugen, Inc. June 9, 2023. Accessed June 13, 2023. https://wugen.com/wugen-presents-initial-data-from-first-in-human-phase-1-2-trial-of-wu-cart-007-at-the-european-hematology-association-eha-2023-congress/
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