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3461 WU-CART-007 (WT-7) Is an Effective Treatment for Adolescent Patients with Relapsed or Refractory (R/R) T-Cell Acute Lymphoblastic Leukemia/ Lymphoblastic Lymphoma (T-ALL/LBL) – Subgroup Analysis of WU-CART-007 1001

Program: Oral and Poster Abstracts
Session: 704. Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical trials, Lymphoid Leukemias, ALL, Clinical Research, Pediatric, Diseases, Lymphoid Malignancies, Young adult , Study Population, Human, Measurable Residual Disease
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Shannon L. Maude, MD1, Deepa Bhojwani, MD2, Alan S. Wayne, MD3, Friso G. J. Calkoen, MD4, André Baruchel, MD, PhD5, Christian Michel Zwaan, MD6, Michael P. Rettig, PhD7, Ouiam Bakkacha, MD8*, Justo L. Gonzalez, MD9*, Deborah Masters, RN MS9*, Maria del Rosario, BA CCRP9*, Laura Simpson, PhD10*, Preeta Dasgupta, PhD11*, Tony Wu, PhD12*, Stephen Moran13*, Michael Munroe, BS PhD9*, Haley Irons14*, Eileen McNulty, MS15*, Matthew L. Cooper, PhD16, Alexander Hamil, PhD17*, John Muth, MSc13*, Brett Ramsey, MBA8*, Jan K Davidson-Moncada, MD, PhD, MSc18 and John F. DiPersio, MD, PhD19

1Division of Oncology, Center for Childhood Cancer Research and Cancer Immunotherapy Program, Children's Hospital of Philadelphia, Philadelphia, PA
2Hematology/Oncology, Children's Hospital of Los Angeles, Los Angeles, CA
3Children's Hospital of Los Angeles, Los Angeles, CA
4Prinses Maxima Centrum Voor Kinderoncologie, Utrecht, Netherlands
5Institut Universitaire d'Hématologie, EA-3518, University Hospital Saint-Louis, Assistance Publique des Hôpitaux de Paris (APHP), Paris, France
6Department of Pediatric Oncology, Erasmus MC/Sophia Children's Hospital, Rotterdam, Netherlands
7Washington Univ. School of Med., Saint Louis, MO
8Wugen, Saint Louis, MO
9Wugen, St Louis
10Wugen, Tarrytown, NY
11Wugen, San Diego, CA
12Wugen, St. Louis
13Wugen, St. Louis, MO
14Wugen, Surprise, AZ
15Wugen, St Louis, MO
16Wugen Inc., Saint Louis, MO
17Wugen, San Diego
18Wugen, Washington, DC
19Division of Oncology, Washington University School of Medicine, Saint Louis, MO

R/R T-ALL/LBL are challenging hematologic cancers with high rates of relapse and mortality in both children and adults. Development of autologous chimeric antigen receptor (CAR) T-cell therapy for T-cell malignancies is complicated by potential for risk of malignant cell contamination and fratricide. WT-7 is an allogeneic CD7-targeted CAR T-cell product with CRISPR/Cas9 deletion of CD7 and T-cell receptor alpha constant (TRAC), to prevent fratricide and enable the use of healthy donor allogeneic T-cells, respectively (Leedom et al. ASH 2021). This off-the-shelf CAR T-cell product is being developed for the treatment of CD7-positive malignancies. WU-CART-007 1001 (NCT04984356) has demonstrated an acceptable safety profile and efficacy in heavily pre-treated R/R T-ALL/LBL pts (Aldoss et al, EHA 2024). Herein, we report data on the adolescent population.

Adolescent patients 12-18 years old were eligible. In the Phase 2 portion, pts received 900M WT-7 cells on Day 1 following lymphodepleting chemotherapy (fludarabine 30 mg/m2/day x 4 days and cyclophosphamide 1000 mg/m2/day x 3 days). Disease response was assessed by a Day 28 bone marrow (BM) assessment and a CT/PET, if applicable. Composite complete remission (CRc) rate was defined as the combination of CR (BM blasts <5% with absolute neutrophil count ≥1,000/μL and platelet count ≥100,000/μL) and CRi (CR with incomplete hematologic recovery), and SUV uptake < than liver/mediastinum for those with extramedullary disease (EMD). Objective response rate (ORR) was defined as CRc plus partial response (PR; reduced uptake compared to baseline in EMD). Pharmacokinetics were measured by ddPCR and immunophenotyping.

As of 24 July 2024, 5 adolescent patients were treated in Phase 2. The median age was 16 years (range 14-17), patients were heavily pre-treated with median of 4 prior lines of therapy (range 2-7), including 2/5 with a history of previous allogeneic hematopoietic stem cell transplantation (HSCT). Disease burden at baseline included median bone marrow blasts of 49.3% (range 5-95%) and one patient with extramedullary disease only. Cytokine release syndrome (CRS) was reported in all patients (Grade [G] 1-2 in 40%, G3 in 20%, and G4 in 40%) and fully resolved with supportive care in all but 1 patient. One patient had a G1 ICANS event. No Graft-versus-Host-Disease or hemophagocytic lymphohistiocytosis were reported. A single G5 event of multi-organ failure occurred in the setting of fulminant disease progression; per protocol, this patient was not evaluable for efficacy.

WT-7 demonstrated significant anti-leukemic activity with a CR/CRi rate of 75% and 1 PR with CD7-negative residual EMD, for an ORR of 100% in evaluable patients (4/4). Minimal residual disease was undetected in 2/3 of CRc patients. All three of the patients who achieved a CR/CRi transitioned to HSCT, two with history of prior transplant, and all remain in complete remission at 9, 8.1, and 6.1 months.

WT-7 has shown preliminary evidence of efficacy and an acceptable safety profile in adolescent patients with R/R T-ALL/LBL. Given these promising results, the follow up Phase 2 trial will expand enrollment to include children 1 year of age and above, with the potential to open an exploratory cohort with patients with MRD positive disease following induction and consolidation chemotherapy will be initiated after additional safety data is collected in the R/R population. This study, NCT06514794, will begin enrolling in late 2024.

Disclosures: Maude: Novartis: Research Funding; Wugen: Honoraria, Research Funding. Wayne: Kite: Research Funding. Baruchel: Wugen: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz: Membership on an entity's Board of Directors or advisory committees; Servier: Other: Travel Grant, Symposium, Research Funding; Novartis: Other: Symposia and Travels. Zwaan: AbbVie: Other: Institutional grant ; Astra Zeneca: Consultancy; Beigene: Consultancy; Innovative Therapies for Children with Cancer: Other: Leadership role; Gilead Sciences, Inc.: Consultancy; Sanofi: Membership on an entity's Board of Directors or advisory committees, Other: Institutional fees; Pfizer: Other: Institutional grant; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional grant ; Incyte Corporation: Consultancy; Bristol Myers Squibb: Consultancy; Takeda Pharmaceuticals: Other: Institutional grant; Kura Oncology: Consultancy, Other: Institutional grant; Chair of the Medical Research committee MERC Utrech: Other: Leadership role; Jazz Pharmaceuticals: Other: Institutional grant; Daiichi Sankyo, Inc.: Other: Institutional grant. Bakkacha: Wugen: Current Employment, Current holder of stock options in a privately-held company. Gonzalez: Wugen: Current Employment, Current holder of stock options in a privately-held company. Masters: Wugen: Current Employment, Current holder of stock options in a privately-held company. del Rosario: Wugen: Current Employment, Current holder of stock options in a privately-held company. Simpson: Wugen: Current Employment, Current holder of stock options in a privately-held company. Dasgupta: Wugen: Current Employment, Current holder of stock options in a privately-held company. Wu: Wugen: Current Employment, Current holder of stock options in a privately-held company. Moran: Wugen: Current Employment, Current equity holder in private company. Munroe: Wugen: Current Employment, Current holder of stock options in a privately-held company. Irons: Wugen: Current Employment. McNulty: Wugen: Current Employment, Current holder of stock options in a privately-held company. Cooper: Wugen: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company. Hamil: Wugen: Current Employment, Current holder of stock options in a privately-held company. Muth: Wugen: Current Employment, Current holder of stock options in a privately-held company. Ramsey: Wugen: Current Employment, Current holder of stock options in a privately-held company. Davidson-Moncada: Wugen: Current Employment, Current holder of stock options in a privately-held company. DiPersio: SPARC: Consultancy; Macrogenics: Research Funding; Magenta Therapeutics: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; WUGEN: Current equity holder in private company, Research Funding; RiverVest Venture Partners: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bioline Rx: Research Funding; Vertex: Consultancy; hC Bioscience, Inc.: Membership on an entity's Board of Directors or advisory committees; NeoImmune Tech: Research Funding.

*signifies non-member of ASH