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
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: Servier: Other: TRavel Grant, Symposium, Research Funding; Jazz: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Research Funding; Wugen: Membership on an entity's Board of Directors or advisory committees. 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.