-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

770 Phase 1/2 Dose-Escalation/Dose-Expansion Study of Anti-CD7 Allogeneic CAR-T Cells (WU-CART-007) in Relapsed or Refractory (R/R) T-Cell Acute Lymphoblastic Leukemia/ Lymphoblastic Lymphoma (T-ALL/LBL)

Program: Oral and Poster Abstracts
Type: Oral
Session: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Novel Approaches to Enhance Cellular Therapies and Immune Responses in Leukemias and Lymphomas
Hematology Disease Topics & Pathways:
adult, Biological therapies, ALL, Lymphoid Leukemias, clinical trials, Research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Clinical Research, Diseases, Therapies, young adult , Lymphoid Malignancies, Human, Study Population
Monday, December 11, 2023: 10:45 AM

Armin Ghobadi, MD1, Ibrahim Aldoss, MD2, Shannon L. Maude, MD3, Deepa Bhojwani, MD4, Alan S. Wayne, MD4, Ashish Bajel, FRACP5, Rawan Faramand, MD6, Ryan J Mattison, MD7, Bhagirathbhai Dholaria, MBBS8, Michael P. Rettig, PhD9,10, Ken Jacobs, MD11*, Ouiam Bakkacha12*, John Muth, MSc13*, Angela Pannunzio14*, Brett Ramsey, MBA12*, Eileen McNulty, MS15*, Matt L. Cooper, PhD16, Jan Davidson-Moncada, MD, PhD, MSc17 and John F. DiPersio, MD, PhD10

1Division of Oncology, Washington University School of Medicine, Saint Louis, MO
2City of Hope, Duarte, CA
3The Children's Hospital of Philadelphia, Philadelphia, PA
4Children's Hospital of Los Angeles, Los Angeles, CA
5Clinical Haematology, Royal Melbourne Hospital, Parkville, Vic, Australia
6Department of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL
7Carbone Comprehensive Cancer Center, Madison, WI
8Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN
9Washington Univ. School of Med., Saint Louis, MO
10Washington University School of Medicine, Saint Louis, MO
11Wugen, St louis, MO
12Wugen, Saint Louis, MO
13Wugen, St. Louis, MO
14Wugen, St Louis
15Wugen, St Louis, MO
16Wugen Inc., Saint Louis, MO
17Wugen, Washington, DC

T-ALL/LBL are challenging hematologic cancers with high rates of relapse and mortality in both children and adults. Despite success in B-cell malignancies, development of CAR-T cell therapy for T cell malignancies has been complicated by induction of fratricide and risk of malignant cell contamination of the drug product in the autologous setting. WU-CART-007 is a CD7-targeted CAR-T cell products 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 allogeneic CAR-T cell product is being developed for the treatment of CD7+ malignancies. WU-CART-007 1001 (NCT04984356) is a global first-in-human, Phase 1/2 single-agent study of WU-CART-007 in patients (pts) with R/R T-ALL/LBL.

The recommended Phase 2 dose (RP2D) of WU-CART-007 is 900 million (M) cells administered on day 1 following lymphodepleting chemotherapy (LDC). Two different LDC regimens have been tested: standard LDC (fludarabine 30 mg/m2/day x 3 days and cyclophosphamide 500 mg/m2/day x 3 days), and enhanced LDC (eLDC; fludarabine 30 mg/m2/day x 4 days and cyclophosphamide 1000 mg/m2/day x 3 days). Disease response is assessed by Day 28 bone marrow (BM) aspirate/biopsy, and CT/PET, if applicable, per NCCN Guidelines Version 2.2022; Pharmacokinetics (PK) are measured by ddPCR; samples are collected for immunophenotyping by flow cytometry (FACS).

As of July 21, 2023, 18 pts have been dosed with WU-CART-007 (n = 11 T-ALL, n = 7 T-LBL); 3 with 100M (DL1), 3 with 300M (DL2), 6 with 600M (DL3), and 6 with 900M (DL4/RP2D) cells in a single infusion. A total of 15 pts received standard LDC while 3 received eLDC at the DL4/RP2D. Median age is 33.5 years (range 20-68). Pts were heavily pretreated with a median of 4 prior lines of therapy (range 2 – 7), 28% (5/18) relapsed following an allogeneic HSCT. Disease burden at baseline consisted of extramedullary disease (EMD) in 28% (5/18) of pts, and a median BM blast count of 60% (range 5-98%) in pts with BM disease (13/18). Overall WU-CART-007 demonstrated manageable safety profile; treatment-related adverse events of ≥ G3 were observed in 8/18 (44%) pts. Cytokine release syndrome (CRS) was observed in 14/18 (78%) pts. Most (72%; 13/18) pts had G1-2 CRS events; a single G3 CRS event was reported which resolved within 72 hours after receiving tocilizumab, dexamethasone, and low-dose vasopressors. Grade 1 ICANS was reported in one patient at DL3, which resolved spontaneously. No GvHD, prolonged T-cell aplasia, or prolonged pancytopenia in the absence of disease were observed. One unrelated DLT lead to cohort expansion at DL3. The majority of deaths were due to disease progression. There were two Grade 5 events not attributed to WU-CART-007, both due to fungal infection.

WU-CART-007 showed dose-dependent anti-tumor activity with no responses seen at DL1. In evaluable patients at DL≥ 2 (n=12) Composite Complete Remission Rate (CRc; CR + CRi + CRh): 58% (86% MRDneg), median duration of response 12.3 weeks (1.1 – 29.4); two patients successfully received a consolidating allogeneic-HSCT. At the RP2D, the CRc rate was 60% (3/5; 2 CR, 1CRi). Molecular expansions of CAR-T cells peaked on day 10 in peripheral blood (mean 66,069 copies/ug DNA) and persisted out to day 56. Of all pts tested (n=15), none developed novel anti-HLA antibodies against the donor, and no anti-drug antibodies against the CAR-construct were detected. Phenotypic analysis revealed in vivo WU-CART-007 cells expressed activation markers (KI67, CD38, HLA-DR) and were largely an effector memory CD45RA+ (EMRA) CM phenotype (CD45RA+, CD197+).

WU-CART-007 has demonstrated an acceptable safety profile and preliminary evidence of anti-leukemic activity. This program advances CAR-T cell therapy in heavily pre-treated patients with R/R T-ALL/LBL. Enrollment is ongoing.

Disclosures: Ghobadi: Kite/Gilead: Consultancy, Honoraria, Research Funding; CRISPR Therapeutics: Consultancy; Wugen Inc: Consultancy; Genentech, Inc.: Research Funding; BMS: Consultancy; Atara: Consultancy; Amgen: Consultancy, Research Funding. Aldoss: Pfizer: Consultancy; Sobi: Consultancy; Jazz: Consultancy; KiTE: Consultancy; Takeda: Consultancy; Amgen: Consultancy, Honoraria. Maude: Wugen: Research Funding; Novartis Pharmaceuticals: Consultancy, Patents & Royalties: PCT/US2017/044425: Combination Therapies of Car and PD-1 Inhibitors, Research Funding. Bajel: Amgen: Honoraria, Speakers Bureau; Pfizer: Honoraria; Abbvie: Honoraria; Novartis: Honoraria; Astellas: Honoraria; Gilead-Kite: Honoraria; Takeda: Honoraria; Jazz: Honoraria; Shoreline: Honoraria; Senti-Bio: Honoraria. Faramand: Kite: Research Funding; Gilead: Research Funding. Mattison: Nkarta: Membership on an entity's Board of Directors or advisory committees. Dholaria: Ellipsis pharma: Consultancy; Lumanity: Consultancy; Janssen: Consultancy, Honoraria, Research Funding; BMS: Research Funding; Poseida: Research Funding; Poseida: Research Funding; Allovir: Research Funding; ADC therapeutics: Consultancy, Honoraria; Orca Bio: Research Funding; MEI: Research Funding; Molecular Templates: Research Funding; AstraZeneca: Research Funding; Arivan: Consultancy; Takeda: Research Funding; gamida cel: Consultancy; BEAM therapeutics: Consultancy; Pfizer: Research Funding; Wugen: Research Funding; Atara: Research Funding; Pluri Biotech: Consultancy; Boxer Capital: Consultancy; Gilead: Research Funding; NCI: Research Funding; Adicet: Research Funding; Angiocrine: Research Funding. Bakkacha: wugen: Current Employment. Muth: Wugen: Current Employment, Current equity holder in private company. Pannunzio: Wugen: Current Employment. Ramsey: Wugen: Current Employment. McNulty: Wugen: Current Employment. Cooper: Wugen: Current Employment, Current equity holder in publicly-traded company. Davidson-Moncada: Wugen: Current Employment, Current equity holder in private company. DiPersio: Macrogenics: Consultancy, Research Funding; NeoImmune Tech: Consultancy; Incyte: Consultancy, Research Funding; Sun Pharma Ltd.: Membership on an entity's Board of Directors or advisory committees; hC Bioscience, Inc.: Membership on an entity's Board of Directors or advisory committees; Vertex: Consultancy; Washington University: Current Employment; WUGEN: Other: Ownership Investment, Patents & Royalties; Magenta: Other: Ownership Investment, Patents & Royalties; Amphivena Therapeutics: Research Funding; BiolineRx Ltd: Consultancy, Research Funding; RiverVest Venture Partners: Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH