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)

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.770-770
• Main Authors: Ghobadi, Armin, Aldoss, Ibrahim, Maude, Shannon L., Bhojwani, Deepa, Wayne, Alan S., Bajel, Ashish, Faramand, Rawan, Mattison, Ryan J, Dholaria, Bhagirathbhai, Rettig, Michael P., Jacobs, Ken, Bakkacha, Ouiam, Muth, John, Pannunzio, Angela, Ramsey, Brett, McNulty, Eileen, Cooper, Matt L., Davidson-Moncada, Jan, DiPersio, John F.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-178723

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/m 2/day x 3 days and cyclophosphamide 500 mg/m 2/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 ICA