Preliminary Results from the Flu/Cy/Alemtuzumab Arm of the Phase I BALLI-01 Trial of UCART22, an Anti-CD22 Allogeneic CAR-T Cell Product, in Adult Patients with Relapsed or Refractory (R/R) CD22+ B-Cell Acute Lymphoblastic Leukemia (B-ALL)

Introduction: UCART22 is a genetically modified allogeneic T-cell product manufactured from non-HLA matched healthy donor cells. Donor-derived T-cells are transduced using a lentiviral vector to express the anti-CD22 chimeric antigen receptor (CAR; anti-CD22 scFv-41BB-CD3ζ) and are further modified using Cellectis' TALEN ® technology to disrupt the T-cell receptor alpha constant (TRAC) and CD52 genes to minimize risk of graft-vs-host disease (GvHD) and allow use of anti-CD52-directed drugs for lymphodepletion (LD). Preliminary results from the phase 1, open-label, dose-escalation BALLI-01 study (NCT04150497) in patients (pts) with R/R B-ALL showed that UCART22 is tolerable and shows anti-leukemic activity after LD with fludarabine and cyclophosphamide (FC) (Jain, ASH 2020). Host T-cell recovery was observed in all pts between days (d) 7-28. Subsequent UCART22 dose-finding cohorts utilized a new LD regimen that included the addition of alemtuzumab to FC (“FCA”), which could potentially deepen and sustain host T-cell depletion and promote CAR T-cell expansion and persistence. Methods: Eligibility criteria include age 15‒70 yrs, adequate organ function, ECOG PS ≤ 1, B-ALL blast CD22 expression ≥ 70% by flow cytometry. Pts must have received ≥ 1 prior standard chemotherapy regimen and 1 salvage regimen. After LD with FCA (F 30 mg/m 2 × 3d, C 0.5 g/m 2 × 3d, A 20 mg/d × 3d), pts receive a single infusion of UCART22 at ~1 ×10 6 cells/kg (FCA-DL2) or ~2.5 ×10 6 cells/kg (FCA-DL2i). The primary endpoint is the safety, tolerability, and MTD of UCART22. DLTs are assessed over a 28d observation period after UCART22 infusion. Additional endpoints include anti-leukemic activity per investigator assessment (NCCN criteria), and the expansion, trafficking, and persistence of UCART22 (assessed in peripheral blood [PB] and bone marrow [BM] by phenotypic analysis using flow cytometry and vector copy number [VCN] using qPCR). Immune reconstitution is assessed by flow cytometry. Results: As of 01 July 2021, a total of 13 pts had provided consent: 3 failed screening, 1 discontinued after LD, and 9 pts received UCART22. Enrollment in FC-DL1 (n = 3), FC-DL2 (n = 2), and FCA-DL2 (n = 3) was complete, and 1 pt had been enrolled in FCA-DL2i. All 3 pts in FCA-DL2 (median age 29 yrs [range 29‒51]; 1 male) had discontinued at data cutoff and 1 remained in long-term follow-up. Pts had received a median of 5 (4-6) prior Tx, including blinatumomab for all 3 pts, inotuzumab for 2 pts, auto