P1408: updated results of the phase i balli-01 trial of ucart22, an anti-cd22 allogeneic car-t cell product, in patients with relapsed or refractory (r/r) cd22+ b-cell acute lymphoblastic leukemia (b-all)

Topic: 25. Gene therapy, cellular immunotherapy and vaccination - Clinical Background: UCART22 is a genetically modified allogeneic T-cell product manufactured from healthy donor cells. Donor T-cells are transduced using a lentiviral vector to express the anti-CD22 chimeric antigen receptor (CAR) 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 an anti-CD52 antibody for lymphodepletion (LD). Aims: Primary endpoints are safety, tolerability, and MTD/RP2D of UCART22. Additional endpoints are anti-leukemic activity and expansion and trafficking of UCART22. Methods: Eligibility criteria include age 15‒70y, B-ALL blast CD22 expression ≥ 70%, and ≥ 2 prior treatment regimens. After LD with FC (F 30 mg/m2 × 3d, C 1.0 g/m2 × 3d) or FCA (F 30 mg/m2 × 3d, C 0.5g/m2 × 3d, A 20 mg/d × 3d), pts received a single infusion of UCART22. Results: Preliminary results from the BALLI-01 study (NCT04150497) showed that UCART22 was well tolerated, and blast reductions were achieved. The fludarabine, cyclophosphamide, and alemtuzumab (FCA) LD regimen was well tolerated and associated with extended host lymphocyte suppression and UCART22 expansion (Jain N, et al. Blood 2021;138(Suppl 1):1746). As of 31 December 2022, 19 pts were enrolled, with a median age 28y (17-61), 42% female, 37% B-ALL with recurrent genetic abnormalities per WHO, 21% with CRLF2 and 5% with BCR-ABL1 rearrangements, and median BM blasts prior to LD 41% (1-99). Pts received a median of 4 (2-8) prior Tx, including blinatumomab (blin,12 pts, 63%), inotuzumab (ino,10 pts, 53%), autologous CD19 CAR T-cell (CAR19, 8 pts, 42%), and prior HSCT (8 pts, 42%). Eighteen pts received UCART22. UCART22 administered after FC or FCA LD regimen was well tolerated. No DLTs nor ICANS were observed; 11/18 (61%) pts reported CRS (G1 [N=9] or G2 [N=2]). One serious AESI of G2 GvHD (skin) was reported in the setting of reactivation of prior allo HSCT donor stem cells. SAEs (G≥3) reported in 13/18 (72%) pts included infections (39%) and febrile neutropenia (28%), and all were not related to UCART22. Responses were assessed beginning on D28. Up to FC/FCA-DL2i, 3 CRi and 1 morphologic leukemia-free state (MLFS) were observed (previously reported, ASH 2021). For FCA-DL3, 3/6 pts (50%) responded: 1 pt who failed 4 prior lines, including multiagent chemotherapy, blin, ino, CAR19, and allo HSCT, achieved an MRD neg CR lasting over 100 days after UCART22 infusion; 1 pt who failed 4 prior lines, including multiagent chemotherapy, venetoclax (ven), CAR19, and allo HSCT, achieved an MRD negative CRi consolidated with DLI after D90; and 1 pt who failed 3 prior lines, including multiagent chemotherapy, ven, CAR19, and allo HSCT, achieved an MRD negative MLFS up to D114. In the FCA arm, host lymphocytes remained suppressed (mean ALC <0.1 x103 cells/mL) through D28 for all pts, and UCART22 cell expansion was observed in 9/13 pts. Peak ferritin levels correlated with UCART22 cell expansion and CRS. Summary/Conclusion: UCART22 continues to be safe and tolerable, with no Tx-related serious TEAEs or DLTs reported. In the FCA-DL3 cohort, 50% of pts responded. UCART22 cells were detected in patients in the FCA arm and associated with clinical activity. Overall, these data support the safety and preliminary efficacy of UCART22 in this heavily pretreated R/R B-ALL population. Keywords: Alemtuzumab, CAR-T, Allogeneic, Acute lymphoblastic leukemia