UCART22

P1/2, N=40, Recruiting, Cellectis S.A. | Trial primary completion date: Dec 2023 --> Jan 2026

The fludarabine, cyclophosphamide, and alemtuzumab (FCA) LD regimen was also shown to extend host lymphocyte suppression and improve UCART22 expansion versus fludarabine and cyclophosphamide (FC) alone (Boissel N, et al...Cytokine release syndrome (CRS) occurred in 2/3 (67%) pts, with one G1 that resolved without treatment and one G2 that resolved after tocilizumab x1...Pt 3 was refractory to treatment, however this pt received bridging therapy with dasatinib for his ABL2 fusion, and on Day -1, only 47% of the leukemic cells expressed CD22 (down from 88% at screening)... As of 01 July 2023, 3 pts were enrolled into the first UCART22 P2 cohort at DL2. Pt 1 is a 17yo female with B-ALL with a hypodiploid karyotype and a germline TP53 mutation whose disease had previously failed to respond to multiagent chemotherapy, blinatumomab (blina), inotuzumab (ino), venetoclax (ven), allogeneic hematopoietic stem cell transplantation (HSCT), and autologous CD19 CAR T-cell therapy (CAR19) x2. Pt 2 is a 68yo female with Ph-negative B-ALL who relapsed with CD19-low disease after multiagent chemotherapy, ino, and blina.

P1/2, N=40, Recruiting, Cellectis S.A. | Trial primary completion date: Jul 2023 --> Dec 2023

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...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%)...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... 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.

P1/2, N=40, Recruiting, Cellectis S.A. | Phase classification: P1 --> P1/2 | N=30 --> 40 | Trial completion date: Jul 2023 --> Jan 2026

P1, N=30, Recruiting, Cellectis S.A. | Trial completion date: Oct 2022 --> Jul 2023 | Trial primary completion date: Oct 2022 --> Jul 2023

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)...Pts had received a median of 5 (4–6) prior Tx, including blinatumomab for all 3 pts, inotuzumab for 2 pts, autologous CAR19 Tx for 1 pt...One pt in FCA-DL2 had Tx-related TEAEs of G1 CRS (requiring a single administration of tocilizumab) and G2 pruritus; both events resolved... The FCA LD regimen was well tolerated and associated with extended host lymphocyte suppression and UCART22 expansion. No Tx-related serious TEAEs were reported at FCA-DL2, and 2 pts achieved significant blast reductions. Detection of UCART22 occurred as early as d9 after infusion and was associated with increases in inflammatory cytokines.

P1, N=30, Recruiting, Cellectis S.A. | N=60 --> 30