UCART22 Earns Orphan Drug Designation for Acute Lymphoblastic Leukemia in Europe

The European Commission (EC) has granted orphan drug designation to the allogeneic CD22-targeted CAR T-cell therapy UCART22 as a potential treatment option for patients with acute lymphoblastic leukemia (ALL).¹

The CAR T-cell therapy is currently being investigated in the phase 1 BALLI-01 trial (NCT04150497) in patients with relapsed or refractory B-cell ALL (B-ALL).

“Patients with relapsed/refractory ALL have limited, if any, treatment options, especially for those who have failed prior CD19-directed CAR T-cell therapy and allogeneic stem cell transplant” Mark Frattini, MD, PhD, chief medical officer of Cellectis Biologics, stated in a news release. “The orphan drug designation for UCART22 marks an important step toward developing allogeneic CAR T products that would be readily available for all patients.”

Previous data from BALLI-01 presented at the 2023 ASH Annual Meeting showed that patients treated with dose level 2 of UCART22 process 2 (P2) at 1.0 x 10⁶ cell/kg (n = 3) experienced an overall response rate (ORR) of 67%. Prior findings had shown that patients administered UCART22 process 1 (P1) at dose level 3 of 5.0 x 10⁶ cells/kg (n = 6) achieved an ORR of 50%.²

Regarding the safety, no dose-limiting toxicities were reported in the 3 patients given UCART22 P2, and no instances of immune effector cell–associated neurotoxicity syndrome or graft-vs-host disease occurred. Cytokine release syndrome (CRS) occurred in 2 of 3 patients, including 1 patient who had grade 1 CRS that resolved without treatment, and another patient who had grade 2 CRS that resolved after treatment with tocilizumab (Actemra). One patient experienced grade 5 sepsis at day 40, which was classified as a serious adverse effect (AE) related to UCART22 and lymphodepletion.

The ongoing, phase 1, open-label, dose-escalation study is enrolling patients between 15 and 70 years of age with B-ALL who have a CD22 expression of at least 70%. At least 1 prior standard chemotherapy regimen and 1 salvage regimen are required for enrollment, and patients also need to have an ECOG performance status of 0 or 1.

UCART22 P1 was first evaluated at 1 x 10⁵ cells/kg and 1 x 10⁶ cells/kg following lymphodepletion consisting of 30 mg/m² of fludarabine for 4 days plus 1 g/m² of cyclophosphamide for 3 days. UCART22 P1 was then examined at 1 x 10⁶ cells/kg, 2.5 x 10⁶ cells/kg, and 5 x 10⁶ cells/kg following lymphodepletion that included 30 mg/m² of fludarabine, 0.5 g/m² of cyclophosphamide, and 20 mg of alemtuzumab (Lemtrada) for 3 days each. UCART22 P2 is being evaluated at 1 x 10⁶ cells/kg and 2.5 x 10⁶ cells/kg after the same lymphodepletion regimen using fludarabine, cyclophosphamide, and alemtuzumab.

Safety, tolerability, and establishing the recommended phase 2 dose are the trial’s primary end points. Additional end points include investigator-assessed ORR; UCART22 expansion in peripheral blood and bone marrow; and immune reconstitution.

The 3 patients treated with UCART22 P2 included a female aged 17 years with Philadelphia chromosome (Ph)–negative B-ALL with a hypodiploid karyotype and a germline TP53 mutation who received prior treatment with multiagent chemotherapy, blinatumomab (Blincyto), inotuzumab ozogamicin (Besponsa), venetoclax (Venclexta), allogeneic stem cell transplant, and tisagenlecleucel (Kymriah). The second patient was a female aged 68 years with Ph-negative B-ALL with relapsed CD19-low disease after multiagent chemotherapy, blinatumomab, and inotuzumab ozogamicin. The third patient was male aged 27 years with B-ALL harboring an ABL2 fusion who received prior treatment with multiagent chemotherapy, blinatumomab, inotuzumab ozogamicin, TKIs, and an experimental autologous CD19-directed CAR T-cell therapy.

Additional any-grade AEs related to UCART22 reported in these 3 patients included asthenia (n = 1), chills (n = 1), pyrexia (n = 1), rash (n = 1), and hypotension (n = 1).

Additional data from BALLI-01 are expected to be reported by the end of 2024.¹

References

1. Cellectis receives orphan drug designation for UCART22, its allogeneic CAR T product for patients with acute lymphoblastic leukemia. News release. Cellectis Biologics. June 4, 2024. Accessed June 5, 2024. https://www.cellectis.com/en/press/cellectis-receives-orphan-drug-designation-for-ucart22-its-allogeneic-car-t-product-for-patients-with-acute-lymphoblastic-leukemia
2. Jain N, Chevallier P, Liu H, et al. Updated results of the phase I BALLI-01 trial of UCART22 process 2 (P2), an anti-CD22 allogeneic CAR-T cell product manufactured by Cellectis Biologics, in patients with relapsed or refractory (R/R) CD22+ B-cell acute lymphoblastic leukemia (B-ALL). Blood. 2023;142(suppl 1):4847. doi:10.1182/blood-2023-187252