First Patient in Europe Dosed With B-cell Acute Lymphoblastic Leukemia CAR-T UCART22
Cellectis noted that the allogeneic product was manufactured at its new in-house facility in Paris.
The first patient in Europe has been dosed with Cellectis’ UCART22, an investigational allogeneic CD22-directed chimeric antigen receptor T-cell (CAR-T) therapy being evaluated for the treatment of relapsed/refractory (r/r) B-cell Acute Lymphoblastic Leukemia (B-ALL) in the phase 1/2a BALLI-01 clinical trial (NCT04150497).1
The company noted that the patient, who was treated in France, has completed the 28-day dose limiting toxicity (DLT) period. Furthermore, the patient received UCART22 product that was manufactured in-house by Cellectis. The company undertook the shift to in-house manufacturing for UCART22 late last year following the completion of its GMP manufacturing facilities in Paris, France and Raleigh, North Carolina.2 Cellectis previously announced that the first patient in the United States who received in-house manufactured UCART22 had reached the end of the 28-day DLT period without complication on December 14, 2022. The company stated that the shift to in-house manufacturing was intended to increase the chances of patients receiving the treatment without delay.1
“Our team has worked tirelessly to expand our BALLI-01 clinical study to Europe,” Mark Frattini, MD, PhD, the chief medical officer of Cellectis, said in a statement.1 “Dosing our first patient in France with our UCART22 product candidate manufactured in-house is an important advancement for Cellectis. By targeting the CD22 antigen, we aim at offering a novel therapeutic alternative to patients living with relapsed/refractory B-cell ALL, including those patients who have relapsed or did not respond to CD19-directed therapy.”
The BALLI-01 trial was originally initiated in the United States in 2019, following the clearance of an investigational new drug application by the FDA in June 2018.3,4 Cellectis announced that the first patient enrolled in the trial’s dose-escalation portion received the treatment at the University of Texas MD Anderson Cancer Center in December 2019. The trial is continuing to actively enroll patients.1
Participants in BALLI-01 receive treatment with UCART22 following lymphodepletion with either fludarabine and cyclophosphamide (FC) or FC with alemtuzumab (FCA). Cellectis announced preliminary data from BALLI-01 in December 2022.5 The results included data from 5 patients who received UCART22 following FCA lymphodepletion at dose level 3 (DL3), 5x106 cells/kg. Among these patients there were no cases of DLT, grade 2 or higher cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or adverse events of special interest. Three of the patients (60%), whose disease had previously not responded to multiple lines of prior therapy, showed evidence of a response to UCART22. The responses varied, with 1 patient achieving a minimal residual disease (MRD)-negative complete response (CR) with incomplete count recovery that remained durable beyond 6 months, another patient achieving an MRD-negative CR that remained durable beyond 56 days, and the third patient achieving a morphologic leukemia-free state that remained durable beyond 84 days. Although, it was noted that the third patient, who remained MRD-negative until 84 days, was MRD-positive at 117 days.
“This is a transformational step forward for Cellectis: our in-house manufacturing capabilities would allow us to move product candidates like UCART22 from R&D to development to a finished UCART product on a timeline that would not have been possible working with a contract manufacturer,” Steven Doares, senior vice president, US Manufacturing and Raleigh site head, said in a December 2022 statement.2 “We believe that having this capability in-house is a great competitive advantage as it would give us the ability to swiftly version our product candidates as we monitor clinical responses, resulting in what we expect to be the best product possible.”
