- The Food and Drug Administration on Monday gave French biotech Cellectis SA a green light to resume two Phase 1 studies of its allogeneic CAR-T candidate, lifting a clinical hold that had been imposed following a patient death in late August.
- Cellectis agreed to reduce the dose level tested and will make changes to the chemotherapy pre-conditioning regimen given to patients before infusion of the CAR-T cells. In addition, enrollment into the two studies will be staggered, with at least 28 days between enrollment of two patients across the trials.
- Cellectis' UCART123 product candidate is the first allogeneic CAR-T product cleared for clinical study. Sometimes referred to as "off-the-shelf," allogeneic CAR-T cells are donor-derived rather than extracted from each individual patient — a potential improvement that would permit more industrialized production.
While the FDA has removed its clinical hold, Cellectis will need to obtain approval from institutional review boards on the revised protocols in order to resume patient enrollment.
Still, the announcement seems to signal the FDA's general comfort with Cellectis' underlying allogeneic CAR-T technology — while taking into consideration the clear safety concerns the patient death presented.
Under the new study protocols, Cellectis will decrease the dose level to 6.25x10^4 UCART123 cells/kg and lower the preconditioning dose of cyclophosphamide to 750mg/m^2/day over three days prior to infusion.
The patient who died — a 78-year-old man with blastic plasmacytoid dendritic cell neoplasm (BPDCN) — had been treated with 1g/m^2/day of cyclophosphamide over three days, followed by a dose of 6.25x10^5 UCART123 cells/kg.
Cellectis also said it will ensure the next three patients treated under each study protocol will be under the age of 65.
In addition to BPDCN, Cellectis is also testing UCART123 in acute myeloid leukemia.
While the allogeneic nature of UCART123 is the principal differentiating feature between Cellectis product and other autologous CAR-Ts in development, UCART123 is also aimed at a different cellular target. UCART123 is designed to target the CD123 antigen that is expressed on the surface of leukemic cells in AML and in BPDCN.
Both Novartis AG's Kymriah (tisagenlecleucel) and Gilead Sciences Inc.'s Yescarta (axicabtagene ciloleucel) are directed against another antigen known as CD19 that is expressed on B cells.
Shares in Cellectis rose as much as 8% in value at Tuesday's open before falling back to trade up around 4% by mid-morning.