The first patient dosed in Cellectis’ new Phase 1 trial for cancer cell therapy UCART123 has died. The therapy’s development trajectory has now been called into question with the FDA placing clinical holds on the two Phase 1 trials investigating UCART123. Cellectis is now required to redesign their protocol alongside the FDA to mitigate further such occurrences. The news also hit the company on the stock markets and it opened down 20% on NASDAQ, and 21% in Europe.
UCART123 is an allogeneic product comprising of chimeric antigen receptor (CAR) T cells which are designed to target the CD123 receptor. The therapy is being investigated for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN), and acute myeloid leukaemia (AML). When initially treated with a low dose of UCART123, the 78 year old BPDCN patient in question did not experience complications. This changed at day 5 when the patient suffered cytokine release syndrome (CRS) followed by a lung infection and grade 4 capillary leak syndrome (CLS) that were ultimately fatal on day 9. On the parallel AML trial, a 58 year old woman was the first to be dosed; she experienced CRS and CLS that subsided by day 12 after a stint in intensive care.
Moving forward, the data safety monitoring board has proposed lowering the dose of UCART123 and capping the amount of the chemotherapy cyclophosphamide patients receive during the preconditioning stage. Jeffries analysts have added that Cellectis may need to re-evaluate the timing of steroid administration and consider a more aggressive approach towards CRS.
Source: FDA hits Cellectis’ off-the-shelf CAR-T program with clinical hold after first patient treated in phase 1 trial dies Press Release