Allogene changes CAR-T study design following patient death from lymphodepletion regimen

Allogene Therapeutics has dropped the arm of its allogeneic CAR-T trial testing a lymphodepletion regimen that utilized ALLO-647, an anti-CD52 mAb, after a patient died from liver failure.

Going forward, in the ALPHA3 study evaluating the company’s cema-cel CAR-T in first-line consolidation for large B-cell lymphoma, Allogene will use the standard fludarabine and cyclophosphamide (FC) as the lymphodepletion regimen. These regimens are used to control host lymphocyte rejection of allogeneic CAR-T cells.

The death, which occurred in the FC plus ALLO-647 arm on day 54 post-infusion, was believed to have resulted from disseminated adenovirus infection in the setting of immune suppression. The event was deemed unrelated to cema-cel.

The adoption of standard FC in the ALPHA3 trial marks a key shift in Allogene’s clinical strategy. Instead, the company will advance its next-generation AlloCAR T product candidates using its proprietary Dagger Platform Technology, which is designed to minimize or potentially eliminate the need for standard lymphodepletion.

 “This event, which prompted an early review of the trial data, compelled us to make a decisive choice — one that may ultimately help bring this potentially life-saving therapy to patients more quickly. The ability to administer cema-cel following standard FC lymphodepletion in an outpatient setting will simplify study treatment and has the potential to accelerate trial enrollment and streamline regulatory review, ultimately transforming care for patients,” said David Chang, MD, Ph.D., Allogene co-founder and CEO.