Allogene Shifts ALPHA3 Trial to Standard FC After Patient Death

Allogene Therapeutics has amended its ALPHA3 clinical trial for cemacabtagene ansegedleucel (cema-cel) in large B-cell lymphoma by discontinuing the FC plus ALLO-647 lymphodepletion regimen after a patient death attributed to ALLO-647-related severe viral infection and hepatic failure. The trial will now proceed with the standard fludarabine and cyclophosphamide (FC) lymphodepletion regimen, a decision made in consultation with the FDA, the ALPHA3 Data and Safety Monitoring Board, and the Steering Committee. This change simplifies treatment, potentially enabling outpatient administration, accelerating enrollment, and streamlining regulatory review. Allogene is also advancing next-generation AlloCAR T products using its Dagger Platform Technology to reduce or eliminate the need for lymphodepletion. The ALPHA3 trial remains a two-arm randomized study comparing cema-cel after FC lymphodepletion to observation, with a futility analysis for minimal residual disease conversion scheduled for the first half of 2026. The company emphasized that the adverse event was unrelated to cema-cel itself, and no adenoviral infections or hepatic failures have occurred with the FC regimen in prior trials.