Allogene Therapeutics has announced changes to its ALPHA3 phase II clinical trial following the death of a patient enrolled in the study.
The ongoing trial, which has been evaluating the cell therapy cemacabtagene ansegedleucel (cema-cel) as a first-line consolidation therapy in large B-cell lymphoma, included an arm combining fludarabine and cyclophosphamide (FC) lymphodepletion with the anti-CD52 monoclonal antibody ALLO-647. A patient in this cohort died from hepatic failure associated with disseminated adenovirus infection, attributed to profound immunosuppression due, in part to ALLO-647. The patient died 54 days post-infusion.
After consulting with the study’s Data and Safety Monitoring Board, the trial steering committee, and the FDA, Allogene has chosen to discontinue the FC plus ALLO-647 arm. In addition, the company has terminated all development activities related to ALLO-647 across its clinical portfolio. Other viral infections, although rare, have been noted in other Allogene trials connected, in part, to immunosuppression with ALLO-647.
The adverse event was assessed as unrelated to the cema-cel cell therapy. A statement from Allogene stressed: “There have been no cases of adenoviral infection or hepatic failure in any participant treated with FC lymphodepletion across Allogene’s trials.”
The ALPHA3 trial will continue using only the standard FC lymphodepletion regimen. The revised study design now compares FC plus cema-cel against observation, with a futility analysis planned for the first half of 2026.
“The loss of a patient is always deeply saddening, and we extend our heartfelt condolences to the patient’s family,” said David Chang, President, Chief Executive Officer, and Co-Founder of Allogene. “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.”
Moving forward, Allogene intends to advance next-generation AlloCAR T product candidates that use its proprietary Dagger Platform Technology – which is designed to minimize or even eliminate the need for standard lymphodepletion.
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