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Allogene Therapeutics has ceased the use of its investigational monoclonal antibody, ALLO-647, in the pivotal phase 2 ALPHA3 trial (NCT06500273) in large B-cell lymphoma (LBCL) following a patient death.1
The clinical trial, which is evaluating the allogeneic CAR T-cell therapy cemacabtagene ansegedleucel (cema-cel) with the novel agent ALLO-647, which was incorporated during the lymphodepletion phase and designed to be used in coordination with cema-cel, will now proceed with a standard lymphodepletion regimen of fludarabine and cyclophosphamide. This decision, prompted by a serious adverse event, marks a significant adjustment in the development strategy for a promising “off-the-shelf” CAR T-cell platform.
Third-party analysts at William Blair agreed with the company that the available evidence supported that the patient death, which was linked to liver failure, was attributable to ALLO-647–mediated T-cell suppression as opposed to cema-cel.
“We are supportive of the company’s decision to discontinue the FCA regimen in the ALPHA3 study,” representatives from William Blair wrote on Friday. They cautioned that “the standard lymphodepletion regimen with FC likely will not lead to as robust cema-cel expansion and persistence.”
About ALPHA3
ALPHA3 is a randomized, open-label, phase 2 study in adult patients who have completed standard first-line therapy for LBCL and have achieved a complete or partial response but still have measurable residual disease (MRD).2 The study’s primary end point is event-free survival, and secondary end points include progression-free survival, overall survival, incidence and severity of adverse events, incidence and severity of laboratory toxicities, and MRD clearance.
Patients were initially randomized to treatment arms receiving cema-cel and fludarabine/cyclophosphamide lymphodepletion with or without ALLO-647 in part A. In part B, patients will receive cema-cel or join the observation arm. To be eligible for study participation, patients must have only received 1 prior line of therapy, have an ECOG performance status of 0 or 1, and have adequate hematological, renal, hepatic, pulmonary, and cardiac functions. Those with LBCL with central nervous system involvement, received prior treatment with anti-CD19–targeted therapies, received anticancer treatment after MRD testing was performed, with active and clinically significant autoimmune disease, with active systemic infection, or with a history of another primary malignancy or bone marrow disorder within 3 years of enrollment were not eligible for study participation.
The study continues to recruit patients at 40 sites across 22 states, the District of Columbia, and Canada.