Allogene Pivoting Lymphodepletion Strategy in ALPHA3 CAR‑T Trial Following Patient Death

Allogene Therapeutics (Nasdaq: ALLO), a pioneer in off-the-shelf CAR T cell therapy, has announced a significant update to its ALPHA3 Phase 2 clinical trial of cemacabtagene ansegedleucel (cema-cel) in first-line consolidation for large B-cell lymphoma (LBCL). In response to an adverse event, the company will now use the standard fludarabine and cyclophosphamide (FC) lymphodepletion regimen exclusively.

The move comes after the trial’s FCA arm—which combined FC with ALLO‑647, an anti-CD52 monoclonal antibody—was halted following a Grade 5 adverse event involving liver failure due to a disseminated adenovirus infection. This fatality, occurring on Day 54 post-infusion, was attributed to ALLO‑647 rather than cema-cel, prompting an immediate safety review.

Allogene will discontinue use of ALLO‑647 in all future protocols. Per CEO David Chang, the decision was made in coordination with the ALPHA3 Data and Safety Monitoring Board (DSMB), Steering Committee, and the U.S. Food and Drug Administration. Chang emphasized that no cases of severe viral infection or hepatic failure have occurred with FC-only lymphodepletion in any trial participants.

Under the revised protocol, ALPHA3 will now proceed as a two‑arm randomized study: cema-cel following standard FC lymphodepletion versus observation alone (current standard of care). The study’s statistical design remains unaltered, with a futility analysis—focused on minimal residual disease (MRD) conversion—expected in the first half of 2026. Over 50 clinical sites across the U.S. and Canada remain active in the study.

Chang commented:

Analysts say this adjustment reinforces Allogene’s strategic pivot toward its Dagger® Platform, which aims to reduce reliance on antibodies like ALLO‑647 and minimize lymphodepletion altogether. All trials and pipeline programs will now focus on Dagger‑enabled candidates such as ALLO‑316 and ALLO‑329, which are being developed for renal cancer and autoimmune diseases, respectively.

This protocol change closely follows a Fierce Biotech report revealing the patient death and Allogene’s swift decision to discontinue its investigational antibody use. The article confirmed that this was the only active trial still utilizing ALLO‑647. About Allogene Therapeutics

Allogene Therapeutics is a clinical-stage biotechnology company at the forefront of developing allogeneic (“off-the-shelf”) chimeric antigen receptor T cell (AlloCAR T™) therapies for cancer and autoimmune diseases. Headquartered in South San Francisco, Allogene is led by a team of industry pioneers with deep expertise in cell therapy and immuno-oncology.

The company’s proprietary technology platform is designed to deliver CAR T cell therapies that are readily available, scalable, and do not require patient-specific cell collection, aiming to make advanced cell therapies more accessible to patients around the world. Allogene’s pipeline includes multiple product candidates, such as cemacabtagene ansegedleucel (cema-cel) for large B-cell lymphoma, as well as innovative programs in solid tumors and autoimmune disorders.