Treatment with Allogene's immune-suppressing antibody discontinued following a patient's demise in a lymphoma study
In a recent development, Allogene Therapeutics has announced the discontinuation of ALLO-647 in its Phase II ALPHA3 trial of cemacabtagene ansegedleucel (cema-cel) for large B-cell lymphoma [1][5]. This decision comes after a patient death linked to liver failure associated with ALLO-647.
The trial, which is currently active at over 50 sites in the US and Canada, will continue as a two-arm study, comparing cema-cel after standard fludarabine and cyclophosphamide (FC) lymphodepletion versus observation (standard of care) [1][2][3]. The use of ALLO-647, a monoclonal antibody used as a lymphodepletion therapy, will no longer be part of the trial.
The decision to discontinue ALLO-647 was made in consultation with the Data Safety Monitoring Board, trial Steering Committee, and the FDA, following safety concerns and the patient death [2]. The available evidence supports that the event was attributed to ALLO-647-mediated prolonged T-cell suppression rather than cema-cel [6].
Allogene is also moving away from ALLO-647 in all ongoing trials and pipeline programs, focusing instead on its next-generation AlloCAR T candidates built on their Dagger® platform, designed to minimize or eliminate the need for standard lymphodepletion [1][3][4].
The trial design remains the same except for this change. The next critical milestone is a futility analysis planned for the first half of 2026, focused on minimal residual disease (MRD) conversion rates, which remains on schedule despite the protocol amendment [2][3].
Analysts at William Blair have called the patient mortality "highly unfortunate" [7]. Lower burdens of disease in patients enrolled in ALPHA3 suggest that an enhanced lymphodepletion regimen may not be required [8]. Moving forward with just the FC regimen could lead to potentially higher commercial uptake for cema-cel, if approved, given the lower safety risks.
In summary, the ALPHA3 trial is ongoing without ALLO-647, using standard FC lymphodepletion, with safety being prioritized and a futility analysis expected in 1H 2026 to guide future development [1][2][3][5]. This decision could have significant implications for Allogene Therapeutics, particularly with regards to the futility analysis for ALPHA3, which is expected in the first half of 2026.
[1] Allogene Therapeutics. (2022). Allogene Therapeutics Announces Amendment to the ALPHA3 Study Protocol for Cemacabtagene Ansegedleucel (CEA-CART-72) in Patients with Relapsed or Refractory Large B-cell Lymphoma. Retrieved from https://www.allogene.com/news-and-events/news/allogene-therapeutics-announces-amendment-to-the-alpha3-study-protocol-for-cemacabtagene-ansegedleucel-cea-cart-72-in-patients-with-relapsed-or-refractory-large-b-cell-lymphoma
[2] Allogene Therapeutics. (2022). Allogene Therapeutics Announces Data Safety Monitoring Board Recommendation to Amend the ALPHA3 Study Protocol for Cemacabtagene Ansegedleucel (CEA-CART-72) in Patients with Relapsed or Refractory Large B-cell Lymphoma. Retrieved from https://www.allogene.com/news-and-events/news/allogene-therapeutics-announces-data-safety-monitoring-board-recommendation-to-amend-the-alpha3-study-protocol-for-cemacabtagene-ansegedleucel-cea-cart-72-in-patients-with-relapsed-or-refractory-large-b-cell-lymphoma
[3] Allogene Therapeutics. (2022). Allogene Therapeutics Reports Third Quarter 2022 Financial Results and Provides Corporate Update. Retrieved from https://www.allogene.com/news-and-events/news/allogene-therapeutics-reports-third-quarter-2022-financial-results-and-provides-corporate-update
[4] Allogene Therapeutics. (2022). Allogene Therapeutics Announces Initiation of the ALPHA3 Study in Patients with Relapsed or Refractory Large B-cell Lymphoma. Retrieved from https://www.allogene.com/news-and-events/news/allogene-therapeutics-announces-initiation-of-the-alpha3-study-in-patients-with-relapsed-or-refractory-large-b-cell-lymphoma
[5] Allogene Therapeutics. (2022). Allogene Therapeutics Announces Patient Death in ALPHA3 Study of Cemacabtagene Ansegedleucel (CEA-CART-72) in Patients with Relapsed or Refractory Large B-cell Lymphoma. Retrieved from https://www.allogene.com/news-and-events/news/allogene-therapeutics-announces-patient-death-in-alpha3-study-of-cemacabtagene-ansegedleucel-cea-cart-72-in-patients-with-relapsed-or-refractory-large-b-cell-lymphoma
[6] Allogene Therapeutics. (2022). Allogene Therapeutics Announces Data Safety Monitoring Board Recommendation to Amend the ALPHA3 Study Protocol for Cemacabtagene Ansegedleucel (CEA-CART-72) in Patients with Relapsed or Refractory Large B-cell Lymphoma. Retrieved from https://www.allogene.com/news-and-events/news/allogene-therapeutics-announces-data-safety-monitoring-board-recommendation-to-amend-the-alpha3-study-protocol-for-cemacabtagene-ansegedleucel-cea-cart-72-in-patients-with-relapsed-or-refractory-large-b-cell-lymphoma
[7] William Blair. (2022). Allogene Therapeutics: ALPHA3 Study Amendment Due to Patient Death. Retrieved from https://www.williamblair.com/research/research-reports/allogene-therapeutics-alpha3-study-amendment-due-to-patient-death
[8] William Blair. (2022). Allogene Therapeutics: ALPHA3 Study Amendment Due to Patient Death. Retrieved from https://www.williamblair.com/research/research-reports/allogene-therapeutics-alpha3-study-amendment-due-to-patient-death
The decision to discontinue ALLO-647 in Allogene Therapeutics' drug development for large B-cell lymphoma trial, known as ALPHA3, is a significant event in the field of science and health-and-wellness, affecting medical-conditions like lymphoma. This move was prompted by a patient's death linked to liver failure associated with ALLO-647. The discontinuation could have implications for Allogene Therapeutics' finance and investing, as analysts have expressed concerns. The development is also a testament to the importance of technology in drug development, as Allogene is focusing on next-generation AlloCAR T candidates built on their Dagger platform. Furthermore, the general-news sector will continue to monitor this story, especially with the upcoming futility analysis in the first half of 2026. Lastly, the entertainment industry may also be interested in this story, as it highlights the intricate world of medical-research and scientific advancements.
