Allogene Therapeutics Moves Forward with Standard Fludarabine and Cyclophosphamide (FC) Lymphodepletion Regimen in the ALPHA3 Trial for Cemacabtagene Ansegedleucel (Cema-Cel) in First-Line Consolidation for Large B-Cell Lymphoma
Allogene Therapeutics (NASDAQ:ALLO) has announced a significant change in its ALPHA3 trial for cemacabtagene ansegedleucel (cema-cel) in first-line consolidation for large B-cell lymphoma. The company will proceed with standard fludarabine and cyclophosphamide (FC) lymphodepletion regimen, discontinuing the FC plus ALLO-647 (FCA) arm following a patient death attributed to ALLO-647.
The decision was made after a Grade 5 adverse event occurred on Day 54 post-infusion, resulting from hepatic failure due to disseminated adenovirus infection. The trial will now continue as a two-arm randomized study comparing cema-cel with standard FC lymphodepletion to observation. The scheduled futility analysis remains planned for 1H 2026.
Allogene is shifting its clinical strategy, removing ALLO-647 from all trials and advancing next-generation AlloCAR T products using their proprietary Dagger® Platform Technology, designed to minimize or eliminate standard lymphodepletion needs.
Allogene Therapeutics (NASDAQ:ALLO) ha annunciato un cambiamento significativo nel suo studio ALPHA3 per cemacabtagene ansegedleucel (cema-cel) come consolidamento di prima linea per il linfoma a grandi cellule B. L'azienda procederà con il regime standard di linfodeplezione con fludarabina e ciclofosfamide (FC), interrompendo il braccio FC più ALLO-647 (FCA) a seguito di un decesso attribuito ad ALLO-647.
La decisione è stata presa dopo un evento avverso di grado 5 verificatosi al 54° giorno dopo l'infusione, dovuto a insufficienza epatica causata da un'infezione da adenovirus disseminato. Lo studio continuerà ora come uno studio randomizzato a due bracci che confronta cema-cel con la linfodeplezione standard FC rispetto all'osservazione. L'analisi di futility programmata rimane prevista per la prima metà del 2026.
Allogene sta modificando la sua strategia clinica, rimuovendo ALLO-647 da tutti gli studi e portando avanti prodotti AlloCAR T di nuova generazione utilizzando la loro tecnologia proprietaria Dagger® Platform Technology, progettata per minimizzare o eliminare la necessità della linfodeplezione standard.
Allogene Therapeutics (NASDAQ:ALLO) ha anunciado un cambio significativo en su ensayo ALPHA3 para cemacabtagene ansegedleucel (cema-cel) como consolidación de primera línea para linfoma de células B grandes. La compañía continuará con el régimen estándar de linfodepleción con fludarabina y ciclofosfamida (FC), discontinuando el brazo FC más ALLO-647 (FCA) tras la muerte de un paciente atribuida a ALLO-647.
La decisión se tomó después de que ocurriera un evento adverso de grado 5 en el día 54 tras la infusión, resultado de insuficiencia hepática causada por una infección diseminada por adenovirus. El ensayo continuará ahora como un estudio aleatorizado de dos brazos que compara cema-cel con linfodepleción estándar FC frente a observación. El análisis de inutilidad programado sigue previsto para el primer semestre de 2026.
Allogene está cambiando su estrategia clínica, eliminando ALLO-647 de todos los ensayos y avanzando con productos AlloCAR T de próxima generación utilizando su tecnología patentada Dagger® Platform Technology, diseñada para minimizar o eliminar la necesidad de linfodepleción estándar.
Allogene Therapeutics (NASDAQ:ALLO)는 대형 B세포 림프종 1차 치료 후 공고를 위한 cemacabtagene ansegedleucel(cema-cel)의 ALPHA3 임상시험에서 중요한 변경 사항을 발표했습니다. 회사는 표준 플루다라빈 및 사이클로포스파미드(FC) 림프절제 요법을 계속 진행하며, ALLO-647에 기인한 환자 사망 사건으로 인해 FC와 ALLO-647(FCA) 병행군을 중단하기로 했습니다.
이 결정은 투여 후 54일째에 발생한 5등급 이상반응으로, 전신 아데노바이러스 감염에 의한 간부전 때문이었습니다. 현재 임상시험은 cema-cel과 표준 FC 림프절제 요법을 비교하는 2개 군 무작위 배정 연구로 계속 진행됩니다. 예정된 무효성 분석은 2026년 상반기로 계획되어 있습니다.
Allogene은 임상 전략을 전환하여 모든 임상시험에서 ALLO-647를 제거하고, 표준 림프절제 필요성을 최소화하거나 제거하도록 설계된 독자적인 Dagger® 플랫폼 기술을 활용한 차세대 AlloCAR T 제품을 개발 중입니다.
Allogene Therapeutics (NASDAQ:ALLO) a annoncé un changement majeur dans son essai ALPHA3 concernant le cemacabtagene ansegedleucel (cema-cel) en consolidation de première ligne pour le lymphome à grandes cellules B. La société poursuivra avec le schéma standard de lymphodéplétion par fludarabine et cyclophosphamide (FC), en arrêtant le bras FC plus ALLO-647 (FCA) suite au décès d'un patient attribué à ALLO-647.
Cette décision fait suite à un événement indésirable de grade 5 survenu au jour 54 après perfusion, résultant d'une insuffisance hépatique due à une infection disséminée par adénovirus. L'essai se poursuivra désormais en tant qu'étude randomisée à deux bras comparant cema-cel avec la lymphodéplétion standard FC à l'observation. L'analyse de futilité programmée reste prévue pour le premier semestre 2026.
Allogene modifie sa stratégie clinique, retirant ALLO-647 de tous les essais et faisant progresser les produits AlloCAR T de nouvelle génération utilisant leur technologie propriétaire Dagger® Platform Technology, conçue pour minimiser ou éliminer les besoins en lymphodéplétion standard.
Allogene Therapeutics (NASDAQ:ALLO) hat eine bedeutende Änderung in seiner ALPHA3-Studie für cemacabtagene ansegedleucel (cema-cel) als Erstlinienkonsolidierung bei großzelligem B-Zell-Lymphom angekündigt. Das Unternehmen wird mit dem Standard-Lymphodepletionsregime aus Fludarabin und Cyclophosphamid (FC) fortfahren und den Arm mit FC plus ALLO-647 (FCA) nach einem patientenbedingten Todesfall, der ALLO-647 zugeschrieben wurde, einstellen.
Die Entscheidung erfolgte nach einem Grad-5-Nebenereignis am Tag 54 nach der Infusion, verursacht durch Leberversagen infolge einer disseminierten Adenovirus-Infektion. Die Studie wird nun als randomisierte Zweiarm-Studie fortgesetzt, in der cema-cel mit der standardmäßigen FC-Lymphodepletion gegen Beobachtung verglichen wird. Die geplante Futility-Analyse ist weiterhin für das erste Halbjahr 2026 vorgesehen.
Allogene ändert seine klinische Strategie, entfernt ALLO-647 aus allen Studien und entwickelt die nächste Generation von AlloCAR T-Produkten unter Verwendung ihrer proprietären Dagger® Platform Technology, die darauf ausgelegt ist, den Bedarf an standardmäßiger Lymphodepletion zu minimieren oder zu eliminieren.
- Simplified study treatment with standard FC lymphodepletion allows for outpatient administration
- Potential acceleration of trial enrollment and streamlined regulatory review
- Over 50 clinical sites activated across US and Canada
- Development of next-generation Dagger® Platform Technology to reduce reliance on traditional lymphodepletion
- Patient death (Grade 5 adverse event) attributed to ALLO-647 treatment
- Discontinuation of FC plus ALLO-647 (FCA) arm in ALPHA3 trial
- Removal of ALLO-647 from all trials and pipeline programs
Insights
Allogene halts ALLO-647 use after patient death, reverts to standard lymphodepletion for CAR-T trial, simplifying development despite safety setback.
Allogene Therapeutics has made a critical protocol change to its ALPHA3 trial for cemacabtagene ansegedleucel (cema-cel) in first-line large B-cell lymphoma (LBCL) following a patient death. The company will now use only standard fludarabine and cyclophosphamide (FC) lymphodepletion, abandoning the arm testing FC plus ALLO-647 (anti-CD52 mAb) after a Grade 5 adverse event attributed to ALLO-647.
The fatality occurred from hepatic failure due to disseminated adenovirus infection at Day 54 post-infusion, highlighting the increased immunosuppression risks associated with ALLO-647. This represents a significant safety signal, particularly as severe viral infections have been rare across Allogene's trials but, when present, have been linked to ALLO-647-induced immunosuppression.
Despite this setback, the unplanned data review revealed encouraging minimal residual disease (MRD) conversion rates and safety profile with standard FC lymphodepletion and cema-cel, suggesting the product maintains efficacy without ALLO-647. This simplifies the treatment regimen and potentially enables outpatient administration, which could accelerate trial enrollment and regulatory review.
The amended ALPHA3 trial now continues as a two-arm study comparing cema-cel with standard FC lymphodepletion versus observation (current standard of care). The scheduled futility analysis remains on track for 1H 2026, focusing on MRD conversion rates.
This strategic pivot extends beyond ALPHA3, as Allogene has now removed ALLO-647 from all enrollment-open trials and pipeline programs. Instead, the company is advancing its next-generation AlloCAR T candidates using their proprietary Dagger® Platform Technology, designed to reduce or eliminate standard lymphodepletion requirements – a significant shift in their clinical development strategy.
- Lymphodepletion Regimen Selection Made in Conjunction with the ALPHA3 Data and Safety Monitoring Board (DSMB) and Steering Committee, and in Consultation with the FDA Following an ALLO-647-Related Death in the FCA (FC plus ALLO-647) Lymphodepletion Arm
- Unplanned Review of Safety and Biomarker Data with Standard FC and Cema-cel Indicates Encouraging MRD Conversion Rate and Safety Profile
- ALPHA3 Study Now Proceeds as a Two-Arm Randomized Study Comparing Cema-cel After Standard FC Lymphodepletion to Observation; Scheduled Futility Analysis Remains 1H 2026, as Planned
- Conference Call and Webcast Scheduled for Today at 8:00 AM PT/11:00 AM ET
SOUTH SAN FRANCISCO, Calif., Aug. 01, 2025 (GLOBE NEWSWIRE) -- Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T™) products for cancer and autoimmune disease, today announced that it has selected standard fludarabine and cyclophosphamide (FC) as the lymphodepletion regimen to be used in its ALPHA3 study evaluating cemacabtagene ansegedleucel (cema-cel) in first-line consolidation for large B-cell lymphoma (LBCL). This lymphodepletion regimen selection was made in conjunction with the ALPHA3 Data and Safety Monitoring Board (DSMB) and Steering Committee and following consultation with the U.S. Food and Drug Administration (FDA).
The arm testing FC plus ALLO-647, an anti-CD52 mAb (FCA), is now closed to further enrollment. This decision, made ahead of the scheduled futility analysis, was prompted by a Grade 5 adverse event in the FC plus ALLO-647 arm that has been attributed to the use of ALLO-647. The event occurred on Day 54 post-infusion from hepatic failure, believed to have resulted from disseminated adenovirus infection in the setting of immune suppression. This event was deemed unrelated to cema-cel. Severe viral infections have been rare across Allogene’s clinical trials. However, when present, they have been attributed to immunosuppression due in part to ALLO-647. There have been no cases of adenoviral infection or hepatic failure in any participant treated with FC lymphodepletion across Allogene’s trials.
“The loss of a patient is always deeply saddening, and we extend our heartfelt condolences to the patient’s family,” said David Chang, M.D., Ph.D., 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.”
The adoption of standard FC in the ALPHA3 trial marks a key shift in Allogene’s clinical strategy. As a result, no trials open to enrollment or pipeline programs include ALLO-647. Instead, the Company is advancing its next-generation AlloCAR T product candidates using the proprietary Dagger® Platform Technology, which is designed to minimize or potentially eliminate the need for standard lymphodepletion. This approach is showcased in the ALLO-316 TRAVERSE trial for advanced renal cell carcinoma and the ALLO-329 RESOLUTION trial for autoimmune diseases, both of which leverage the Dagger® Technology to reduce reliance on traditional lymphodepletion strategies.
The amended ALPHA3 trial now proceeds as a randomized study with two arms, comparing cema-cel after standard FC lymphodepletion to observation, the current standard of care. Statistical design of the trial and the prespecified study conduct remain the same. The next milestone will be the futility analysis comparing MRD conversion and is expected to occur 1H 2026. To date, over 50 clinical sites are activated across the United States and Canada, including community cancer centers and major academic institutions.
Conference Call and Webcast Details
Allogene will host a live conference call and webcast today at 8:00 a.m. PT / 11:00 a.m. ET to discuss this recent update. If you would like the option to ask a question on the conference call, please use this link to register. Upon registering for the conference call, you will receive a personal PIN to access the call, which will identify you as the participant and allow you the option to ask a question. The listen-only webcast will be made available on the Company's website at www.allogene.com under the Investors tab in the News and Events section. Following the live audio webcast, a replay will be available on the Company's website for approximately 30 days.
About Cemacabtagene Ansegedleucel (cema-cel)
Cemacabtagene ansegedleucel, or cema-cel, is a next generation anti-CD19 AlloCAR T™ investigational product for the treatment of large B cell lymphoma (LBCL). The ALPHA3 pivotal Phase 2 trial in first line (1L) consolidation for the treatment of LBCL launched in June 2024. Allogene has oncology rights to cema-cel in the US, EU and UK with options for rights in China and Japan.
About the ALPHA3 Trial
Over 60,000 patients are expected to be treated for LBCL annually in the US, the EU and the UK. While first line (1L) R-CHOP or other chemoimmunotherapy is effective for most patients, approximately
About Allogene Therapeutics
Allogene Therapeutics, with headquarters in South San Francisco, is a clinical-stage biotechnology company pioneering the development of allogeneic chimeric antigen receptor T cell (AlloCAR T™) products for cancer and autoimmune disease. Led by a management team with significant experience in cell therapy, Allogene is developing a pipeline of “off-the-shelf” CAR T cell product candidates with the goal of delivering readily available cell therapy on-demand, more reliably, and at greater scale to more patients. For more information, please visit www.allogene.com, and follow Allogene Therapeutics on X and LinkedIn.
Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The press release may, in some cases, use terms such as “indicates,” “deem,” “expected,” “next,” “potential,” “transform,” “believe,” “will,” “to see,” “scheduled,” “reduce,” “advancing,” “may,” “could,” “designed to,” “comparing,” “can,” “accelerate,” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Forward-looking statements include statements regarding intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: ALPHA3 being a pivotal trial and the extent to which it will support regulatory approval of cema-cel; the potential for preliminary encouraging MRD conversion rate and safety profile being consistent with future trial results; the potential cause of the Grade 5 adverse event; the possibility that the selection of the FC arm will bring life-saving therapy to patients more quickly, simplify study treatment, accelerate trial enrollment, streamline regulatory review, or transform care for patients; the Company’s clinical strategy; the design and potential benefits of our Dagger® platform technology, including it becoming the next-generation allogeneic platform, or reducing reliance on traditional lymphodepletion strategies; the potential for cema-cel to be a one-time off-the-shelf treatment or become the standard “7th cycle” of frontline treatment; that cema-cel can be administered immediately upon discovery of MRD following six cycles of R-CHOP or other chemoimmunotherapy; the timing for completion of ALPHA3 milestones, including the futility analysis; the potential for our product candidates to be approved; the potential benefits of the ALPHA3 trial and of AlloCAR T™ products; cema-cel’s safety profile; our ability to deliver cell therapy on-demand, more reliably, and at greater scale to more patients; the expected annual patient population for LBCL in the US and EU; and other statements related to future events or conditions. Various factors may cause material differences between Allogene’s expectations and actual results, including, risks and uncertainties related to: our product candidates are based on novel technologies, which makes it difficult to predict the time and cost of product candidate development and obtaining regulatory approval; the limited nature of our pre-clinical, and Phase 1 and Phase 2 data and the extent to which such data may or may not be validated in any future clinical trial; our product candidates in the past have and may in the future cause undesirable side effects or have other properties that could halt their clinical development, prevent their regulatory approval or limit their commercial potential; the extent to which the Food and Drug Administration disagrees with our clinical or regulatory plans or the import of our clinical results, which could cause future delays to our clinical trials, including initiation of clinical trials, or require additional clinical trials; we may encounter difficulties enrolling patients in our clinical trials; we may not be able to demonstrate the safety and efficacy of our product candidates in our clinical trials, which could prevent or delay regulatory approval and commercialization; and the challenges with manufacturing or optimizing manufacturing of our product candidates. Additional factors that could cause actual results to differ materially from those stated or implied by the Company’s forward-looking statements are disclosed in the Company’s filings with the Securities and Exchange Commission (SEC), including in the section captioned “Risk Factors” in the Company’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2025, filed with the SEC on May 13, 2025. These forward-looking statements represent the Company’s judgment as of the time of this press release. The Company disclaims any intent or obligation to update these forward-looking statements, other than as may be required under applicable law.
AlloCAR T™ and Dagger® are trademarks of Allogene Therapeutics, Inc.
Allogene’s investigational AlloCAR T™ oncology products utilize Cellectis technologies. The anti-CD19 oncology products are developed based on an exclusive license granted by Cellectis to Servier. Servier, which has an exclusive license to the anti-CD19 AlloCAR T investigational products from Cellectis, has granted Allogene exclusive rights to these products in the U.S., all EU Member States and the United Kingdom.
Allogene Media/Investor Contact:
Christine Cassiano
EVP, Chief Corporate Affairs & Brand Strategy Officer
Christine.Cassiano@allogene.com
FAQ
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