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

August 01, 2025 08:30 ET | Source: Allogene Therapeutics, Inc. 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 ArmUnplanned Review of Safety and Biomarker Data with Standard FC and Cema-cel Indicates Encouraging MRD Conversion Rate and Safety ProfileALPHA3 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 PlannedConference 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 DetailsAllogene 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 TrialOver 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 30% who initially respond will relapse and require subsequent treatment. The current standard of care after 1L treatment has been simply to “watch and wait” to see if the disease relapses. The pivotal Phase 2 ALPHA3 study takes advantage of cema-cel as a one-time, “off-the-shelf” treatment that can be administered immediately upon discovery of MRD following six cycles of R-CHOP or other chemoimmunotherapy, positioning it to become the standard “7th cycle” of frontline treatment available to all eligible patients with MRD. About Allogene TherapeuticsAllogene 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 StatementsThis 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 CassianoEVP, Chief Corporate Affairs & Brand Strategy OfficerChristine.Cassiano@allogene.com

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

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