SOUTH SAN FRANCISCO, Calif. — 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 reported data from the planned interim futility analysis of its pivotal, randomized Phase 2 ALPHA3 trial in first-line (1L) consolidation large B-cell lymphoma (LBCL).
At the protocol-defined data cutoff, which was triggered when the 24th patient completed Day 45 MRD assessment, 58.3% (7/12) of patients in the cemacabtagene ansegedleucel (cema-cel) arm achieved minimal residual disease (MRD) negativity compared to 16.7% (2/12) in the observation arm. This represents a 41.6% absolute difference in MRD clearance between the two arms. Based on literature,1 2 3 a difference in percentage points of 25-30% in the MRD clearance could translate into meaningful clinical benefit at study completion. In addition, at the first MRD assessment (Day 45), plasma ctDNA levels decreased from baseline by a median of 97.7% in the cema-cel arm compared to a 26.6% median increase in the observation arm. The Company believes these interim data provide initial support for cema-cel’s potential as a novel strategy for treating high-risk patients at the end of first-line treatment.
MRD status post-treatment has emerged as a strong predictor of relapse in LBCL, creating a potential opportunity to intervene earlier in the course of disease, when disease burden is low, but the risk of progression remains high.4 5 The ALPHA3 trial is the first randomized study in LBCL designed to assess whether MRD-guided intervention before relapse can eliminate residual disease and potentially prevent recurrence. The study identifies high-risk patients using Natera’s CLARITY™ MRD assay which is powered by its phased variant MRD technology. Patients with LBCL who have completed curative-intent treatment in both front-line and later line settings, including autologous CAR T therapy, and who achieve MRD negative status by technology have demonstrated improved progression-free survival (PFS) and EFS compared to those who do not attain MRD-negative status.6 7
“Early MRD clearance in this setting is encouraging and supports the potential for cema-cel to change how we approach high-risk LBCL at the end of first-line therapy,” said Zachary Roberts, M.D., Ph.D., EVP, Research and Development and Chief Medical Officer of Allogene. “These interim data suggest that an off-the-shelf CAR T may be able to intervene during that important window before clinical relapse to eliminate residual disease and make earlier intervention feasible in routine clinical practice. We look forward to the next study milestones as the trial continues to further define the potential of cema-cel.”
“Our goal has always been to move CAR T from a bespoke procedure available at a limited number of centers to a scalable therapy that can reach patients more broadly,” said David Chang, M.D., Ph.D., President, Chief Executive Officer and Co-Founder of Allogene. “Although still early, the ALPHA3 results show encouraging MRD clearance and a favorable safety profile. Combined with the advantages of an off-the-shelf CAR T platform—rapid availability, operational simplicity, and potential for outpatient use—cema-cel, if approved, could leapfrog existing options and enable earlier intervention in the disease course.”
SAFETY & HOSPITALIZATION
Cema-cel has been generally well-tolerated as of the data cutoff with no serious adverse events related to treatment. There were no cases of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) or graft-versus-host disease (GvHD) in the Treatment Emergent Adverse Events (TEAEs) of Special Interest category, which captures adverse events associated with CAR T.
| TEAEs of Special Interest | Cema-cel Arm (N=12) n (%) |
Observation Arm (N=12) n (%) |
| CRS (Any Grade) | 0 | – |
| ICANS (Any Grade) | 0 | – |
| GvHD (Any Grade) | 0 | – |
| Infection* | 2 (16.7%) | 2 (16.7%) |
| Infection (Grade ≥3) | 0 | 0 |
| Other Neurologic Events** | 6 (50.0%) | 1 (8.3%) |
| Other Neurologic Events (Grade ≥3) | 0 | 0 |
*Infection events were low grade and limited to urinary tract infection, subcutaneous abscess, COVID19, and skin infection
**Other neurologic events were low grade and limited to headache, dizziness, numbness or tingling in the hands or feet, and altered taste
No Hospitalizations for Treatment Related Adverse Events: Ten of 12 patients who received cema-cel were managed entirely outpatient post-infusion. The remaining two patients were briefly hospitalized for events deemed unrelated to cema-cel treatment (atrial fibrillation and non-cardiac chest pain). One patient in the observation arm was hospitalized for febrile neutropenia. This contrasts with the broader CAR T experience where hospitalization for toxicity management remains common, even in outpatient programs, with approximately 70–90% of patients requiring admission and roughly 75% hospitalized for adverse events within 30 days.8
“The early safety profile, characterized by an absence of CRS and ICANS, is encouraging given its potential to enable safe outpatient management,” said Nancy L. Bartlett, M.D., Professor of Medicine, Division of Oncology, Washington University School of Medicine in St. Louis and a Siteman Cancer Center physician. “When considered alongside the availability of an off-the-shelf product, these findings suggest the possibility of overcoming key logistical barriers that have historically limited broader use of CAR T, particularly in earlier lines of therapy. Coupled with the encouraging MRD clearance data, this approach may represent an important step toward improving outcomes while expanding patient access.”
REAL-WORLD FEASIBILITY AND COMMUNITY USE
At the time of the interim futility analysis, community cancer centers accounted for approximately 33% of screening activity and cema-cel infusions, including several sites with little to no prior CAR T experience. Participation from these centers, where most patients receive care, underscores the feasibility of offering cema-cel in these settings and supports potential for broader adoption.
“In busy community practices, the goal is simple: bring the therapy to the patient, not the patient to the therapy,” said Jeff Sharman, M.D., Chair, Lymphoma Research Executive Committees, SCRI at Willamette Valley Cancer Institute & Research Center. “Historically, CAR T has largely been out of reach for community practices. The ability to deliver an off-the-shelf CAR T safely in the community setting, potentially outpatient, could address far more patients and extend treatment reach across the communities we serve.”
PATIENT CHARACTERISTICS
Both study arms consisted of patients with high-risk, aggressive lymphomas. Although limited by the small sample size, baseline characteristics show that a numerically greater number of patients in the cema-cel arm had more aggressive disease features, specifically stage III-IV disease and higher IPI scores, compared to the observation arm.
| At Original Diagnosis | Cema-cel Arm (N=12) n (%) |
Observation Arm (N=12) n (%) |
| History of Bone Marrow Involvement | 4 (33.3%) | 3 (25.0%) |
| Disease Stage | ||
| I – II | 0 | 2 (16.7%) |
| III – IV | 12 (100%) | 10 (83.3%) |
| IPI Score | ||
| 0 to 1 | 0 | 4 (33.3%) |
| 2 to 3 | 7 (58.3%) | 5 (41.7%) |
| 4 to 5 | 5 (41.7%) | 2 (16.7%) |
| Unknown | 0 | 1 (8.3%) |
| Gene Alterations/Over Expression | ||
| Double Hit | 6 (50.0%) | 2 (16.7%) |
| Triple Hit | 0 | 2 (16.7%) |
| Double Expressor | 2 (16.7%) | 0 |
First-Line Regimens and PET/CT Response to the 1L Regimen: A high-intensity variant of R-CHOP, DA-EPOCH-R, was the most commonly administered 1L therapy across both arms, with a slightly higher proportion of patients in the cema-cel arm receiving this first line treatment regimen (58.3% vs. 41.7%). Twenty-five percent of patients in each arm entered the study after achieving a partial remission to 1L therapy.
| Cema-cel Arm (N=12) n (%) |
Observation Arm (N=12) n (%) |
|
| First-Line Treatment | ||
| R-CHOP | 2 (16.7%) | 3 (25.0%) |
| R-Pola-CHP | 2 (16.7%) | 2 (16.7%) |
| DA-EPOCH-R | 7 (58.3%) | 5 (41.7%) |
| R-miniCHOP | 1 ( 8.3%) | 2 (16.7%) |
| Most Recent PET/CT Response Before Randomization | ||
| CR | 9 (75.0%) | 9 (75.0%) |
| PR | 3 (25.0%) | 3 (25.0%) |
ALPHA3 TRIAL AND TIMELINE
This interim futility analysis was based on the first 24 patients randomized (12 in the cema-cel arm and 12 in the observation arm) and followed for post-treatment MRD assessment. MRD is assessed on Day 45, Month 3, and every 3 months during the first year of follow-up. The primary endpoint of EFS, along with key secondary endpoints of PFS and overall survival (OS), remains blinded. The study is enrolling across more than 60 sites, with additional sites coming online, and is expected to enroll approximately 220 patients. Study accrual is anticipated to be complete by the end of 2027. The study is powered to detect a 50% reduction in the risk of EFS events. EFS events include the initiation of new anti-lymphoma therapy, disease progression, or death. The Company anticipates an interim EFS analysis in mid-2027 and the primary EFS analysis in mid-2028. If positive, these results could support a Biologics License Application (BLA) submission.
Conference Call and Webcast Details
Allogene will host a live conference call and webcast today at 5:30 a.m. PT / 8:30 a.m. ET to discuss the interim futility analysis. 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. Please use this link to register for the listen-only webcast. The 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 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 cell therapy veterans applying proven CAR T experience, 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.
Allogene Media/Investor Contact
Christine Cassiano
EVP, Chief Corporate Affairs & Brand Strategy Officer
[email protected]
References
1 Tilly, H., et al. (2022). Polatuzumab vedotin in previously untreated diffuse large B-cell lymphoma. New England Journal of Medicine, 386(4), 351–363. https://doi.org/10.1056/NEJMoa2115304
2 Kite Pharma, Inc. (2023). Yescarta (axicabtagene ciloleucel) US prescribing information. Gilead Sciences, Inc.
3 Powles, T., et al. (2025). ctDNA-guided adjuvant atezolizumab in muscle-invasive bladder cancer. New England Journal of Medicine, 393, 2395–2408. https://doi.org/10.1056/NEJMoa2511885
4 Kurtz, et.al. Circulating Tumor DNA Measurements as Early Outcome Predictors in Diffuse Large B-Cell Lymphoma, JCO 2018
5 Alig, et.al., Short Diagnosis-to-Treatment Interval Is Associated with Higher Circulating Tumor DNA Levels in Diffuse Large B-Cell Lymphoma, JCO 2021
6 Roschewski M, Kurtz D M, Westin J R, et al: Remission Assessment by Circulating Tumor DNA in Large B-Cell Lymphoma. J Clin Oncol 10.1200/JCO-25-01534
7 Stepan, L., et al. (2024). Circulating tumor DNA (ctDNA) as an early outcome predictor in patients with second-line large B-cell lymphoma after lisocabtagene maraleucel versus standard of care treatment from the phase 3 TRANSFORM study. Blood, 144(Suppl. 1), Abstract 72. Presented at the American Society of Hematology Annual Meeting. https://doi.org/10.1182/blood-2024-199813
8 Majhail NS, Cox T, Larson S, et al. Outpatient administration of chimeric antigen receptor T-cell therapy using remote patient monitoring. JCO Oncology Practice. 2025;21(11):1601-1608. doi:10.1200/OP-25-00062