Allogene Therapeutics Announces Publication of Durable Response Data from Phase 1 ALPHA/ALPHA2 Trials of the Allogeneic CAR T Cemacabtagene Ansegedleucel/ALLO-501 in Relapsed/Refractory Large B-Cell Lymphoma in the Journal of Clinical Oncology
- Efficacy Comparable to Approved Autologous CD19 CAR Ts: Achieved Overall Response (ORR) and Complete Response (CR) Rates of 58% and 42% Across the Study and 67% and 58% with Pivotal Study Regimen, Respectively
- Durability of Response: Among Patients Who Achieved CR, Median Duration of Response (DOR) of 23.1 Months and Median Overall Survival (OS) Not Reached
- Manageable Safety Profile Consistent with Approved Autologous CD19 CAR T: No Graft-versus-Host Disease (GvHD), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), or High-Grade Cytokine Release Syndrome (CRS)
- On-Demand Treatment: Median Time to Treatment Two Days from Enrollment
- Foundation for Cema-Cel in ALPHA3 Trial in First Line (1L) Consolidation: Achieved 100% CR in Patients with Low Disease Burden
SOUTH SAN FRANCISCO, Calif., Feb. 13, 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 the publication of data from its Phase 1 ALPHA and ALPHA2 clinical studies of cemacabtagene ansegedleucel (cema-cel; formerly ALLO-501/A) in relapsed/refractory (R/R) large B-cell lymphoma (LBCL) as a Rapid Communication in the Journal of Clinical Oncology. These results represent the largest dataset of LBCL patients treated with an allogeneic CAR T product and, with a minimum of two years of follow-up, the longest follow-up to date.
“Publication of the Phase 1 ALPHA/ALPHA2 trials in R/R LBCL mark a landmark moment for the field. These findings represent the most robust allogeneic CAR T experience yet presented and show, for the first time, that an “off-the-shelf” CAR T can induce durable complete remissions in a large fraction of patients with heavily pretreated LBCL,” said Frederick L. Locke, MD, Chair of the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center and Research Institute (Tampa, FL). “These peer-reviewed results highlight how cema-cel development is on the cutting edge of lymphoma care, particularly with the ALPHA3 trial targeting only those patients who are MRD positive at the end of first-line treatment. If successful, ALPHA3 and cema-cel could transform the treatment paradigm for newly diagnosed patients.”
"With multiple patients in ongoing complete remissions beyond four years, the lingering question of whether an allogeneic CAR T could deliver durable responses has now been answered," said Zachary Roberts, M.D., Ph.D., Executive Vice President, Research and Development and Chief Medical Officer of Allogene. "Furthermore, these results provide potent evidence supporting the use of CAR T in patients with low disease burden and the unique opportunity for the ALPHA3 trial to achieve something novel in this disease – predict and intervene before relapse. Opportunities to redefine the standard of care in oncology are rare, but if successful, ALPHA3 has the potential to achieve precisely that."
Key Findings from the PublicationThe ALPHA/ALPHA2 studies were single-arm, multicenter, open-label, Phase 1 trials. As of the data cutoff date (September 26, 2024), 87 heavily pretreated patients with R/R non-Hodgkin lymphoma (NHL) were treated in the ALPHA/ALPHA2 studies between May 2019 and September 2022. In total, 33 CD19 CAR T-naive patients with R/R LBCL received cema-cel/ALLO-501 manufactured with the process selected for use in pivotal studies and were the focus of this publication.
- Overall Response Rate (ORR) and Complete Response (CR) Rate: ORR and CR rates in the ALPHA/ALPHA2 trials were consistent with those observed with approved autologous CD19 CAR T cell products for patients with R/R LBCL after two or more lines of systemic therapy. All treatment regimens studied demonstrated clinical benefit. The selected Phase 2 regimen (fludarabine/cyclophosphamide lymphodepletion with 90 mg of ALLO-647 (FCA90) followed by a single dose of CAR+ cells) yielded the highest ORR and CR of 67% and 58%, respectively.
- Durability of Response (DOR): Patients who achieved a CR had excellent outcomes with a median DOR, PFS (progression free survival) and OS of 23.1 months, 24 months, and not reached, respectively. For patients receiving the selected Phase 2 regimen, median DOR was 23.1 months and median OS was not reached.
- Safety Profile: The overall safety profile, including incidence of cytopenias and infections, was manageable and consistent with that of approved autologous CD19 CAR T cell therapies. There were no dose-limiting toxicities, graft-versus-host disease (GvHD), immune effector cell-associated neurotoxicity syndrome (ICANS), or high-grade cytokine release syndrome (CRS). The most common any-grade treatment emergent adverse events (TEAE) (≥25%) were neutropenia (85%), anemia (67%), thrombocytopenia (58%), infusion-related reactions (IRRs; 58%), fatigue (52%), and pyrexia (49%), nausea (39%), lymphopenia (36%), hypotension (36%), peripheral edema (33%), decreased white blood cell count (30%), CMV reactivation (30%), decreased appetite (30%), chills (30%), and hypoxia (27%).
- Time to Treatment: The median time to start of treatment was two days from study enrollment. In contrast, autologous CAR T cell products require wait times often longer than 1 month despite incremental advancements in manufacturing and supply chains.
Potential in Low Disease Burden SettingsA growing body of evidence indicates that treatment with CAR T at times when the disease burden is low leads to improved safety and efficacy outcomes and this study reported similar findings. Among patients with baseline tumor burden
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