Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer, today announced the initiation of the potentially pivotal Phase 2 clinical trial of ALLO-501A (ALPHA2 trial) in patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL). The Company is also in the process of initiating the EXPAND trial, which is intended to demonstrate the contribution of ALLO-647 to the standard fludarabine/cyclophosphamide lymphodepletion regimen. Assuming favorable outcomes and subject to discussions with the U.S. Food and Drug Administration (FDA), the Company expects these studies to support the regulatory approval of both ALLO-501A and ALLO-647.
We are proud to initiate the industrys first potentially pivotal Phase 2 trial for an allogeneic CAR T product. This milestone paves the road for both ALLO-501A and our broader pipeline of innovative products with the potential to greatly increase patient access to cell therapy, said David Chang, M.D., Ph.D., President, Chief Executive Officer and Co-Founder of Allogene. It is a culmination of years of hard work and perseverance, which could only be accomplished in collaboration with our dedicated staff, investigators, clinical trial site coordinators, regulatory authorities and most importantly the patients who have paraticipated in our studies.
Allogene conducted an extensive Phase 1 program designed to evaluate and optimize all aspects of AlloCAR T, including doses and schedules of ALLO-501A and ALLO-647. In addition, the Company recently conducted a review of the Phase 1 program which determined a manufacturing process associated with robust clinical performance. Allogenes selected manufacturing process, named Alloy, will be deployed in the ALPHA2 and EXPAND trials.
Allogene received Chemistry Manufacturing and Controls (CMC) clearance to use newly manufactured product that did not utilize the Alloy process from its manufacturing facility, Cell Forge 1 (CF1). The Company is now in the process of implementing Alloy in this facility. As such, the Phase 2 trial will begin with previously manufactured material with the intent of transitioning to product from CF1 during the course of the ALPHA2 and EXPAND trials.
The single-arm Phase 2 ALPHA2 trial in r/r LBCL will utilize a single dose of ALLO-501A at 120 million CAR+ cells with an intended lymphodepletion regimen (FCA90) comprised of fludarabine (30 mg/m2/day x 3 days) and cyclophosphamide (300 mg/m2/day x 3 days) plus ALLO-647 (90 mg). The ALPHA2 trial will enroll approximately 100 patients who have received at least two prior lines of therapy and have not received prior anti-CD19 therapy. The primary endpoint is objective response rate (ORR).
The EXPAND trial is a separaate potentially registrational trial for ALLO-647. Allogene is developing ALLO-647, its anti-CD52 monoclonal antibody, with the goal of potentially enabling expansion, persistence and improved clinical outcomes of AlloCAR T product candidates, including ALLO-501A. The randomized EXPAND trial is expected to enroll approximately 70 patients with r/r LBCL and is intended to demonstrate the safety of ALLO-647 and its contribution to the overall effectiveness of the lymphodepletion regimen. Patients will be randomized to receive the same single 120 million cell dose of ALLO-501A as in the ALPHA2 trial and either lymphodepletion with fludarabine and cyclophosphamide alone (control arm) or the same lymphodepletion regimen of the ALPHA2 trial (active arm).
In June, the FDA granted Regenerative Medicine Advanced Therapy (RMAT) designation to ALLO-501A in r/r LBCL. RMAT designation was based on data demonstrating the potential of ALLO-501A to address an unmet need for patients with relapsed/refractory disease. Previously presented data support the potential of ALLO-501A as an alternative to approved autologous CAR T therapies. In the ALLO-501A Phase 1 study, nearly all enrolled patients were able to receive therapy with the median time from enrollment to initiation of treatment of two days.
Allogene expects to provide an update on its CD19 program toward the end of 2022. This will include longer-term follow-up from the ALPHA and ALPHA2 Phase 1 trials, including patients treated with the Alloy manufacturing technology process.
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. Led by a management team with significant experience in cell therapy, Allogene is developing a pipeline of off-the-shelf CAR T cell candidates with the goal of delivering readily available cell therapy on-demand, more reliably, and at greater scale to more patients.