Allogene presents comprehensive safety data of Phase 1 ALPHA/ALPHA2 trials

Allogene Therapeutics announced the presentation of data from a comprehensive safety review of patients treated in the Phase 1 ALPHA/ALPHA2 trials with ALLO-501/501A at the 65th Annual Meeting of the American Society of Hematology in San Diego, CA. The safety review, which encompasses all 87 Phase 1 patients treated in both relapsed/refractory Large B Cell Lymphoma and follicular lymphoma, demonstrates that investigational ALLO-647 added to standard lymphodepletion can safely provide a window for the expansion and persistence of AlloCAR T cells, and has the potential to induce deep and durable remissions in relapsed and treatment-refractory cancers. The inclusion of ALLO-647 candidate in the lymphodepletion regimen is designed to selectively prevent host rejection of allogeneic CAR T cell products. As previously presented in the Phase 1 ALPHA/ALPHA2 studies, CAR T cell-naive patients with r/r LBCL were able to obtain a durable response, including a complete remission rate of 42% and a median duration of response of 23.1 months. In the studies, lymphodepletion consisted of three daily doses of fludarabine 30 mg/m2 and cyclophosphamide 300-500 mg/m2 and 39, 60, or 90 mg of ALLO-647 in divided doses prior to ALLO-501/501A infusion. The addition of ALLO-647 to standard lymphodepletion did not result in adverse events beyond those commonly observed with autologous CAR T cell therapy. No unexpected safety concerns were observed. There were no reports of graft-versus-host disease or Grade 3 or higher immune effector cell-associated neurotoxicity syndrome. In total, 24% of patients experienced low-grade CRS, and there was 1 Grade 3 CRS event. Infection events were primarily low grade and manageable. Incidence of infections were consistent with that reported for autologous therapy following lymphodepletion. Eight patients experienced fatal adverse events not related to study treatment. The EXPAND trial, currently enrolling in the United States and Europe, is expected to support licensure of ALLO-647, used in conjunction with standard low-dose FC lymphodepletion regimens. The trial will enroll approximately 70 patients with r/r LBCL who will be randomized to lymphodepletion with FCA90 versus FC alone before receiving a single 120 million cell dose of ALLO-501A. The primary endpoint of the study is progression free survival. Separately, the company announced that the U.S. Food and Drug Administration granted Fast Track Designation for the investigation of ALLO-647 in adult patients with r/r LBCL based on its potential to enhance standard lymphodepletion.