Safety and Efficacy of ALLO-501A Anti-CD19 Allogeneic CAR T Cells in Adults With Relapsed/Refractory Large B Cell Lymphoma (ALPHA2) (ALPHA2)

Safety and Efficacy of ALLO-501A Anti-CD19 Allogeneic CAR T Cells in Adults With Relapsed/Refractory Large B Cell Lymphoma (ALPHA2)

A Single-Arm, Open-Label, Phase 1/2 Study Evaluating the Safety, Efficacy, and Cellular Kinetics/Pharmacodynamics of ALLO-501A, an Anti-CD19 Allogeneic CAR T Cell Therapy, and ALLO-647, an Anti-CD52 Monoclonal Antibody, in Subjects With Relapsed/Refractory Large B-Cell Lymphoma (LBCL)

The purpose of the ALPHA-2 study is to assess the safety, efficacy, and cell kinetics of ALLO-501A in adults with relapsed or refractory large B-cell lymphoma after a lymphodepletion regimen comprising fludarabine, cyclophosphamide, and ALLO-647

CAR T, Cell Therapy, Allogeneic Cell Therapy, Cellular Immuno-therapy, AlloCAR T, ALLO-501A, ALLO-647, LBCL, Lymphoma, Large B-Cell Lymphoma

Phase 1: Proportion of subjects experiencing Dose Limiting Toxicities (DLT) at increasing doses of ALLO-501A

Dose limiting toxicity is defined as protocol-defined ALLO-501A-related adverse events with onset within 28 days following infusion

Phase 1: Proportion of patients experiencing Dose Limiting Toxicity with ALLO-647 in combination with fludarabine/cyclophosphamide administered prior to ALLO-501A

DLT is defined as protocol-defined ALLO-647-related adverse events with onset within 33 days following 1st infusion

DOR is defined only for subjects who experience an objective response and is the time from the first objective response to disease progression or death, whichever comes first per (Cheson et al, 2014)

Phase 1 and 2: Best overall response (CR, PR, SD, PD) assessed per IRC (Phase 2 only) and per investigator

Phase 1 and 2: Serum concentration of ALLO-647 as measured by microgram per microliter for use in a population PK model

Phase 1 and 2: Adverse Events (AEs) as characterized by preferred term, frequency, severity timing, seriousness, and relationship to ALLO-501A

The incidence and severity of Cytokine Release Syndrome (CRS), Graft-Versus-Host Disease (GVHD), infections, cytopenias, and neurotoxicity

Phase 1 and 2: AEs as characterized by preferred term, frequency, severity, timing, seriousness, and relationship to ALLO-647

Inclusion Criteria: Histologically confirmed diagnosis of relapsed/refractory large B-cell lymphoma at last relapse per WHO 2017 At least 1 measurable lesion at time of enrollment Relapsed or refractory disease after at least 2 lines of chemotherapy ECOG performance status 0 or 1 Absence of donor (product)-specific anti-HLA antibodies (DSA) Adequate hematological, renal, and liver function Exclusion Criteria: Active central nervous system (CNS) involvement by malignancy Current thyroid disorder (including hyperthyroidism), except for subjects with hypothyroidism controlled on a stable dose of hormone replacement therapy Any other active malignancies that required systemic treatment within 3 years prior to enrollment Radiation therapy within 2 weeks prior to ALLO-647 Prior irradiation to >25% of the bone marrow Hypocellular bone marrow for age by institutional standard as determined from a bone marrow biopsy performed at time of screening Autologous hematopoietic stem cell transplant (HSCT) within last 6 months (24 weeks) Systemic anti-cancer therapy within 2 weeks prior to receiving ALLO-647 Subjects with active systemic bacterial, fungal, or viral infection requiring systemic treatment (including positive blood cultures within 7 days before starting lymphodepletion)