A Study of AZD0486 in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

Inclusion Criteria:

Biopsy proven B-NHL, including DLBCL, HGBL, or FL.
For Arm B Only: Subject has biopsy proven DLBCL or HGBL
For Arm C only: Subject has biopsy proven FL
Subject has received at least 2 lines of therapy to which the subject has been either refractory or has subsequently relapsed. In order to be eligible for this study subjects must not be candidates for treatment regimens known to provide clinical benefit in B-NHL.
Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
Subject must have adequate liver, bone marrow and kidney function (eGFR ≥ 50 mL/min).
Subject must have locally confirmed CD19 positivity (must be documented after time of progression from last CD19-targeted therapy, if received)
Subject must have at least 1 measurable disease site
Subject must have ANC >/= 1000/mm3, platelets >/= 50,000 mm3, hemoglobin >/= 8.0 g/dL. Transfusion and/or growth factor are allowed but counts must be stable for at least 72 hours afterwards prior to screening
Subject must have a total bilirubin <1.5x ULN, AST/ALT < 3xULN

Exclusion Criteria:

Subject has been diagnosed with or treated for another malignancy whose natural history or treatment may interfere with the safety or efficacy assessment of the investigational regimen.
Subject has a history of central nervous system (CNS) involvement by their B-NHL
Subject has a history of leukemic presentation of their B-NHL.
Subject has history or presence of clinically significant CNS pathology
Subject has CNS involvement from active or history of autoimmune disease.
Subject experienced Grade ≥ 3 cytokine release syndrome (CRS) following prior T-cell engager (TCE) or CAR T-cell therapy.
Subject experienced Grade ≥ 2 neurotoxicity/immune effector cell-associated neurotoxicity syndrome (ICANS) following prior TCE or CAR T-cell therapy.
Subject has received a peripheral autologous stem cell transplant (SCT) within 12 weeks, or an allogeneic SCT within 1 year of the first dose of study drug treatment or has received an SCT and requires ongoing immunosuppressive therapy.
Subjects with human immunodeficiency virus (HIV) infection, or subjects with chronic or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Subjects with chronic HBV may be enrolled if the HBV viral load is undetectable on suppressive therapy, or if the subject has a documented cure. Subjects with HCV who have a documented cure may be enrolled.
Subject has a history of major cardiac abnormalities.
If female, subject must not be pregnant or breastfeeding.