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

Inclusion Criteria:

• Biopsy proven B-NHL, including DLBCL, HGBL, or FL.

• Relapsed/refractory cohorts:

In order to be eligible subjects must have received at least 2 prior lines of therapy and not be candidates for treatment regimens known to provide clinical benefit in B-NHL. CAR T-naive subjects are allowed if they have declined, are considered ineligible for, or do not have timely access to CAR T cell therapies.

• 1L FL cohorts: Subject has biopsy-proven FL Grade 1-3a per WHO 2016 classification,Stage II-IV, FL International Prognostic Index 2-5 that has not been treated withprior systemic lymphoma-directed therapy and requires initiation of treatment basedon GELF criteria. Radiation to localized disease prior to study entry is allowed if >14 days from first dose.

• All Cohorts:

Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.

• Subject must have adequate liver, bone marrow and kidney function (eGFR ≥ 50mL/min).

• Subject must have locally confirmed CD19 positivity (must be documented after timeof 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 >/= 8.0g/dL. Transfusion and/or growth factor are allowed but counts must be stable for atleast 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 naturalhistory or treatment may interfere with the safety or efficacy assessment of theinvestigational regimen.

• Subject has active central nervous system (CNS) involvement by their B-NHL. --Subjects may be eligible with a distant history of CNS involvement that has beenadequately treated with no evidence of recurrence within last 6 months fromscreening.

• Subject has a history of leukemic presentation of their B-NHL (>5,000 circulatinglymphoma cells/uL in the peripheral blood).

• Subject has history or presence of clinically significant CNS pathology

• Subject has CNS involvement from active or history of autoimmune disease.

• Subject received CD19 CAR T therapy within 3 months prior to first dose.

• Subject experienced Grade ≥ 3 cytokine release syndrome (CRS) following prior T-cellengager (TCE) or CAR T-cell therapy.

• Subject experienced Grade ≥ 2 neurotoxicity/immune effector cell-associatedneurotoxicity syndrome (ICANS) following prior TCE or CAR T-cell therapy.

• Subject has received a peripheral autologous stem cell transplant (SCT) within 12weeks, or an allogeneic SCT within 1 year of the first dose of study drug treatmentor has received an SCT and requires ongoing immunosuppressive therapy.

• Subjects with human immunodeficiency virus (HIV) infection, or subjects with chronicor active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).HIV-infected patients on effective anti-retroviral therapy with undetectable viralload within 6 months are eligible for this trial. Subjects with chronic HBV may beenrolled if the HBV viral load is undetectable on suppressive therapy, or if thesubject has a documented cure. Subjects with HCV who have a documented cure may beenrolled.

• Subject has a history of major cardiac abnormalities.

• If female, subject must not be pregnant or breastfeeding.