Inclusion Criteria:

• Aged 18 to 80 years old

• Histologically confirmed relapsed refractory FL (Module 1) and DLBCL (Module 2) after at least 2 prior lines of therapy

• ECOG performance status 0 to 2

• Locally confirmed CD-19 expression in lymphoma cells after progression from last CD 19 directed therapy

• FDG-avid disease with at least one bi-dimensionally measurable nodal lesion (defined as > 1.5 cm in its longest dimension), or extranodal lesion (defined as > 1.0 cm in its longest dimension)

• Adequate hematological function: ANC ≥ 1000/mm3, platelets

  • 75,000/mm3, hemoglobin ≥ 9 g/dL. Transfusion and/or growth factor are allowed but counts must be stable for at least 72 hours afterwards prior to screening

• Adequate liver function: total bilirubin <1.5x ULN, AST/ALT ≤ 3xULN Note: Patients with documented history of Gilbert's Syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible)

• Adequate renal function: creatinine clearance (CrCl) of ≥ 45 mL/min

Exclusion Criteria:

• Diagnosis of CLL, Burkitt lymphoma, or Richter's transformation

• Active CNS involvement by B-NHL

• Leukemic presentation of B-NHL

• History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis

• Prior therapy with T-cell engager (TCE) within 8 weeks, CAR T- cell therapy or autologous Hematopoietic Stem Cell Transplantation (HSCT) within 12 weeks, or prior allogeneic HSCT within 24 weeks of first dose of AZD0486

• Requires chronic immunosuppressive therapy

• Unresolved non hematological AEs ≥ Grade 2 from prior therapies; history of ≥ Grade 3 CRS or neurotoxicity from prior CAR-T or TCE therapy

• History of major cardiac abnormalities.

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

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

 Eligibility last updated 05/27/2025. Questions regarding updates should be directed to the study team contact.