A Study of AZD0486 Monotherapy or in Combination with Other Anti-Cancer Agents for Mature B-Cell Malignancies - Soundtrack-E

Inclusion Criteria

• Inclusion Criteria:
• Master Inclusion Criteria applicable to all substudies:
• - Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• - Contraception use during treatment and at least 90 days after final dose.
• - Confirmed CD19 expression if prior anti-CD19 therapy.
• Substudy 1 Specific Inclusion Criteria:
• - Participants with CLL must require treatment according to the international workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria.
• - SLL: at least 1 measurable site per Lugano.
• - Absolute lymphocytes <10,000.
• - Cohort 1A and 1C: at least 2 prior lines of systemic therapy for CLL/SLL.
• - Cohort 1B: at least 1 prior line of therapy and is bruton tyrosine kinase inhibitor (BTKi)-sensitive.
• Substudy 2 Specific Inclusion Criteria:
• - MCL diagnosis per WHO.
• - Clinical Stage II, III, or IV by Ann Arbor Classification.
• - At least 1 measurable site per Lugano.
• - ALC < 10,000.
• - Cohort 2A and 2C: Relapse or progressed after 2 or more lines of therapy including BTKi.
• Substudy 3 Specific Inclusion Criteria:
• - Large B-cell lymphoma per WHO 2022.
• - R/R B-NHL after at least 1 prior line of therapy.
• - International Prognostic Index (IPI) 2-5.
• - At least 1 measurable site as per Lugano.
• - Left ventricular ejection fraction (LVEF) >50%.
• - Contraception at least 90 days after last dose of AZD0486 or 4 months after last dose of vincristine, and 6 months after the last dose of cyclophosphamide, or doxorubicin.
• Exclusion Criteria:
• Master Exclusion Criteria applicable to all substudies:
• - Central nervous system (CNS) lymphoma.
• - Surgery within 14 days of study drug.
• - Clinically significant cardiovascular (CV) disease.
• - Unresolved Grade >2 AEs from prior anticancer therapy (except alopecia or fatigue).
• - Any anticancer therapy within 5 half-lives or 21 days (whichever is shorter) prior to treatment.
• - Radiation therapy within 28 days.
• - Prior CAR T-cell therapy or autologous-haematopoietic stem cell transplant (HSCT) within 12 weeks or prior T-cell engager (TCE) within 8 weeks.
• - Prior Grade > 3 cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) event.
• - Prior allogeneic HSCT or solid organ transplantation within 24 weeks of starting Cycle 1 Day 1.
• Substudy 1 Specific Exclusion Criteria:
• - CLL transformation to more aggressive lymphoma.
• - Cohort 1B: bleeding diathesis, CYP3A inhibitor or inducer, history of ICH or stroke within 24 weeks, GI malabsorption, receiving vitamin K antagonist.
• Substudy 3 Specific Exclusion Criteria:
• - Mediastinal grey-zone lymphoma, Burkitt, Richter’s transformation, primary effusion large B-cell lymphoma (LBCL).
• - Cumulative dose of anthracycline >150 mg/m2.