A Phase I/II Open-Label Multi-Centre Master Protocol to Evaluate the Safety and Efficacy of AZD0486 Monotherapy or in Combination With Other Anticancer Agents in Participants With Mature B-Cell Malignancies
The purpose of this study is to assess the safety and efficacy of AZD0486 administered as monotherapy or in combination with other anticancer agents in participants with hematological malignancies.
⁃ 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.