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

Trial Title: A Study of AZD0486 Monotherapy or in Combination With Other Anti-Cancer Agents for Mature B-Cell Malignancies

NCT ID: NCT06564038

Condition: Chronic Lymphocytic Leukaemia
Small Lymphocytic Leukaemia
Mantle-cell Lymphoma
Large B-cell Lymphoma
B-cell Non-Hodgkin Lymphoma

Conditions: Official terms:
Lymphoma
Leukemia
Lymphoma, B-Cell
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Prednisone
Cyclophosphamide
Rituximab
Doxorubicin
Vincristine
Acalabrutinib

Conditions: Keywords:
IgG4 fully human CD19xCD3 bispecific T-cell engager
B cell lymphoma
Subcutaneous
AZD0486
Acalabrutinib
Prednisone
Rituximab
Cyclophosphamide
Vincristine
Doxorubicin

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Sequential Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: AZD0486
Description: AZD0486 will be administered as either SC injection (substudies 1 and 2) or IV infusion (substudy 3).
Arm group label: Substudy 1 (RR CLL/SLL): Cohort 1A (AZD0486 Monotherapy)
Arm group label: Substudy 1 (RR CLL/SLL): Cohort 1B (AZD0486 + Acalabrutinib)
Arm group label: Substudy 2 (RR MCL): Cohort 2A (AZD0486 Monotherapy)
Arm group label: Substudy 2 (RR MCL): Cohort 2B (AZD0486 + Acalabrutinib)
Arm group label: Substudy 3 (LBCL): AZD0486 + R-CHOP

Other name: TNB-486

Intervention type: Drug
Intervention name: Acalabrutinib
Description: Acalabrutinib tablet will be administered orally twice daily.
Arm group label: Substudy 1 (RR CLL/SLL): Cohort 1B (AZD0486 + Acalabrutinib)
Arm group label: Substudy 2 (RR MCL): Cohort 2B (AZD0486 + Acalabrutinib)

Intervention type: Drug
Intervention name: Prednisone
Description: Prednisone will be administered either oral or IV infusion as per standard of care.
Arm group label: Substudy 3 (LBCL): AZD0486 + R-CHOP

Intervention type: Drug
Intervention name: Rituximab
Description: Rituximab will be administered as IV infusion as per standard of care.
Arm group label: Substudy 3 (LBCL): AZD0486 + R-CHOP

Intervention type: Drug
Intervention name: Cyclophosphamide
Description: Cyclophosphamide will be administered as IV infusion as per standard of care.
Arm group label: Substudy 3 (LBCL): AZD0486 + R-CHOP

Intervention type: Drug
Intervention name: Vincristine
Description: Vincristine will be administered as IV infusion as per standard of care.
Arm group label: Substudy 3 (LBCL): AZD0486 + R-CHOP

Intervention type: Drug
Intervention name: Doxorubicin
Description: Doxorubicin will be administered as IV infusion as per standard of care.
Arm group label: Substudy 3 (LBCL): AZD0486 + R-CHOP

Summary: 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.

Detailed description: This is open-label, multi-center study to evaluate the safety and preliminary efficacy of AZD0486 administered as monotherapy and in combination with other anticancer agents in participants with mature B-cell hematologic malignancies. This master study currently includes 3 substudies and each substudy focusing on a defined population: Substudy 1: Relapsed/refractory (R/R) Chronic lymphocytic leukaemia (CLL)/ Small lymphocytic leukaemia (SLL) Substudy 2: R/R Mantle-cell lymphoma (MCL) Substudy 3: Large B-cell lymphoma (LBCL) or R/R B-cell non-Hodgkin lymphoma (B-NHL) (not applicable to US) The study will have the following sequential periods: 1. Screening period of 28 days 2. Treatment period 3. Follow-up period

Criteria for eligibility:
Criteria:
Inclusion Criteria: Master Inclusion Criteria applicable to all substudies: - Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. - Contraception during treatment and at least 6 months 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: at least 2 prior lines of therapy, including a Bruton tyrosine kinase inhibitor (BTKi) and B-cell lymphoma 2 inhibitor (BCL2i). - Cohort 1B: at least 1 prior line of therapy and is 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: Relapse or progressed after 2 or more lines of therapy including BTKi. - Cohort 2B: Relapse or progressed after 1 or more line of therapy, not including a 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 12 months after last dose of R-CHOP or 6 months after last dose of AZD0486. 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 or auto-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. 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 6 months, GI malabsorption, receiving vitamin K antagonist Substudy 2 Specific Exclusion Criteria: - Cohort 2B: bleeding diathesis, CYP3A inhibitor or inducer, history of ICH or stroke within 6 months, 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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Start date: September 13, 2024

Completion date: January 31, 2031

Lead sponsor:
Agency: AstraZeneca
Agency class: Industry

Source: AstraZeneca

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06564038