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

Phase 1

Not yet recruiting

• Conditions: Chronic Lymphocytic Leukaemia; Small Lymphocytic Leukaemia; Mantle-cell Lymphoma; Large B-cell Lymphoma; B-cell Non-Hodgkin Lymphoma

• Registration Number: NCT06564038
• Lead Sponsor: AstraZeneca

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-8-19
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: Not yet recruiting
• Sex: All
• Target Recruitment: 180

Inclusion Criteria

Inclusion Criteria:<br><br>Master Inclusion Criteria applicable to all substudies:<br><br> - Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.<br><br> - Contraception during treatment and at least 6 months after final dose.<br><br> - Confirmed CD19 expression if prior anti-CD19 therapy.<br><br>Substudy 1 Specific Inclusion Criteria:<br><br> - Participants with CLL must require treatment according to the international workshop<br> on Chronic Lymphocytic Leukemia (iwCLL) criteria.<br><br> - SLL: at least 1 measurable site per Lugano.<br><br> - Absolute lymphocytes <10,000.<br><br> - Cohort 1A: at least 2 prior lines of therapy, including a Bruton tyrosine kinase<br> inhibitor (BTKi) and B-cell lymphoma 2 inhibitor (BCL2i).<br><br> - Cohort 1B: at least 1 prior line of therapy and is BTKi-sensitive.<br><br>Substudy 2 Specific Inclusion Criteria:<br><br> - MCL diagnosis per WHO.<br><br> - Clinical Stage II, III, or IV by Ann Arbor Classification.<br><br> - At least 1 measurable site per Lugano<br><br> - ALC < 10,000.<br><br> - Cohort 2A: Relapse or progressed after 2 or more lines of therapy including BTKi.<br><br> - Cohort 2B: Relapse or progressed after 1 or more line of therapy, not including a<br> BTKi.<br><br>Substudy 3 Specific Inclusion Criteria:<br><br> - Large B-cell lymphoma per WHO 2022.<br><br> - R/R B-NHL after at least 1 prior line of therapy.<br><br> - International Prognostic Index (IPI) 2-5.<br><br> - At least 1 measurable site as per Lugano.<br><br> - Left ventricular ejection fraction (LVEF) >50%.<br><br> - Contraception at least 12 months after last dose of R-CHOP or 6 months after last<br> dose of AZD0486.<br><br>Exclusion Criteria:<br><br>Master Exclusion Criteria applicable to all substudies:<br><br> - central nervous system (CNS) lymphoma.<br><br> - Surgery within 14 days of study drug.<br><br> - Clinically significant cardiovascular (CV) disease.<br><br> - Unresolved Grade >2 AEs from prior anticancer therapy (except alopecia or fatigue).<br><br> - Any anticancer therapy within 5 half-lives or 21 days (whichever is shorter) prior<br> to treatment.<br><br> - Radiation therapy within 28 days.<br><br> - Prior CAR-T or auto-haematopoietic stem cell transplant (HSCT) within 12 weeks or<br> prior T-cell engager (TCE) within 8 weeks.<br><br> - Prior Grade > 3 cytokine release syndrome (CRS) or immune effector cell-associated<br> neurotoxicity syndrome (ICANS) event.<br><br>Substudy 1 Specific Exclusion Criteria:<br><br> - CLL transformation to more aggressive lymphoma<br><br> - Cohort 1B: bleeding diathesis, CYP3A inhibitor or inducer, history of ICH or stroke<br> within 6 months, GI malabsorption, receiving vitamin K antagonist<br><br>Substudy 2 Specific Exclusion Criteria:<br><br> - Cohort 2B: bleeding diathesis, CYP3A inhibitor or inducer, history of ICH or stroke<br> within 6 months, GI malabsorption, receiving vitamin K antagonist<br><br>Substudy 3 Specific Exclusion Criteria:<br><br> - Mediastinal grey-zone lymphoma, Burkitt, Richter's transformation, primary effusion<br> large B-cell lymphoma (LBCL)<br><br> - Cumulative dose of anthracycline >150 mg/m2

Exclusion Criteria

Not provided

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Number of Participants with Adverse Events, Serious Adverse Events and Adverse Events of Special Interest;Number of Participants with Dose Limiting Toxicity (DLTs)

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR);Complete Response (CR) Rate;Duration of Response (DoR);Maximum Observed Concentration (Cmax);Area Under the Concentration-time Curve (AUC);Minimum Observed Concentration (Cmin);Time to Reach Maximum Concentration (Tmax);Trough Plasma Concentration (Ctrough);Half Life (t1/2) of AZD0486;Clearance (CL) of AZD0486;Number of Participants with Anti-drug Antibody (ADA) for AZD0486