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

JRCT ID: jRCT2041240182

Registered date:04/02/2025

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: chronic lymphocytic leukaemia, Small lymphocytic leukaemia, mantle cell lymph,large B-cell lymphoma
• Date of first enrollment: 10/02/2025
• Target sample size: 13
• Countries of recruitment: Australia,Japan,China,Japan,Czech Republic,Japan,Denmark,Japan,France,Japan,Germany,Japan,South Korea,Japan,Spain,Japan,Taiwan,Japan,United Kingdom,Japan,United States of America,Japan
• Study type: Interventional

Intervention(s)

Substudy-1:
In Cohort 1A, Participants will receive AZD0486 monotherapy as subcutaneous (SC) injection.
In Cohort 1B, Participants will receive AZD0486 as SC injection. Participants will receive acalabrutinib tablet orally twice daily.

Substudy-2:
In Cohort 2A, Participants will receive AZD0486 monotherapy as SC injection.
In Cohort 2B, Participants will receive AZD0486 monotherapy as SC injection. Participants will receive acalabrutinib tablet orally twice daily.

Substudy-3:
Participants will receive AZD0486 as intravenous (IV) infusion in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy as per standard of care. For participants achieving CR or PR, AZD0486 will be administered every 3 weeks.

Outcome(s)

Primary Outcome

- Number of Participants with Adverse Events, Serious Adverse Events and Adverse Events of Special Interest
- Number of Participants with Dose Limiting Toxicity (DLTs)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable

Include 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.

Exclude 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

Related Information

• Primary Sponsor: Hibi Kazushige
• Secondary ID(s): NCT06564038