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

Study identifier:D7407C00001

ClinicalTrials.gov identifier:NCT06564038

EudraCT identifier:N/A

CTIS identifier:2024-515034-33-00

Recruiting

Official Title

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

Medical condition

Chronic lymphocytic leukaemia

Phase

Phase 1/2

Healthy volunteers

Study drug

AZD0486, Acalabrutinib, Prednisone, Rituximab, Cyclophosphamide, Vincristine, Doxorubicin

Sex

All

Estimated Enrollment

180

Study type

Interventional

Age

18 Years - n/a

Date

Study Start Date: 30 Jan 2025

Estimated Primary Completion Date: 25 Apr 2031

Estimated Study Completion Date: 25 Apr 2031

Study design

Allocation: Non-randomized
Endpoint Classification: -
Intervention Model: Sequential Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Feb 2025 by AstraZeneca

Collaborators

Inclusion and exclusion 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

Sort by status

No locations available

Arms	Assigned Interventions
Experimental: Substudy 1 (RR CLL/SLL): Cohort 1A (AZD0486 Monotherapy) Participants will receive AZD0486 monotherapy as subcutaneous (SC) injection.	Drug: AZD0486 AZD0486 will be administered as either SC injection (substudies 1 and 2) or IV infusion (substudy 3). Other Name: TNB-486
Experimental: Substudy 1 (RR CLL/SLL): Cohort 1B (AZD0486 + Acalabrutinib) Participants will receive AZD0486 as SC injection. Participants will receive acalabrutinib tablet orally twice daily.	Drug: AZD0486 AZD0486 will be administered as either SC injection (substudies 1 and 2) or IV infusion (substudy 3). Other Name: TNB-486 Drug: Acalabrutinib Acalabrutinib tablet will be administered orally twice daily.
Experimental: Substudy 2 (RR MCL): Cohort 2A (AZD0486 Monotherapy) Participants will receive AZD0486 monotherapy as SC injection.	Drug: AZD0486 AZD0486 will be administered as either SC injection (substudies 1 and 2) or IV infusion (substudy 3). Other Name: TNB-486
Experimental: Substudy 2 (RR MCL): Cohort 2B (AZD0486 + Acalabrutinib) Participants will receive AZD0486 monotherapy as SC injection. Participants will receive acalabrutinib tablet orally twice daily.	Drug: AZD0486 AZD0486 will be administered as either SC injection (substudies 1 and 2) or IV infusion (substudy 3). Other Name: TNB-486 Drug: Acalabrutinib Acalabrutinib tablet will be administered orally twice daily.
Experimental: Substudy 3 (LBCL): AZD0486 + R-CHOP 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.	Drug: AZD0486 AZD0486 will be administered as either SC injection (substudies 1 and 2) or IV infusion (substudy 3). Other Name: TNB-486 Drug: Prednisone Prednisone will be administered either oral or IV infusion as per standard of care. Drug: Rituximab Rituximab will be administered as IV infusion as per standard of care. Drug: Cyclophosphamide Cyclophosphamide will be administered as IV infusion as per standard of care. Drug: Vincristine Vincristine will be administered as IV infusion as per standard of care. Drug: Doxorubicin Doxorubicin will be administered as IV infusion as per standard of care.

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]