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Evaluating AZD0486 for treating mature B-cell cancers

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

Phase1; Phase2 Interventional AstraZeneca · NCT06564038

This study is testing a new treatment called AZD0486 to see if it can help people with certain types of mature B-cell cancers feel better and improve their health.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment408 (estimated)
Ages18 Years and up
SexAll
SponsorAstraZeneca Industry-sponsored
Drugs / interventionsCAR T, Radiation, cyclophosphamide, doxorubicin
Locations64 sites (Boston, Massachusetts and 63 other locations)
Trial IDNCT06564038 on ClinicalTrials.gov

What this trial studies

This clinical trial assesses the safety and efficacy of AZD0486, both as a standalone treatment and in combination with other anti-cancer agents, for patients with mature B-cell hematologic malignancies. The study is open-label and multi-center, focusing on three specific subpopulations: relapsed/refractory chronic lymphocytic leukaemia, mantle-cell lymphoma, and large B-cell lymphoma or B-cell non-Hodgkin lymphoma. Participants will undergo a screening period followed by treatment and a follow-up period to monitor outcomes.

Who should consider this trial

Good fit: Ideal candidates include individuals with relapsed or refractory mature B-cell malignancies who have received prior therapies.

Not a fit: Patients with early-stage B-cell malignancies or those who have not received prior treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat B-cell malignancies.

How similar studies have performed: Other studies utilizing bispecific T-cell engagers have shown promise, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

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 lymphocyte count (ALC) \<25000 cells/mcL.
* 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 \< 25000 cells/mcL.
* Cohort 2A and 2C: Relapse or progressed after 2 or more lines of therapy including BTKi.

Substudy 3 Specific Inclusion Criteria:

* At least 1 measurable site as per Lugano.
* Left ventricular ejection fraction (LVEF) ≥50%.
* Participant must be no older than 79 years of age at the time of signing ICF.
* Contraception at least 90 days after last dose of surovatamig or 4 months after last dose of vincristine, and 6 months after the last dose of cyclophosphamide, or doxorubicin.
* Cohort 3A:

  1. Histologically confirmed diagnosis of previously untreated large B-cell Lymphoma (LBCL) per WHO 2022.
  2. R/R B-NHL after at least 1 prior lines of systemic therapy.
  3. International Prognostic Index (IPI) 2-5.
* Cohort 3B:

  1. Histologically confirmed diagnosis of previously untreated large B-cell Lymphoma (LBCL) per WHO 2022.
  2. IPI score of 2 to 5.

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 systemic therapy within 5 half-lives or 21 days (whichever is shorter) prior to treatment.
* Radiation therapy within 28 days.
* Prior CAR T-cell therapy or autologous-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.
* Prior allogeneic HSCT or solid organ transplantation within 24 weeks of starting Cycle 1 Day 1.
* Active, significant, uncontrolled infection or autoimmune disease requiring systemic therapy including participants with known history of haemophagocytic lymphohistiocytosis (HLH).

Substudy 1 Specific Exclusion Criteria:

* CLL/SLL transformation to more aggressive form of lymphoma.
* Cohort 1B: bleeding diathesis, CYP3A inhibitor or inducer, history of ICH or stroke within 24 weeks, 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.

Where this trial is running

Boston, Massachusetts and 63 other locations

+14 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Chronic Lymphocytic LeukaemiaSmall Lymphocytic LymphomaMantle-cell LymphomaLarge B-cell LymphomaB-cell Non-Hodgkin LymphomaIgG4 fully human CD19xCD3 bispecific T-cell engagerB cell lymphomaSubcutaneous
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.