UPCC 53424 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 (Soundtrack-E)

Study on Safety and Efficacy of Investigational Medication in Blood Cancers Affecting B-Cells

Enrolling By Invitation
18 years or above
All
Phase 1/2
408 participants needed
1 Location

Brief description of study

The purpose of this study is to assess the safety and efficacy of surovatamig (formerly AZD0486) administered as monotherapy or in combination with other anticancer agents in participants with hematological malignancies

Detailed description of study

This is open-label, multi-center study to evaluate the safety and preliminary efficacy of surovatamig 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 lymphoma (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

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Chronic Lymphocytic Leukaemia, Small Lymphocytic Lymphoma, Mantle-cell Lymphoma, Large B-cell Lymphoma, B-cell Non-Hodgkin Lymphoma
  • Age: 18 years or above
  • Gender: All

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.

This study investigates the safety and efficacy of an investigational medication, surovatamig, administered alone or with other anticancer agents in individuals with mature B-cell malignancies. This study is open-label, meaning both researchers and participants know what treatment is being administered. It includes three substudies, each focusing on different types of B-cell malignancies, such as Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), Mantle-Cell Lymphoma (MCL), and Large B-Cell Lymphoma (LBCL).

Participants will undergo several procedures during the study, including a screening period lasting 28 days to assess eligibility, a treatment period where the investigational medication is administered, and a follow-up period to monitor health outcomes. The study aims to gather data on how the investigational medication works alone and in combination with other treatments, focusing on its safety and potential benefits for patients with these types of blood cancers.

  • Who can participate: Participants must have a performance status of 0 to 2 and use contraception during treatment and for 90 days after the final dose.
  • Study details: Participants will receive the investigational medication as monotherapy or with other anticancer agents, focusing on assessing the safety and efficacy of these treatments in people with mature B-cell malignancies.
Updated on 20 Jul 2026. Study ID: 24-2232
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