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

May 12, 2026 updated by: AstraZeneca

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

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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

Study Type

Interventional

Enrollment (Estimated)

408

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
      • Heidelberg, Australia, 3084
        • Recruiting
        • Research Site
      • Melbourne, Australia, 3004
        • Recruiting
        • Research Site
      • Nedlands, Australia, 6009
        • Recruiting
        • Research Site
  • China
      • Beijing, China, 100044
        • Recruiting
        • Research Site
      • Guangzhou, China, 510060
        • Recruiting
        • Research Site
      • Jinan, China, 250013
        • Withdrawn
        • Research Site
      • Tianjin, China, 300060
        • Recruiting
        • Research Site
      • Zhengzhou, China, 450008
        • Recruiting
        • Research Site
  • Czechia
      • Ostrava - Poruba, Czechia, 708 52
        • Recruiting
        • Research Site
      • Prague, Czechia, 12808
        • Recruiting
        • Research Site
      • Praha 2 - Nové Město, Czechia, 12820
        • Recruiting
        • Research Site
  • Denmark
      • Aalborg, Denmark, 9000
        • Recruiting
        • Research Site
      • Aarhus N, Denmark, 8200
        • Recruiting
        • Research Site
      • Copenhagen, Denmark, 2100
        • Recruiting
        • Research Site
      • Odense C, Denmark, 5000
        • Recruiting
        • Research Site
  • France
      • Clermont-Ferrand, France, 63000
        • Not yet recruiting
        • Research Site
      • Montpellier, France, 34295
        • Recruiting
        • Research Site
      • Paris, France, 75010
        • Recruiting
        • Research Site
      • Saint-Cloud, France, 92210
        • Recruiting
        • Research Site
      • Villejuif, France, 94805
        • Recruiting
        • Research Site
  • Germany
      • Cologne, Germany, 50937
        • Not yet recruiting
        • Research Site
      • Homburg, Germany, 66421
        • Not yet recruiting
        • Research Site
      • Kiel, Germany, 24105
        • Recruiting
        • Research Site
      • Mainz, Germany, 55131
        • Not yet recruiting
        • Research Site
      • München, Germany, 81377
        • Recruiting
        • Research Site
      • Würzburg, Germany, 97080
        • Recruiting
        • Research Site
  • Italy
      • Bologna, Italy, 40138
        • Not yet recruiting
        • Research Site
      • Milan, Italy, 20141
        • Not yet recruiting
        • Research Site
  • Japan
      • Kōtoku, Japan, 135-8550
        • Recruiting
        • Research Site
      • Matsuyama, Japan, 791-0280
        • Recruiting
        • Research Site
      • Nagoya, Japan, 464-8681
        • Recruiting
        • Research Site
  • South Korea
      • Busan, South Korea, 48108
        • Recruiting
        • Research Site
      • Seoul, South Korea, 03080
        • Recruiting
        • Research Site
      • Seoul, South Korea, 06351
        • Recruiting
        • Research Site
      • Seoul, South Korea, 05505
        • Recruiting
        • Research Site
      • Seoul, South Korea, 06591
        • Recruiting
        • Research Site
      • Seoul, South Korea, 02841
        • Recruiting
        • Research Site
  • Spain
      • Barcelona, Spain, 8036
        • Recruiting
        • Research Site
      • Madrid, Spain, 28034
        • Recruiting
        • Research Site
      • Madrid, Spain, 28040
        • Recruiting
        • Research Site
      • Palma de Mallorca, Spain, 7120
        • Recruiting
        • Research Site
      • Santiago de Compostela, Spain, 15706
        • Recruiting
        • Research Site
      • Valencia, Spain, 46026
        • Recruiting
        • Research Site
  • Taiwan
      • Changhua, Taiwan, 500
        • Recruiting
        • Research Site
      • Kaohsiung City, Taiwan, 83301
        • Recruiting
        • Research Site
      • Tainan, Taiwan, 710
        • Recruiting
        • Research Site
      • Taipei, Taiwan, 100
        • Recruiting
        • Research Site
  • United Kingdom
      • Derriford, United Kingdom, PL6 5FP
        • Recruiting
        • Research Site
      • London, United Kingdom, SE5 9RS
        • Recruiting
        • Research Site
      • Oxford, United Kingdom, 0X3 7LJ
        • Recruiting
        • Research Site
      • Southampton, United Kingdom, SO16 6YD
        • Recruiting
        • Research Site
  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Research Site
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Not yet recruiting
        • Research Site
      • New Brunswick, New Jersey, United States, 08901
        • Recruiting
        • Research Site
    • New York
      • New York, New York, United States, 10065
        • Withdrawn
        • Research Site
      • New York, New York, United States, 10029
        • Recruiting
        • Research Site
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Recruiting
        • Research Site
      • Charlotte, North Carolina, United States, 28204
        • Not yet recruiting
        • Research Site
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Research Site
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Research Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Research Site
      • Pittsburgh, Pennsylvania, United States, 15232
        • Recruiting
        • Research Site
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Recruiting
        • Research Site
    • Texas
      • Houston, Texas, United States, 77030
        • Not yet recruiting
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Substudy 1 (RR CLL/SLL): Cohort 1A (Surovatamig Monotherapy)
Participants will receive surovatamig monotherapy as subcutaneous (SC) injection.
Drug: Surovatamig
Surovatamig will be administered as either SC injection or IV infusion.
Other Names:
  • TNB-486
  • AZD0486
Experimental: Substudy 1 (RR CLL/SLL): Cohort 1B (Surovatamig + Acalabrutinib)
Participants will receive surovatamig as SC injection. Participants will receive acalabrutinib tablet orally twice daily.
Drug: Acalabrutinib
Acalabrutinib will be administered orally
Drug: Surovatamig
Surovatamig will be administered as either SC injection or IV infusion.
Other Names:
  • TNB-486
  • AZD0486
Experimental: Substudy 1 (RR CLL/SLL): Cohort 1C (Surovatamig Monotherapy)
Participants will receive surovatamig monotherapy as intravenous (IV) infusion.
Drug: Surovatamig
Surovatamig will be administered as either SC injection or IV infusion.
Other Names:
  • TNB-486
  • AZD0486
Experimental: Substudy 2 (RR MCL): Cohort 2A (Surovatamig Monotherapy)
Participants will receive surovatamig monotherapy as SC injection.
Drug: Surovatamig
Surovatamig will be administered as either SC injection or IV infusion.
Other Names:
  • TNB-486
  • AZD0486
Experimental: Substudy 2 (RR MCL): Cohort 2C (Surovatamig Monotherapy)
Participants will receive surovatamig monotherapy as IV infusion.
Drug: Surovatamig
Surovatamig will be administered as either SC injection or IV infusion.
Other Names:
  • TNB-486
  • AZD0486
Experimental: Substudy 3 (LBCL): Cohort 3A 2SUD (Surovatamig + RCHOP)
Participants will receive surovatamig as IV infusion with a 2SUD (double step-up dosing) schedule for priming in combination with RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy.
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.
Drug: Prednisone (or equivalent)
Prednisone (or equivalent) will be administered either oral or IV infusion as per standard of care.
Drug: Surovatamig
Surovatamig will be administered as either SC injection or IV infusion.
Other Names:
  • TNB-486
  • AZD0486
Experimental: Substudy 3 (LBCL): Cohort 3B 3SUD (Surovatamig + RCHOP)
Participants will receive surovatamig as IV infusion with a 3SUD (triple step-up dosing) schedule for priming in combination with RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy.
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.
Drug: Prednisone (or equivalent)
Prednisone (or equivalent) will be administered either oral or IV infusion as per standard of care.
Drug: Surovatamig
Surovatamig will be administered as either SC injection or IV infusion.
Other Names:
  • TNB-486
  • AZD0486

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants with Adverse Events, Serious Adverse Events and Adverse Events of Special Interest
Time Frame: Up to 6 years 4 months
Safety and tolerability of surovatamig as monotherapy and in combination with other anticancer agents across mature B-cell malignancies.
Up to 6 years 4 months
Number of Participants with Dose Limiting Toxicity (DLTs)
Time Frame: Up to 2 months
Safety and tolerability of surovatamig as monotherapy and in combination with other anticancer agents across mature B-cell malignancies.
Up to 2 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete Response (CR) Rate
Time Frame: Up to 6 years 4 months
CR rate is defined as percentage of participants achieving CR as best response based on response criteria for iwCLL 2018 and Lugano 2014 assessed by investigator (substudy 1) and percentage of participants achieving CR as best response based on Lugano 2014 Response Criteria by investigator assessment (substudies 2 and 3).
Up to 6 years 4 months
Duration of Response (DoR)
Time Frame: Up to 6 years 4 months
DoR is defined as time from the date of first documented response until date of documented progression based on response criteria for iwCLL 2018 and Lugano 2014 assessed by investigator, relapse or death (substudy 1) and time from the date of first documented response until date of documented progression based on Lugano 2014 Response Criteria by investigator assessment, relapse or death (substudies 2 and 3).
Up to 6 years 4 months
Overall Response Rate (ORR)
Time Frame: Up to 6 years 4 months
ORR is defined as percentage of participants achieving either a partial response (PR) or complete response (CR) based on response criteria for International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 and Lugano 2014 assessed by investigator (substudy 1) and percentage of participants achieving either PR or CR based on Lugano 2014 Response Criteria by investigator assessment (substudies 2 and 3).
Up to 6 years 4 months
Maximum Observed Concentration (Cmax)
Time Frame: Up to 90 days after last dose
The PK (Cmax) of surovatamig as monotherapy and in combination with other anti-cancer agents will be evaluated.
Up to 90 days after last dose
Area Under the Concentration-time Curve (AUC)
Time Frame: Up to 90 days after last dose
The PK (AUC) of surovatamig as monotherapy and in combination with other anti-cancer agents will be evaluated.
Up to 90 days after last dose
Minimum Observed Concentration (Cmin)
Time Frame: Up to 90 days after last dose
The PK (Cmin) of surovatamig as monotherapy and in combination with other anti-cancer agents will be evaluated.
Up to 90 days after last dose
Time to Reach Maximum Concentration (tmax)
Time Frame: Up to 90 days after last dose
The PK (tmax) of surovatamig as monotherapy and in combination with other anti-cancer agents will be evaluated.
Up to 90 days after last dose
Trough Plasma Concentration (Ctrough)
Time Frame: Up to 90 days after last dose
The PK (Ctrough) of surovatamig as monotherapy and in combination with other anti-cancer agents will be evaluated.
Up to 90 days after last dose
Half Life (t1/2) of surovatamig
Time Frame: Up to 90 days after last dose
The PK (t1/2) of surovatamig as monotherapy and in combination with other anti-cancer agents will be evaluated.
Up to 90 days after last dose
Clearance (CL) of surovatamig
Time Frame: Up to 90 days after last dose
The PK (CL) of surovatamig as monotherapy and in combination with other anti-cancer agents will be evaluated.
Up to 90 days after last dose
Number of Participants with Anti-drug Antibody (ADA) for surovatamig
Time Frame: Up to 90 days after last dose
The incidence of immunogenicity of SC surovatamig as monotherapy and in combination with other anti-cancer agents will be evaluated.
Up to 90 days after last dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 30, 2025

Primary Completion (Estimated)

February 28, 2028

Study Completion (Estimated)

June 11, 2029

Study Registration Dates

First Submitted

August 19, 2024

First Submitted That Met QC Criteria

August 19, 2024

First Posted (Actual)

August 21, 2024

Study Record Updates

Last Update Posted (Actual)

May 14, 2026

Last Update Submitted That Met QC Criteria

May 12, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D7407C00001
  • 2024-515034-33-00 (Registry Identifier: EU CT)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via there quest portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure."Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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