AZD0486 as Monotherapy in B-cell Acute Lymphoblastic Leukaemia (SYRUS)

August 18, 2026 updated by: AstraZeneca

A Phase 1/2 Study to Evaluate the Safety and Efficacy of AZD0486 in Adolescent and Adult Participants With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukaemia

This is a Phase 1/2, global multicentre, open-label, single-arm, dose escalation and dose optimization study of surovatamig (AZD0486) to evaluate the safety, tolerability, and efficacy of surovatamig (AZD0486) monotherapy in participants with R/R B ALL. The study will consist of 4 parts. Part A: monotherapy dose escalation in 3L+ B-ALL. Part B: dose optimization in 3L+ B-ALL. Part C: Dose expansion in 3L+ B-ALL. Part D: Dose optimization and efficacy expansion in R/R B-ALL (2L+)

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This dose escalation and optimization study is evaluating the safety, tolerability, PK, PD and clinical activity of surovatamig (AZD0486) monotherapy in r/r B-ALL.

Study Type

Interventional

Enrollment (Estimated)

255

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
      • Melbourne, Australia, 3000
        • Withdrawn
        • Research Site
  • Brazil
      • Porto Alegre, Brazil, 90035903
        • Suspended
        • Research Site
      • São Paulo, Brazil, 01401-002
        • Suspended
        • Research Site
      • São Paulo, Brazil, 05652-900
        • Suspended
        • Research Site
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Suspended
        • Research Site
    • Quebec
      • Montreal, Quebec, Canada, H4A 3J1
        • Withdrawn
        • Research Site
      • Montreal, Quebec, Canada, H3T1C5
        • Withdrawn
        • Research Site
  • China
      • Changsha, China, 410008
        • Recruiting
        • Research Site
      • Chengdu, China, 610041
        • Recruiting
        • Research Site
      • Guangzhou, China, 510280
        • Recruiting
        • Research Site
      • Guangzhou, China, 510060
        • Recruiting
        • Research Site
      • Hangzhou, China, 310003
        • Recruiting
        • Research Site
      • Nanjing, China, 210009
        • Recruiting
        • Research Site
      • Nanjing, China, 210008
        • Recruiting
        • Research Site
      • Suzhou, China, 215004
        • Recruiting
        • Research Site
      • Tianjin, China, 300020
        • Recruiting
        • Research Site
      • Zhengzhou, China, 450008
        • Recruiting
        • Research Site
  • France
      • Caen, France, 14033
        • Suspended
        • Research Site
      • Marseille, France, 13009
        • Suspended
        • Research Site
      • Nantes, France, 44000
        • Suspended
        • Research Site
      • Paris, France, 75019
        • Suspended
        • Research Site
      • Pierre-Bénite, France, 69495
        • Suspended
        • Research Site
      • Toulouse, France, 31059
        • Suspended
        • Research Site
  • Germany
      • Berlin, Germany, 13353
        • Not yet recruiting
        • Research Site
      • Cologne, Germany, 50924
        • Suspended
        • Research Site
      • Düsseldorf, Germany, 40225
        • Suspended
        • Research Site
      • Essen, Germany, 45147
        • Withdrawn
        • Research Site
      • Frankfurt, Germany, 60590
        • Suspended
        • Research Site
      • Freiburg im Breisgau, Germany, 79106
        • Suspended
        • Research Site
      • Halle, Germany, 06120
        • Suspended
        • Research Site
      • Hamburg, Germany, 20246
        • Suspended
        • Research Site
      • Kiel, Germany, 24105
        • Suspended
        • Research Site
      • München, Germany, D-81337
        • Suspended
        • Research Site
      • Münster, Germany, 48149
        • Suspended
        • Research Site
      • Würzburg, Germany, 97080
        • Suspended
        • Research Site
  • Italy
      • Bergamo, Italy, 24127
        • Suspended
        • Research Site
      • Bologna, Italy, 40138
        • Suspended
        • Research Site
      • Monza, Italy, 20900
        • Suspended
        • Research Site
      • Naples, Italy, 80123
        • Suspended
        • Research Site
      • Roma, Italy, 00165
        • Suspended
        • Research Site
  • Japan
      • Bunkyō City, Japan, 113-8677
        • Recruiting
        • Research Site
      • Chiba, Japan, 260-8677
        • Recruiting
        • Research Site
      • Chūōku, Japan, 104-0045
        • Recruiting
        • Research Site
      • Fukuoka, Japan, 810-8563
        • Recruiting
        • Research Site
      • Kashiwa, Japan, 277-8577
        • Recruiting
        • Research Site
      • Kyoto, Japan, 606-8507
        • Recruiting
        • Research Site
      • Okayama, Japan, 701-1192
        • Recruiting
        • Research Site
      • Osaka, Japan, 545-8586
        • Recruiting
        • Research Site
      • Sapporo, Japan, 003-0006
        • Recruiting
        • Research Site
      • Toyohashi, Japan, 441-8570
        • Recruiting
        • Research Site
      • Yamagata, Japan, 990-9585
        • Recruiting
        • Research Site
  • South Korea
      • Seoul, South Korea, 03080
        • Recruiting
        • Research Site
      • Seoul, South Korea, 06351
        • Recruiting
        • Research Site
      • Seoul, South Korea, 03722
        • Recruiting
        • Research Site
      • Seoul, South Korea, 6591
        • Recruiting
        • Research Site
      • Seoul, South Korea, 05505
        • Not yet recruiting
        • Research Site
  • Spain
      • Barcelona, Spain, 8035
        • Suspended
        • Research Site
      • Barcelona, Spain, 08036
        • Suspended
        • Research Site
      • Madrid, Spain, 28046
        • Suspended
        • Research Site
      • Madrid, Spain, 28025
        • Suspended
        • Research Site
      • Salamanca, Spain, 37007
        • Suspended
        • Research Site
      • Valencia, Spain, 46026
        • Completed
        • Research Site
  • Taiwan
      • Kaohsiung City, Taiwan, 833401
        • Suspended
        • Research Site
      • Taichung, Taiwan, 40705
        • Suspended
        • Research Site
      • Tainan, Taiwan, 70403
        • Suspended
        • Research Site
      • Taipei, Taiwan, 10002
        • Suspended
        • Research Site
      • Taoyuan, Taiwan, 333
        • Suspended
        • Research Site
  • United Kingdom
      • London, United Kingdom, EC1A 7BE
        • Suspended
        • Research Site
      • Manchester, United Kingdom, M20 4BX
        • Suspended
        • Research Site
      • Surrey, United Kingdom, SM1 2DL
        • Suspended
        • Research Site
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35205
        • Withdrawn
        • Research Site
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • Research Site
      • Los Angeles, California, United States, 90048
        • Recruiting
        • Research Site
      • Palo Alto, California, United States, 94304
        • Recruiting
        • Research Site
    • Florida
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Research Site
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Research Site
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • Research Site
    • New York
      • New York, New York, United States, 10016
        • Recruiting
        • Research Site
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • Research Site
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Recruiting
        • Research Site
    • Washington
      • Seattle, Washington, United States, 98109
        • Withdrawn
        • Research Site
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • 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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age: 12 years and above (Parts A, B, C and D).

  • Participants with B-cell Acute Lymphoblastic Leukemia with CD19 expression by local lab with:

    1. Bone marrow infiltration with >/= 5% blasts
    2. Either relapsed or refractory after a minimum of 2 prior therapies or after 1 prior line of therapy if no SOC available option (Parts A, B, C); or relapsed or refractory to ≥1 prior line of therapy (Part D).
    3. Philadelphia positive participants are allowed in all parts of the study, if intolerant or refractory to TKIs.
  • For participants older than 16 years, Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2. For Participants 16 years or younger, Lansky score more or equal to 50%.

The above is a summary, other inclusion criteria details may apply.

Exclusion Criteria:

  • Active CNS involvement by B-ALL, defined by presence of ALL blasts in CSF (CNS2 and CNS3 criteria), or signs of CNS involvement.
  • Isolated extramedullary disease relapse.
  • Testicular leukemia
  • History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis; or prior Grade 4 neurotoxicity with CAR-T or TCE therapy.
  • History of other malignancy (with certain exceptions).
  • Unresolved AEs >/= Grade 2, from prior therapies
  • Prior therapy with ADCs within 3 weeks, TCEs within 4 weeks, CAR T-cell therapy or autologous HSCT within 8 weeks or prior alloSCT within 12 weeks of start of therapy.
  • GVHD requiring immunosuppressive therapy within 3 weeks prior to AZD0486 treatment.

The above is a summary, other exclusion criteria details may apply.

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: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A: AZD0486 Dose Escalation
Ascending dose level cohorts of surovatamig (AZD0486) in B-ALL participants aged 12 years and above.
Drug: Surovatamig
Investigational Product administered via intravenous infusion.
Other Names:
  • AZD0486
Experimental: Part B: Dose Optimization
Up to 2 cohorts will be evaluated prior declared safe-doses and schedules in order to determine the recommended phase 2 dose (RP2D). Participants, aged 12 years and above, will receive surovatamig (AZD0486) IV infusions and will be randomized in a 1:1 ratio.
Drug: Surovatamig
Investigational Product administered via intravenous infusion.
Other Names:
  • AZD0486
Experimental: Part C: Dose Expansion
Part C will consist of 1 cohort of participants aged 12 years and above, treated with the optimal dose selected in Part B and receive IV surovatamig (AZD0486) monotherapy.
Drug: Surovatamig
Investigational Product administered via intravenous infusion.
Other Names:
  • AZD0486
Experimental: Part D: Dose Optimization and Efficacy Expansion in 2L+
Part D will enroll participants aged 12 years and above with Ph(+) and Ph(-) B-ALL relapsed/refractory to ≥1 prior line of therapy. Participants will be randomized 1:1 to 2 dose levels of surovatamig IV.
Drug: Surovatamig
Investigational Product administered via intravenous infusion.
Other Names:
  • AZD0486

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A: Frequency of DLTs
Time Frame: Up to 28 days
DLTs are dose-limiting toxicities as defined in the study protocol
Up to 28 days
Parts A & B: Safety Evaluation of AZD0486
Time Frame: From signing of informed consent through data cutoff, up to 57 months
Frequency, severity, and relationship to study drug of AEs and SAEs; dose modifications; changes in laboratory evaluations; QTc, and vital signs changes.
From signing of informed consent through data cutoff, up to 57 months
Parts B & C: Rate of CR within 3 cycles
Time Frame: Up to three cycles of 28 days each
To evaluate the efficacy of surovatamig based on NCCN response criteria (in Part B and C).
Up to three cycles of 28 days each
Part D: CR/CRh within 3 cycles
Time Frame: Up to three cycles of 28 days each
To evaluate the efficacy of surovatamig in Part D based on NCCN response criteria. CR/CRh is defined as a best response of CR/CRh within 3 cycles.
Up to three cycles of 28 days each

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A: Rate of CR within 3 cycles
Time Frame: Up to 3 cycles of 28 days each
the percentage of participants with a best response of CR within 3 cycles based on NCCN response criteria by investigators
Up to 3 cycles of 28 days each
Part A,B,C: Rate of CR/CRh and CR/CRh/CRi within 3 cycles
Time Frame: Up to 3 cycles of 28 days each
proportion of participants achieving CR/CRh/CRi within 3 cycles based on NCCN response criteria by investigators (Part A) based on the response evaluable population, and by central review confirmation (Parts B and C) based on the FAS.
Up to 3 cycles of 28 days each
Parts A, B, C, D: Rate of CR, CR/CRh and CR/CRh/CRi at any time during the study
Time Frame: From first dose to end of treatment or data cutoff, whichever comes first, assessed up to 57 months
Rate of CR, CR/CRh and CR/CRh/CRi at any time during study (Best CR, best CR/CRh and best CR/CRh/CRi)
From first dose to end of treatment or data cutoff, whichever comes first, assessed up to 57 months
Parts A, B, C, D: Duration of CR/CRh
Time Frame: From first dose to last progression or data cutoff, whichever comes first, assessed up to 57 months
the time from the date of first documented CR, CR/CRh, or CR/CRh/CRi response, respectively, until the date of documented relapse or death due to any cause in the absence of disease progression or relapse, whichever occurs earlier.
From first dose to last progression or data cutoff, whichever comes first, assessed up to 57 months
Parts A, B, C, D: Event-free survival (EFS)
Time Frame: From First dose to last progression or data cutoff, whichever comes first, assessed up to 57 months
Event-free survival is defined as the time from the date of the first dose until the date of a relapse after achieving a CR, or death due to any cause, whichever occurs first.
From First dose to last progression or data cutoff, whichever comes first, assessed up to 57 months
Parts A, B, C, D: Overall Survival (OS)
Time Frame: From First dose to data cutoff, up to 57 months
The OS is defined as the time from date of first dose until death due to any cause regardless of whether the participant withdraws from treatment or receives a TTNT.
From First dose to data cutoff, up to 57 months
Parts B, C & D: Subsequent alloSCT or donor lymphocyte infusion if used as an alloSCT substitute
Time Frame: From first dose to EOT, up to 57 Months
Percentage of participants who received a subsequent alloSCT, or DLI if used as an alloSCT substitute, post surovatamig treatment
From first dose to EOT, up to 57 Months
Part A, B, C, D: MRD-negative rate of CR, CR/CRh and CR/CRh/CRi
Time Frame: From First dose to data cutoff, up to 57 months
To evaluate the impact of suravatomig on MRD-negative rate of CR, CR/CRh and CR/CRi
From First dose to data cutoff, up to 57 months
Parts A, B, C, & D: PK characterization of suravatomig
Time Frame: From first dose to data cutoff, up to 57 months
Derived PK parameter: AUC
From first dose to data cutoff, up to 57 months
A, B, C, & D: PK Characterization of suravatomig
Time Frame: From first dose to data cutoff, up to 57 months
Derived PK parameter: Cmax
From first dose to data cutoff, up to 57 months
A, B, C, & D: PK Characterization of suravatomig
Time Frame: From first dose to data cutoff, up to 57 months
Derived PK Parameter: tmax
From first dose to data cutoff, up to 57 months
A, B, C, & D: PK Characterization of suravatomig
Time Frame: From first dose to data cutoff, up to 57 months
Derived PK parameter: Ctrough
From first dose to data cutoff, up to 57 months
A, B, C, & D: PK Characterization of suravatomig
Time Frame: From first dose to data cutoff, up to 57 months
Derived PK Parameter: t1/2
From first dose to data cutoff, up to 57 months
A, B, C, & D: PK Characterization of surovatamig
Time Frame: From first dose to data cutoff, up to 57 months
Derived PK Parameter: CL of surovatamig
From first dose to data cutoff, up to 57 months
Parts A, B, C, D: ADA characterization of suravatomig
Time Frame: From First dose to EOT, up to 57 months
Summary of pre-existing and treatment-induced ADAs for suravatomig (positive or negative, titres)
From First dose to EOT, up to 57 months
Part C, D: Safety Evaluation of suravatomig
Time Frame: From signing of informed consent through completion of study treatment, an average of 6 months
Frequency, severity, and relationship to study drug of AEs and SAEs; dose modifications; changes in laboratory evaluations; QTc, and vital signs changes.
From signing of informed consent through completion of study treatment, an average of 6 months
Part D: Rate of CR and CR/CRh/CRi within 3 cycles
Time Frame: Up to 3 cycles of 28 days each
CR/CRh within 3 cycles based on NCCN response criteria by BM central review confirmation.
Up to 3 cycles of 28 days each

Collaborators and Investigators

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

Sponsor

AstraZeneca

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

December 29, 2023

Primary Completion (Estimated)

February 11, 2028

Study Completion (Estimated)

September 15, 2028

Study Registration Dates

First Submitted

November 3, 2023

First Submitted That Met QC Criteria

November 13, 2023

First Posted (Actual)

November 18, 2023

Study Record Updates

Last Update Posted (Actual)

August 19, 2026

Last Update Submitted That Met QC Criteria

August 18, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D7405C00001
  • 2018-002011-10 (EudraCT Number)

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 the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer 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 de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

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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