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

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 optimisation study of AZD0486 to evaluate the safety, tolerability, and efficacy of AZD0486 monotherapy in participants with R/R B ALL who have received ≥ 2 prior lines of therapies. The study will consist of 3 parts. Part A monotherapy dose escalation. Part B dose optimisation. Part C Dose expansion at the recommended phase 2 dose (RP2D)

Study Overview

• Status: Recruiting
• Conditions: B-cell Acute Lymphoblastic Leukemia (B-ALL)
• Intervention / Treatment: Drug: AZD0486

Detailed Description

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

• Study Type: Interventional
• Enrollment (Estimated): 236
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Australia
  • Melbourne, Australia, 3000
    • Recruiting
    • 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      • Withdrawn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      • Withdrawn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
  • 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
• 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
    • Active, not recruiting
    • 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, 35233
      • 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

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 and C).

• 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.
  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).
• 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 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

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: AZD0486 Dose Escalation; Ascending dose level cohorts of AZD0486 in B-ALL participants aged 12 years and above.	Drug: AZD0486; Investigational Product administered via intravenous infusion.
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 AZD0486 IV infusions and will be randomized in a 1:1 ratio.	Drug: AZD0486; Investigational Product administered via intravenous infusion.
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 AZD0486 monotherapy.	Drug: AZD0486; Investigational Product administered via intravenous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Frequency of DLTs	DLTs are dose-limiting toxicities as defined in the study protocol	Up to 28 days
Parts A & B: Safety Evaluation of AZD0486	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 42 months
Parts B & C: Rate of CR within 3 cycles	To evaluate the efficacy of AZD0486 based on NCCN response criteria (in Part B and C).	Up to three cycles of 28 days each

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part C: Safety Evaluation of AZD0486	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 A: Rate of CR within 3 cycles	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	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: Rate of CR, CR/CRh and CR/CRh/CRi at any time during the study	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 42 months
Parts A, B, C: Duration of CR, CR/CRh and CR/CRh/CRi	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 42 months
Parts A, B, C: Event-free survival (EFS)	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/CRh/CRi, or death due to any cause, whichever occurs first.	From First dose to last progression or data cutoff, whichever comes first, assessed up to 42 months
Parts A, B, C: Overall Survival (OS)	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 42 months
Parts B &C: Subsequent alloSCT or donor lymphocyte infusion if used as an alloSCT substitute	Percentage of participants who received a subsequent alloSCT, or DLI if used as an alloSCT substitute, post AZD0486 treatment	From first dose to EOT, up to 42 Months
Part A, B, C:MRD-negative rate of CR	To evaluate the impact of AZD0486 on MRD-negative rate of CR, CR/CRh and CR/CRi	From First dose to data cutoff, up to 42 months
Parts A, B, & C: PK characterization of AZD0486	Derived PK parameter: AUC	From first dose to data cutoff, up to 42 months
Parts A, B & C: PK Characterization of AZD0486	Derived PK parameter: Cmax	From first dose to data cutoff, up to 42 months
Parts A, B, C: PK Characterization of AZD0486	Derived PK Parameter: tmax	From first dose to data cutoff, up to 42 months
Parts A, B, C: PK Characterization of AZD0486	Derived PK parameter: Ctrough	From first dose to data cutoff, up to 42 months
Parts A, B, C: PK Characterization of AZD0486	Derived PK Parameter: t1/2	From first dose to data cutoff, up to 42 months
Parts A, B, C: PK Characterization of AZD0486	Derived PK Parameter: CL of AZD0486	From first dose to data cutoff, up to 42 months
Parts A, B, C: ADA characterization of AZD0486	Summary of pre-existing and treatment-induced ADAs for AZD0486 (positive or negative, titres)	From First dose to EOT, up to 42 months

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• Davis KL, Yao CC, Zimmerman JAO, Rau RE. Immunotherapy in B-Cell Acute Lymphoblastic Leukemia. J Natl Compr Canc Netw. 2025 Dec;23(12):e257067. doi: 10.6004/jnccn.2025.7067.

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2023
• Primary Completion (Estimated): November 13, 2026
• Study Completion (Estimated): June 29, 2027

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): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 25, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Leukemia; B-cell acute lymphoblastic leukemia; B-lymphocytes; AZD0486
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Infections; Virus Diseases; Neoplasms by Histologic Type; Hematologic Diseases; DNA Virus Infections; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Epstein-Barr Virus Infections; Herpesviridae Infections; Tumor Virus Infections; Hemic and Lymphatic Diseases; Leukemia; Burkitt Lymphoma
• 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