B-cell Acute Lymphoblastic Leukemia (B-ALL)Phase 1/2SYRUSNCT06137118
AZD0486 as Monotherapy in B-cell Acute Lymphoblastic Leukaemia
A Phase 1/2 study testing Surovatamig in people with B-cell Acute Lymphoblastic Leukemia (B-ALL), run by AstraZeneca at 83 sites in 13 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- B-cell Acute Lymphoblastic Leukemia (B-ALL)
- What is being tested?
- Surovatamig
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 255 participants
- Where
- 83 sitesin 13 countries
- Study dates
- 29 Dec 2023to 10 Aug 2028
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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:
- Bone marrow infiltration with >/= 5% blasts
- 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).
- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
83 sites in 13 countries. Contact the study team or a site near you to ask about taking part.
AstraZeneca Clinical Study Information Center contact
83 sites in 13 countries
United States12 sites, 10 recruiting
- Recruiting
Research Site
Atlanta, Georgia, 30322
- Withdrawn
Research Site
Birmingham, Alabama, 35205
- Recruiting
Research Site
Chicago, Illinois, 60637
- Recruiting
Research Site
Duarte, California, 91010
- Recruiting
Research Site
Houston, Texas, 77030
- Recruiting
Research Site
Los Angeles, California, 90048
- Recruiting
Research Site
Milwaukee, Wisconsin, 53226
- Recruiting
Research Site
New York, New York, 10016
- Recruiting
Research Site
Palo Alto, California, 94304
- Recruiting
Research Site
Richmond, Virginia, 23298
- Withdrawn
Research Site
Seattle, Washington, 98109
- Recruiting
Research Site
Tampa, Florida, 33612
Germany12 sites, 11 recruiting
- Not yet recruiting
Research Site
Berlin, 13353
- Recruiting
Research Site
Cologne, 50924
- Recruiting
Research Site
Düsseldorf, 40225
- Withdrawn
Research Site
Essen, 45147
- Recruiting
Research Site
Frankfurt, 60590
- Recruiting
Research Site
Freiburg im Breisgau, 79106
- Recruiting
Research Site
Halle, 06120
- Recruiting
Research Site
Hamburg, 20246
- Recruiting
Research Site
Kiel, 24105
- Recruiting
Research Site
München, D-81337
- Recruiting
Research Site
Münster, 48149
- Recruiting
Research Site
Würzburg, 97080
Japan11 sites, 11 recruiting
- Recruiting
Research Site
Bunkyō City, 113-8677
- Recruiting
Research Site
Chiba, 260-8677
- Recruiting
Research Site
Chūōku, 104-0045
- Recruiting
Research Site
Fukuoka, 810-8563
- Recruiting
Research Site
Kashiwa, 277-8577
- Recruiting
Research Site
Kyoto, 606-8507
- Recruiting
Research Site
Okayama, 701-1192
- Recruiting
Research Site
Osaka, 545-8586
- Recruiting
Research Site
Sapporo, 003-0006
- Recruiting
Research Site
Toyohashi, 441-8570
- Recruiting
Research Site
Yamagata, 990-9585
China10 sites, 10 recruiting
- Recruiting
Research Site
Changsha, 410008
- Recruiting
Research Site
Chengdu, 610041
- Recruiting
Research Site
Guangzhou, 510060
- Recruiting
Research Site
Guangzhou, 510280
- Recruiting
Research Site
Hangzhou, 310003
- Recruiting
Research Site
Nanjing, 210008
- Recruiting
Research Site
Nanjing, 210009
- Recruiting
Research Site
Suzhou, 215004
- Recruiting
Research Site
Tianjin, 300020
- Recruiting
Research Site
Zhengzhou, 450008
Spain7 sites, 6 recruiting
- Recruiting
Research Site
Barcelona, 08036
- Recruiting
Research Site
Barcelona, 8035
- Recruiting
Research Site
Madrid, 28025
- Recruiting
Research Site
Madrid, 28046
- Recruiting
Research Site
Salamanca, 37007
- Not yet recruiting
Research Site
Seville, 41013
- Completed
Research Site
Valencia, 46026
France6 sites, 2 recruiting
- Suspended
Research Site
Caen, 14033
- Recruiting
Research Site
Marseille, 13009
- Suspended
Research Site
Nantes, 44000
- Recruiting
Research Site
Paris, 75019
- Suspended
Research Site
Pierre-Bénite, 69495
- Suspended
Research Site
Toulouse, 31059
Italy5 sites, 5 recruiting
- Recruiting
Research Site
Bergamo, 24127
- Recruiting
Research Site
Bologna, 40138
- Recruiting
Research Site
Monza, 20900
- Recruiting
Research Site
Naples, 80123
- Recruiting
Research Site
Roma, 00165
South Korea5 sites, 5 recruiting
- Recruiting
Research Site
Seoul, 03080
- Recruiting
Research Site
Seoul, 03722
- Not yet recruiting
Research Site
Seoul, 05505
- Recruiting
Research Site
Seoul, 06351
- Recruiting
Research Site
Seoul, 6591
Taiwan5 sites
- Suspended
Research Site
Kaohsiung City, 833401
- Suspended
Research Site
Taichung, 40705
- Suspended
Research Site
Tainan, 70403
- Suspended
Research Site
Taipei, 10002
- Suspended
Research Site
Taoyuan, 333
Brazil3 sites
- Suspended
Research Site
Porto Alegre, 90035903
- Suspended
Research Site
São Paulo, 01401-002
- Suspended
Research Site
São Paulo, 05652-900
Canada3 sites, 1 recruiting
- Withdrawn
Research Site
Montreal, Quebec, H3T1C5
- Withdrawn
Research Site
Montreal, Quebec, H4A 3J1
- Recruiting
Research Site
Toronto, Ontario, M5G 2M9
United Kingdom3 sites, 1 recruiting
- Suspended
Research Site
London, EC1A 7BE
- Recruiting
Research Site
Manchester, M20 4BX
- Suspended
Research Site
Surrey, SM1 2DL
About this study
Official title: 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+)
Read the 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.
- Being tested
- Surovatamig
- Keywords
- B-cell acute lymphoblastic leukemia, Leukemia, B-lymphocytes, Surovatamig, AZD0486
- Medical subject headings
- Burkitt Lymphoma, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SurovatamigDrug
Also called AZD0486
Investigational Product administered via intravenous infusion.
| Study group | Role | What they receive |
|---|---|---|
| Part A: AZD0486 Dose Escalation | Experimental | Ascending dose level cohorts of surovatamig (AZD0486) in B-ALL participants aged 12 years and above. Receives: Drug: Surovatamig |
| Part B: Dose Optimization | Experimental | 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. Receives: Drug: Surovatamig |
| Part C: Dose Expansion | Experimental | 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. Receives: Drug: Surovatamig |
| Part D: Dose Optimization and Efficacy Expansion in 2L+ | Experimental | 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. Receives: Drug: Surovatamig |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: Frequency of DLTs
DLTs are dose-limiting toxicities as defined in the study protocol
Measured: 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.
Measured: From signing of informed consent through data cutoff, up to 57 months
Parts B & C: Rate of CR within 3 cycles
To evaluate the efficacy of surovatamig based on NCCN response criteria (in Part B and C).
Measured: Up to three cycles of 28 days each
Part D: CR/CRh within 3 cycles
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.
Measured: Up to three cycles of 28 days each
Secondary outcomes (17)
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
Measured: 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.
Measured: 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
Rate of CR, CR/CRh and CR/CRh/CRi at any time during study (Best CR, best CR/CRh and best CR/CRh/CRi)
Measured: 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
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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
Percentage of participants who received a subsequent alloSCT, or DLI if used as an alloSCT substitute, post surovatamig treatment
Measured: 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
To evaluate the impact of suravatomig on MRD-negative rate of CR, CR/CRh and CR/CRi
Measured: From First dose to data cutoff, up to 57 months
Parts A, B, C, & D: PK characterization of suravatomig
Derived PK parameter: AUC
Measured: From first dose to data cutoff, up to 57 months
A, B, C, & D: PK Characterization of suravatomig
Derived PK parameter: Cmax
Measured: From first dose to data cutoff, up to 57 months
A, B, C, & D: PK Characterization of suravatomig
Derived PK Parameter: tmax
Measured: From first dose to data cutoff, up to 57 months
A, B, C, & D: PK Characterization of suravatomig
Derived PK parameter: Ctrough
Measured: From first dose to data cutoff, up to 57 months
A, B, C, & D: PK Characterization of suravatomig
Derived PK Parameter: t1/2
Measured: From first dose to data cutoff, up to 57 months
A, B, C, & D: PK Characterization of surovatamig
Derived PK Parameter: CL of surovatamig
Measured: From first dose to data cutoff, up to 57 months
Parts A, B, C, D: ADA characterization of suravatomig
Summary of pre-existing and treatment-induced ADAs for suravatomig (positive or negative, titres)
Measured: From First dose to EOT, up to 57 months
Part C, D: Safety Evaluation of suravatomig
Frequency, severity, and relationship to study drug of AEs and SAEs; dose modifications; changes in laboratory evaluations; QTc, and vital signs changes.
Measured: 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
CR/CRh within 3 cycles based on NCCN response criteria by BM central review confirmation.
Measured: Up to 3 cycles of 28 days each
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2023
- Study start29 Dec 2023
- Primary completion6 Jan 2028 (estimated)
- Study completion10 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for B-cell Acute Lymphoblastic Leukemia (B-ALL)Studies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- The trial will assess surovatamig (AZD0486) IV infusion in monotherapy. Part A will evaluate ascending dose levels of surovatamig (AZD0486) in participants 12 years and above with 3L+ B-ALL. Part B will evaluate up to 2 safe-declared dose levels in participants with both Ph(+) and Ph(-) 3L+ B-ALL aged 12 years and above to select an RP2D. Part C will expand the RP2D from part B to assess efficacy in a large number of 3L+ participants. Part D will evaluate 2 dose levels in a broader 2L+ B-ALL population, further optimizing dose and evaluating efficacy
- Masking
- None (open label)
- Enrolment
- 255 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06137118
- Sponsor's protocol ID
- D7405C00001
- Acronym
- SYRUS
- Status last verified
- Oct 2026
- First submitted
- 3 Nov 2023
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
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.
PubMed 41671463