RecruitingInterventionalPhase 1/Phase 2

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

NCT ID: NCT06137118Sponsor: AstraZenecaLast updated: 2026-05-27

Summary

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)

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.

Arms & interventions

DrugAZD0486
Investigational Product administered via intravenous infusion.

Outcome measures

Primary

Part A: Frequency of DLTs
DLTs are dose-limiting toxicities as defined in the study protocol
Time frame: 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.
Time frame: 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).
Time frame: Up to three cycles of 28 days each

Secondary

Part A: Rate of CR within 3 cycles
Time frame: 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
Parts A, B, C: 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 42 months
Parts A, B, C: Duration of CR, CR/CRh and CR/CRh/CRi
Time frame: 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)
Time frame: From First dose to last progression or data cutoff, whichever comes first, assessed up to 42 months
Parts A, B, C: Overall Survival (OS)
Time frame: 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
Time frame: From first dose to EOT, up to 42 Months
Part A, B, C:MRD-negative rate of CR
Time frame: From First dose to data cutoff, up to 42 months
Parts A, B, & C: PK characterization of AZD0486
Time frame: From first dose to data cutoff, up to 42 months
Parts A, B & C: PK Characterization of AZD0486
Time frame: From first dose to data cutoff, up to 42 months
Parts A, B, C: PK Characterization of AZD0486
Time frame: From first dose to data cutoff, up to 42 months
Parts A, B, C: PK Characterization of AZD0486
Time frame: From first dose to data cutoff, up to 42 months
Parts A, B, C: PK Characterization of AZD0486
Time frame: From first dose to data cutoff, up to 42 months
Parts A, B, C: PK Characterization of AZD0486
Time frame: From first dose to data cutoff, up to 42 months
Parts A, B, C: ADA characterization of AZD0486
Time frame: From First dose to EOT, up to 42 months
Part C: Safety Evaluation of AZD0486
Time frame: From signing of informed consent through completion of study treatment, an average of 6 months

Eligibility criteria

Sex: AllAge: 12 Years and olderHealthy volunteers: No

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 locations (12)

Research Site

Birmingham, Alabama, 35233

Withdrawn

Research Site

Duarte, California, 91010

Recruiting

Research Site

Los Angeles, California, 90048

Recruiting

Research Site

Palo Alto, California, 94304

Recruiting

Research Site

Tampa, Florida, 33612

Recruiting

Research Site

Atlanta, Georgia, 30322

Recruiting

Research Site

Chicago, Illinois, 60637

Recruiting

Research Site

New York, New York, 10016

Recruiting

Research Site

Houston, Texas, 77030

Recruiting

Research Site

Richmond, Virginia, 23298

Recruiting

Research Site

Seattle, Washington, 98109

Withdrawn

Research Site

Milwaukee, Wisconsin, 53226

Recruiting

References

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)