A trial to understand if AZD0486 is safe and helps in people with Relapsed or Refractory B-cell acute lymphoblastic leukemia (B-ALL)

Phase 1/2

Recruiting

• Conditions: B-Cell Acute Lymphoblastic Leukaemia

• Registration Number: 2023-505840-20-00
• Lead Sponsor: Astrazeneca AB

Brief Summary

Part A: To assess the safety and tolerability of AZD0486 in participants with Ph(+) or Ph(-) R/R B-ALL, aged 12 years and above

Part B: To assess the safety and tolerability of AZD0486 in participants with R/R Ph(-) B-ALL, aged 12 years and above

Parts B & C: To evaluate the efficacy of AZD0486 in participants with R/R Ph(-) B-ALL, aged 12 years and above

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 Timeline

• Study First Submitted: 2023-11-03
• Study First Submitted QC: 2023-11-13
• Study First Posted: 2023-11-18
• Study Start: 2023-12-29
• Status Verified: 2025-08
• Last Update Submitted: 2025-08-21
• Last Update Posted: 2025-08-27
• Primary Completion: 2026-11-13
• Study Completion: 2027-06-29

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 142

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Primary Outcome Measures

Name	Time	Method
Part A: Frequency of DLTs	Up to 28 days	DLTs are dose-limiting toxicities as defined in the study protocol
Parts A & B: Safety Evaluation of AZD0486	From signing of informed consent through data cutoff, up to 42 months	Frequency, severity, and relationship to study drug of AEs and SAEs; dose modifications; changes in laboratory evaluations; QTc, and vital signs changes.
Parts B & C: Rate of CR within 3 cycles	Up to three cycles of 28 days each	To evaluate the efficacy of AZD0486 based on NCCN response criteria (in Part B and C).

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Research Site; 🇬🇧 Surrey, United Kingdom

Research Site

🇬🇧Surrey, United Kingdom