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NCT Number: NCT07109219

Study of AZD4512 Monotherapy or in Combination With Anticancer Agents in Participants With Acute Lymphoblastic Leukemia

The study is intended to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of AZD4512 in patients with relapsed/refractory B-Cell acute lymphoblastic leukemia (r/r B-ALL).

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Key information

Conditions

B-cell Acute Lymphoblastic Leukemia (B-ALL) Burkitt Lymphoma DNA Virus Infections Epstein-Barr Virus Infections Hematologic Diseases Hemic and Lymphatic Diseases Herpesviridae Infections Immune System Diseases Immunoproliferative Disorders Infections Leukemia Leukemia, Lymphoid Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Precursor Cell Lymphoblastic Leukemia-Lymphoma Tumor Virus Infections Virus Diseases

Age range

12 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Research Site, Melbourne, Australia

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About this study

In this Phase I/II, open-label multi-center study AZD4512 will be administered to adult/young adult patients (Module 1: >=16 years; Module 2: >=12 years) with relapsed/refractory B-Cell acute lymphoblastic leukemia (B-ALL). This study will have 2 parts: Module 1 - Dose Escalation and Module 2 - Dose Optimization.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 1. Age:
  • 16 years old in Module 1 (US only: ≥18year)
  • 12 years old in Module 2
  • Diagnosis: Known Diagnosis of CD22-positive B-ALL based on criteria established by WHO (Alaggio et al. 2022).
  • Participants must have relapsed or refractory B-ALL ('relapsed' defined as bone marrow blasts > 5% or reappearance of blasts in PB)
  • Module 1 (DE): Ph(-) B-ALL and Ph(+) B-ALL - R/R
  • Backfill of Module 1 and Module 2 (DO): R/R Ph(-) B-ALL
  • Performance status (ECOG ≤ 2; KPS ≥ 50; LPS ≥ 50)
  • Peripheral lymphoblast count < 10,000/µL (may receive cytoreduction prior to C1D1 per protocol-specified criteria)
  • At least 2 prior therapies with refractoriness or relapse, or 1 prior therapy with refractoriness or relapse and no standard options available. Participants who have received prior CD22 targeted therapies are eligible.
  • Ph+ B-ALL (Module 1 DE only): intolerant to or have contraindications to TKI therapy or R/R disease despite treatment with at least 2 prior TKIs or at least one 3rd generation TKI
  • Prior DLI >4 weeks, prior cell therapy or autoHSCT >8 weeks, alloHSCT >12 weeks

Exclusion criteria

  • Burkitt lymphoma and leukemia
  • Isolated extramedullary disease; Active testicular or CNS (> CNS1) involvement
  • Unresolved non-heme toxicities Grade ≥ 2 (except alopecia, stable Grade ≤ 2 neuropathy, vitiligo, endocrine disorders controlled with therapy)
  • History of drug-induced non-infectious ILD/pneumonitis requiring oral or IV steroids or supplemental oxygen or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
  • Prior/concomitant therapy
  • Cytotoxic treatment within 14 days (except ALL maintenance medications or cytoreduction)
  • Biologic (immuno-oncology) treatment within 28 days or 5 half-lives (whichever is shorter)
  • Non-CNS radiation within 2 weeks & CNS radiation within 4 weeks
  • Medications known to prolong QTc and/or associated with Torsades de Pointes within 5 half-lives
  • Strong inhibitors of CYP 3A4 within 14 days or 5 half-lives (whichever is longer)
  • Investigational agents or study interventions in the last 30 days or 5 half-lives prior to the first dose of AZD4512 whichever is longer. If the investigational product is an agent to treat B-ALL and meets the modality criteria, then a specific washout period must be adhered to instead.

Treatment and study plan

AZD4512 monotherapy

Combination Product

Patients will receive AZD4512 as monotherapy via intravenous infusion. AZD4512 is an antibody-drug conjugate targeting CD22

Primary outcomes

  1. Module 1 (Dose Escalation): Number of participants with dose-limiting toxicities (DLTs).

    Time frame: From first dose up to 21 days (DLT period).

    DLTs are dose-limiting toxicities as defined in the study protocol.

  2. Module 1 (Dose Escalation): Frequency, duration and severity of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs)

    Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

    Assessed by the CTCAE criteria version 5.0

  3. Module 1 (Dose Escalation): Frequency of dose interruptions, modifications, delays, and discontinuations due to AEs

    Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

  4. Module 1 (Dose Escalation): Number of participants with clinically significant changes in laboratory values, ECGs, performance status, and vital signs

    Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

  5. Module 2 (Dose Optimization): Overall response rate (ORR) in participants with R/R Ph(-) B-ALL

    Time frame: From date of first dose of AZD4512 up until end of study, up to 38 months

    To evaluate the efficacy based on NCCN response criteria, measured by ORR (CR/CRh)

  6. Module 2 (Dose Optimization): Frequency, duration and severity of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs)

    Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

    Assessed by the CTCAE criteria version 5.0

  7. Module 2 (Dose Optimization): Frequency of dose interruptions, modifications, delays, and discontinuations due to AEs

    Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

  8. Module 2 (Dose Optimization): Number of participants with clinically significant changes in laboratory values, ECGs, performance status, and vital signs

    Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

Secondary outcomes

  1. Module 1 (Dose Escalation): Plasma PK parameters of AZD4512

    Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

    To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL.

  2. Module 1 (Dose Escalation): Total antibody and total unconjugated payload

    Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

    To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL.

  3. Module 1 (Dose Escalation): Area Under Curve (AUC)

    Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

    To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL.

  4. Module 1 (Dose Escalation): Peak Plasma Concentration (Cmax)

    Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

    To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL.

  5. Module 1 (Dose Escalation): Time to max concentration (Tmax)

    Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

    To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL.

  6. Module 1 (Dose Escalation): Half life (T1/2)

    Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

    To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL.

  7. Module 1 (Dose Escalation): Clearance (CL)

    Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

    To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL.

  8. Module 1 (Dose Escalation): Volume of distribution (Vz)

    Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

    To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL.

  9. Module 1 (Dose Escalation): Number and percentage of participants who develop anti-drug antibodies (ADAs)

    Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

    To determine the immunogenicity of AZD4512 as monotherapy in participants with R/R B-ALL.

  10. Module 1 (Dose Escalation): Objective Response Rate (ORR): proportion of participants with CR or CRh

    Time frame: From date of first dose of AZD4512 up until end of study, up to 38 months

    To evaluate the preliminary efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-) and Ph(+)] as defined by NCCN guidelines

  11. Module 1 (Dose Escalation): Composite Complete Remission (CRc) rate: proportion of participants with CR, CRh, or CRi

    Time frame: From date of first dose of AZD4512 up until end of study, up to 38 months

    To evaluate the preliminary efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-) and Ph(+)] as defined by NCCN guidelines

  12. Module 1 (Dose Escalation): Complete Remission (CR) rate

    Time frame: From date of first dose of AZD4512 up until end of study, up to 38 months

    To evaluate the preliminary efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-) and Ph(+)] as defined by NCCN guidelines

  13. Module 1 (Dose Escalation): Time to Response (TTR)

    Time frame: From date of first dose of AZD4512 up until end of study, up to 38 months

    To evaluate the preliminary efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-) and Ph(+)] as defined by NCCN guidelines

  14. Module 1 (Dose Escalation): Duration of Response (DoR)

    Time frame: From date of first dose of AZD4512 up until end of study, up to 38 months

    • To evaluate the preliminary efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-) and Ph(+)] as defined by NCCN guidelines

  15. Module 1 (Dose Escalation): Event-Free Survival (EFS)

    Time frame: From date of first dose of AZD4512 up until end of study, up to 38 months

    • To evaluate the preliminary efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-) and Ph(+)] as defined by NCCN guidelines

  16. Module 1 (Dose Escalation): Overall Survival (OS)

    Time frame: From date of first dose of AZD4512 up until end of study, up to 38 months

    • To evaluate the preliminary efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-) and Ph(+)] as defined by NCCN guidelines

  17. Module 1 (Dose Escalation): Percentage of participants who receive subsequent allogeneic hematopoietic stem cell transplant (HSCT)

    Time frame: From date of first dose of AZD4512 up until end of study, up to 38 months

    • To evaluate the preliminary efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-) and Ph(+)] as defined by NCCN guidelines

  18. Module 2 (Dose Optimization): Complete Remission (CR) rate

    Time frame: From date of first dose of AZD4512 up until end of study, up to 38 months

    To evaluate the efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)] as defined by NCCN guidelines

  19. Module 2 (Dose Optimization):Composite Complete Remission (CRc) rate: proportion of participants with CR, CRh, or CRi

    Time frame: From date of first dose of AZD4512 up until end of study, up to 38 months

    To evaluate the efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)] as defined by NCCN guidelines

  20. Module 2 (Dose Optimization):Time to Response (TTR)

    Time frame: From date of first dose of AZD4512 up until end of study, up to 38 months

    To evaluate the efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)] as defined by NCCN guidelines

  21. Module 2 (Dose Optimization): Duration of Response (DoR)

    Time frame: From date of first dose of AZD4512 up until end of study, up to 38 months

    To evaluate the efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)] as defined by NCCN guidelines

  22. Module 2 (Dose Optimization):Event-Free Survival (EFS)

    Time frame: From date of first dose of AZD4512 up until end of study, up to 38 months

    To evaluate the efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)] as defined by NCCN guidelines

  23. Module 2 (Dose Optimization): Overall Survival (OS)

    Time frame: From date of first dose of AZD4512 up until end of study, up to 38 months

    To evaluate the efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)] as defined by NCCN guidelines

  24. Module 2 (Dose Optimization): Percentage of participants who receive subsequent allogeneic hematopoietic stem cell transplant (HSCT)

    Time frame: From date of first dose of AZD4512 up until end of study, up to 38 months

    To evaluate the efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)] as defined by NCCN guidelines

  25. Module 2 (Dose Optimization): MRD-negative CR rate, CR/CRh (ORR), CR/CRi/CRh (CRc) rate

    Time frame: From date of first dose of AZD4512 up until end of study, up to 38 months

    To evaluate the impact of AZD4512 on MRD as assessed by NGS (central)

  26. Module 2 (Dose Optimization): Plasma PK parameters of AZD4512

    Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

    To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)]

  27. Module 2 (Dose Optimization): total antibody and total unconjugated payload

    Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

    To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)]

  28. Module 2 (Dose Optimization): Area Under Curve (AUC)

    Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

    To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)]

  29. Module 2 (Dose Optimzation): Peak Plasma Concentration (Cmax)

    Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

    To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)]

  30. Module 2 (Dose Optimization): Time to max concentration (Tmax)

    Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

    To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)]

  31. Module 2 (Dose Optimization): Half life (T1/2)

    Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

    To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)]

  32. Module 2 (Dose Optimization): Clearance (CL)

    Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

    To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)]

  33. Module 2 (Dose Optimization): Volume of distribution (Vz)

    Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

    To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)]

  34. Module 2 (Dose Optimization): Summary of of pre-existing and treatment induced ADAs for AZD4512 (positive or negative, titers)

    Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

    To determine the immunogenicity of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)]

Study contacts

Contact information is provided by the study sponsor or research team.

AstraZeneca Clinical Study Information Center

CONTACT

[email protected]

1-877-240-9479

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Collaborators

  • Fortrea

Registry information

Official study title

A Modular Phase I/II, Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Preliminary Efficacy of AZD4512 Monotherapy or in Combination With Anticancer Agent(s) in Participants With Acute Lymphoblastic Leukemia

Acronym: ALLight

Important dates

Study start
2025
Primary completion
2028
Study completion
2028
First posted
Aug 7, 2025
Registry last updated
Jul 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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