RecruitingInterventionalPhase 1/Phase 2

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

NCT ID: NCT07109219Sponsor: AstraZenecaLast updated: 2026-06-11

Summary

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).

Detailed description

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.

Arms & interventions

Combination ProductAZD4512 monotherapy
Patients will receive AZD4512 as monotherapy via intravenous infusion. AZD4512 is an antibody-drug conjugate targeting CD22

Outcome measures

Primary

Module 1 (Dose Escalation): Number of participants with dose-limiting toxicities (DLTs).
DLTs are dose-limiting toxicities as defined in the study protocol.
Time frame: From first dose up to 21 days (DLT period).
Module 1 (Dose Escalation): Frequency, duration and severity of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs)
Assessed by the CTCAE criteria version 5.0
Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)
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)
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)
Module 2 (Dose Optimization): Overall response rate (ORR) in participants with R/R Ph(-) B-ALL
To evaluate the efficacy based on NCCN response criteria, measured by ORR (CR/CRh)
Time frame: From date of first dose of AZD4512 up until end of study, up to 38 months
Module 2 (Dose Optimization): Frequency, duration and severity of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs)
Assessed by the CTCAE criteria version 5.0
Time frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)
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)
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

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)
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)
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)
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)
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)
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)
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)
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)
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)
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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)
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)
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)
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)
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)
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)
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)
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)
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)

Eligibility criteria

Sex: AllAge: 12 Years and olderHealthy volunteers: No

Inclusion Criteria: * 1\. Age: * 16 years old in Module 1 (US only: ≥18year) * 12 years old in Module 2 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 3\. Performance status (ECOG ≤ 2; KPS ≥ 50; LPS ≥ 50) 4\. Peripheral lymphoblast count \< 10,000/µL (may receive cytoreduction prior to C1D1 per protocol-specified criteria) 5\. 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 6\. Prior DLI \>4 weeks, prior cell therapy or autoHSCT \>8 weeks, alloHSCT \>12 weeks Exclusion Criteria: 1. Burkitt lymphoma and leukemia 2. Isolated extramedullary disease; Active testicular or CNS (\> CNS1) involvement 3. Unresolved non-heme toxicities Grade ≥ 2 (except alopecia, stable Grade ≤ 2 neuropathy, vitiligo, endocrine disorders controlled with therapy) 4. 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 5. 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.

Study locations (6)

Research Site

Duarte, California, 91010

Recruiting

Research Site

Jacksonville, Florida, 32224

Withdrawn

Research Site

Chicago, Illinois, 60611

Recruiting

Research Site

Iowa City, Iowa, 52242

Recruiting

Research Site

Franklin, Tennessee, 37067

Recruiting

Research Site

Houston, Texas, 77030

Recruiting