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

NCT07109219 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: D9891C000012025-522372-93-00
• Study Type: interventional
• Target: 83
• Locations: 9 countries
• Sites: 26

Brief 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).

Conditions

B-cell Acute Lymphoblastic Leukemia (B-ALL)

Keywords

Acute lymphoblastic leukemia (B-ALL); Dose escalation; Dose optimization; Cluster of differentiation 22 (CD22); Antibody-drug conjugate (ADC)

Outcome Measures

Primary Outcomes (8)

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

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

  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

  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

  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

  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)

  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

  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

  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

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

Secondary Outcomes (34)

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

  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

  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)

  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)

  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)

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

Study Arms (2)

Module 1 Dose Escalation

EXPERIMENTAL

Module 1 will evaluate escalating doses of AZD4512 as monotherapy to determine the maximum tolerated dose (MTD) and/or doses of AZD4512 for subsequent evaluation in Module 2 (dose optimization), in participants with relapsed/refractory (R/R) Philadelphia chromosome positive (Ph\[+\]) and negative (Ph\[-\]) B-ALL, R/R as defined by National Comprehensive Cancer Network (NCCN) guidelines.

Combination Product: AZD4512 monotherapy

Module 2 Dose Optimization

EXPERIMENTAL

Module 2 will randomize participants with R/R (as defined by NCCN guidelines) Ph(-) BALL only across 2 to 3 dose levels identified in Module 1 to receive AZD4512 monotherapy for further exploration of the doses. The aim of Module 2 is to identify the recommended Phase 2 dose (RP2D) of AZD4512 monotherapy, evaluate the efficacy and further define the safety profile of AZD4512.

Combination Product: AZD4512 monotherapy

Interventions

AZD4512 monotherapy COMBINATION_PRODUCT

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

Module 1 Dose Escalation; Module 2 Dose Optimization

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age:
• years old in Module 1 (US only: ≥18year)
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Fortrea: collaborator

Study Sites (26)

Research Site

Duarte, California, 91010, United States

RECRUITING

Research Site

Jacksonville, Florida, 32224, United States

WITHDRAWN

Research Site

Chicago, Illinois, 60611, United States

NOT YET RECRUITING

Research Site

Iowa City, Iowa, 52242, United States

RECRUITING

Research Site

Franklin, Tennessee, 37067, United States

RECRUITING

Research Site

Houston, Texas, 77030, United States

RECRUITING

Research Site

Melbourne, 3000, Australia

RECRUITING

Research Site

Vancouver, British Columbia, V5Z 1M9, Canada

NOT YET RECRUITING

Research Site

Toronto, Ontario, M5G 1X6, Canada

RECRUITING

Research Site

Guangzhou, 510515, China

NOT YET RECRUITING

Research Site

Tianjin, 301600, China

NOT YET RECRUITING

Research Site

Bunkyō City, 113-8677, Japan

RECRUITING

Research Site

Chūōku, 104-0045, Japan

RECRUITING

Research Site

Seoul, 03080, South Korea

RECRUITING

Research Site

Seoul, 06351, South Korea

RECRUITING

Research Site

Seoul, 06591, South Korea

RECRUITING

Research Site

Seoul, 3722, South Korea

RECRUITING

Research Site

Badalona(Barcelona), 08916, Spain

NOT YET RECRUITING

Research Site

Barcelona, 08035, Spain

RECRUITING

Research Site

Salamanca, 37007, Spain

RECRUITING

Research Site

Santander, 39008, Spain

RECRUITING

Research Site

Valencia, 46026, Spain

WITHDRAWN

Research Site

Taichung, 40705, Taiwan

RECRUITING

Research Site

Taipei, 106, Taiwan

RECRUITING

Research Site

Bloomsbury, W1T 7HA, United Kingdom

RECRUITING

Research Site

Manchester, M20 4BX, United Kingdom

RECRUITING

MeSH Terms

Conditions

Burkitt Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2025
• First Posted: August 7, 2025
• Study Start: November 12, 2025
• Primary Completion (Estimated): April 28, 2028
• Study Completion (Estimated): July 3, 2028
• Last Updated: March 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

GB (2); CA (2); JP (2); US (6); AU (1); TW (2); KR (4); ES (5); CN (2)