AZD4512 monotherapy: Patients will receive AZD4512 as monotherapy via intravenous infusion. AZD4512 is an antibody-drug conjugate targeting CD22
Study 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).
Eligibility
Sex
ALL
Min age
12 Years
Max age
—
Healthy 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.
Primary outcome measure(s)
Module 1 (Dose Escalation): Number of participants with dose-limiting toxicities (DLTs). — From first dose up to 21 days (DLT period). DLTs are dose-limiting toxicities as defined in the study protocol.
Module 1 (Dose Escalation): Frequency, duration and severity of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs) — 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
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 — 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)
Module 2 (Dose Optimization): Frequency, duration and severity of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs) — 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
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)
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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