AZD4512 for B-cell acute lymphoblastic leukemia (B-ALL)

Inclusion criteria

• {"criterion_text":"- 1. Age: ≥ 16 years old in Module 1 (US only: ≥18year) ≥ 12 years old in Module 2"}
• {"criterion_text":"- 2. Diagnosis: Diagnosis of B-ALL WHO (WHO-HAEM5) 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 (BM blasts >5%)"}
• {"criterion_text":"- 3. Performance status (ECOG ≤ 2; KPS ≥ 50; LPS ≥ 50)"}
• {"criterion_text":"- 4. Peripheral lymphoblast count < 10,000/µL (may receive cytoreduction prior to C1D1 per protocol-specified criteria)"}
• {"criterion_text":"- 5. At least 2 prior therapies with refractoriness or relapse, or 1 prior therapy with refractoriness or relapse and no standard options available -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"}
• {"criterion_text":"- 6. Prior DLI >4 weeks, prior cell therapy or autoHSCT >8 weeks, alloHSCT >12 weeks"}

Exclusion criteria

• {"criterion_text":"- 1. Burkitt lymphoma and leukemia"}
• {"criterion_text":"- 2. Isolated extramedullary disease; Active testicular or CNS (> CNS1) involvement"}
• {"criterion_text":"- 3. Unresolved non-heme toxicities Grade ≥ 2 (except alopecia, stable Grade ≤ 2 neuropathy, vitiligo, endocrine disorders controlled with therapy)"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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 endpoints

• {"endpoint_text":"- Module 1 Dose Escalation: Safety and Tolerability of AZD4512 -Assessment of DLT -Assessment of TEAEs/TRAEs/SAEs -Interruptions, modifications, delays and discontinuations -Clinically significant changes from baseline","definition_or_measurement_approach":"Assessment of dose limiting toxicities (DLT); monitoring and recording of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs); tracking interruptions, modifications, delays and discontinuations; evaluation of clinically significant changes from baseline."}
• {"endpoint_text":"- Module 1 Dose Escalation: Determine the MTD and/or doses to explore in Module 2","definition_or_measurement_approach":"Determination of maximum tolerated dose (MTD) and identification of doses for subsequent evaluation based on safety/tolerability data from dose escalation."}
• {"endpoint_text":"- Module 2 Dose Optimization: Antitumour activity and determine the RP2D of AZD4512 -Response Rate: ORR (CR/CRh)","definition_or_measurement_approach":"Assessment of antitumour activity using response rate measures per NCCN response criteria: Overall Response Rate (ORR), including Complete Remission (CR) and CR with hematologic recovery (CRh); used to determine recommended Phase 2 dose (RP2D)."}
• {"endpoint_text":"- Module 2 Dose Optimization:Safety and Tolerability of AZD4512 -Assessment of TEAEs/TRAEs/SAEs -Interruptions, modifications, delays and discontinuations -Clinically significant changes from baseline","definition_or_measurement_approach":"Assessment of TEAEs/TRAEs/SAEs; tracking interruptions, modifications, delays and discontinuations; evaluation of clinically significant changes from baseline."}

Secondary endpoints

• {"endpoint_text":"- Module 1 Dose Escalation: Characterize AZD4512 PK as monotherapy","definition_or_measurement_approach":"Pharmacokinetic (PK) characterization of AZD4512 when administered as monotherapy (plasma concentration-time profiling, PK parameters)."}
• {"endpoint_text":"- Module 1 Dose Escalation: Immunogenicity as monotherapy -ADA development","definition_or_measurement_approach":"Measurement of anti-drug antibody (ADA) development to assess immunogenicity."}
• {"endpoint_text":"- Module 1 Dose Escalation: Preliminary Antitumour Activity of AZD4512 -Response Rate: ORR (CR/CRh), CR and CRc rate, TTR, DoR, EFS, OS, subsequent HSCT","definition_or_measurement_approach":"Assessment of preliminary antitumour activity using ORR (CR/CRh), CR and CRc rates, time to response (TTR), duration of response (DoR), event-free survival (EFS), overall survival (OS), and subsequent hematopoietic stem cell transplant (HSCT)."}
• {"endpoint_text":"- Module 2 Dose Optimization: Antitumour Activity of AZD4512 -Response Rate: CR and CRc rate, TTR, DoR, EFS, OS, subsequent HSCT","definition_or_measurement_approach":"Assessment of antitumour activity using CR and CRc rates, TTR, DoR, EFS, OS, and subsequent HSCT."}
• {"endpoint_text":"- Module 2 Dose Optimization: Effect of AZD4512 on MRD (NGS) -MRD-negative CR rate, CR/CRh (ORR), CRc (CR/CRi/CRh) rate","definition_or_measurement_approach":"Assessment of minimal residual disease (MRD) by central next-generation sequencing (NGS): MRD-negative CR rate and associated response rates (CR/CRh, CRc)."}
• {"endpoint_text":"- Module 2 Dose Optimization: PK of AZD4512 as monotherapy","definition_or_measurement_approach":"Pharmacokinetic (PK) characterization of AZD4512 in Module 2 as monotherapy."}
• {"endpoint_text":"- Module 2 Dose Optimization: Immunogenicity as monotherapy -ADA development","definition_or_measurement_approach":"Assessment of immunogenicity via measurement of anti-drug antibodies (ADA) during Module 2."}

Spain

Earliest CTIS Part Ii Submission Date

19-08-2025

Latest Decision Or Authorization Date

31-03-2026

Processing Time Days

224

Number Of Sites

4

Number Of Participants

13

Primary sponsor

Full Name

AstraZeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden