Overview
Sponsor-declared trial summary
Phase
Phase I and Phase II (Integrated) - First administration to humans
Status
Ongoing, recruiting
Participants planned
83
Countries
1
Sites
4
B-cell acute lymphoblastic leukemia (B-ALL)
Module 1 Dose Escalation: To assess the safety and tolerability of AZD4512 in participants with R/R B-ALL [Ph(-) and Ph(+)] as defined by NCCN guidelines Module 1 Dose Escalation: To identify the MTD and/or doses of AZD4512 for subsequent evaluation in Module 2 Module 2 Dose Optimization:To evaluate the efficacy and de…
Key facts
- Sponsor
- AstraZeneca AB
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Hemic and Lymphatic Diseases [C15]
- Trial duration
- 13 Jan 2026 → ongoing
- Decision date (initial)
- 2025-11-24
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
External identifiers
- EU CT number
- 2025-522372-93-00
- ClinicalTrials.gov
- NCT07109219
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacokinetic, Pharmacodynamic, Dose response, Safety, Efficacy
Module 1 Dose Escalation: To assess the safety and tolerability of AZD4512 in participants with R/R B-ALL [Ph(-) and Ph(+)] as defined by NCCN guidelines
Module 1 Dose Escalation: To identify the MTD and/or doses of AZD4512 for subsequent evaluation in Module 2
Module 2 Dose Optimization:To evaluate the efficacy and determine the RP2D of AZD4512 in participants with R/R Ph(-) B-ALL based on NCCN response criteria
Module 2 Dose Optimization: To assess the safety and tolerability of AZD4512 in participants with R/R Ph(-) B-ALL
Secondary objectives 7
- Module 1 Dose Escalation: To characterize the PK of AZD4512 as monotherapy
- Module 1 Dose Escalation: To determine the immunogenicity of AZD4512 as monotherapy
- Module 1 Dose Escalation: To evaluate the preliminary efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-) and Ph(+)] as defined by NCCN guidelines
- Module 2 Dose Optimization: To evaluate the efficacy of AZD4512 based on NCCN response criteria
- Module 2 Dose Optimization: To evaluate the impact of AZD4512 on MRD by NGS [central]
- Module 2 Dose Optimization: To characterize the PK of AZD4512 as monotherapy
- Module 2 Dose Optimization: To determine the immunogenicity of AZD4512 as monotherapy
Conditions and MedDRA coding
B-cell acute lymphoblastic leukemia (B-ALL)
Study design 2 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Module 1 Dose Escalation 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
|
2 | None | Module 1 Dose Escalation: 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 | |
| 2 | Module 2 Dose Optimization 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.
|
Randomised Controlled | None | Module 2 Dose Optimization: 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. |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- 1. Age: ≥ 16 years old in Module 1 (US only: ≥18year) ≥ 12 years old in Module 2
- 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%)
- 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 -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 5
- 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.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 4
- 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
- Module 1 Dose Escalation: Determine the MTD and/or doses to explore in Module 2
- Module 2 Dose Optimization: Antitumour activity and determine the RP2D of AZD4512 -Response Rate: ORR (CR/CRh)
- Module 2 Dose Optimization:Safety and Tolerability of AZD4512 -Assessment of TEAEs/TRAEs/SAEs -Interruptions, modifications, delays and discontinuations -Clinically significant changes from baseline
Secondary endpoints 7
- Module 1 Dose Escalation: Characterize AZD4512 PK as monotherapy
- Module 1 Dose Escalation: Immunogenicity as monotherapy -ADA development
- Module 1 Dose Escalation: Preliminary Antitumour Activity of AZD4512 -Response Rate: ORR (CR/CRh), CR and CRc rate, TTR, DoR, EFS, OS, subsequent HSCT
- Module 2 Dose Optimization: Antitumour Activity of AZD4512 -Response Rate: CR and CRc rate, TTR, DoR, EFS, OS, subsequent HSCT
- Module 2 Dose Optimization: Effect of AZD4512 on MRD (NGS) -MRD-negative CR rate, CR/CRh (ORR), CRc (CR/CRi/CRh) rate
- Module 2 Dose Optimization: PK of AZD4512 as monotherapy
- Module 2 Dose Optimization: Immunogenicity as monotherapy -ADA development
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
AstraZeneca AB
- Sponsor organisation
- AstraZeneca AB
- Address
- -
- City
- Sodertalje
- Postcode
- 151 85
- Country
- Sweden
Scientific contact point
- Organisation
- AstraZeneca AB
- Contact name
- AstraZeneca Clinical Study Information Center
Public contact point
- Organisation
- AstraZeneca AB
- Contact name
- AstraZeneca Clinical Study Information Center
Locations
1 EU/EEA country · 4 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Spain | Ongoing, recruiting | 13 | 4 |
| Rest of world
Japan, Australia, Canada, United States, China, United Kingdom, Taiwan, Korea, Democratic People's Republic of
|
— | 70 | — |
Investigational sites
Hospital Universitario De Salamanca
Servicio de Hematologia, Paseo De San Vicente 58-182, 37007, Salamanca
Hospital Universitari Vall D Hebron
Servicio de Hematologia, Passeig De La Vall D'Hebron 119-129, 08035, Barcelona
Hospital Universitario Marques De Valdecilla
Servicio de Hematologia, Avenida Valdecilla Sn, 39008, Santander
Hospital Germans Trias I Pujol
Servicio de Hematologia, Carretera Canyet 1a Planta, 08916, Badalona
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Spain | 2026-01-13 | 2026-01-19 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 10 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2025-522372-93-00_redacted | 4 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Optional Genomics Redacted | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Paediatric Study Subject Assent Form Redacted | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnant partner Redacted | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Adult participant ICF_redacted | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Appendix 1 Data protection | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Paediatric Study Participant Redacted | 3 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis ES_2025-522372-93-00_Redacted | 2 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_all markets_redacted | 2 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2025-08-07 | Spain | Acceptable 2025-11-20
|
2025-11-24 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2026-01-23 | Spain | Acceptable 2025-11-20
|
2026-01-23 |
| 3 | SUBSTANTIAL MODIFICATION | SM-1 | 2026-02-12 | Spain | Acceptable 2026-03-27
|
2026-03-31 |
| 4 | SUBSTANTIAL MODIFICATION | SM-2 | 2026-05-01 | Spain | Acceptable | 2026-05-26 |