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

AstraZeneca

Status and phase: Begins enrollment in 2 months; Phase 2; Phase 1

Conditions: B-cell Acute Lymphoblastic Leukemia (B-ALL)

Treatments: Combination Product: AZD4512 monotherapy

Study type: Interventional

Funder types: Industry

Identifiers

NCT07109219

2025-522372-93-00 (Other Identifier)

D9891C00001

Details and patient eligibility

About

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).

Full 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.

Enrollment: 83 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 1. Age:

  • 16 years old in Module 1

  • 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) or R/R with MRD ≥ 1% to ≤5%

• The nº of enrolled participants with MRD ≥ 1 to ≤ 5% will be limited to 25% of the DE cohort

• Module 1 (DE): Ph(-) B-ALL and Ph(+) B-ALL - R/R or with MRD ≥ 1% to ≤5%

• 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

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 21 days or 5 half-lives (whichever is longer)
   • Strong inhibitors of CYP 3A4 within 21 days or 5 half-lives (whichever is longer)
   • Investigational agents or study interventions in the last 30 days

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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83 participants in 2 patient groups

Module 1 Dose Escalation

Experimental group

Description:

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, or with measurable residual disease (MRD) ≥ 1% to ≤ 5% after failing or relapsing after standard of care therapies.

Treatment:

Combination Product: AZD4512 monotherapy

Module 2 Dose Optimization

Experimental group

Description:

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.

Treatment:

Combination Product: AZD4512 monotherapy