Phase 2 study

Reproduced exactly, unedited. Written for researchers rather than for patients.

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).

• All Participants must have relapsed or refractory B-ALL ('relapsed' defined as bone marrow blasts > 5% or reappearance of blasts in PB)

• Module 1 (DE): R/R B-ALL [Ph(-) and Ph(+)]

• Backfill of Module 1 and Module 2 (DO): R/R B-ALL [Ph(-)] with demonstration of CD22 expression by local assessment in screening.

  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. Prior therapies:

• Module 1 (DE): At least 2 prior therapies with refractoriness or relapse, or 1 prior therapy with refractoriness or relapse and no standard options available. For Ph+ B-ALL: 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

• Backfill of Module 1 (backfills) and Module 2 (DO): at least one prior line of therapy (SOC or clinical trial) to which the participant has been either refractory or has subsequently relapsed.

• Participants who have received prior CD22 targeted therapies and were not refractory to these therapies are eligible

  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.