Study of AZD4512 monotherapy or in combination with anticancer agents in participants with acute lymphoblastic leukemia - ALLight

Inclusion Criteria

• Inclusion Criteria:
• -1. Age: 
• ≥ 16 years old in Module 1
• ≥ 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 (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. 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 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 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.