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

Other illness

• Isolated extramedullary disease; Active testicular or CNS (\> CNS1) involvement
• Unresolved non-heme toxicities Grade ≥ 2 (except alopecia, stable Grade ≤ 2 neuropathy, vitiligo, endocrine disorders controlled with therapy)
• 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

Lab values

• 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.

Other

• Burkitt lymphoma and leukemia

• 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