A Study of Sonrotoclax (BGB-11417) in Children With Relapsed or Refractory Acute Myeloid Leukemia and B-cell Acute Lymphoblastic Leukemia

• sonrotoclax (Drug), also known as BGB-11417: Administered orally as a tablet
• Azacitidine (Drug): administered intravenously or subcutaneously
• Inotuzumab ozogamicin (Drug), also known as Besponsa: administered via intravenous infusion
• Dexamethasone (Drug): administered via intravenous injection or orally

Primary outcomes

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [From first dose of study drug to 30 days after last dose; up to approximately 12 months in cohort 1 and 4 months in cohort 2.]: Assessed by treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and laboratory abnormalities,. Includes adverse events meeting protocol-defined dose-limiting toxicity (DLT) criteria.
• Part 1: Recommended Dose for Expansion (RDFE) of Sonrotoclax [From first dose through end of Cycle 1 (each cycle is 28 days); approximately 2 months]: Dose selected based on safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity observed in Part 1, as determined by the Safety Monitoring Committee (SMC)

Secondary outcomes

• Complete Remission (CR) Rate [Up to approximately 2 months]: Percentage of participants achieving a best overall response of complete remission (CR), as assessed by investigator's review
• Area Under the Curve From Time Zero to Last Measurable Concentration (AUClast) for Sonrotoclax [Up to approximately 1 month]
• Maximum Observed Plasma Concentration (Cmax) for Sonrotoclax [Up to approximately 1 month]
• Plasma Concentration Measured Immediately Prior to the Next Scheduled Dose (Ctrough) for Sonrotoclax [Up to approximately 1 month]
• Time to Maximum Observed Plasma Concentration (Tmax) for Sonrotoclax [Up to approximately 1 month]

Sex: All, ages: 6 Months to 17 Years

Key Inclusion Criteria

Participants must meet all of the following criteria to be eligible for participation:

1. Have a performance status of Lansky ≥50 for participants ≤16 years of age or Karnofsky ≥50 for participants >16 years of age.
2. Have adequate renal function, defined as an estimated or measured glomerular filtration rate (GFR) ≥60 mL/min.
3. Have adequate hepatic function, defined as:

   * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5 × the institutional upper limit of normal (ULN)
   * Total bilirubin ≤1.5 × the institutional ULN.
4. Have minimum cardiac function as defined in the study protocol.

Acute Myeloid Leukemia (AML)-Specific Inclusion Criteria

1. Have a histologically confirmed diagnosis of acute myeloid leukemia (AML) that is relapsed or refractory (R/R) after ≥2 prior lines of systemic therapy.
2. Have ≥5% blasts in a bone marrow aspirate or biopsy sample, as assessed by morphology. Participants with extramedullary, non-central nervous system (CNS) disease are eligible.

B-Cell Precursor Acute Lymphoblastic Leukemia (ALL)-Specific Inclusion Criteria

1. Have a histologically confirmed diagnosis of B-cell precursor acute lymphoblastic leukemia (ALL) that is R/R after ≥2 prior lines of systemic therapy, including at least 1 line of blinatumomab-based therapy.
2. Have ≥5% blasts in a bone marrow aspirate or biopsy sample, as assessed by morphology.
3. Have leukemic blasts expressing cluster of differentiation 22 (CD22) on the cell surface, as assessed by flow cytometry of a bone marrow aspirate.

Key Exclusion Criteria

Participants will be excluded from participation if any of the following apply:

1. Have central nervous system (CNS) 2 or CNS 3 disease at screening.
2. Have toxicity from prior anticancer therapy that has not recovered to ≤Grade 1, as defined by the applicable toxicity grading criteria.
3. Have a history of prior allogeneic stem cell transplantation <90 days from enrollment or if if ≥ 90 days from enrollment, with active graft-versus-host disease (GVHD), or requiring immunosuppressive drugs for treatment of GVHD, or have taken calcineurin inhibitors within 4 weeks prior to consent.

AML-Specific Exclusion Criteria

1. Have a diagnosis of acute promyelocytic leukemia (APL) or juvenile myelomonocytic leukemia (JMML).
2. Have AML with fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD), as determined by local assessment.

ALL-Specific Exclusion Criteria

1. Have Philadelphia chromosome-positive (Ph+) ALL with a breakpoint cluster region::Abelson murine leukemia viral oncogene homolog 1 (BCR::ABL1) fusion.
2. Have received prior therapy with a B-cell lymphoma 2 (BCL-2) inhibitor.

Note: Other eligibility criteria may apply.

• Study Director, Study director, BeOne Medicines