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

A Phase 1/2a, Open-Label, Dose Finding and Expansion Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of Sonrotoclax (BGB-11417) in Combination With Other Agents in Pediatric Patients Aged 6 Months to 17 Years, With Relapsed or Refractory Acute Myeloid Leukemia and B-cell Acute Lymphoblastic Leukemia

The goal of this clinical trial is to learn if sonrotoclax (BGB-11417) is safe and may help treat children and adolescents with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) that has come back after treatment or has not responded to treatment. The study will also learn how the body processes sonrotoclax when it is given with other medicines. The main questions it aims to answer are:

• Is sonrotoclax safe and well tolerated when given with other anti-cancer medicines?
• How does the body absorb, process, and remove sonrotoclax?
• Does treatment with sonrotoclax, in combination with other medicines, help reduce or eliminate leukemia?

Researchers will give sonrotoclax together with other anti-cancer medicines to participants with relapsed or refractory AML or ALL. Participants will:

• Take sonrotoclax in combination with other anti-cancer medicines
• Have regular clinic visits for physical exams, blood tests, heart monitoring, and other safety assessments.
• Provide blood samples to measure how the body processes sonrotoclax.
• Have tests to evaluate how their leukemia responds to treatment.
• Continue treatment as long as it is helping and side effects remain manageable, according to the study plan.

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.