A Phase II, Multicenter, Open-label, Single Arm Study to Evaluate the Safety and Efficacy of Asciminib in Pediatric Participants Newly Diagnosed or Previously Treated With Philadelphia Positive Chronic Myelogenous Leukemia in Chronic Phase (Ph+ CML-CP) With or Without Known T315I Mutation
The aim of this study is to support development of asciminib in the pediatric population (1 to \< 18 years) with Ph+ CML-CP. The study will evaluate the efficacy and safety of asciminib in pediatric formulation (weigh-based dose, fed state) or adult formulation (fasted) in newly diagnosed and resistant or intolerant Ph+ CML-CP with or without T315I mutation.
⁃ Participants eligible for inclusion in this study must meet all of the following criteria:
• Signed informed consent must be obtained prior to participation in the study.
• Male or female participants 1 and \< 18 years of age at study enrollment
• Diagnosis of CML-CP (Apperley et al 2025) with cytogenetic confirmation of Philadelphia positive (Ph+) chromosome
• For participants with CML-CP newly diagnosed within 3 months of screening OR 5 For participants with CML - CP with high risk of developing resistance or intolerance to previous TKI:
‣ Unfavourable response to TKI is defined following the Apperley et al 2025 guidelines as:
• At three months after the initiation of therapy: BCR::ABL1 ratio \> 10% IS (if confirmed within 1-3 months)
∙ At six months after the initiation of therapy: BCR::ABL1 ratio \> 10% IS
∙ At twelve months after initiation of therapy: BCR::ABL1 ratio \> 1% IS
∙ At any time loss of previous response
∙ At any time emergent resistant BCR::ABL1 mutations or high-risk ACA from prior TKI treatment as per local test results
⁃ Intolerance to TKI is defined as:
• Non-hematologic intolerance: participants with grade 3 or 4 toxicity while on therapy (in which case the patient is eligible whether or not there was a dose reduction); or with persistent grade 2 toxicity unresponsive to optimal management including dose adjustments (unless dose reduction is not considered in the best interest of the patient if response is already suboptimal)
∙ Hematologic intolerance: participants with grade 3 or 4 toxicity (absolute neutrophil count \[ANC\] or platelets) while on therapy that is recurrent after dose reduction to the lowest doses of the TKI
⁃ 6\. Evidence of typical BCR::ABL1 transcript \[e14a2 and/or e13a2\] at the time of screening which are amenable to standardized RQ-PCR quantification.
⁃ 7\. Performance status: Karnofsky ≥ 50% for participants ≥ 16 years of age, and Lansky ≥ 50 for participants \< 16 years of age at the time of screening.