Asciminib in Monotherapy for Chronic Myeloid Leukemia in Chronic Phase (CML-CP) With and Without T315I Mutation

Inclusion Criteria

Participants eligible for inclusion in this study must meet all of the following criteria:

• Written informed consent must be obtained and signed prior to participation in the study
• Male or female patients with a diagnosis of CML-CP ≥ 18 years of age
• Patients must meet all of the following laboratory values at the screening visit:
• 10% BCR-ABL1 on International Scale (IS) if confirmed within 1-3 months
• Six months after the initiation of therapy: BCR-ABL1 ratio > 10% IS
• Twelve months after initiation of therapy: BCR-ABL1 ratio > 1% IS
• At any time after the initiation of therapy, loss of CHR, MR2
• At any time after the initiation of therapy, the development of new BCR-ABL1 mutations which potentially cause resistance to current treatment
• At any time 12 months after the initiation of therapy, BCR-ABL1 ratio ≥ 1% IS or loss of MMR
• At any time after the initiation of therapy, new clonal chromosome abnormalities in Ph+ cells: CCA/Ph+
• Intolerance is defined as:
• Non-hematologic intolerance: Patients with grade 3 or 4 toxicity while on therapy, 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: Patients 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 recommended by manufacturer
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2
• Evidence of typical BCR-ABL1 transcript [e14a2 and/or e13a2] at the time of screening which are amenable to standardized RQ-PCR quantification.
• Adequate end organ function, within 12 days before the first dose of asciminib treatment. Patients with mild to moderate renal and hepatic impairment are eligible if:
• Total bilirubin ≤ 3.0 x ULN without AST/ALT increase
• Aspartate transaminase (AST) ≤ 5.0 x ULN
• Alanine transaminase (ALT) ≤ 5.0 x ULN
• Serum lipase ≤ 1.5 x ULN. For serum lipase > ULN - ≤ 1.5 x ULN, value should be considered not clinically significant and not associated with risk factors for acute pancreatitis
• Alkaline phosphatase ≤ 2.5 x ULN
• Creatinine clearance ≥ 30 mL/min as calculated using Cockcroft-Gault formula
• Patients must avoid consumption of grapefruit, Seville oranges or products containing the juice of each during the entire study and preferably 7 days before the first dose of study medications, due to potential CYP3A4 interaction with the study medications. Orange juice is allowed.
• Treatment with medications that meet one of the following criteria is allowed if used with caution at least one week prior to the start of treatment with study treatment:
• Moderate or strong inducers of CYP3A
• Moderate or strong inhibitors of CYP3A
• Patients must have the following electrolyte values (as per central laboratory tests) within normal limits or corrected to be within normal limits with supplements prior to first dose of study medication:
• Potassium (potassium increase of up to 6.0 mmol/L is acceptable at study entry if associated with creatinine clearance within normal limits)
• Total calcium (corrected for serum albumin); (calcium increase of up to 12.5 mg/dl or 3.1 mmol/L is acceptable at study entry if associated with creatinine clearance within normal limits)
• Magnesium, with the exception of magnesium increase > ULN - 3.0 mg/dL; > ULN - 1.23 mmol/L associated with creatinine clearance (calculated using Cockcroft-Gault formula) within normal limits.

Exclusion Criteria

Patients eligible for this study must not meet any of the following criteria:

• Known second chronic phase of CML after previous progression to AP/BC
• Previous treatment with a hematopoietic stem-cell transplantation
• Cardiac or cardiac repolarization abnormality, including any of the following:
• History within 6 months prior to s