Comparing Asciminib and Bosutinib in Resistant CML
Posted: Thursday, August 8, 2019
After a phase I trial revealed that the BCR-ABL1 inhibitor asciminib demonstrated clinical activity and a tolerable safety profile in patients with chronic myeloid leukemia (CML) who are intolerant or resistant to current BCR-ABL1 ATP-binding site–targeted tyrosine kinase inhibitors (TKIs), investigators announced at the 2019 American Society of Clinical Oncologists (ASCO) Annual Meeting a phase III study to evaluate asciminib versus bosutinib in this patient population (Abstract TPS7070). The study is being conducted by Michael J. Mauro, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues.
Previously, the phase I study (ClinicalTrials.gov identifier NCT02081378) revealed that for patients with CML who were resistant or intolerant to two or more TKIs, or who had T3151 mutation, asciminib showed clinical activity and safety. For the patients without T3151 mutation, the trial established that 40 mg of asciminib administered twice daily was the recommended dose.
In the ongoing phase III trial (NCT03106779), which is being conducted in 149 sites in 30 countries, the investigators anticipate an enrollment of 222 patients diagnosed with chronic phase CML. Patients must have received two or more TKIs and have exhibited an intolerance or failure to the most recent TKI. Patients with T3151 or V299L mutation will be excluded from the study.
Patients will be randomly assigned to receive either 40 mg of asciminib twice daily or 500 mg of bosutinib once daily. The investigators will compare the rate of major molecular responses between the two therapies at 24 and 96 weeks. Dr. Mauro and colleagues recently lowered the baseline BCR-ABL1 threshold for patient enrollment from at least 1% or more to more than 0.1%. This revision was added to be consistent with current clinical practices and to “satisfy the treatment need to avoid waiting for an increase in BCR-ABL1 levels to ≥ 1%.”
Disclosure: The study authors’ disclosure information may be found at coi.asco.org.