Asciminib Monotherapy, With Dose Escalation, for 2nd and 1st Line Chronic Myelogenous Leukemia

Summary

Objectives

This trial consists of three periods: screening and baseline for up to 28 days, active
treatment for up to 104 weeks and a safety follow up period for 30 days.

Ninety-two (92) 2L patients with CML-CP without T315I mutation who had 1 prior
ATP-binding site TKI discontinued due to treatment failure, warning or intolerance will
be considered for the current study. Patients will be tested at screening for the T315I
mutation and excluded if the mutation is found.

To gain additional insights into the effect of asciminib in the 1L setting, an additional
cohort of newly diagnosed CML-CP patients will be enrolled in the study. Based on the
number of participating sites, it is approximated that between 60 and 90 patients could
be enrolled. Enrollment of the 1L cohort will be stopped when a maximum of 90 patients
have been enrolled or when approximately 60 patients have been enrolled and the 2L cohort
is fully recruited, whichever comes first.

Informed consent will be obtained before any procedures are performed for the study
including eligibility assessments.

All eligible patients will be initially treated with asciminib at 80 mg QD. At 6 months
of study treatment, patients who have achieved BCR-ABL1IS =1% will continue on the same
dose whereas those who have not will increase dose to 200mg QD.

At 12 months of study treatment, patients will be evaluated for the primary endpoint of
the study (MMR at 12 month in 2L patient cohort) and will pursue one of the following:

- Continue on the current dose of asciminib if MMR is achieved

- Increase dose to 200 mg QD if on 80 mg QD dosing and MMR is not achieved

- Increase dose to 200 mg BID if on 200 mg QD dosing and MMR is not achieved

- Take the patient off the study and switch to Investigator's agent of choice if MMR
is not achieved and it is in the interest of the patient based on investigator's
clinical judgment of prospect treatment benefit.