Study to Determine the Dose and Safety of Asciminib in Pediatric Patients With Chronic Myeloid Leukemia

The aim of this study is to support development of asciminib in the pediatric population
(1 to <18 years) previously treated with one or more TKIs. Full extrapolation of the
efficacy of asciminib from adult to pediatric patients will be conducted. Full
extrapolation is based on the concept that CML in the pediatric population has the same
pathogenesis, similar clinical characteristics and progression pattern as in adults. The aim of this study is to support development of asciminib in the pediatric population
(1 to <18 years) with Philadelphia chromosome positive chronic myeloid leukemia in
chronic phase (PH+ CML-CP) previously treated with one or more Tyrosine kinase inhibitor
(TKIs).

The primary objective of this study is to characterize the pharmacokinetic (PK) profile
of asciminib in pediatric patients with the goal of identifying the pediatric formulation
dose (fed) leading to asciminib exposure comparable to 40 mg BID in adult patients
(fasted).

The pediatric formulation group will include at least 15 participants in each of the
following two age categories: 1 to <12 years and 12 to <18 years; leading to at least 30
participants enrolled treated with the pediatric formulation. It will consist of a dose
determination part (Part 1) and a cohort expansion (Part 2 BID regimen and Part 3 QD
regimen).

In Part 1, 4-6 participants will be enrolled in order to obtain at least 4 participants
evaluable for PK (these participants may be from either of the age categories described
above). The initial starting dose will be based on body weight and will be administered
BID with food.

Once the body weight adjusted dose has been determined in Part 1 of the study, the
patients will be enrolled in Part 2 until at least 20 participants, including those who
were included in Part 1, have been enrolled (10 per age group) in the pediatric
formulation group. Once the interim safety and PK analysis 2 is completed for one of the
age groups, the Part 3 QD regimen will open for the respective age group to enroll 10
patients (5 patients by age group).

Due to the fact that the pediatric formulation was in development and was not available,
this study started with the recruitment of adolescent patients. These participants aged
14 to <18 years, weighing at least 40 kg receive the adult formulation at a flat dose of
40 mg BID under fasted conditions.

The total duration of the treatment period of the study will be 5 years (260 weeks).
Participants who, according to Investigator's judgement, are benefiting from study
treatment will remain on treatment up to the completion of the treatment period (Week
260/5 years). The primary analysis for the BID regimen is planned after all participants
in Part 1 and 2 have completed at least 52 weeks of study treatment or discontinued
earlier.

The primary analysis for combined regimen (BID+QD) is planned after all participants in
Part 1, 2 and 3 have completed at least 52 weeks of study treatment or discontinued
earlier.