Study to Determine the Efficacy and Safety of Asciminib in Pediatric Patients With Ph+ CML-CP

This is a multi-center, open-label, single arm study of asciminib in pediatric participants aged

1 to \<18 years old with Ph+ CML-CP newly diagnosed and previously treated with TKI treatment, with or without T315I mutation.

The study population will consist of three cohorts of Ph+ CML-CP pediatric participants:

• Newly-diagnosed Ph+ CML-CP participants without known T315I mutation
• Ph+ CML-CP participants resistant or intolerant to previous TKI without known T315I mutation
• Ph+ CML-CP participants with known T315I mutation irrespective of prior TKI treatment

There is no fixed duration of study treatment for the participants. The study will end 5 years (240 weeks) after the last enrolled participants received their first dose of treatment in the study. The objective is to have enough follow up for safety, including growth and development and efficacy.

This study will enroll pediatric patients (≥ 1 and \< 18 years of age) with newly diagnosed or previously treated with Philadelphia positive Chronic Myelogenous Leukemia in Chronic Phase (Ph+ CML-CP) with or without known T315I mutation

Drug: Asciminib single agent

Asciminib (labelled as ABL001) administered as 40 mg tablet (adult formulation) or as 1 mg film-coated granules mini-tablets (pediatric formulation)

Plazo: 48 weeks

MMR is defined as BCR::ABL1 IS ≤0.1%. MMR is defined as a ≥ 3.0 log reduction in BCR::ABL1 transcripts compared to the standardized baseline equivalent to ≤ 0.1 % BCR::ABL1/ABL % by international scale as measured by RQ-PCR.

Plazo: 96 weeks

MMR is defined as BCR::ABL1 IS ≤0.1%. MMR is defined as a ≥ 3.0 log reduction in BCR::ABL1 transcripts compared to the standardized baseline equivalent to ≤ 0.1 % BCR::ABL1/ABL % by international scale as measured by RQ-PCR.

Plazo: Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, and 96

MMR is defined as BCR::ABL1 IS ≤0.1%. MMR is defined as a ≥ 3.0 log reduction in BCR::ABL1 transcripts compared to the standardized baseline equivalent to ≤ 0.1 % BCR::ABL1/ABL % by international scale as measured by RQ-PCR.

Plazo: Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, and 96

Complete hematologic response (CHR) is defined as all of the following present for ≥ 4 weeks (which means present at least at 2 visits 4-week apart, with no intermediate visit showing no CHR):

• White blood cell(s) (WBC) count \< 10 x 10\^9/L
• Platelet count \< 450 x 10\^9/L
• Basophils \< 5%
• No blasts and promyelocytes in peripheral blood
• Myelocytes + metamyelocytes \< 5% in peripheral blood
• No evidence of extramedullary disease, including spleen and liver

Plazo: 5 years

Cytogenetic response is defined as follows:

• Complete (CCyR) - 0% Ph+ metaphases
• Partial (PCyR) - \>0 to 35% Ph+ metaphases
• Major\* (MCyR) - 0 to 35% Ph+ metaphases
• Minor (mCyR) - \>35 to 65% Ph+ metaphases
• Minimal - \>65 to 95% Ph+ metaphases
• None - \>95 to 100% Ph+ metaphases Bone marrow aspirate for cytogenetic analyses will be performed at screening, and upon unfavorable response to treatment at the physician's discretion.

Plazo: 240 weeks after the last participant enrolled in the study received the first dose of treatment

Time to the first response is defined as: date of the first documented occurrence of the response or time from first study drug intake to first response - date of the first study treatment intake + 1.

Plazo: 240 weeks after the last participant enrolled in the study received the first dose of treatment

Duration of response is defined as the time between the date of the first documented occurrence of the response and the earliest date of confirmed loss of the response, progression to accelerated phase/blast crisis (AP/BC) or CML-related death for participants in the respective Responder Set.

Plazo: 240 weeks after the last participant enrolled in the study received the first dose of treatment

TTF is defined as the time from the first study drug intake to the first/earliest documented date of any of the following events: unfavorable response to treatment, confirmed loss of MMR at any time while on study treatment and discontinuation from study treatment due to any reason.

Plazo: 5 years

No informado en este registro.

Plazo: 240 weeks after the last participant enrolled in the study received the first dose of treatment

EFS is defined as the time from the first study drug intake to the earliest occurrence of the following events: unfavorable response to treatment, confirmed loss of MMR at any time while on study treatment, discontinuation from the study treatment due to an adverse event (AE) and death due to any cause.

Plazo: 240 weeks after the last participant enrolled in the study received the first dose of treatment

OS is defined as the time from the first study drug intake to the date of death from any cause during the study (including death observed during the survival follow-up period after discontinuation of study treatment).

Plazo: 240 weeks after the last participant enrolled in the study received the first dose of treatment

To assess growth and sexual maturation. An X-ray of the left hand and wrist to assess bone age will be performed at screening and every 48 weeks until end of treatment (EOT). This assessment will no longer be required for participants once bone maturity in post-puberty stage is confirmed by the last X-ray.

Plazo: 240 weeks after the last participant enrolled in the study received the first dose of treatment

To assess growth and sexual maturation. Tanner staging will be based on external genitalia, breast and pubic hair examination. Tanner staging will be assessed for all study participants at screening. Participants who do not have a baseline Tanner Stage of 5 will continue to be assessed every 24 weeks until achievement of Tanner Stage 5 on both secondary sexual characteristics or EOT, whichever comes first. Once a participant reaches stage 5, examinations do not need to be conducted anymore. For all male participants, Tanner Stage 5 will be achieved once the participant has demonstrated both stage 5 genitalia development and stage 5 pubic hair development. For all female participants, Tanner Stage 5 will be achieved once the participant has demonstrated both stage 5 breast development and stage 5 pubic hair development.

Plazo: Week 2, Day 1 at 1, 3 and 6 hours post dose

AUClast: The AUC from time zero to the last measurable concentration sampling time.

Plazo: Week 2, Day 1: pre dose (0 hour), Week 2: Day 1 at 1, 2, 3, and 6 hours post-dose

AUCtau: The AUC calculated to the end of a dosing interval (tau) at steady-state.

Plazo: Week 2, Day 1 at 1, 3, and 6 hours post dose

Cmax is the maximum (peak) observed plasma drug concentration after single dose administration.

Plazo: Week 2, Day 1 at 1, 3, and 6 hours post dose

Tmax is the time to reach maximum (peak) plasma drug concentration (h) after administration.

Plazo: Week 2, Day 1: pre-dose (0 hr), Week 24: pre-dose (0 hr), Week 48: Pre-dose (0 hr)

Ctrough refers to the lowest concentration a drug reaches in the bloodstream immediately before the next dose is administered.

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