Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Neoplasms by Histologic Type

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Myeloid Leukemia

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

All Drugs and Chemicals

Amino Acids

Asciminib

Bosutinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients were randomized to asciminib 40mg BID

Patients were randomized to bosutinib 500mg QD

40 mg tablets was taken orally twice a day (BID)

500 mg tablets was taken orally once daily (QD)

Novartis Pharmaceuticals

The purpose of this pivotal study was to compare the efficacy of asciminib (ABL001) with that of bosutinib in the treatment of patients with CML-CP having previously been treated with a minimum of two prior ATP-binding site TKIs.

Patients intolerant to the most recent TKI therapy must have had BCR-ABL1 ratio \> 0.1% IS at screening and patients failing their most recent TKI therapy must have met the definition of treatment failure as per the 2013 European LeukemiaNet (ELN) recommendations.

Patients with documented treatment failure as per 2013 ELN recommendations while on bosutinib treatment had the option to switch to asciminib treatment within 96 weeks after the last patient has been randomized on study.

Patients were randomized in a 2:1 ratio to asciminib 40 mg BID or bosutinib 500 mg QD. Randomization was stratified by major cytogenetic response (MCyR) at screening. Patients with documented treatment failure (specifically meeting lack of efficacy criteria adapted from the 2013 ELN recommendations) while on bosutinib treatment were offered the option to switch to asciminib treatment within 96 weeks after the last patient was randomized to the study.

Study of Efficacy of CML-CP Patients Treated With ABL001 Versus Bosutinib, Previously Treated With 2 or More TKIs

A Phase 3, Multi-center, Open-label, Randomized Study of Oral ABL001 Versus Bosutinib in Patients With Chronic Myelogenous Leukemia in Chronic Phase (CML-CP), Previously Treated With 2 or More Tyrosine Kinase Inhibitors

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com

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

To compare additional parameters of the efficacy asciminib versus bosutinib

To compare additional parameters of the efficacy of asciminib versus bosutinib. Cytogenic response will include Complete, Partial, Major, Minor, Minimal and no response.

To compare additional parameters of the efficacy of asciminib versus bosutinib

To characterize the PK of asciminib in the CML-CP population

Adverse Event (AE): Any sign or symptom that occurs during treatment plus 30 days after study treatment discontinuation.

Adverse events were analyzed in the Safety analysis set, which comprises all patients who received at least one dose of study treatment.

Patients randomized to asciminib 40mg BID

Patients randomized to bosutinib 500mg QD

Total

Age, Continuous

Sex: Female, Male

White

Asian

Black or African American

American Indian or Alaska Native

Other

Unknown

Race/Ethnicity, Customized

Full Analysis Set (FAS): The FAS comprised of all randomized patients.

In the asciminib arm, 2 patients died on-treatment and 2 patients died during survival follow-up. In the bosutinib arm, 1 patient died on-treatment.

Clinical Disclosure Office

Number of Participants With Major Molecular Response (MMR) Rate at 24 Weeks

Number of Participants With Major Molecular Response (MMR) Rate

Complete Cytogenetic Response Rate

Time to MMR

Duration of MMR

Time to CCyR

Duration of CCyR

Time to Treatment Failure

Progression Free Survival

Overall Survival

Trough Plasma Concentrations

PK Parameter: Cmax,

PK Parameter: Tmax

PK Parameter: AUC0-12h

PK Parameter: CL/F

Overall Study

Antineoplastic Agents

Micronutrients

Vasodilator Agents

Lipid Regulating Agents

Hematinics

Vitamins

Nilotinib

Imatinib Mesylate

Niacinamide

Niacin

Nicotinic Acids

Folic Acid

Vitamin B Complex

Trace Elements

Nicotinamide

Nicotinic Acid

Vitamin B3

Folate

Vitamin B9

Asciminib 60 mg taken once daily in combination with Imatinib 400 mg taken once daily

Asciminib 40 mg taken once daily in combination with Imatinib 400 mg taken once daily

Asciminib 60 mg or 40 mg taken orally once daily.

Asciminib add-on

Imatinib

Nilotinib 300 mg taken orally twice daily (total daily dose of 600 mg)

Asciminib single agent

To evaluate efficacy, safety and pharmacokinetic profile of asciminib 40mg+imatinib or asciminib 60mg+imatinib versus continued imatinib and versus nilotinib versus asciminib 80mg in pre-treated patients with Chronic Myeloid Leukemia in chronic phase (CML-CP)

The study is a Phase 2, multi-center, open-label, randomized study of asciminib in two different doses (40 mg or 60 mg) in combination with imatinib 400 mg versus continued imatinib versus switch to nilotinib, versus asciminib 80mg single agent in subjects with chronic myeloid leukemia in chronic phase (CML-CP) who have been previously treated with imatinib first line therapy for at least one year and have not achieved deep molecular response (DMR). Eighty-four eligible subjects were randomized 1:1:1:1 to receive asciminib 60 mg once daily (QD) as add-on therapy to imatinib 400 mg QD, or 40 mg QD as add-on therapy to imatinib 400 mg QD, or to continue imatinib 400 mg QD, or to switch to nilotinib 300 mg twice a day (BID).

The asciminib single agent cohort will be conducted as an open label cohort. Approximately 20 eligible subjects will be enrolled to receive asciminib 80 mg QD. Amendment 3 aims to add the asciminib single agent cohort to assess whether asciminib single agent at the recommended dose of 80mg QD leads to similar efficacy and safety as observed in the add-on arms of asciminib and imatinib. This additional cohort will help to evaluate if the combination of asciminib with imatinib is needed to increase the likelihood of achieving DMR, or if this can be achieved by asciminib alone.

An interim analysis was performed to gain an early insight into the safety and efficacy of the asciminib add-on combination. The interim analysis was planned to be performed when at least 40 (50%) patients have been randomized and have been followed for their 24 weeks visit assessment or have discontinued treatment. The interim analysis cut-off was on 22-July-2020. No change in study conduct were performed based on the benefit/risk balance.

The primary analysis cut-off was on 10-Jan-2022. Eighty-four patients have been randomized in the study.

Subjects on the imatinib continuation arm who had not achieved MR4.5 at 48 weeks were allowed to cross-over (CO) to receive the add-on treatment within 4 weeks after week 48 visit. to receive the asciminib 60 mg combination add-on treatment, as this dose provided higher exposure. The cross-over is at the discretion of the investigator and the patient. Apart from a polymerase chain reaction (PCR) result of below MR4.5 at Week 48 visit, there are no other entry criteria for the cross-over part. Subjects on nilotinib are not allowed to cross- over to receive the add-on treatment.

Subjects on the study will continue on the allocated treatment until treatment failure, intolerability, or for up to 96 weeks (in arms 1 to 4) / or 48 weeks (in asciminib single agent cohort) after the last randomized subject received the first dose of treatment. After the last dose received, every subject will be followed up for safety for 30 days.

Treatment arms 1 - 4 randomized; New Treatment arm 5 (asciminib single agent cohort) not randomized

Study of Efficacy and Safety of Asciminib in Combination With Imatinib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP)

A Phase 2, Multi-center, Open-label, Randomized Study of Oral Asciminib Added to Imatinib Versus Continued Imatinib Versus Switch to Nilotinib in Patients With CML-CP Who Have Been Previously Treated With Imatinib and Have Not Achieved Deep Molecular Response

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

Percentage of subjects still treated with the randomized treatment at 48 weeks and are in MR4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 48 weeks (± assessment window), among all subjects randomized to the respective treatment arm.

Percentage of subjects with MR\^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 48 weeks between asciminib+imatinib and nilotinib

Difference in the percentage of subjects with MR\^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 48 weeks between asciminib+imatinib and nilotinib

Percentage of subjects with MR\^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 96 weeks

Best observed rate of MR\^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) under randomized treatment up to the specific time point

Percentage of participants who are in MR\^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 96 weeks and who have no loss of MR\^4.5.

Time to MR\^4.5 is the time from randomization to first MR\^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) computed only for subjects who achieved MR\^4.5

Time from first MR\^4.5 until loss of MR\^4.5 (BCR-ABL1 ratio of ≤ 0.0032%).

To characterize the safety and tolerability profile of asciminib 60 mg or 40 mg + imatinib vs continued imatinib or switch to nilotinib or asciminib 80mg QD

The maximum (peak) observed drug concentration after dose administration

The time to reach maximum (peak) drug concentration after dose administration

The AUC from time zero to the last measurable concentration sampling time (Tlast)

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

The percentage of subjects on asciminib 80mg QD with MR\^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 48 weeks

For subjects on asciminib 80mg QD: Time to MR\^4.5 is the time from randomization to first MR\^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) computed only for subjects who achieved MR\^4.5

Time from first MR\^4.5 until loss of MR\^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) for subjects on asciminib 80mg QD

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Efficacy of CML-CP Patients Treated With ABL001 Versus Bosutinib, Previously Treated With 2 or More TKIs	NCT03106779	Chronic Myeloge...	Asciminib Bosutinib	18 Years -	Novartis
Study of Efficacy and Safety of Asciminib in Combination With Imatinib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP)	NCT03578367	CML Chronic Myeloge... Leukemia, Myelo... Hematologic Dis...	Asciminib add-o... Imatinib Nilotinib Asciminib singl...	18 Years -	Novartis
Study of Efficacy and Safety of Asciminib in Combination With Imatinib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP)	NCT03578367	CML Chronic Myeloge... Leukemia, Myelo... Hematologic Dis...	Asciminib add-o... Imatinib Nilotinib Asciminib singl...	18 Years -	Novartis
Study of Efficacy of CML-CP Patients Treated With ABL001 Versus Bosutinib, Previously Treated With 2 or More TKIs	NCT03106779	Chronic Myeloge...	Asciminib Bosutinib	18 Years -	Novartis

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