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Amino Acids

Asciminib

Tyrosine Kinase Inhibitors

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Tyrosine

80 mg once daily at approximately the same time each day or 40 mg twice daily per Investigator's discretion at approximately 12-hour intervals

200 mg twice daily at approximately 12-hour intervals

Film-coated tablets with 40 mg dose strength taken orally

Novartis Pharmaceuticals

The Drugs Controller General of India (DCGI) has granted approval for Asciminib film-coated 40 mg tablets on 20 Oct 2023 with the condition to perform a Phase IV clinical study in Indian patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) per the India Prescribing Information (PI). The purpose of this prospective, multicenter, single-arm, open-label, Phase IV study is, therefore, to confirm the safety and efficacy of Asciminib in Indian patients with Ph+ CML-CP (without threonine-315 residue with isoleucine \[T315I\] mutation), previously treated with 2 or more tyrosine kinase inhibitors (TKIs) and patients with Ph+ CML-CP with T315I mutation.

This is a Phase IV, prospective, multicenter, single-arm, open-label, post-authorization interventional study to assess the safety and efficacy of asciminib in Indian participants with Ph+ CML-CP (without T315I mutation), previously treated with 2 or more TKIs and participants with Ph+ CML-CP with T315I mutation irrespective of the line of treatment.

The study will include 3 periods: a screening period (up to 21 days), a treatment period of up to 6 months with asciminib (with dosing according to mutation status), and a safety follow-up period for 30 days after the last dose of the study treatment. Completion of the safety follow-up period after the last dose of the study treatment will be considered as the End of Study (EOS).

After obtaining the written informed consent form (ICF) from the participant or their legally authorized representatives (LARs), the participants will undergo screening procedures to confirm their eligibility for the study.

The results of the breakpoint cluster region gene-Abelson proto-oncogene 1, nonreceptor tyrosine kinase gene (BCR::ABL1) real-time quantitative polymerase chain reaction (RQ-PCR) as well as the T315I mutation report need to be established and documented prior to enrollment into the study in the screening period in line with the inclusion criteria of the study. Participants with previously documented T315I mutated CML-CP will be directly considered for the screening procedures. If the status of the T315I mutation is not known, the participant will undergo a standardized Sanger sequencing/PCR/next-generation sequencing (NGS)-based T315I mutation test (as per the availability at the site).

Clinical Study of Asciminib in Previously Treated Indian Patients With Ph+ CML-CP Without T315I Mutation and in Patients With Ph+ CML-CP With T315I Mutation

A Prospective, Multicenter, Single-arm, Open-label, Phase IV, Post-authorization Interventional Study to Assess the Safety and Efficacy of Asciminib in Indian Patients With Ph+ CML-CP (Without T315I Mutation), Previously Treated With Two or More Tyrosine Kinase Inhibitors and Ph+ CML-CP With T315I Mutation

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 review 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 availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Frequency and severity of adverse events(AEs)/serious AEs (SAEs) in participants with Ph+ CML-CP (without T315I mutation), previously treated with 2 or more TKIs up to 6 months

Frequency and severity of AEs/SAEs in participants with Ph+ CML-CP with T315I mutation up to 6 months

Percentage of participants with dose interruptions, reductions, and discontinuation up to 6 months.

A CHR is defined as the presence of all of the following for ≥4 weeks: white blood count (WBC) \<10 x 109/L, platelet count \<450 x 109/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.

Levels of BCR::ABL1 transcripts will be determined by RQ-PCR testing of peripheral blood and analyzed at a central testing laboratory. Log reduction in BCR::ABL1 transcripts levels from the standardized baseline value, or the percent ratio of BCR::ABL1 transcripts versus control gene (ABL1) transcripts converted to a reference standard, will be calculated for each sample.

Early molecular response (EMR) is defined as ≤10% BCR::ABL1 international scale (IS).

Levels of BCR::ABL1 transcripts will be determined by RQ-PCR testing of peripheral blood and analyzed at a central testing laboratory. Log reduction in BCR::ABL1 transcripts levels from the standardized baseline value, or the percent ratio of BCR::ABL1 transcripts versus control gene (ABL1) transcripts converted to a reference standard, will be calculated for each sample. The rate of MR2 is defined as ≥2 log reduction of BCR::ABL (transcript from standardized baseline or ≤1% BCR::ABL/ABL1 % by IS), measured by RQ-PCR.

Levels of BCR::ABL1 transcripts will be determined by RQ-PCR testing of peripheral blood and analyzed at a central testing laboratory. Log reduction in BCR::ABL1 transcripts levels from the standardized baseline value, or the percent ratio of BCR::ABL1 transcripts versus control gene (ABL1) transcripts converted to a reference standard, will be calculated for each sample. Major molecular response (MMR) is defined as ≤0.1% BCR::ABL1 on the IS.

Levels of BCR::ABL1 transcripts will be determined by RQ-PCR testing of peripheral blood and analyzed at a central testing laboratory. Log reduction in BCR::ABL1 transcripts levels from the standardized baseline value, or the percent ratio of BCR::ABL1 transcripts versus control gene (ABL1) transcripts converted to a reference standard, will be calculated for each sample.

MR4 is defined ≤0.01% BCR::ABL1 on the IS. MR4.5 is defined as ≤0.0032% BCR::ABL1 on the IS.

Time to achieve a response level (hematologic or molecular) is defined as the time from the date of the first dose of study treatment to the first documented achievement of each defined response level. It will be calculated for the treatment duration ie, up to 6 months from baseline.

Duration of Response (DOR) is the time from the date of the first documented hematologic or molecular response level to the date of the first documented loss of the response level or death due to any cause, whichever occurs first. It will be calculated for the treatment duration ie, up to 6 months from baseline.

ime to achieve a response level (hematologic or molecular) is defined as the time from the date of the first dose of study treatment to the first documented achievement of each defined response level. It will be calculated for the treatment duration ie, up to 6 months from baseline.

Spots Global Cancer Trial Database for with the t315i mutation