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

Inclusion Criteria:

• Signed informed consent must be obtained prior to participation in the study.

• Male or female participants ≥18 years of age at the screening visit with a confirmeddiagnosis of Ph+ CML-CP.

Participants must meet all of the following laboratory values as confirmed by the available reports of the peripheral blood test or bone marrow examination (performed within 12 months before the screening) at the screening visit to meet the criteria of Ph+ CML-CP:

• <15% blasts in peripheral blood and/or bone marrow

• <30% blasts plus promyelocytes in peripheral blood and/or bone marrow

• <20% basophils in the peripheral blood

• ≥50 x 109/L (≥50,000/mm3) platelets#

• No evidence of extramedullary leukemic involvement, apart from hepatosplenomegaly.

#Transient prior therapy related thrombocytopenia (<50,000/mm3 for ≤30 days prior toscreening) is acceptable.

• a. For Ph+ CML-CP participants with T315I mutation, mutational analysis testing atany time point showing a documented T315I mutation. b. For Ph+ CML-CP participants without T315I mutation, at least 2 prior ATP-siteTKIs (i.e., imatinib, nilotinib, bosutinib, dasatinib, or ponatinib) with failure* (adapted from the 2020 European LeukemiaNet [ELN] Recommendations) or intolerance**to the most recent TKI therapy at the time of screening.

*Failure for Ph+ CML-CP participants (CP at the time of initiation of last therapy)is defined as meeting at least one of the following criteria:

• Three months after the initiation of therapy: >10% BCR::ABL1 on IS if confirmedwithin 1-3 months

• Six months after the initiation of therapy: BCR::ABL1 ratio >10% IS

• Twelve months after initiation of therapy: BCR::ABL1 ratio >1% IS

• At any time after the initiation of therapy, loss of CHR, MR2

• At any time after the initiation of therapy, the development of new BCR::ABL1mutations which potentially cause resistance to current treatment

• At any time 12 months after the initiation of therapy, BCR::ABL1 ratio ≥1% IS orloss of MMR

• At any time after the initiation of therapy, new clonal chromosome abnormalities inPh+ cells (CCA/Ph+)

**Intolerance is defined as:

• Non-hematologic toxicity: Participants with grade .3 or 4 toxicity while on therapy,or with persistent grade 2 toxicity, unresponsive to optimal management,includingdose adjustments (unless dose reduction is not considered in the best interest ofthe participant if the response is already suboptimal)

• Hematologic toxicity: Participants with grade 3 or 4 toxicity (absolute neutrophilcount [ANC] or platelets) while on therapy that is recurrent after dose reduction tothe lowest doses recommended by India PI.

• ECOG performance status of 0, 1, or 2.

• Evidence of typical BCR::ABL1 transcript (e14a2 and/or e13a2) at the time ofscreening which is amenable to standardized RQ-PCR quantification.

• Participants must have adequate end organ function as per the investigator'sjudgement.

• Participants must have the following electrolyte values within normal limits orcorrected to be within normal limits with supplements prior to the first doseof study treatment:

• Potassium (potassium increase of up to 6.0 mmol/L is acceptable at study entry ifassociated with creatinine clearance within normal limits)

• Total calcium (corrected for serum albumin); (calcium increase of up to 12.5 mg/dLor 3.1 mmol/L is acceptable at study entry if associated with creatinine clearancewithin normal limits)

• Magnesium, except for magnesium increase >upper level of normal (ULN) - 3.0 mg/dL or >ULN - 1.23 mmol/L associated with creatinine clearance (calculated usingCockcroft-Gault formula) within normal limits.

Exclusion Criteria:

• Known second chronic phase of CML after previous progression to CML-AP/CML-BC.

• Previous treatment with a hematopoietic stem-cell transplantation.

• Cardiac or cardiac repolarization abnormality, including any of the following:

• History within 6 months prior to starting study treatment of myocardialinfarction (MI), angina pectoris, and coronary artery bypass graft (CABG)

• Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia),complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third-degree AV block)

• QT corrected for heart rate by Fridericia's cube root formula (QTcF) atscreening ≥450 msec (both male and female participants)

• Long QT syndrome, family history of idiopathic sudden death or congenital longQT syndrome, or any of the following:

• Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia orhypomagnesemia, history of cardiac failure, or history of clinicallysignificant/symptomatic bradycardia.

• Inability to determine the QTcF interval.1. Known second chronic phase of CML afterprevious progression to CML-AP/CML-BC.

• Previous treatment with a hematopoietic stem-cell transplantation.

• Cardiac or cardiac repolarization abnormality, including any of the following:

• History within 6 months prior to starting study treatment of myocardialinfarction (MI), angina pectoris, and coronary artery bypass graft (CABG)

• Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia),complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third-degree AV block)

• QT corrected for heart rate by Fridericia's cube root formula (QTcF) atscreening ≥450 msec (both male and female participants)

• Long QT syndrome, family history of idiopathic sudden death or congenital longQT syndrome, or any of the following:

• Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia orhypomagnesemia, history of cardiac failure, or history of clinicallysignificant/symptomatic bradycardia.

• Inability to determine the QTcF interval

• Concomitant medication(s) with a "Known risk of TdP" (per www.crediblemeds.org) thatcannot be discontinued or replaced 7 days prior to starting study treatment by safealternative medication.

• Severe and/or uncontrolled concurrent medical disease that in the opinion of theinvestigator could cause unacceptable safety risks or compromise compliance with theprotocol (e.g., uncontrolled diabetes, active or uncontrolled infection, pulmonaryhypertension).

• History of acute pancreatitis within 1 year of study entry or past medical historyof chronic pancreatitis.

• Known infection with human immunodeficiency virus (HIV) or active hepatitis B or C.

• Known presence of significant congenital or acquired bleeding disorder unrelated tocancer.

• History of other active malignancy within 3 years prior to study entry with theexception of previous or concomitant basal cell skin cancer and previous carcinomain situ treated curatively.

• Impairment of gastrointestinal (GI) function or GI disease that may significantlyalter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea,vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypasssurgery).

• Previous treatment with or known/suspected hypersensitivity to asciminib or any ofits excipients.

• Participants must avoid consumption of grapefruit, Seville oranges, or productscontaining the juice of each during the entire study and 7 days before the firstdose of study treatment, due to potential CYP3A4 interaction with the studytreatment. Orange juice is allowed. Participants must avoid consumption ofover-the-counter medications or herbal supplements as these can interact with eachother and may alter the effects of asciminib.

• Participation in a prior investigational study within 30 days prior to enrollment orwithin 5 half-lives of the investigational product, whichever is longer.

• Pregnant or breastfeeding women.

• Women of childbearing potential, defined as all women physiologically capable ofbecoming pregnant unless they are using highly effective methods of contraception.

Highly effective contraception methods include:

• Total abstinence (when this is in line with the preferred and usual lifestyle of theparticipant). Note that periodic abstinence (e.g., calendar, ovulation,symptothermal, post-ovulation methods) and withdrawal are not acceptable methods ofcontraception.

• Female sterilization (have had surgical bilateral oophorectomy (with or withouthysterectomy) total hysterectomy or bilateral tubal ligation at least 6 weeks beforetaking study treatment). In the case of oophorectomy alone, only when thereproductive status of the woman has been confirmed by follow-up hormone levelassessment.

• Male sterilization (vasectomy) of the male partner(s) of the female participant atleast 6 months prior to screening. The vasectomized male partner should be the solepartner for that participant.

• Use of oral, injected, or implanted hormonal methods of contraception or placementof an intrauterine device (IUD) or intrauterine system (IUS), or other forms ofhormonal contraception that have comparable efficacy (failure rate <1%), forexample, hormone vaginal ring or transdermal hormone contraception. In the case ofthe use of oral contraception, women should have been stable on the same pill for aminimum of 3 months before taking study treatment.

• Women are considered post-menopausal and not of childbearing potential if they havehad 12 months of natural (spontaneous) amenorrhea with an appropriate clinicalprofile (e.g., age-appropriate history of vasomotor symptoms) or have had surgicalbilateral oophorectomy (with or without hysterectomy) at least 6 weeks before takingstudy treatment. In the case of oophorectomy alone, women are considered menopausaland not of childbearing potential only when the reproductive status of the woman hasbeen confirmed by a follow-up hormone level assessment.

• If a participant is presenting with symptoms suggestive of possible CoronavirusDisease (COVID-19) infection, advise ruling it out by appropriate testingrecommended by health authorities.

• Nucleic acid amplification tests for viral RNA (polymerase chain reaction), tomeasure current infection with SARS-CoV-2

• Antigen tests for rapid detection of SARS-CoV-2

• Antibody (serology) tests to detect the presence of antibodies to SARS-CoV-2.