A Study of Treatment-free Remission in Chronic Phase Chronic Myeloid Leukemia in Combination With Asciminib and Tyrosine Kinase Inhibitors
Phase: PHASE2
Conditions: Chronic Myeloid Leukemia, Chronic Phase
Sponsor: Korean Society of Hematology

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NCI Protocol #: 
 
 
Local Protocol #:  
 
ClinicalTrials.gov Identifier:   
 
TITLE:  A study of treatment-free remission in chronic phase chronic myeloid leukemia 
in combination with asciminib and tyrosine kinase inhibitors 
 
SHORT TITLE: ASTER-A 
 
Corresponding Organization: 
The Korean Society of Hematology Chronic 
Myeloid Leukemia Working Party 
 
 
 
Coordinating Center: 
Gachon University Gil Medical Center 
 
 
Principal Investigator: 
Hawk Kim, M.D., Ph.D. 
 
Executive Investigator: 
Name:  Jieun Uhm, M.D., Ph.D. 
Institution: Hanyang University Seoul Hospital 
 
 
 
 
 

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SYNOPSIS  
 
Title 
A study of treatment-free remission in chronic phase chronic myeloid leukemia 
in combination with asciminib 
Background 
and Rationale 
Tyrosine kinase inhibitors (TKIs) havebeen standard of treatment in chronic 
phase (CML-CP)as a first line therapy and its efficacy and safety have been 
consistantly proved for a long time use.1-6 Recent study suggested that patients who 
took imatinib for 10 years or more had a tendency of increasing renal insufficiency. 
Nilotinib and dasatinib have increased risk of peripheral artery occlusive disease and 
pulmonary complications, respectively.3,4,7 This raised reasonable suspicion for the 
long-term safety of all TKIs. 
Recently we come to know that chronic phase CML (CP-CML) patients could 
expect as good survial as normal population in the era of tyrosine kinase inhibitor 
(TKI) therapy, and STIM and KIDS trial showed that some patients who were in 
sustainable MR4.5 for several years (usually over 2 years) could stop imatinib safely. 
This means that the ultimate goal of CP-CML treatment could be remission free 
survival (RFS) beyond prolongation of survival.8,9  
Despite of those promising data, 30-60% patients who had stopped imatinib loss 
their MR3.0 response and had to restart imatinib almost within 6 months although 
re-challenging imatinib after loss of MR3.0 made almost all patients regain MR4.5.8-
10 There is a small report for second stop trial of imatinib after failure of first imatinib 
stop study.11 Among 16 patients, 4/16 (25%) remained in major molecular response 
(MMR) and 2/16 (12.5%) remained in molecularly undetectable leukemia (MUL). 
This result implies that second trial of imatinib stopping is quite disappointing and 
there needs to be another approach for second cessation trial. The disadvantages 
of life long TKIs are not only discomforts and adverse events but also the increasing 
burden of total cost in health care system. Therefore, successful second TKIs stop 
is mandatory to achieve. 
Asciminib (ABL001) is a potent, specific, orally bioavailable BCR-ABL1 inhibitor 
that is distinct from approved other ABL1 kinase inhibitors, that does not bind to the 
ATP-binding site of the kinase.12-14 Asciminib is a suitable candidate drug for adding 
to TKIs for the purpose of molecular relapse free survival (MRFS) since asciminib 
was active in heavily pretreated patients with CML who had resistance to or 
unacceptable side effects from TKIs, including patients who failed to ponatinib and 
those with a T315I mutation.15 Also asciminib can give an additional synergistic 
effect with TKIs to ensure profound BCR/ABL1 suppression for successful second 
TKI stop. 
We expect that patients who lost MR3.0 after stopping TKIs, thus failed to 
maintain treatment-free remission can achieve second sustainable MR4.5 by 
sustainable MR4.5 for more than 3 years once regained and prolong MRFS by 
adding asciminib to TKIs. Patients will be restarted on TKIs when they fail sustaining 
MR3.0 after cessation because restarting TKIs when loss of MR3.0 is reasonable in 
this situation.16  
 
Hypothesis 
• 
This trial will evaluate the efficacy and safety of combined therapy of asciminib 
and TKIs in patients who attempt second cessation of TKIs after first cessation 
trial failure. 
• 
The hypothesis of this trial is that asciminib can achieve at least 40% 
sustainable MR3.0 after stopping CML therapy in CP-CML patients who have 
lost MR3.0 after 1 or more previous cessation trial of TKIs. 
 
Objective of 
study 
To evaluate the efficacy of asciminib adding on tyrosine-kinase inhibitors (TKI) to 
achieve treatment-free remission (TFR) in chronic myeloid leukemia (CML) patients in 
chronic phase who failed prior cessation study of TKI 

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End points 
Primary end point:  
1. To evaluate the cumulative incidence of sustained MR3.0 or less by 1 year of 
cessation of TKI and asciminib 
Secondary end points:   
1. To evaluate the re-achievement rate of MR4.5 adding asciminib on TKI. 
2. To evaluate molecular relapse-free survival (MRFS), overall survival (OS), time 
to loss of MR3.0/4.0/4.5, and treatment-free survival (TFS) 
3. To evaluate safety profiles of additional asciminib on TKI. 
4. To analyze prognostic factors to predict the successful TFR after combination 
therapy of asciminib and TKI. 
Target 
Population  
Patients with CML-chronic phase (CML-CP) who failed previous trial of TKI cessation. 
Inclusion 
criteria 
1. 
19 year or older 
2. 
CP-CML patients who are taking current TKIs (imatinib, nilotinib or 
dasatinib) for 5 years or more  
3. 
Patients who have failed maintaining MR3.0 after 1 or more cessation 
trial of TKIs.  
4. 
Patients who regained MR3.0 or deeper molecular response by TKIs 
retrial after TKI cessation failure at the time of screening 
5. 
Taking TKIs over 12 weeks for the retrial of TKIs after TKI cessation 
failure 
6. 
Patients who agree with stopping asciminib and TKIs after maintaining 2 
year-duration of MR4.5 
7. 
Adequate end organ function as defined by: 
• 
Total bilirubin (TBL) < 3 x upper limit of normal (ULN); patients with Gilbe
rt’s syndrome may only be included if TBL ≤ 3.0 x ULN or direct bilirubin 
≤ 1.5 x ULN 
• 
Creatinine clearance (ClCr) ≥ 30 mL/min as calculated using Cockcroft-G
ault formula 
• 
Serum lipase ≤ 1.5 x ULN. For serum lipase > ULN - ≤ 1.5 x ULN, value 
must be considered not clinically significant and not associated with risk f
actors for acute pancreatitis 
8. 
Patients who can sign the informed consent of their own free will 
 
Exclusion 
criteria 
1. 
Patients who experienced grade 3 or higher adverse events 
with TKIs (imatinib, dasatinib, and nilotinib). 
2. 
Patients who are receiving any other investigational agents. 
3. 
Patients who currently have uncontrolled infections 
4. 
Patients who previously received Chimeric antigen receptor 
T-cell (CAR-T cell) therapy, allogeneic hematopoietic stem 
cell transplantation (allo-HSCT) or biologic therapy. 
5. 
Patients with clinically significant cardiovascular disease or 
gastrointestinal dysfunction. 
6. 
Patients who have a history of thromboembolic episodes 
within 3 months prior to the study enrollment. 
7. 
Patients with active hepatitis B or C with uncontrolled 
disease activity. 
8. 
Patients who have active malignancies requiring treatment 
other than CML. 
9. 
Patients with any severe and/or uncontrolled medical 
conditions or other conditions that could adversely impact on 

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patients’ ability to participate in the study. 
10. 
Patients with psychiatric illness/social situations that would 
limit compliance with study requirements. 
11. 
Pregnant women are excluded from this study Because there 
is an unknown but potential risk for adverse events in nursing 
infants secondary to treatment of the mother with asciminib 
and TKIs, breastfeeding should be discontinued if the mother 
is treated with asciminib and TKIs. 
TFR eligibility 
1. Patients have received asciminib along with one of TKIs over 3 years 
2. MUL duration is over 2 years. 
3. MUL is confirmed (2 consecutively at least 4 weeks apart). 
Study 
procedures 
• 
Patients will start Asciminib in addition to previously treated TKIs when eligibility is 
confirmed after taking signed informed consent. 
• 
Asciminib treatment 
 
Asciminib (80mg qd for nilotinib; 60mg qd for imatinib; 80mg qd for dasatinib) 
will be added at 12 weeks after the re-initiation of TKIs. 
 
Patients will be dropped out from this study if patients are intolerant to 
asciminib 20mg qod or loss of MR3.0 occurs twice consecutively. 
• 
Cessation of Asciminib and TKIs for TFR 
 
When a patient achieves molecularly undetectable leukemia (MUL; at least 
MR4.0 detection limit) and there is no loss of MUL for 2 years, the patient will 
stop asciminib and TKIs. RQ-PCR will be performed 2 times consecutively, 4 
weeks apart for the confirmation of MUL just prior to stopping Asciminib and 
TKIs.  
 
The duration of asciminib and TKIs treatment should be 3 years or more and 
the duration of sustained MUL should be 2 years or more before stopping 
asciminib and TKIs. If a patient fails achieving MUL after 3 years of TKIs and 
asciminib combination, the patient will be dropped from the study. 
 
TKIs only without asciminib will be restarted, or other treatment can be tried 
when loss of MR3.0 is found consecutively 2 times after stopping asciminib 
and TKIs by above condition. 
 
Therapeutic schedules 

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Study design 
A prospective, multi-center, open-label, single arm, phase II study 
Outcomes and 
Efficacy evaluation 

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measures 
- 
CBC, Chemistry at every visit 
- 
BCR-ABL1 RQ-PCRis every month for 6 months, then every 2 months for next 
6 months, and then every 3 months until loss of MR3.0 or 36 months from the 
cessation of asciminib and TKI combination. 
Safety evaluation 
NCI-CTCAE v5.0  
Statistical 
considerations 
Sample size calculations: 
The sample size is calculated based on Simon’s exact sing-stage phase II design 
assuming that P0=0.25; P1=0.4; α-error=0.05; β-error=0.2. The final number of patients 
required will be 69 with consideration of 10% of drop-out rate. 
Total planned 
number of 
patients 
69 patients from at least 10 centres of Korea 
 

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TABLE OF CONTENTS 
 
Synopsis .........................................................................................................................................2 
1. 
OBJECTIVES & end points ...........................................................................................10 
1.1 
Objective of study .................................................................................... 10 
1.2 
Primary endpoint ...................................................................................... 10 
1.3 
Secondary Objectives .............................................................................. 10 
2. 
BACKGROUND ...............................................................................................................10 
2.1 
Study background .................................................................................... 10 
2.2 
Hypothesis ............................................................................................... 11 
3. 
STUDY DRUG INFORMATION ....................................................................................11 
3.1 
Drug substance – physical and chemical properties ................................ 11 
3.2 
Drug product – pharmaceutical properties ............................................... 12 
3.3 
Pharmacokinetics, metabolism and pharmacodynamics in humans ........ 12 
3.4 
Safety in humans ..................................................................................... 21 
4. 
ELIGIBILITY .....................................................................................................................26 
4.1 
Inclusion Criteria ...................................................................................... 26 
4.2 
Exclusion Criteria ..................................................................................... 26 
4.3 
TFR eligibility ........................................................................................... 27 
5. 
TREATMENT PLAN........................................................................................................27 
5.1 
General principle ...................................................................................... 27 
5.2 
Agent Administration ................................................................................ 27 
5.3 
Asciminib ................................................................................................. 27 
5.4 
Concurrent TKIs ....................................................................................... 28 
5.5 
Treatment scheme ................................................................................... 29 
5.6 
Duration of Therapy ................................................................................. 29 
5.7 
Reinitiation of CML therapy ...................................................................... 30 
5.8 
Duration of Follow-Up .............................................................................. 30 
5.9 
BCR/ABL1 RQ PCR................................................................................. 30 
5.10 
Dosing delays/dose modifications ............................................................ 31 
6. 
SUPPORTIVE CARE AND GENERAL CONCOMITANT 
MEDICATION GUIDELINES .........................................................................................35 
6.1 
Supportive care ........................................................................................ 35 
6.2 
General concomitant medication ............................................................. 35 
7. 
STUDY CONDUCT .........................................................................................................35 
7.1 
Schedule of assessment .......................................................................... 35 
7.2 
Table for study assessments/Procedures for Asciminib phase ................ 36 
7.3 
Table for study assessments/Procedures for TFR phase ........................ 36 
8. 
STUDY VISITS ................................................................................................................37 

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8.1 
Asciminib phase ....................................................................................... 37 
8.2 
TFR Phase ............................................................................................... 39 
8.3 
Unscheduled visit ..................................................................................... 40 
8.4 
End-of-Study visit ..................................................................................... 41 
9. 
STUDY ASSESSMENTS ...............................................................................................41 
9.1 
Demographic Information, Medical and Medication History ..................... 41 
9.2 
Contraception Requirements ................................................................... 41 
9.3 
Efficacy/Effectiveness Assessments ........................................................ 43 
9.4 
BCR/ABL1 monitoring laboratory ............................................................. 43 
9.5 
Definitions of time-dependent variables ................................................... 43 
9.6 
Safety assessment .................................................................................. 43 
10. 
ADVERSE EVENTS:  LIST AND REPORTING REQUIREMENTS ........................45 
10.1 
Adverse Event List(s) for asciminib .......................................................... 45 
10.2 
Adverse Event Characteristics ................................................................. 46 
10.3 
Adverse Event Reporting ......................................................................... 47 
10.4 
Pregnancy ................................................................................................ 46 
10.5 
Secondary Malignancy............................................................................. 47 
10.6 
Second Malignancy ................................................................................. 47 
11. 
STATISTICAL CONSIDERATIONS .............................................................................48 
11.1 
Study populations .................................................................................... 48 
11.2 
General consideration for data analysis ................................................... 48 
11.3 
Subject Demographic and Disposition Data ............................................. 48 
11.4 
Analysis of Efficacy Variables .................................................................. 49 
11.5 
Sample Size Calculation .......................................................................... 49 
11.6 
Statistical analysis ................................................................................... 49 
12. 
STUDY ADMINISTRATION ...........................................................................................50 
12.1 
Study Monitoring ...................................................................................... 50 
12.2 
Audits and Inspections ............................................................................. 50 
12.3 
Institutional review board (IRB) ................................................................ 51 
12.4 
Serious Breaches of GCP ........................................................................ 51 
13. 
QUALITY CONTROL AND QUALITY ASSURANCE ................................................51 
13.1 
Quality control .......................................................................................... 51 
13.2 
Quality assurance .................................................................................... 51 
14. 
IRB .....................................................................................................................................51 
14.1 
IRB Review .............................................................................................. 51 
14.2 
Ethical Conduct of the Study .................................................................... 52 
14.3 
Written Informed Consent ........................................................................ 52 
15. 
DATA HANDLING AND RECORDKEEPING .............................................................52 
15.1 
Inspection of Records .............................................................................. 52 
15.2 
Retention of Records ............................................................................... 53 

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15.3 
Confidentiality of Information and Data .................................................... 53 
16. 
PUBLICATION POLICY .................................................................................................53 
16.1 
General policy .......................................................................................... 53 
17. 
REFERENCES ................................................................................................................54 
APPENDIX A ................................................................................................... PERFORMANCE STATUS 
CRITERIA .........................................................................................................................56 
APPENDIX B ..................... FORMULA TO ESTIMATE RENAL FUNCTION USING SERUM 
CREATININE ...................................................................................................................57 
 
 
 

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1. OBJECTIVES & END POINTS 
1.1 Objective of study 
1.1.1 To evaluate the efficacy of asciminib adding on tyrosine-kinase 
inhibitors (TKI) to achieve treatment-free remission (TFR) in chronic 
myeloid leukemia (CML) patients who failed prior cessation study of 
TKI 
1.2 Primary endpoint 
1.2.1 To evaluate the cumulative incidence of sustained MR3.0 or less by 1 
year of cessation of TKI and asciminib 
1.3 Secondary Objectives 
1.3.1 To evaluate the re-achievement rate of MR4.5 adding asciminib on 
TKI. 
1.3.2 To evaluate molecular relapse-free survival (MRFS), overall survival 
(OS), time to loss of MR3.0/4.0/4.5, and treatment-free survival (TFS). 
1.3.3 To evaluate safety profiles of additional asciminib on TKI. 
1.3.4 To analyze prognostic factors to predict the successful TFR after 
combination therapy of asciminib and TKI. 
2. BACKGROUND 
2.1 Study background 
2.1.1 Tyrosine kinase inhibitors (TKIs) have been standard of treatment for 
chronic myeloid leukemia (CML) as a first line therapy and its efficacy 
and safety have been consistently proved for a long time use.1-6 In the 
era of TKIs, life expectancy of chronic phase CML (CP-CML) patients 
approaches that of general population.17  
2.1.2 Long-term follow-up of IRIS study reported that 45% of patients had to 
stop imatinib and 12% of among those discontinued imatinib due to 
intolerance.18 About 10% of patients who treated with second 
generation TKI (2G-TKI) such as dasatinib and nilotinib also 
discontinued TKI due to toxicities.19,20 Another study suggested that 
patients who took imatinib for 10 years or more had a tendency of 
increasing renal insufficiency. Nilotinib and dasatinib also have 
increased risk of peripheral artery occlusive disease and pulmonary 
complications, respectively.3,4,7 This raised reasonable suspicion for 
the long-term safety of all TKIs. 
2.1.3 With successful treatment outcomes, the balance between disease 
control and quality of life with issues of long-term safety led to conduct 
the trials of discontinuation of TKI. Early trials, such as STIM, and 
KIDS trial showed that some patients who were able to maintain 
sustainable MR4.5 for several years (usually over 2 years) could stop 
imatinib safely. This lifted the ultimate goal of CP-CML treatment up to 
molecular relapse survival (MRFS) from prolongation of survival.8,9  
2.1.4 Despite of those promising data, 30-60% patients who had stopped 
imatinib loss their MR3.0 response and had to restart imatinib almost 
within 6 months although re-challenging imatinib after loss of MR3.0 
made almost all patients regain MR4.5.8-10 The largest trial of TKI 
discontinuation which included 758 patients who maintained MR4.0 at 

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least 1 year reported treatment-free remission (TFR) of 50% at 24 
months.21 
2.1.5 There is a small report for second discontinuation trial of imatinib after 
failure of first imatinib TFR study.11 Among 16 patients, 4/16 (25%) 
remained in major molecular response (MMR) and 2/16 (12.5%) 
remained in molecularly undetectable leukemia (MUL). This result 
suggested that second attempt of imatinib discontinuation is quite 
disappointing and other approach for second cessation trial is 
warranted. The disadvantages of life long TKIs are not only affecting 
on quality of life and adverse events but also the increasing burden of 
total cost in health care system. Therefore, successful second TKIs 
stop is worthy the goal to achieve. 
2.1.6 Asciminib (ABL001) is a potent, allosteric, orally bioavailable BCR-
ABL1 inhibitor binding a myristoyl site of the BCR-ABL1 protein, 
locking BCR-ABL1 into an inactive conformation  that is distinct from 
approved other ABL1 kinase inhibitors.12-14 Asciminib was active in 
heavily pretreated patients with CML who had resistance to or 
unacceptable side effects from TKIs, including patients who failed to 
ponatinib and those with a T315I mutation.15 Asciminib is a suitable 
candidate drug adding its potent activity to other TKIs to achieve 
deeper molecular response translating into molecular relapse free 
survival (MRFS). Also, asciminib can give an additional synergistic 
effect with other TKIs to ensure profound BCR/ABL1 suppression for 
successful second TKI stop given its different mechanism of action. 
2.1.7 The phase I trial of asciminib combined with dasatinib or nilotinib 
showed the 4 of 13 and 5 of 14 achieved MMR by 48 weeks without 
baseline MMR in patients who failed at least 2 prior lines of TKIs.22 
Combination of asciminib and imatinib also demonstrated promising 
efficacy with 42% of MMR by 48 weeks.23  
2.1.8 We expect that patients who lost MR3.0 since stopping TKIs, thus 
failed to maintain TFR can achieve second sustainable MR4.5 and 
prolong MRFS by adding asciminib to TKIs with condition of 
sustainable MR4.5 for more than 3 years once regained. Patients will 
restart TKIs when they fail sustaining MR3.0 after cessation because 
restarting TKIs when loss of MR3.0 is reasonable in this situation.16  
2.2 Hypothesis 
2.2.1 This trial will evaluate the efficacy and safety of combined therapy of 
asciminib and TKIs in patients who attempt second cessation of TKIs 
after first cessation trial failure. 
2.2.2 The hypothesis of this trial is that asciminib can achieve at least 40% 
sustainable MR3.0 after stopping CML therapy in CP-CML patients 
who have lost MR3.0 after 1 or more previous cessation trial of TKIs. 
3. STUDY DRUG INFORMATION 
3.1 Drug substance – physical and chemical properties 
3.1.1 The free-base form of asciminib has been used for early clinical 
investigation with capsules. Following polymorphism evaluation, a 

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hydrochloride form was identified as better suited for development and 
is used for late phase clinical development with tablets 
3.1.2 The molecular formula for ABL001 free base is C20H18ClF2N5O3 
(relative molecular weight 449.8). The molecular formula for ABL001 
HCl salt is C20H18ClF2N5O3. HCl (relative molecular weight 486.3). 
3.2 Drug product – pharmaceutical properties 
3.2.1 Description and composition 
3.2.1.1 Film-coated tablets and capsules of asciminib hydrochloride 
may be used in the clinic.  
3.2.2 Storage condition 
3.2.2.1 Asciminib drug products packaged in either high density 
polyethylene (HDPE) bottles or PCTFE-PVC/Alu blister pack, 
and should not be stored above 25 °C and should be protected 
from moisture. Please refer to clinical labels and/or the 
Pharmacy Manual for current shelf life, in-use period, and 
additional storage instructions, as applicable. 
3.2.3 Hazards and precautions 
3.2.3.1 Asciminib is a potent investigational new drug that has not been 
fully evaluated. Exercise appropriate hygiene and clinical 
practice precautions. 
3.3 Pharmacokinetics, metabolism, and pharmacodynamics in humans 
3.3.1 Relative bioavailability and food effect assessments in healthy 
subjects 
3.3.1.1 Study CABL001A2101 evaluated the relative bioavailability of 
the two asciminib tablet formulations in comparison to the 
clinical supply formulation (CSF) of capsule (used in the 
first-in-human study X2101) in healthy subjects.  
3.3.1.2 The effect of food was assessed using the tablet formulations. 
Median Tmax was around 2 hr. and was similar between the 
three formulations under fasted condition. The concentration-
time profiles revealed comparable rate and extent of absorption 
of asciminib when administered as tablet containing the HCl salt 
form/CSF capsule or free form tablet variant /CSF capsule 
under fasted conditions.  
3.3.1.3 Tablets made from asciminib HCl salt versus CSF capsule 
under fasted condition indicated similar exposure: The 
exposures were 11%-12% higher in the tablet variant as 
compared to the capsule. The geometric mean ratios (GMRs) 
for AUCinf, AUClast, and Cmax were 1.12 (90% CI: 0.998, 
1.25), 1.12 (90% CI: 1.00, 1.26), and 1.11 (90% CI: 0.949, 
1.29), respectively. 
3.3.1.4 Tablets made with asciminib free form variant versus CSF 
capsule under fasted condition: The exposures were 18%-22% 
higher in the tablet variant as compared to the capsule. The 
GMRs for AUCinf, AUClast, were 1.18 (90% CI: 1.05, 1.33) and 
1.18 (90% CI: 1.05, 1.33), respectively. There was a 22% 

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increase in asciminib peak concentration Cmax with GMR of 
1.22 (90% CI: 1.05, 1.42). 
3.3.1.5 Study CABL001A2104 evaluated the relative bioavailability of 
orally administered asciminib CSF capsule and the final market 
image (FMI) tablet formulation in healthy subjects under fasted 
condition. The concentration-time profiles revealed similar rate 
and extent of absorption of asciminib when administered either 
as a tablet or as capsule under fasted conditions. The median 
Tmax was 2 hr. and 3 hr. for tablet and capsule formulations, 
respectively.  
3.3.1.6 The bioavailability of tablet formulation was similar to that of the 
capsule formulation. The GMR (tablet vs capsule) and 90% CIs 
for AUCinf, AUClast and Cmax were 1.00 (90% CI: 0.909, 
1.10), 1.01 (90% CI: 0.911, 1.11), and 0.909 (90% CI: 0.805, 
1.03), respectively. 
3.3.1.7 In conclusion, the systemic exposure in terms of Cmax and 
AUC was similar between the FMI tablet and the capsule 
formulation. Therefore, the capsule formulation was switched to 
the FMI tablet in study X2101 without dose adjustment. A 
negative food effect was observed following low and high fat 
meals (CABL001A2101, CABL001E2101). Low-fat and high-fat 
meals decreased the bioavailability of asciminib by ~30% and 
~60%, respectively 
3.3.2 Absorption and distribution 
3.3.2.1 Based on PBPK modeling, asciminib is believed to be almost 
completely absorbed in humans. 
3.3.2.2 The estimated fraction absorbed (Fa) was approximately 100% 
in humans. Based on PBPK modeling, the estimated absolute 
bioavailability was 73% (DMPK-R2000208). 
3.3.2.3 Asciminib is poorly soluble in aqueous solution and possesses 
a high permeability; hence, asciminib was classified as a BCS 
class II compound. However, in vitro dissolution experiments 
across the physiological pH range (2-stage dissolution) a 
pronounced super saturation effect of asciminib was observed, 
explaining the almost complete fraction absorbed 
(ARD000059). 
3.3.2.4 The apparent volume of distribution (Vz/F) was geo-mean 
(CV%) 89.0 L (6.1%) based on the human ADME study (Study 
CABL001A2102) and based on popPK analysis, for a typical 
individual (70 kg male), the combined volumes of central and 
peripheral compartments were approximately 111 L (V1 (+/-
SE): 46.5 (1.71) + V2: 64.5 (7.92)), suggesting distribution into 
tissues. 
3.3.3 Pharmacokinetics 
3.3.3.1 The PK profile of asciminib has been evaluated as single agent 
in patients with CML and Ph+ ALL at a dose range between 10 

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mg to 280 mg b.i.d. and 80 mg to 200 mg q.d., as well as in 
healthy subjects. 
3.3.3.2 Asciminib was rapidly absorbed following single dose and 
repeated administration with a median time to reach maximum 
plasma concentration (Tmax) of 2 to 3 hr., independent of dose.  
3.3.3.3 Systemic exposure of asciminib, after oral administration of a 
single dose and multiple doses, as measured by Cmax and 
AUC, increased in a slightly more than dose proportional 
manner. Steady state was reached by day 3 (CABL001A2106).  
3.3.3.4 The apparent terminal elimination half-life (T1/2) was estimated 
to be between 7 and 15 hr., the apparent clearance (CL/F) of 
asciminib was 4.34 L/hr. (based on non-compartmental PK 
analysis of a single dose of 80 mg in hADME study 
[CABL001A2102] in healthy subjects). 
3.3.3.5 Based on population PK, the asciminib clearance for a typical 
individual was 6.31 L/hr. for a total daily dose of 80 mg. 
3.3.3.6 Plasma concentrations of asciminib generally declined in a bi-
phasic manner. No time dependent PK was observed. 
3.3.3.7 In Study X2101, the geometric mean average accumulation 
ratio at steady state (Cycle 2 Day 1) ranged from 1.65 to 2.29 
for the b.i.d. dosing (1.65 at 40 mg b.i.d. and 1.92 at 200 mg 
b.i.d.) and from 1.12 to 1.30 for the q.d. dosing (1.30 at 80 mg 
q.d.) (Study X2101-Table 14.2-11.1.1). 
3.3.3.8 Generally, the variability of exposure was low to moderate with 
inter-subject variability (CV %) ranging from approximately 17% 
to 69% for AUClast and from 14% to 74% for Cmax.  
3.3.3.9 The intrasubject variability ranged from 13.3% to 28.9% for 
Cmax and 5.6 to 22.7% for AUClast. 
3.3.3.10 
The inter-subject geoCV% in Study X2101 Cycle 2 Day 1 
at 40 mg b.i.d. was 49.6% and 48.9% for AUClast and Cmax. In 
line with that, the inter-subject geoCV% in A2301 at 40 mg b.i.d. 
was 47.8% and 46.7% for AUClast and Cmax. 
3.3.3.11 
There was no apparent difference in PK between the 
patients with CML-CP harboring the T315I mutation compared 
to the patients with disease not harboring the T315I mutation 
and between patients with CML and ALL. 
3.3.4 Metabolism 
3.3.4.1 In human CYP3A4, UGT2B7, UGT2B17 and UGT1A3/4 were 
estimated to contribute to 36.0%, 13.3%, 7.8% and 6.8%, 
respectively, of the total clearance of asciminib based on in 
vitro human hepatocyte clearance and enzyme reaction 
phenotyping studies and clinical human ADME data (DMPK 
R1709012), (CABL001A2102). Based on PBPK simulations 
biliary secretion via BCRP was estimated to contribute to total 

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systemic clearance with about 31.1% (DMPK-R2000208).   
3.3.4.2 Schematic description of disposition pathways 
 
3.3.4.3 Asciminib is eliminated via parent drug excretion and 
metabolism. 
3.3.4.4 The metabolism of asciminib involved the following primary 
biotransformation pathways: oxidation at the pyrrolidinol ring, 
direct glucuronidation, O-dealkylation, and amide hydrolysis. 
Oxidative opening of the pyrrolidinol ring, led to the formation of 
several metabolites (M29.5, M37, M39 and M43.3), which 
accounted for approximately 17% of the dose elimination in 
human excreta. 
3.3.4.5 About 7% of the radioactivity excreted were M30.5, M44 
contributed with 0.8% (CABL001A2102).  
3.3.4.6 No major metabolite was identified (<10% of total drug-related 
material). 
3.3.5 Excretion/Elimination 
3.3.5.1 Following oral administration, the absorbed asciminib is mainly 
cleared through hepatic metabolism and biliary secretion 
through the fecal pathway with renal excretion playing a minor 
role. Following a single oral dose of 80 mg of [14C] labelled 
asciminib to healthy subjects, 80% of the radiolabeled material 
was excreted into feces and 11% into urine (Study 
CABL001A2102). 
3.3.5.2 In feces, asciminib was the major component, accounting 
accounted for 53.7% to 58.5% of the 
administered radioactive dose, with an average value of 56.7%. 
3.3.5.3 In human, asciminib in feces is believed to originate from biliary 
secretion of unchanged asciminib via BCRP and direct 
glucuronide metabolites as indicated by results from bile-duct 
cannulated rats. The glucuronides are assumed to be back-

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converted to the parent drug by intestinal bacteria, as 
evidenced by stability investigations of asciminib glucuronides 
in human feces, where an almost complete back-conversion 
was observed (DMPK R2000268). 
3.3.6 Drug-drug interactions 
3.3.6.1 Interaction potential with inhibitors and inducers of CYP3 
3.3.6.1.1 A drug-drug interaction study (CABL001A2107) in 
healthy volunteers assessed the interaction of strong 
CYP3A inhibitors and inducers with asciminib (single 
dose of 40 mg).  
3.3.6.1.2 Following multiple doses of the strong CYP3A inducer 
rifampicin, the geo-mean AUCinf, AUClast of single 
dose asciminib decreased by 14.9% and 12.7%, 
respectively, with co-administration of rifampicin. 
Cmax was increased by 9% when asciminib is 
administered with rifampicin. 
3.3.6.1.3 Following multiple doses of the strong CYP3A4 
inhibitor clarithromycin, the geo-mean AUCinf, 
AUClast, and Cmax of single dose asciminib increased 
by 36%, 37%, and 19%, respectively with co-
administration of clarithromycin. 
3.3.6.1.4 These data suggest only a weak interaction of 
asciminib with CYP3A inhibitors and inducers. 
3.3.6.2 Interaction potential with P-gp inhibitors 
3.3.6.2.1 A drug-drug interaction study (CABL001A2107) in 
healthy volunteers assessed the interaction of a P-gp 
inhibitor with asciminib (single dose of 40 mg). 
Following multiple doses of the P-gp inhibitor 
quinidine, the geo-mean AUCinf, AUClast, and Cmax 
of single dose asciminib decreased by 12.9%, 16.0%, 
and 11.3%, respectively with co-administration of 
quinidine. 
3.3.6.2.2 These data suggest no relevant interaction of 
asciminib with P-gp inhibitors. 
3.3.6.3 Interaction potential with acid-reducing agents 
3.3.6.3.1 Study CABL001A1101 assessed the effect of multiple 
doses of rabeprazole, a proton pump inhibitor, on the 
PK of a single oral dose (fasted) of 40 mg asciminib in 
healthy subjects.  
3.3.6.3.2 Coadministration of rabeprazole (regarded as the 
worst-case scenario with regards to pH alteration) in 
combination with a single 40-mg oral dose of asciminib 
had no effect on the bioavailability of asciminib, hence 
asciminib can be administered with acid reducing 

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agents. 
3.3.6.4 Interaction potential with BCRP inhibitors 
3.3.6.4.1 Asciminib is a substrate of BCRP in vitro with an 
apparent Km of 1.83 µM, an intra-cellular Km of 0.14 
µM was calculated. At clinically relevant doses, i.e., 40 
mg, the intestinal asciminib concentrations are high 
(356 µM). Therefore, intestinal BCRP is expected to 
be almost completely saturated and co-administration 
of a BCRP inhibitor is unlikely to impact the absorption 
of asciminib. 
3.3.6.4.2 In the dedicated DDI study (CABL001E2101) with 
asciminib (40 mg single dose) and imatinib (400 mg 
q.d.), an inhibitor of CYP3A4, BCRP and UGT2B7 
resulted in an asciminib AUC increase of 2.08-fold. 
Based on PBPK predictions, the interaction potential of 
BCRP inhibitors (using imatinib only with BCRP 
inhibition in the model) on asciminib decreases with 
increasing doses of asciminib due to saturation of 
BCRP (DMPK-R2001088). 
3.3.6.4.3 In summary, co-administration of asciminib with BCRP 
inhibitors are not expected to result in a clinically 
relevant asciminib exposure increase. 
3.3.6.5 Interaction potential with UGT inhibitors 
3.3.6.5.1 Imatinib and nilotinib are both moderate CYP3A4 and 
UGT inhibitors (UGT2B17 and UGT1A3/4) as well as 
BCRP inhibitors. In addition, imatinib has been shown 
to be a potent P-gp inhibitor. The PK of asciminib in 
combination with imatinib and nilotinib was assessed 
in CML patients in study X2101. In addition, a 
dedicated DDI study evaluated the effect of imatinib on 
the PK of asciminib (40 mg single dose) in healthy 
subjects (CABL001E2101). Collectively, an 
approximately 2-fold increase in asciminib exposure 
when administered together either with imatinib or 
nilotinib. 
3.3.6.5.2 In conclusion, co-administration of strong UGT 
inhibitors is not expected to result in clinically relevant 
asciminib exposure changes. 
3.3.6.6 Interaction potential with UGT inducers 
3.3.6.6.1 In the CABL001A2107 study, a small decrease of 
approximately 15% in asciminib exposure was 
observed with rifampicin, which is besides CYP3A4 at 
least partly also inducing UGT1A3/4, UGT2B7 and 
UGT2B17 enzymes.  
3.3.6.6.2 In conclusion, the low asciminib exposure reduction by 
rifampicin suggests that UGT induction did not 

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relevantly influence the PK of asciminib. 
3.3.6.7 Imatinib interaction in healthy subjects 
3.3.6.7.1 Study CABL001E2101 assessed the effect of multiple 
doses of imatinib on the pharmacokinetics of a single 
oral dose (low-fat meal) of 40 mg asciminib in healthy 
subjects. 
3.3.6.7.2 The analysis showed that the exposure of asciminib 
was higher when administered in combination with 
imatinib compared to when asciminib was 
administered alone.  
3.3.6.7.3 The asciminib exposure (AUCinf) was approximately 
108% higher and Cmax was 59% higher when 
administered in combination with imatinib compared to 
when administered alone. The Tmax was not impacted 
by the co-administration of imatinib. The effect of 
imatinib on asciminib may result from the inhibition of 
several metabolism and transport pathways that are 
involved in the disposition of asciminib. Considering 
the positive effect of imatinib (400 mg q.d.) on 
asciminib exposure, 40 mg q.d. and 60 mg q.d. given 
with low-fat meal are being evaluated in the add-on 
phase 2 study (E2201). 
3.3.6.8 Asciminib in combination with nilotinib in CML-CP/-AP 
3.3.6.8.1 Asciminib PK: Following administration of the first oral 
dose of asciminib on Cycle 1 Day 1 and after repeated 
administration of asciminib at steady state, asciminib 
was rapidly absorbed with a median Tmax of 2-3 hr. 
across all cohorts and independent of study day. 
Accumulation of asciminib exposure was observed at 
steady state (Cycle 2 Day 1) with the geometric mean 
accumulation ratio of 2.03 and 2.28 when administered 
at 20 mg b.i.d. and 40 mg b.i.d., respectively in 
combination with nilotinib 300 mg b.i.d. 
3.3.6.8.2 Steady state was reached by Cycle 1 Day 15 as 
similar exposures were observed on Cycle 1 
Day 15 and Cycle 2 Day 1. No time-dependent PK 
was observed. At steady state of asciminib 40 mg 
b.i.d. in combination with nilotinib 300 mg b.i.d. (Cycle 
2 Day 1), the geometric mean Cmax and AUCtau of 
asciminib were 1113 ng/mL and 7908 ng.hr/mL, 
respectively, vs 793 ng/mL and 5262 ng.hr/mL for 
single agent asciminib 40 mg b.i.d. Hence, comparing 
the exposure of single agent asciminib 40 mg b.i.d. vs 
asciminib 40 mg b.i.d. in combination with 300 mg 
nilotinib b.i.d., Cmax and AUCtau of asciminib in 
combination appeared to be moderately increased by 

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1.4- and 1.5-fold, respectively (Cycle 2 Day 1). 
3.3.6.8.3 Nilotinib PK: Following administration of the first oral 
dose of nilotinib on Cycle 1 Day 1 and after repeated 
administration of nilotinib at steady state, nilotinib was 
rapidly absorbed with a median Tmax of approximately 
1-3 hr. across all cohorts and independent of study 
day. At steady state (Cycle 2 Day 1), the geometric 
mean Cmax and AUClast of nilotinib 300 mg b.i.d. 
when given in combination with asciminib 20 mg b.i.d. 
were 996 ng/mL and 5890 ng.hr/mL, respectively and 
in combination with asciminib 40 mg b.i.d. were 1082 
ng/mL and 5870 ng.hr/mL, respectively. Hence, there 
was no change in the nilotinib Cmax and AUClast 
when administered in combination with asciminib 40 
mg b.i.d. vs 20 mg b.i.d.  
3.3.6.8.4 Overall, considering sample size and variability, there 
was no relevant difference in nilotinib exposure across 
the different dose groups. Accumulation of nilotinib 
exposure was observed at steady state (Cycle 2 Day 
1) with the geometric mean accumulation ratio of 2.48 
when administered in combination with asciminib 40 
mg b.i.d. 
3.3.6.9 Asciminib in combination with imatinib in CML-CP/-AP 
3.3.6.9.1 Asciminib PK: Following administration of the first oral 
dose of imatinib on Cycle 1 Day 1 and after repeated 
administration of asciminib at steady state, asciminib 
was rapidly absorbed with a median Tmax of 
approximately 1.5-4 hr. across all cohorts and 
independent of study day. Asciminib exposure did not 
appear to accumulate at steady state (Cycle 2 Day 1) 
as indicated by the geometric mean accumulation ratio 
of approximately 1.0 for asciminib when administered 
at 40 to 80 mg q.d. in combination with imatinib 400 
mg q.d.; the ratio was 2.54 when asciminib 
administered at 40 mg and b.i.d. regimen. At steady 
state of asciminib 40 mg b.i.d. in combination with 
imatinib 400 mg q.d. (Cycle 2 Day 1), the geometric 
metric mean Cmax and AUCtau of asciminib were 981 
ng/ml and 9841 ng.hr/mL (n=5 for Cmax and n=3 for 
AUCtau), respectively, vs 793 ng/ml and 5262 
ng.hr/mL for single agent asciminib 40 mg b.i.d. Based 
on very limited data, comparing the exposure of single 
agent asciminib 40 mg b.i.d. (fasted) vs asciminib in 
combination with imatinib 400 mg q.d. (fed), Cmax and 
AUCtau of asciminib in combination appeared to be 
moderately increased by 1.2- and 1.9-fold (Cycle 2 

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Day 1), respectively. 
3.3.6.9.2 Imatinib PK: The Tmax for imatinib in combination with 
asciminib was approximately 2-4 hr. across cohorts, 
and independent of study day. Accumulation of 
imatinib exposure was observed at steady state (Cycle 
2 Day 1) with the geometric mean accumulation ratio 
of 3.20 and 1.81 when administered with asciminib 40 
mg and 60 mg q.d., respectively. 
3.3.6.9.3 Overall, considering sample size and variability, there 
was no clinically relevant difference in imatinib 
exposure across the different dose groups. The overall 
increase of asciminib when co-administered with 
imatinib or nilotinib could be explained by their 
potential to inhibit BCRP, CYP3A4, UGT2B17 and 
UGT1A3/4. Both nilotinib and imatinib are UGT 
inhibitors and moderate CYP3A4 inhibitors. In addition, 
imatinib has been shown to be a potent P-gp and 
BCRP inhibitor. 
3.3.6.10 
Asciminib in combination with dasatinib in CML-CP/-AP 
3.3.6.10.1 
Asciminib PK: Following administration of the 
first oral dose of asciminib on Cycle 1 Day 1 and after 
repeated administration of asciminib at steady state, 
asciminib was rapidly absorbed with a median Tmax of 
approximately 2 hr. across all cohorts and independent 
of study day. Accumulation of asciminib exposure was 
observed at steady state (Cycle 2 Day 1) with the 
geometric mean accumulation ratio of 1.22 to 2.04 
when administered at 40 mg b.i.d., 80 mg q.d. or 160 
mg q.d. in combination with dasatinib 100 mg q.d. At 
steady state of asciminib 40 mg b.i.d. in combination 
with dasatinib100 mg q.d. (Cycle 2 Day 1), the 
geometric mean Cmax and AUCtau of asciminib were 
823 ng/mL and 5243 ng.hr/mL (n=9 for Cmax and n=7 
for AUCtau), respectively, vs 793 ng/mL and 5262 
ng.hr/mL for single agent asciminib 40 mg b.i.d. 
Comparing the exposure of single agent asciminib 40 
mg b.i.d. (fasted) vs asciminib in combination with 
dasatinib 100 mg q.d., there was no difference 
observed in Cmax and AUCtau of asciminib in 
combination with dasatinib. 
3.3.6.10.2 
Dasatinib PK: The Tmax for dasatinib in 
combination with asciminib was approximately 0.5-1.5 
hr. across cohorts, and independent of study day. 
Accumulation of dasatinib exposure was observed at 
steady state (Cycle 2 Day 1) with the geometric mean 
accumulation ratio of 0.83 to 1.21 when administered 

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with asciminib 40 mg b.i.d., 80 mg q.d. or 160 mg q.d. 
Overall, considering sample size and variability, there 
was no clinically relevant difference in dasatinib 
exposure across the different dose groups. 
3.3.7 Pharmacokinetics in special patient populations 
3.3.7.1 Hepatic impairment 
3.3.7.1.1 Study CABL001A2103 assessed the effect of varying 
degrees on hepatic impairment on the PK of asciminib. 
Compared to the control group: i) mild hepatic 
impairment group exhibited a trend to slightly higher 
exposure with 22% higher AUCinf, 21% higher 
AUClast, 26% higher Cmax, although considered 
globally comparable to normal subjects; ii) moderate 
hepatic impairment group had similar exposure; iii) 
severe hepatic impairment group had 66% higher 
AUCinf, 55% higher AUClast, 29% higher Cmax.  
3.3.7.1.2 Median asciminib Tmax were similar in normal, mild, 
moderate groups (2 hr.) and slightly shorter (1.5 hr.) in 
severe hepatic impairment group Protein binding of 
asciminib was similar across groups. Based on the 
unbound fraction of asciminib and compared to the 
control group: i) the mild hepatic impairment group had 
15% higher AUCinf, 14% higher AUClast, 19% higher 
Cmax; ii) moderate hepatic impairment group had 
similar exposure; iii) severe hepatic impairment group 
had 51% higher AUCinf, 44% higher AUClast, 20% 
higher Cmax.  
3.3.7.1.3 Treatment with asciminib 40 mg was well tolerated in 
healthy subjects and in subjects with varying degrees 
of hepatic impairment. 
3.3.7.2 Renal impairment 
3.3.7.2.1 Study CABL001A2105 assessed the effect of severe 
renal impairment on the PK of asciminib. The 
exposure of asciminib as assessed by AUClast and 
AUCinf, which were 49% (geo mean ratio [90% CI]: 
1.49 [1.01, 2.20]) and 56% (geo mean ratio [90% CI]: 
1.56 [1.05, 2.30]) higher in the severe renal 
impairment cohort compared to the normal renal 
function cohort.  
3.3.7.2.2 The Cmax and Tmax values were similar in both 
cohorts, suggesting there was no difference in the 
absorption of the drug. 
3.4 Safety in humans 
3.4.1 Asciminib single agent 
3.4.1.1 The most common AEs reported in at least 50 patients among 
the 200 with CML-CP or AP-CML treated with asciminib single 

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agent when considering all doses and all grades were fatigue 
(29.0%), headache, lipase increase, nausea (26.0%, each) and 
diarrhea (25.5%). 
3.4.1.2 Serious adverse events suspected to be drug related by system 
organ class, preferred term, and treatment single agent 
asciminib in CML-CP and CML-AP 
All subjects 
N=200 
Primary system organ class  
SAE 
Preferred term  
n (%) 
Number of subjects with at least one event  
18 (9.0) 
Blood and lymphatic system disorders  
3 (1.5) 
Thrombocytopenia  
2 (1.0) 
Febrile neutropenia  
1 (0.5) 
Cardiac disorders  
5 (2.5) 
Angina pectoris  
2 (1.0) 
Atrial fibrillation  
1 (0.5) 
Pericardial effusion  
1 (0.5) 
Acute coronary syndrome  
1 (0.5) 
Cyanosis  
1 (0.5) 
Myocardial infarction  
1 (0.5) 
Gastrointestinal disorders  
4 (2.0) 
Pancreatitis  
2 (1.0) 
Pancreatitis acute  
2 (1.0) 
General disorders and administration site conditions  
3 (1.5) 
Non-cardiac chest pain  
2 (1.0) 
Immune system disorders  
1 (0.5) 
Hypersensitivity  
1 (0.5) 
Investigations  
1 (0.5) 
Platelet count decreased  
1 (0.5) 
Musculoskeletal and connective tissue disorders  
2 (1.0) 
Myalgia  
1 (0.5) 
Bone pain  
1 (0.5) 
Fibromyalgia  
1 (0.5) 
Osteonecrosis  
1 (0.5) 
Nervous system disorders  
3 (1.5) 
Cerebrovascular accident  
1 (0.5) 
IIIrd nerve paralysis  
1 (0.5) 
Ischemic stroke  
1 (0.5) 
Respiratory, thoracic, and mediastinal disorders  
4 (2.0) 
Dyspnea  
1 (0.5) 
Pleural effusion  
2 (1.0) 
Bronchospasm  
1 (0.5) 
Pleurisy  
1 (0.5) 
Skin and subcutaneous tissue disorders  
1 (0.5) 
Urticaria  
1 (0.5) 
Numbers (n) represent counts of subjects. 
Sort SOC by alphabetical order, and then PTs within each SOC by descending 
frequency in ‘All grades’ column. 
Only AEs occurring during treatment or within 30 days of the last study 
medication are reported. 
MedDRA version 23.0, CTCAE version 4.03 
 
3.4.2 Asciminib and imatinib combination 
3.4.2.1 Asciminib has been studied in 25 patients with CML-CP or 
CML-AP at dose levels of 40 mg b.i.d., 40 mg q.d., 60 mg q.d., 

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80 mg q.d. in combination with imatinib 400 mg q.d. Twelve 
patients (48.0%) discontinued study treatment. The most 
frequent primary reason for discontinuation was physician’s 
decision due to lack of efficacy (16.0%). Adverse events leading 
to treatment discontinuation were reported in 2 patients (8.0%). 
Dose limiting toxicities (DLT) have been reported in six out of 25 
evaluable patients (24.0%) treated with a combination of 
asciminib and imatinib as follows: 
3.4.2.1.1 • Pancreatitis, n=2 (40 mg b.i.d., 80 mg q.d.), 
3.4.2.1.2 • Abdominal pain, n=1 (60 mg q.d.),  
3.4.2.1.3 • Nausea, n=1 (60 mg q.d.),  
3.4.2.1.4 • Lipase increase, n=1 (80 mg q.d.).  
3.4.2.1.5 • Neutrophil count decreased, n=1 (40 mg q.d.)  
3.4.2.2 Based on totality of data, asciminib 40 mg and 60 mg q.d. 
doses have been recommended in combination with imatinib 
400 mg q.d. in CML-CP or CML-AP patients for further 
development. 
3.4.2.3 The safety profile from these cohorts and for the overall 
population is presented below. All 25 patients were evaluable 
for safety. Overall, by cut-off date, the median duration of 
exposure was longer for asciminib (129.3 weeks) than with 
imatinib (84.9 weeks) No on-treatment deaths were reported.  
3.4.2.4 Nausea was the most common AE reported in patients with 
CML-CP or CML-AP treated with a combination of asciminib 
and imatinib (all cohorts) regardless of relationship to study 
drug or suspected to be related to study drug. 
3.4.2.5 In this clinical trial, 40-60 mg of asciminib per day was 
confirmed to be similar to 40 mg bid administration when used 
with imatinib in previous studies, so asciminib 60 mg qd is used. 
3.4.2.6 Serious adverse events suspected to be related to study drug 
by system organ class, preferred term, and treatment – 
asciminib in combination with Imatinib in CML-CP and CML-AP
 
 
All subjects 
N=25 
Primary system organ class  
SAE 
Preferred term  
n (%) 
Number of subjects with at least one event  
4 (16.0) 
Gastrointestinal disorders  
1 (4.0) 
Pancreatitis  
1 (4.0) 
Hepatobiliary disorders  
1 (4.0) 
Hepatitis  
1 (4.0) 
Investigations  
1 (4.0) 
Neutrophil count decreased  
1 (4.0) 
Musculoskeletal and connective tissue disorders  
1 (4.0) 
Myopathy  
1 (4.0) 
Numbers (n) represent counts of subjects. 
Sort SOC by alphabetical order, and then PTs within each SOC by descending 
frequency in ‘All grades’ column. 
Only AEs occurring during treatment or within 30 days of the last study medication 

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are reported. 
MedDRA version 23.0, CTCAE version 4.03. 
3.4.3 Asciminib and nilotinib combination 
3.4.3.1 Asciminib has been studied in 26 patients with CML-CP or 
CML-AP at dose levels of 20 mg b.i.d. or 40 mg b.i.d. in 
combination with nilotinib 300 mg q.d. Eleven patients (42.3%) 
discontinued study treatment. The most frequent primary 
reason for discontinuation was physician’s decision (26.9%, 
mainly due to lack of efficacy). Only one patient (3.8%) 
discontinued study treatment due to adverse events. 
3.4.3.2 Dose limiting toxicities (DLT) have been reported in one out of 
sixteen evaluable patients (6.3%) treated with a combination of 
asciminib with nilotinib as follow: • maculopapular rash 
(asciminib 20 mg b.i.d. + nilotinib 300 mg b.i.d.).  
3.4.3.3 Based on the safety and tolerability data, PK data, preliminary 
efficacy observed, the combined dose of asciminib 40 mg b.i.d. 
+ nilotinib 300 mg b.i.d. was recommended for expansion 
cohort to collect additional safety and tolerability data. All 26 
patients enrolled were evaluable for safety. 
3.4.3.4 In this clinical trial, the dose of asciminib is set to 80 mg qd 
when administered in combination with nilotinib. 
3.4.3.5 Overall, by cut-off date, the median duration of exposure was 
similar for both study drugs (36.6 weeks with asciminib and 34.8 
weeks with nilotinib). No on-treatment deaths occurred. Lipase 
increased (38.5%), myalgia (34.6%), pruritus (30.8%), 
abdominal pain, amylase increase, and thrombocytopenia 
(26.9%, each) were the most common AEs reported in at least 
7 patients with CML-CP or CML-AP treated with a combination 
of asciminib and nilotinib (all cohorts) regardless of relationship 
to study drug. 
3.4.3.6 Serious adverse events suspected to be drug related by system 
organ class, preferred term, and treatment – asciminib in 
combination with nilotinib in CML-CP and CML-AP 
All subjects 
N=26 
Primary system organ class  
SAE 
Preferred term  
n (%) 
Number of subjects with at least one event  
3 (11.5) 
Cardiac disorders  
2 (7.7) 
Angina pectoris  
1 (3.8) 
Atrial fibrillation  
1 (3.8) 
Atrioventricular block  
1 (3.8) 
Metabolism and nutrition disorders  
1 (3.8) 
Hyponatremia  
1 (3.8) 
Neoplasms benign, malignant, and unspecified (incl cysts and 
polyps)  
1 (3.8) 
Myelodysplastic syndrome  
1 (3.8) 
Respiratory, thoracic, and mediastinal disorders  
1 (3.8) 
Pleural effusion  
1 (3.8) 
Vascular disorders  
1 (3.8) 
Peripheral arterial occlusive disease  
1 (3.8) 

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Numbers (n) represent counts of subjects. 
Sort SOC by alphabetical order, and then PTs within each SOC by descending 
frequency in ‘All grades’ column. 
Only AEs occurring during treatment or within 30 days of the last study medication 
are reported. 
MedDRA version 23.0, CTCAE version 4.03. 
3.4.4 Asciminib and dasatinib combination 
3.4.4.1 Asciminib has been studied in 23 patients with CML-CP or 
CML-AP at dose levels of 40 mg b.i.d., 80 mg q.d. and 160 mg 
q.d. in combination with dasatinib 100 mg q.d. Six patients 
(26.1%) discontinued study treatment; half of them due to 
physician’s decision and the other half due to adverse events. 
3.4.4.2 Dose limiting toxicities (DLT) have been reported in 2 out of 22 
evaluable patients (9.1%) treated with a combination of 
asciminib and dasatinib as follows: 
3.4.4.2.1 lipase increased (asciminib 40 mg b.i.d. + dasatinib 
100 mg q.d.)  
3.4.4.2.2 thrombocytopenia (asciminib 160 mg q.d. + dasatinib 
100 mg q.d.)  
3.4.4.3 Based on the overall safety, PK, and preliminary efficacy data, 
asciminib at 80 mg q.d. + dasatinib at 100 mg q.d. was selected 
as RDE in this combination and recruitment was ongoing at 
time of the safety cut-off date. 
3.4.4.4 In this clinical trial, asciminib 80 mg qd is set when combined 
with dasatinib. 
3.4.4.5 All 23 patients were evaluable for safety. Overall, by cut-off date 
the median duration of exposure was longer for asciminib 
(102.3 weeks) than with dasatinib (79.4 weeks). No on-
treatment deaths were reported.  
3.4.4.6 Fatigue (34.8%), thrombocytopenia (30.4%), abdominal pain, 
cough, lipase increase, nausea, and pleural effusion (26.1%, 
each) were the most common AEs reported in at least 6 
patients with CML-CP or CML-AP treated with a combination of 
asciminib and dasatinib (all cohorts) regardless of relationship 
to study drug. 
3.4.4.7 Serious adverse events suspected to be drug related by system 
organ class, preferred term, and treatment – asciminib in 
combination with dasatinib in CML-CP and CML-AP 
All subjects 
N=43 
Primary system organ class  
SAE 
Preferred Term  
n (%) 
Number of subjects with at least one event  
7 (16.3) 
Blood and lymphatic system disorders  
1 (2.3) 
Febrile neutropenia  
1 (2.3) 
Gastrointestinal disorders  
2 (4.7) 
Pancreatitis  
2 (4.7) 
Investigations  
4 (9.3) 
Lipase Increased  
2 (4.7) 
Blood Alkaline Phosphatase increased  
1 (2.3) 
Gamma-glutamyl transferase increased  
1 (2.3) 

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Alanine aminotransferase increased  
2 (4.7) 
Aspartate aminotransferase increased  
2 (4.7) 
Blood alkaline phosphatase increased  
1 (2.3) 
Nervous system disorders  
1 (2.3) 
Cerebrovascular accident  
1 (2.3) 
- Preferred terms are sorted in descending frequency of ‘All grades’ column, as 
reported in the ‘All subjects’ column. 
- A patient with multiple occurrences of an AE under one treatment is counted only 
once in the AE category for that treatment. 
- Only AEs occurring during treatment or within 30 days of the last study 
medication are reported. 
- AEs occurred after the intra-patient dose escalation are summarized under the 
patient's initial treatment group. 
MedDRA version 23.0, CTCAE version 4.03. 
4. ELIGIBILITY 
4.1 Inclusion Criteria  
4.1.1 19 year or older 
4.1.2 CP-CML patients who are taking current TKIs (imatinib, nilotinib or 
dasatinib) for 5 years or more. 
4.1.3 Patients who have failed maintaining MR3.0 after 1 or more cessation 
trial of TKIs. 
4.1.4 Patients who regained MR3.0 or deeper molecular response by TKIs 
retrial after TKI cessation failure at the time of screening 
4.1.5 Taking TKIs over 12 weeks for the retrial of TKIs after TKI cessation 
failure 
4.1.6 Patients who agree with stopping asciminib and TKIs after maintaining 
2year-duration of MR4.5 
4.1.7 Adequate end organ function as defined by: 
4.1.7.1 Total bilirubin (TBL) < 3 x upper limit of normal (ULN); patients 
with Gilbert’s syndrome may only be included if TBL ≤ 3.0 x 
ULN or direct bilirubin ≤ 1.5 x ULN 
4.1.7.2 Creatinine clearance (ClCr) ≥ 30 mL/min as calculated using 
Cockcroft-Gault formula 
4.1.7.3 Serum lipase ≤ 1.5 x ULN. For serum lipase > ULN - ≤ 1.5 x 
ULN, value must be considered not clinically significant and not 
associated with risk factors for acute pancreatitis 
4.1.8 Patients who can sign the informed consent of their own free will 
4.2 Exclusion Criteria 
4.2.1 Patients who experienced grade 3 or higher adverse events with TKIs 
(imatinib, dasatinib, and nilotinib). 
4.2.2 Patients who are receiving any other investigational agents. 
4.2.3 Patients who currently have uncontrolled infections 
4.2.4 Patients who previously received Chimeric antigen receptor T-cell 
(CAR-T cell) therapy, allogeneic hematopoietic stem cell 
transplantation (allo-HSCT) or biologic therapy. 
4.2.5 Patients with clinically significant cardiovascular disease or 
gastrointestinal dysfunction 
4.2.6 Patients who have a history of thromboembolic episodes within 3 

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months prior to the study enrollment. 
4.2.7 Patients with active hepatitis B or C with uncontrolled disease activity. 
4.2.8 Patients who have active malignancies requiring treatment other than 
CML. 
4.2.9 Patients with any severe and/or uncontrolled medical conditions or 
other conditions that could adversely impact on patients’ ability to 
participate in the study. 
4.2.10 Patients with psychiatric illness/social situations that would limit 
compliance with study requirements. 
4.2.11 Pregnant women are excluded from this study Because there is an 
unknown but potential risk for adverse events in nursing infants 
secondary to treatment of the mother with asciminib and TKIs, 
breastfeeding should be discontinued if the mother is treated with 
asciminib and TKIs 
4.3 TFR eligibility 
4.3.1 Patients have received asciminib along with one of TKIs over 3 years 
4.3.2 MUL duration is over 2 years after TKIs+asciminib. 
4.3.3 MUL is confirmed (2 consecutively at least 4 weeks apart). 
5. TREATMENT PLAN 
5.1 General principle 
5.1.1 The patient will be enrolled when achieving MR3.0 or deeper 
molecular response after re-initiation of TKIs. 
5.1.2 The TKIs are the same drug and dose when attempting TKI cessation. 
5.1.3 Asciminib will be added to the each TKIs when confirming MR3.0 or 
deeper molecular response and the duration of re-initiation of TKIs are 
at least 12 weeks. 
5.1.4 The change of concurrent TKI or dosage during this trial is not 
recommended. 
5.2 Agent Administration 
5.2.1 Treatment will be administered on an outpatient basis.   
5.2.2 Reported adverse events and potential risks are described in Section 
3.4 and 10.1.   
5.2.3 Appropriate dose modifications are described in Section 5.9.   
5.2.4 No investigational or commercial agents or therapies other than those 
described below may be administered with the intent to treat the 
patient's CML. 
5.2.5 The study treatment will be the combination of asciminib and one of 
concurrent TKIs. 
5.3 Asciminib 
5.3.1 Asciminib will be started after failure of TKIs cessation trial and 
subsequent re-achievement of MR3.0 or deeper molecular response. 
5.3.2 Asciminib (80mg qd for nilotinib; 60mg qd for imatinib; 80mg qd for 
dasatinib) will be added to each concurrent TKI. 
5.3.3 Patients will be dropped out from this study if patients are intolerant to 
asciminib 20mg qod or loss of MR3.0 occurs. 
5.3.4 Tyrosine-kinase inhibitors allowed for co-treatment: imatinib, dasatinib, 

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and nilotinib 
5.3.5 Asciminib should be added at least 12 weeks after TKI resumed. 
5.4 Concurrent TKIs 
5.4.1 The principle of choosing TKI for re-initiation after TFR failure is to 
start the same TKI that patients have took when trying TFR. 
5.4.2 Concurrent TKIs will be started at least 12 weeks prior to the start of 
asciminib. 
5.4.3 The dosage each TKI  
5.4.3.1 The dosage will be the same as the dose of re-initiation of TKI. 
5.4.3.2 The change of concurrent each TKI dose combined with 
asciminib will be permitted at the discrete of attending 
physician. 
5.4.4 The concurrent TKIs will be one of Imatinib, Nilotinib, or Dasatinib 
5.4.5 Change of TKIs 
5.4.5.1 The change of concurrent TKIs when combined with asciminib 
is not recommended. 
5.4.5.2 The change of concurrent TKIs when combined with asciminib 
will be permitted at the discrete of attending physician among 

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imatinib, nilotinib or dasatinib. 
5.5 Treatment scheme 
5.6 Duration of Therapy 
5.6.1 In the absence of treatment delays due to adverse event(s), treatment 

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may continue until one of the following criteria applies: 
5.6.2 Fulfillment of the criteria for cessation of therapy to attempt TFR 
5.6.2.1 When a patient achieves molecularly undetectable leukemia 
(MUL; at least MR4.0 detection limit) and there is no loss of 
MUL for 2 years, the patient will stop asciminib and TKIs.  
5.6.2.2 RQ-PCR will be performed 2 times consecutively, 4 weeks 
apart for the confirmation of MUL just prior to stopping 
Asciminib and TKIs. 
5.6.2.3 The minimum duration of asciminib and TKIs treatment should 
be 3 years or longer and the duration of sustained MUL should 
be 2 years or longer before stopping asciminib and TKIs.  
5.6.2.4 If a patient fails achieving MUL after 3 years of TKIs and 
asciminib combination, the patient will be dropped from the 
study.  
5.6.3 Disease progression: loss of MR3.0 twice a month apart, 
consecutively or progression to accelerated phase or blast crisis while 
on asciminib and TKIs 
5.6.4 Intercurrent illness that prevents further administration of treatment 
5.6.5 Unacceptable adverse event(s) 
5.6.6 Patient decides to withdraw from the study 
5.6.7 General or specific changes in the patient's condition render the 
patient unacceptable for further treatment in the judgment of the 
investigator 
5.6.8 Patient non-compliance 
5.6.9 Pregnancy 
5.6.9.1 All women of childbearing potential should be instructed to 
contact the investigator immediately if they suspect they might 
be pregnant (e.g., missed, or late menstrual period) at any time 
during study participation. 
5.6.10 Termination of the study by sponsor 
5.6.11 The drug manufacturer can no longer provide the study agent 
5.6.12 The reason(s) for protocol therapy discontinuation, the reason(s) for 
study removal, and the corresponding dates must be documented in 
the Case Report Form (CRF). 
5.7 Reinitiation of CML therapy 
5.7.1 TKIs will be restarted, or other treatment without asciminib can be tried 
when loss of MR3.0 is detected consecutively 2 times after 
discontinuation of asciminib and TKIs by above condition. 
5.8 Duration of Follow-Up 
5.8.1 Patients will be followed 30 days after removal from study or until 
death, whichever occurs first.  Patients removed from study for 
unacceptable adverse event(s) will be followed until resolution or 
stabilization of the adverse event. 
5.9 BCR/ABL1 RQ PCR 
5.9.1 While on asciminib and TKIs, BCR/ABL1 RQ PCR will be performed 

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every 3 months. 
5.9.2 After discontinuation of asciminib and TKIs to attempt TFR, RQ PCR 
should be repeated every month for 6 months, then every 2 months for 
next 6 months, and then every 3 months for 2 years. 
5.9.3 BCR/ABL1 RQ PCR will be analyzed at the central lab. 
 
5.10 Dosing delays/dose modifications 
5.10.1 Dose Escalations: For asciminib, dose escalation beyond the standard 
dose (80mg qd for nilotinib; 60mg qd for imatinib; 80mg qd for 
dasatinib) is not permitted.  
5.10.2 Dose Modifications: For patients who do not tolerate their protocol-
specified dosing schedule, dose interruptions and/or reductions are 
either recommended or mandated (depending on the specific event 
and grade) to allow continuation of study treatment. Dose reduction 
will be based on worst toxicity demonstrated at the last dose. 
Asciminib dose reduction below 20 mg qod will not be allowed. The 
dose can be reduced by 1 dose level in a stepwise manner (dose level 
0 to -1; dose level -1 to -2; dose level -2 to -3).  
5.10.3 Asciminib dose level 
Dose level 
Nilotinib 
Imatinib 
Dasatinib 
0 
80mg qd 
60mg qd 
80mg qd 
-1 
40mg qd 
40mg qd 
40mg qd 
-2 
20mg qd 
20mg qd 
20mg qd 
-3 
20mg qod 
20mg qod 
20mg qod 
 
5.10.4 Patients must discontinue treatment with either agent if, after 
treatment is resumed at a lower dose level, the toxicity recurs at the 
same or worse severity—except for recurrence of cytopenias.  
5.10.5 If a patient requires a dose interruption of >28 days for each 
nonhematologic toxicity, they must discontinue study treatment.  
5.10.6 If a hematologic toxicity (cytopenia grade 3/4) lasts for >42 days 
without recovery to grade ≤2, despite TKI interruption and adequate 
management (including hematopoietic growth factors), the patient 

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must discontinue study treatment. 
5.10.7 adjustment of nilotinib capacity by extending the QT interval 
ECGs QTc > 480 msec  
 
1.  Stop nilotinib to measure serum potassium and 
magnesium, and correct it to a normal level if it is 
below the normal lower limit. You need to check which 
drugs are administered together. 
2.  QTcF <450 msec, within 20 msec of the target base 
value, start over with the previous capacity within two 
weeks. 
3.  If QTcF falls between 450 and 480 msec after two 
weeks, the dose is reduced to 400 mg once a day. 
4. If the dose reaches QTcF > 480 msec even though 400 
mg is reduced to one dose a day, stop the nilotinib. 
5.  ECG follow-up tests shall be performed within 7 days 
of capacity adjustment. 
 
5.10.8 Criteria for dose reduction/interruption and reinitiation of asciminib and 
bosutinib treatment for adverse drug reactions 
Dose modifications* 
Worst toxicity 
CTCAE grade 4.03 
Asciminib 
Hematologic toxicity† 
 
Neutropenia 
 
Grade 1 (ANC <LLN-1.5 × 
109/L) 
or grade 2 (ANC <1.5-1.0 × 
109/L) 
Recommendation: Maintain dose level 
Grade 3 (ANC <1.0-0.5 × 
109/L) or 
grade 4 (ANC <0.5 × 109/L) 
Mandatory: Hold dose until resolved to grade ≤2 (recheck CBC 2 
times/week), then: If resolved in ≤14 days, maintain dose level  
If resolved in >14 days, reduce dose 1 dose level 
Febrile neutropenia (ANC <1.0 
× 
109/L; fever ≥38.5°C) 
Mandatory: Hold dose until resolved, then reduce dose by 1 dose 
level 
Thrombocytopenia 
 
Grade 1 (PLT <LLN-75 × 
109/L) or 
grade 2 (PLT <75-50 × 109/L) 
Recommendation: Maintain dose level 
Grade 3 (PLT <50-25 × 109/L) 
or 
grade 4 (PLT <25 × 109/L) 
Mandatory: Hold dose until resolved to grade ≤2 (recheck CBC 2 
times/week), the If resolved in ≤14 days, maintain dose level 
If resolved in >14 days, reduce dose by 1 dose level 
Recurrence of all cytopenias  
Recommendation: Hold dose until resolved to grade ≤2, then 
maintain current dose level 
Nonhematologic toxicity 
 
Grade 1  
Recommendation: Maintain dose level 

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Grade 2  
Recommendation: Hold dose until resolved to grade ≤1, then 
maintain dose level 
Grade 3  
Mandatory: Hold dose until resolved to grade ≤1, then reduce 
dose by 1 dose level 
Grade 4  
Mandatory: Permanently discontinue patient from study drug 
treatment 
Renal 
 
Serum creatinine 
Grade 1 (>ULN-1.5 × ULN)  
Recommendation: Maintain dose level 
Grade 2 (>1.5-3.0 × ULN)  
Recommendation: Hold dose until resolved to grade ≤1 or 
baseline, then maintain dose level 
Grade 3 (>3.0-6.0 × ULN) or 
grade 
4 (>6.0 × ULN) 
Mandatory: Permanently discontinue patient from study drug 
treatment 
Hepatic 
 
Isolated total bilirubin elevation 
 
>ULN-1.5 × ULN  
Recommendation: Maintain dose level 
>1.5-3.0 × ULN  
Recommendation: Hold dose. 
Monitor LFTs‡ weekly, or more frequently if clinically indicated, 
until resolved to ≤1.5 × ULN: 
If resolved in ≤14 days, maintain dose level  
If resolved in >14 days, reduce dose by 1 dose level 
>3.0-10.0 × ULN§  
Mandatory: Hold dose. Monitor LFTs‡ weekly, or more frequently 
if clinically indicated, until resolved to ≤1.5 × ULN: 
If resolved in ≤14 days, reduce dose by 1 dose level If resolved in 
>14 days, discontinue patient from study drug treatment. The 
patient should be monitored weekly (including LFTs‡), or more 
frequently if clinically indicated, until total bilirubin has resolved to 
baseline or stabilized over 4 weeks 
>10.0 × ULN§  
Mandatory: Permanently discontinue patient from study drug 
treatment. The patient should be monitored weekly (including 
LFTs‡), or more frequently if clinically indicated, until total bilirubin 
has resolved to baseline stabilized over 4 weeks 
Isolated AST or ALT elevation 
 
>ULN-3.0 × ULN  
Recommendation: Maintain dose level 
>3.0-5.0 × ULN  
Recommendation: Maintain dose level. Repeat LFTs‡ as soon 
as possible, preferably within 48 to 72 hours from awareness of 
the abnormal results; if abnormal laboratory values are confirmed, 
monitor LFTs‡ weekly, or more frequently if clinically indicated, 
until resolved to ≤3.0 × ULN 
>5.0-10.0 × ULN  
Mandatory: Hold dose. Repeat LFTs‡ as soon as possible, 
preferably within 48 to 72 hours from awareness of the abnormal 
results; monitor LFTs‡ weekly, or more frequently if clinically 
indicated, until resolved to ≤3.0 ULN, then: If resolved in ≤14 
days, maintain dose level  
If resolved in >14 days, reduce dose by 1 dose level 
>10.0-20.0 × ULN  
Mandatory: Hold dose. Repeat LFTs‡ as soon as possible, 
preferably within 48 to 72 hours from awareness of the abnormal 
results; monitor LFTs‡ weekly, or more frequently if clinically 
indicated, until resolved to ≤ baseline and then reduce dose by 1 
dose level 
>20.0 × ULN  
Mandatory: Permanent discontinuation 
Combined¶ elevations of AST or ALT and total bilirubin 
For patients with normal 
baseline ALT and AST and 
Mandatory: Permanently discontinue patient from study drug 
treatment. Repeat as soon as possible, preferably within 48 hours 

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total bilirubin value: AST or 
ALT >3.0 × ULN combined, 
with total bilirubin >2.0 × ULN 
without evidence of 
cholestasis# 
For patients with elevated 
baseline AST or ALT or total 
bilirubin 
value: AST or ALT >2 × 
baseline and >3.0 × ULN 
from awareness of the abnormal results, then monitor LFTs‡ 
weekly or more frequently if clinically indicated, until AST, ALT, or 
bilirubin have resolved to baseline or stabilized over 4 weeks. 
Additional follow-up evaluations may be needed 
Metabolic 
 
Asymptomatic amylase and/or 
lipase elevation 
 
Grade 1 (>ULN-1.5 × ULN) or 
grade 2 (>1.5-2.0 × ULN) 
Recommendation: Maintain dose level; measure 2 times/week 
Grade 3 (>2.0-5.0 × ULN)  
Mandatory: Hold dose until resolved to grade ≤1 or baseline, 
then: If resolved in ≤7 days, reduce dose by 1 dose level 
If resolved in >7 days, discontinue treatment and obtain 
appropriate 
imaging (MRI, CT scan, or ultrasonography) 
Grade 4 (>5.0 × ULN)  
Mandatory: Permanently discontinue patient from study drug 
treatment. Obtain appropriate imaging (MRI, CT scan, or 
ultrasonography) 
Vascular disorders 
 
Hypertension 
 
CTCAE grade 3  
Mandatory: Hold dose until resolved to grade ≤1, then reduce 
dose by 1 dose level 
CTCAE grade 4  
Mandatory: Permanently discontinue patient from study drug 
treatment 
Gastrointestinal 
 
Pancreatitis 
 
Grade 2 (radiologic findings for 
pancreatitis as per CTCAE 
v5.0) 
Mandatory: If asymptomatic radiologic pancreatitis, hold 
treatment until recovery of the radiologic findings. If treatment 
delay is ≤21 days, reduce dose by 1 dose level. If treatment delay 
>21 days, discontinue treatment and keep monitoring with 
appropriate imaging (MRI, CT scan, or ultrasonography) 
Grade ≥3  
Mandatory: Permanently discontinue patient from study drug 
treatment. Obtain appropriate imaging (MRI, CT scan, or 
ultrasonography) 
Diarrhea** 
 
Grade 1  
Recommendation: Maintain dose level, but initiate anti-diarrhea 
treatment 
Grade 2  
Recommendation: Hold dose until resolved to grade ≤1, then 
maintain dose level. If diarrhea returns as grade ≥2, hold dose 
until resolved to grade ≤1 and then reduce dose by 1 dose level 
Grade 3  
Recommendation: Hold dose and discontinue patient from study 
drug 
treatment 
Grade 4  
Mandatory: Permanently discontinue patient from study drug 
treatment 
Skin and subcutaneous tissue 
disorders 
 
Rash/photosensitivity 
 
Grade 1  
Recommendation: Maintain dose level. Consider initiating 
appropriate skin toxicity therapy 

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(such as antihistamines, topical 
corticosteroids, and low-dose 
systemic corticosteroids) 
Grade 2  
Recommendation: Maintain dose level, but initiate/intensify 
appropriate skin toxicity therapy (such as antihistamines, topical 
corticosteroids, and low-dose systemic corticosteroids) 
Grade 3, despite skin toxicity 
therapy 
Recommendation: Hold dose until resolved to grade ≤1, then: If 
resolved in ≤7 days, reduce dose by 1 dose level If resolved in >7 
days (despite appropriate skin toxicity therapy), discontinue 
patient from study drug treatment 
Grade 4, despite skin toxicity 
therapy 
Mandatory: Permanently discontinue patient from study drug 
treatment 
General disorders and 
administration-site conditions 
 
Fatigue/asthenia 
 
Grade 1 or 2  
Recommendation: Maintain dose level 
Grade 3  
Recommendation: Hold dose until resolved to grade ≤1, then: If 
resolved in ≤7 days, maintain dose level If resolved in >7 days, 
reduce dose by 1 dose level 
6. SUPPORTIVE CARE AND GENERAL CONCOMITANT MEDICATION 
GUIDELINES 
6.1 Supportive care 
6.1.1 A characteristic polymyalgia-like syndrome of musculoskeletal and/or 
joint pain beginning the first weeks or months after TKI discontinuation 
has been reported in about 20–30% of patients. This phenomenon is 
likely due to undefined off-target effect(s) of the TKI. In most patients 
the symptoms are mild and self-limited, but some patients may require 
temporary treatment with acetaminophen, nonsteroidal anti-
inflammatory drugs or in some instances a short course of oral 
corticosteroids. 
6.1.2 Management for cytopenia 
6.1.2.1 G-CSF or GM-CSF will be permitted. 
6.1.2.2 Transfusion will be permitted. 
6.2 General concomitant medication 
6.2.1 Except for prohibited and restricted medications detailed below 
(Section 6.2.3), subjects should continue their normal medications.  
6.2.2 Vaccinations During Study: Investigators should also review each 
subject’s vaccination status at periodic intervals to ensure that any 
needed booster vaccinations are administered at the optimal timing 
during the study. Please contact the PI for any questions. 
6.2.3 Prohibited and restricted medications 
6.2.3.1 Generally, there is no prohibited and restricted medications for 
asciminib. 
6.2.3.2 Please refer to package insert for each concurrent TKI for 
prohibited and restricted medications. 
7. STUDY CONDUCT 
7.1 Schedule of assessment 
7.1.1 The schedule of study assessments/procedures of this study is 
presented in 7.2 and 7.3. Assessments in the study are intended to be 

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conducted in clinic; they may be conducted remotely under 
extenuating circumstances (e.g., COVID-19 restrictions), which will be 
determined individually for each site and/or subject. 
7.1.2 The study schedule has 2 phases 
7.1.2.1 Asciminib phase 
7.1.2.1.1 Screening: confirming MR3 or deeper molecular 
response 
7.1.2.1.2 Baseline: Start asciminib along with TKIs 
7.1.2.1.3 Asciminib: Asciminib for 3 years 
7.1.2.2 TFR phase 
7.1.2.2.1 Screening: confirming MUL (2 consecutively, 4 weeks 
apart) 
7.1.2.2.2 Baseline: Stop TKIs+Asciminib 
7.1.2.2.3 TFR: BCR/ABL1 RQ-PCR 
7.1.2.2.4 End of treatment: TFR for 3 years 
7.2 Table for study assessments/Procedures for Asciminib phase 
Assessment/Proc
edure  
Screening 1 
(M-4 to D-1) 
Baseline 
D1 
Asciminib 
Unscheduled 
Visit 
 
Mth 3 
Mth 6 
Mth 9 
(Mth 12-
36) 
Written informed 
consent 
X 
 
 
 
 
 
 
Review eligibility 
criteria  
X 
X 
 
 
 
 
 
Demographics  
X 
 
 
 
 
 
 
Medical & 
medication history 
X 
 
 
 
 
 
 
Height, body 
weight & BMI 
X 
 
 
 
 
 
 
Physical 
examination  
X 
X 
X 
X 
X 
X 
X 
Vital signs (ECG) 
X 
X 
X 
X 
X 
X 
X 
Hematology & 
chemistry  
X 
X 
X 
X 
X 
X 
X 
BCR/ABL1 RQ-
PCR  
X 
X 
X 
X 
X 
X 
 
Pregnancy test 
X 
X 
 
 
 
 
 
HBV, HCV, HIV, 
testing 
X 
 
 
 
 
 
 
Study drug 
administration 
 
X 
X 
X 
X 
X 
 
Drug 
accountability 
 
X 
X 
X 
X 
X 
X 
Record AEs, 
concomitant 
medications 
 
 
 
 
 
 
 
7.3 Table for study assessments/Procedures for TFR phase 
Assessment/Proc
edure  
Screening 
(D-56 to D-1) 
Baseline 
D1 
TFR 
Unscheduled 
Visit 
EOT 
 
Mth 1-6 
Mth 7-
12 
Mth 
15-36 
 
 

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Review TFR 
eligibility criteria  
X  
X 
 
 
 
 
 
Physical 
examination 
X  
X  
X  
X 
X 
X 
X 
Vital signs  
X  
X  
X  
X 
X 
X 
X 
Hematology & 
chemistry  
X  
X  
X  
X 
X 
X 
X 
MUL confirmation  
X* 
 
 
 
 
 
 
BCR/ABL1 RQ-
PCR, monthly 
 
 
X  
 
 
 
 
BCR/ABL1 RQ-
PCR, bimonthly 
 
 
 
X 
 
 
 
BCR/ABL1 RQ-
PCR, q 3M 
 
 
 
 
X 
 
 
Stop study drug 
administration 
 
X 
X 
X 
X 
X 
 
TKI stop 
syndrome survey 
 
X 
X 
X 
X 
X 
X 
Record AEs 
 
 
 
 
 
 
 
* 2 consecutive MUL confirmations during the screening phase before stopping asciminib & TKIs 
 
8. STUDY VISITS 
8.1 Asciminib phase 
8.1.1 Screening  
8.1.1.1 Subjects who are received TKIs after TKI cessation failure by 
the loss of MR3 and re-achieved MR3/deeper response after 12 
weeks of re-initiation of TKIs may be screened for this study. 
Written informed consent must be obtained from each subject 
before initiation of any screening assessments or procedures. 
Signing of the informed consent form (ICF) may occur prior to 
the first on-study visit, which is defined as the visit where site-
conducted procedures are first performed.  
8.1.1.2 A 4-month window is provided to qualify subjects for the study 
requiring MR3 or deeper molecular responses. All screening 
procedures do not need to be completed on the same day, but 
all screening procedures must be completed, and the results 
reviewed and approved by the investigator (or designee) prior to 
asciminib start. An important consideration for the timing of the 
screening visit is the collection of BCR/ABL1 RQ-PCR results.  
8.1.1.3 The following assessments will be performed at the screening 
visit(s):  
8.1.1.3.1 Obtain written informed consent  
8.1.1.3.2 Obtain demographic information  
8.1.1.3.3 Review of inclusion-exclusion criteria  
8.1.1.3.4 Medical history, including collection of CML history and 
confirmation of adequate molecular result status.  
8.1.1.3.5 Review medication history, including prohibited and 
restricted medications (see Section 6.2.3). All 
medications administered specifically for CML and 

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within 30 days prior to screening visit for all other 
medications will be recorded.  
8.1.1.3.6 Full physical examination  
8.1.1.3.7 Height, weight, and body mass index (BMI) estimation  
8.1.1.3.8 Vital signs (resting blood pressure and pulse rate, and 
temperature)  
8.1.1.3.9 Blood collection for clinical laboratory evaluations (see 
7.2): - Blood for hematology, clinical chemistry, Blood 
for HBV, HCV, HIV testing, Serum pregnancy test for 
female subjects of childbearing potential or who are 
postmenopausal for ≤ 2 years at screening, Blood 
collection for follicle-stimulating hormone (FSH) to 
confirm postmenopausal state in women who are 
postmenopausal for ≤ 2 years at screening 
8.1.1.3.10 
BCR/ABL1 RQ-PCR for confirming MR3 or 
deeper molecular response 
8.1.2 Rescreening/Retesting 
8.1.2.1 Rescreening of ineligible subjects, where there is a reasonable 
expectation that the subject will become eligible, is permitted up 
to 2 times. If a subject is unable to be qualified in the 4-month 
window, e.g., due to BCR/ABL1 RQ-PCR or acute illness, the 
screening window may be extended up to 28 additional days. 
Retesting of specific assessments without entirely rescreening a 
subject may be permitted with the approval of the sponsor 
medical monitor (or designee). 
8.1.3 Baseline visit 
8.1.3.1 Before any study drug is administered, the following 
assessments will be completed: 
8.1.3.2 Review and update medical history, including CML history, as 
needed  
8.1.3.3 Review and update medication history, including prohibited and 
restricted medications. Record all medications administered 
specifically for CML and all other medications since screening 
visit.  
8.1.3.4 Targeted physical examination  
8.1.3.5 Body weight  
8.1.3.6 Vital signs (resting blood pressure and pulse rate, and 
temperature)  
8.1.3.7 Blood collection for clinical laboratory evaluations (see 7.2): - 
Blood for hematology, clinical chemistry 
8.1.3.8 A negative pregnancy test result must be recorded for the 
subject to receive study drug.  
8.1.3.9 Review of inclusion-exclusion criteria (to confirm study 

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eligibility)  
8.1.3.10 
Review/record AEs since screening visit  
8.1.4 Asciminib visit 
8.1.4.1 All subjects will return to the clinic during Month 1 (± 7 days), 
Month 2 (± 7 day), Month 3 (± 7 days), and every 3 months (± 
14 days) until 3 years of asciminib administration.  
8.1.4.2 Subjects do not need to withhold any doses on clinic days or 
take a dose in the clinic unless the clinic visit falls during the 
subject’s normal time of dosing.  
8.1.4.3 The following assessments will be performed at each visit 
unless otherwise indicated:  
8.1.4.3.1 Targeted physical examination  
8.1.4.3.2 Body weight  
8.1.4.3.3 Vital signs (resting blood pressure and pulse rate, and 
temperature)  
8.1.4.3.4 Blood collection for clinical laboratory evaluations (see 
7.2): - Blood for hematology, clinical chemistry and 
BCR/ABL1 RQ-PCR 
8.1.4.3.5 Study drug dispensing and drug accountability review 
8.1.4.3.6 Review/record AEs, concomitant medication use, 
including prohibited and restricted medications. 
8.2 TFR Phase 
8.2.1 Screening 
8.2.1.1 Subjects who are received TKIs+asciminib and the duration of 
asciminib is over 3 years may be screened for this TFR phase.  
8.2.1.2 Subjects who did not achieved MUL will be dropped out from 
this study when the subjects had received TKIs+asciminib for 3 
years. 
8.2.1.3 If subjects who have achieved MUL but the duration of MUL is 
less than 2 years, the subjects can receive TKIs+asciminib 
further until MUL duration reaches 2 years.  
8.2.1.4 A 2-month window is provided to qualify subjects for the study 
requiring 2 consecutive MUL molecular responses (at least 4 
weeks apart). All screening procedures do not need to be 
completed on the same day, but all screening procedures must 
be completed, and the results reviewed and approved by the 
investigator (or designee) prior to stopping TKIs+asciminib. An 
important consideration for the timing of the screening visit is 
the collection of BCR/ABL1 RQ-PCR results.  
8.2.1.5 The following assessments will be performed at the screening 
visit(s):  
8.2.1.5.1 Review of TFR eligibility criteria  
8.2.1.5.2 Full physical examination  
8.2.1.5.3 Vital signs (resting blood pressure and pulse rate, and 
temperature)  
8.2.1.5.4 Blood collection for clinical laboratory evaluations (see 

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7.2): - Blood for hematology, clinical chemistry 
8.2.1.5.5 BCR/ABL1 RQ-PCR for confirming 2 consecutive MUL 
(at least 4 weeks apart) 
8.2.2 Rescreening/Retesting 
8.2.2.1 Rescreening of ineligible subjects, where there is a reasonable 
expectation that the subject will become eligible, is permitted up 
to 2 times. If a subject is unable to be qualified in the 56-day 
window, e.g., due to BCR/ABL1 RQ-PCR or acute illness, the 
screening window may be extended up to 28 additional days. 
Retesting of specific assessments without entirely rescreening a 
subject may be permitted with the approval of the sponsor 
medical monitor (or designee). 
8.2.3 Baseline visit 
8.2.3.1 Before stopping TKIs+asciminib, the following assessments will 
be completed: 
8.2.3.2 Targeted physical examination  
8.2.3.3 Vital signs (resting blood pressure and pulse rate, and 
temperature)  
8.2.3.4 Blood collection for clinical laboratory evaluations (see 7.3): 
Blood for hematology, clinical chemistry 
8.2.3.5 Review of TFR eligibility criteria (to confirm TFR eligibility)  
8.2.4 TFR visit 
8.2.4.1 All subjects will return to the clinic during Month 1 (± 7 days), 
Month 2 (± 7 day), Month 3 (± 7 days), Month 4 (± 7 days), 
Month 5 (± 7 days), Month 6 (± 7 days), Month 8 (± 14 days), 
Month 10 (± 14 days), Month 12 (± 14 days), and every 3 
months (± 14 days) until 3 years of TFR follow-up.  
8.2.4.2 The following assessments will be performed at each visit 
unless otherwise indicated:  
8.2.4.2.1 Targeted physical examination  
8.2.4.2.2 Vital signs (resting blood pressure and pulse rate, and 
temperature)  
8.2.4.2.3 Blood collection for clinical laboratory evaluations (see 
7.2): - Blood for hematology, clinical chemistry  
8.2.4.2.4 BCR/ABL1 RQ-PCR 
8.2.4.2.5 Review/record AEs or TKI stop syndrome 
8.3 Unscheduled visit 
8.3.1 At the investigator’s discretion, an unscheduled visit may be 
completed at any time during the study prior to the EOS visit. 
Depending on the reason for the visit, any of the below assessments 
may be performed as appropriate. If subjects attend an unscheduled 
visit to assess acute symptoms, all the following assessments should 
be performed. If applicable, dosing compliance should also be 
reviewed to ensure that the subject is taking the drug correctly. Any 
missed doses should be recorded.  
8.3.1.1 Review/record AEs, concomitant medication use, including 

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prohibited and restricted medications  
8.3.1.2 Vital signs (resting blood pressure, pulse rate, and temperature)  
8.3.1.3 Targeted physical examination  
8.3.1.4 Blood collection for clinical laboratory evaluations (see 7.2 and 
7.3): - Blood for hematology, clinical  
8.3.1.5 Consider testing for acute SARS-CoV-2 infection (the causative 
agent of COVID-19) in the correct setting. 
8.4 End-of-Study visit 
8.4.1 All subjects who complete the 3 years TFR phase visit will be asked to 
return to the clinic approximately 3 weeks (21 ± 3 days) for an EOS 
visit. In addition, any subject who discontinues study treatment over 3 
years and did not achieved MUL will be asked to complete the same 
procedures at an ET visit approximately 3 months (21 weeks ± 3 days) 
after the date of the last dose of asciminib. The following assessments 
will be performed at the EOS/ET visit:  
8.4.2 Targeted physical examination  
8.4.3 Vital signs (resting blood pressure and pulse rate, and temperature)  
8.4.4 Blood collection for clinical laboratory evaluations (see 7.3 and 7.3): - 
Blood for hematology, clinical chemistry  
8.4.5 Drug accountability (if not completed earlier)  
8.4.6 Review/record AEs, concomitant medication use 
8.4.7 If an AE, including a clinically significant laboratory abnormality, is 
ongoing at the end of study visit, additional clinic visit(s) or telephone 
contact(s) may be warranted. 
9. STUDY ASSESSMENTS 
9.1 Demographic Information, Medical and Medication History 
9.1.1 Demographic information, and medical and medication history will be 
captured for each subject participating in the study at the screening 
visit. Medical history, medication review, and review of inclusion and 
exclusion criteria and prohibited and restricted medications will also be 
updated and rechecked at baseline (Day 1) as outlined in Section 7. A 
CML history will be taken to document CML clinical characteristics and 
disease burden, including time since diagnosis and history of TKIs. 
Medication history will include details of all treatments administered 
specifically for CML (including any prior tyrosine kinase inhibitor 
therapies); all other medications will be documented beginning 30 
days prior to screening   
9.2 Contraception Requirements 
9.2.1 The following represents the minimum contraception that should be 
used by study participants and their partners. Additional contraceptive 
requirements (e.g., requiring the female partners of male subjects to 
additionally use highly effective contraception) may be required by 
local site practice and/or the governing ethics committee. It is 
anticipated that that not all contraceptive methods may be available in 
all countries/regions, so the list should be modified accordingly. For 
the purposes of this study, females are considered fertile following 

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menarche and until becoming postmenopausal, unless permanently 
sterile (i.e., premenopausal with one of the following: documented 
hysterectomy, documented bilateral salpingectomy, or documented 
bilateral oophorectomy). Documentation can come from site 
personnel’s review of the subject’s medical records, medical 
examination, or medical history interview. Female participants must 
meet at least one of the following requirements: 
1. Be a woman of nonchildbearing potential, either postmenopausal 
(defined as without menses for ≥ 12 months without an alternative 
medical cause with an FSH > 40 mIU/mL) or had a hysterectomy, 
bilateral salpingectomy, or bilateral oophorectomy. 2. Be a woman of 
childbearing potential (defined as a female following menarche and 
prior to becoming post-menopausal who has not had a hysterectomy, 
bilateral salpingectomy, or bilateral oophorectomy) who agrees to use 
a highly effective contraceptive method while enrolled in the study and 
for a duration of 30 days after last dose of study drug. The following 
methods are acceptable: - surgical sterilization (i.e., bilateral tubal 
occlusion or vasectomy of the sole male partner and the vasectomized 
partner has received medical assessment of surgical success) - 
intrauterine device (IUD) or intrauterine system (IUS) - combined 
(estrogen and progestogen containing) hormonal contraception 
associated with inhibition of ovulation (oral, intravaginal, transdermal) - 
progestogen only hormonal contraception associated with inhibition of 
ovulation (oral, injectable, implantable) Women of childbearing 
potential who declare themselves sexually abstinent or exclusively 
having female sexual partners do not need to use highly effective 
contraception. Abstinence in this study is defined as true abstinence 
when it is in line with the subject’s preferred and usual lifestyle. If a 
subject is usually not sexually active but becomes active, she, with her 
partner, must meet the requirements listed above. Female subjects 
must abstain from egg donation throughout the study and for a 
duration of 30 days after last dose of study drug. Male participants 
must meet at least one of the following requirements: 1. Males with a 
female partner of childbearing potential (as defined above) must agree 
to use condoms while enrolled in the study and for at least 90 days 
after the last dose of study drug unless their partner is using a highly 
effective contraceptive method as defined above independent of the 
study. 2. Males who declare themselves sexually abstinent or having 
exclusively male partners are not required to use contraception. 
Abstinence in this study is defined as true abstinence when it is in line 
with the subject’s preferred and usual lifestyle. If a subject is usually 
not sexually active but becomes active, the criteria listed above must 
be met. Male subjects must abstain from sperm donation throughout 
the study and for a duration of 90 days after last dose of study drug. 
Methods of contraception, as applicable, for both male and female 

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participants should be documented in the source documentation. 
9.3 Efficacy/Effectiveness Assessments  
9.3.1 Response monitoring 
9.3.1.1 Response monitoring for TFR will start after 3 years of 
asciminib treatment. 
9.3.1.2 Blood samples for BCR-ABL1 quantification by real-time 
quantitative polymerase chain reaction (RQ-PCR) will be 
collected at enrollment period (twice, 4 weeks apart) and at 
months 1, 2, 3, 4, 5, 6, 8, 10, 12 and every 3 months thereafter 
for more 2 years after cessation of asciminib/TKIs; samples will 
be analyzed at a central laboratory.  
9.3.1.3 Flow for BCR/ABL1 monitoring 
 
9.4 BCR/ABL1 monitoring laboratory 
9.4.1 BCR/ABL1 RQ-PCR will be tested in the central laboratory. 
9.4.2 All BCR/ABL1 RQ-PCR sample should be transported to the central 
laboratory. 
9.5 Definitions of time-dependent variables 
9.5.1 Molecular relapse-free survival: MRFS is defined as the duration of 
time from the cessation of treatment to time of reoccurrence of 
BCR/ABL1 transcript at the detectable level by RQ-PCR. 
9.5.2 Treatment-free survival: TFS is defined as the duration of time from 
the cessation of treatment to time of reinitiation of CML therapy 
resulting from loss of MR3.0 or MMR (major molecular response) by 
RQ-PCR.  
9.5.3 Overall survival: OS is defined as the duration of time from the 
cessation of treatment till death from any causes.  
9.6 Safety assessment 
9.6.1 Vital Signs 
9.6.1.1  Vital signs comprising blood pressure, pulse rate, and 
temperature will be recorded at every visit. Measurements of 
vital signs should be obtained after the subject has rested for at 
least 5 minutes in a quiet room at a comfortable temperature, 
with the subject’s arm unconstrained by clothing or other 
material. Blood pressure measurements will be obtained with 
the appropriate cuff size, with the subject’s arm supported at the 
level of the heart, while the subject is resting in a semi-supine 
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pressure or ECG machine. 
9.6.2 Body Weight, Height, and Body Mass Index 
9.6.2.1 Body weight will be recorded at all visits; height and BMI will be 
recorded at screening only. For determination of height and 
body weight, subjects should be clothed with shoes removed 
9.6.3 Physical Examination 
9.6.3.1  Subjects will undergo a physical examination at every visit. A 
full physical examination should be performed per normal site 
practice as part of the screening evaluation (e.g., genitourinary 
and breast examinations may be omitted when not required by 
normal site practice). A targeted (i.e., symptom driven) physical 
examination will be performed at subsequent study visits to 
assess for any changes from the previous examination, 
including, at a minimum, evaluation of new or worsening signs 
or symptoms. 
9.6.4 Clinical Chemistry, Hematology, Urinalysis, and Other Laboratory 
Assessments 
9.6.4.1  Blood and urine samples will be obtained per the schedule of 
assessments as specified in 7.2 for asciminib phase and 7.3 for 
TFR phase. All BCR/ABL RQ-PCR samples will be collected for 
the designated central laboratory, which will analyze all 
samples. However, local laboratories may be used in place of 
the central laboratory at the sponsor’s request (e.g., for 
logistical reasons) or for analysis of samples collected for 
assessment of possible AEs (e.g., when emergent safety 
concerns require expedited turnaround times for safety 
laboratory assessments). The use of a local laboratory in this 
manner, and any differences in analyte panels between the 
central and local laboratories, based on the availability of testing 
at the local laboratory, will not be considered protocol deviations 
for the purposes of this protocol. All laboratory tests except for 
BCR/ABL1 RQ-PCR will be performed using the local 
laboratory. In the event of delays in transport to the designated 
central laboratory (e.g., due to COVID-19), the local laboratory 
should be utilized. Results from the laboratory values should be 
reviewed as received by the investigator. Evidence of this 
review should be provided in the source records and may 
include printing of the laboratory reports with a signature 
attesting to a review. For out-of-range laboratory findings, the 
interpretation of clinically significant or not clinically significant 
should be denoted in the source records. Clinically significant 
laboratory findings, as assessed by the investigator, should be 
recorded as AEs as described in the protocol (Section 10) 
9.6.5 Menopause and Pregnancy Testing 
9.6.5.1 FSH will be measured at screening in women declaring 
themselves postmenopausal ≤ 2 years to confirm non-

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childbearing status if above the reference range. At screening, a 
serum pregnancy test should also be drawn if a female subject 
who is postmenopausal ≤ 2 years is found to be of childbearing 
potential. For all women of childbearing potential, a serum β-
human chorionic gonadotropin (β-hCG) test will be performed at 
screening. Urine pregnancy tests will be assessed at all 
subsequent visits or as required per normal site practice. A 
serum pregnancy test should immediately be drawn and sent 
for analysis for any positive urine pregnancy test. For female 
participants who meet the criteria for postmenopausal status, an 
FSH can be measured during the study; pregnancy testing will 
continue until postmenopausal status by the above definition is 
met.     
10. ADVERSE EVENTS:  LIST AND REPORTING REQUIREMENTS  
10.1 Adverse Event List(s) for asciminib 
Asciminib Safety pool 
N=356 n (%) 
 
All grades  
Grade >=3 
Preferred term  
n (%)  
n (%) 
Number of subjects with at least one event  
340 (95.5)  
214 (60.1) 
Thrombocytopenia  
78 (21.9)  
51 (14.3) 
Headache  
77 (21.6)  
7 (2.0) 
Fatigue  
74 (20.8)  
3 (0.8) 
Nausea  
70 (19.7)  
3 (0.8) 
Diarrhea  
69 (19.4)  
2 (0.6) 
Arthralgia  
66 (18.5)  
3 (0.8) 
Hypertension  
61 (17.1)  
31 (8.7) 
Lipase increased  
60 (16.9)  
35 (9.8) 
Vomiting  
53 (14.9)  
8 (2.2) 
Neutropenia  
52 (14.6)  
40 (11.2) 
Rash  
52 (14.6)  
0 
Abdominal pain  
44 (12.4)  
4 (1.1) 
Pain in extremity  
44 (12.4)  
2 (0.6) 
Pruritus  
43 (12.1)  
1 (0.3) 
Upper respiratory tract infection  
42 (11.8)  
1 (0.3) 
Anemia  
41 (11.5)  
17 (4.8) 
Back pain  
40 (11.2)  
4 (1.1) 
Cough  
39 (11.0)  
0 
Nasopharyngitis  
39 (11.0)  
0 
Constipation  
38 (10.7)  
0 
Dizziness  
38 (10.7)  
1 (0.3) 
Amylase increased  
36 (10.1)  
8 (2.2) 
Myalgia  
33 (9.3)  
2 (0.6) 
Alanine aminotransferase increased  
31 (8.7)  
9 (2.5) 
Oedema peripheral  
30 (8.4)  
2 (0.6) 
Pyrexia  
29 (8.1)  
3 (0.8) 
Abdominal pain upper  
27 (7.6)  
0 
Dyspnea  
27 (7.6)  
2 (0.6) 
Insomnia  
27 (7.6)  
2 (0.6) 
Aspartate aminotransferase increased  
26 (7.3)  
5 (1.4) 
Hyperuricemia  
24 (6.7)  
6 (1.7) 
Decreased appetite  
23 (6.5)  
1 (0.3) 
Hypertriglyceridemia  
23 (6.5)  
7 (2.0) 
Dyspepsia  
22 (6.2)  
0 
Muscle spasms  
22 (6.2)  
1 (0.3) 

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Non-cardiac chest pain  
22 (6.2)  
3 (0.8) 
Anxiety  
21 (5.9)  
3 (0.8) 
Bone pain  
20 (5.6)  
1 (0.3) 
Hyperglycemia  
20 (5.6)  
6 (1.7) 
Oropharyngeal pain  
20 (5.6)  
0 
Blood creatinine increased  
19 (5.3)  
0 
Gamma-glutamyl transferase increased  
19 (5.3)  
7 (2.0) 
Platelet count decreased  
19 (5.3)  
14 (3.9) 
Dry eye  
18 (5.1)  
0 
Dry skin  
18 (5.1)  
0 
Hyperhidrosis  
18 (5.1)  
0 
Hypophosphatasemia  
18 (5.1)  
5 (1.4) 
10.2 Adverse Event Characteristics  
10.2.1 Definition of adverse event: an AE is any untoward medical 
occurrence in a patient administered a pharmaceutical product and 
that does not necessarily have to have a causal relationship with this 
treatment. An AE can therefore be any unfavorable and unintended 
sign (including an abnormal laboratory finding, for example), symptom, 
or disease temporarily associated with the use of a medical product 
whether considered related to the medical product. 
10.2.2 CTCAE term (AE description) and grade:  The descriptions and 
grading scales found in the revised NCI Common Terminology Criteria 
for Adverse Events (CTCAE) version 5.0 will be utilized for AE 
reporting. All appropriate treatment areas should have access to a 
copy of the CTCAE version 5.0.  A copy of the CTCAE version 5.0 can 
be downloaded from the CTEP website 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc
.htm. 
10.2.3 A serious adverse event (SAE) is any untoward medical occurrence 
that at any dose: 
10.2.3.1 
Results in death, 
10.2.3.2 
Is life-threatening, 
10.2.3.3 
Requires inpatient hospitalization or prolongation of 
existing hospitalization, 
10.2.3.4 
Results in persistent or significant disability/incapacity, 
10.2.3.5 
Is a congenital anomaly/birth defect, or 
10.2.3.6 
Is an important medical event. 
10.2.4 Attribution of the AE: 
10.2.4.1 
Definite – The AE is clearly related to the study 
treatment. 
10.2.4.2 
Probable – The AE is likely related to the study 
treatment. 
10.2.4.3 
Possible – The AE may be related to the study treatment. 
10.2.4.4 
Unlikely – The AE is doubtfully related to the study 
treatment. 
10.2.4.5 
Unrelated – The AE is clearly NOT related to the study 
treatment. 
10.3 Pregnancy 
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outcome must be documented. Any pregnancy occurring in a patient 
or patient’s partner from the time of consent to 90 days after the last 
dose of study drug must be reported and then followed for outcome.  
Newborn infants should be followed until 30 days old.  
10.4 Secondary Malignancy 
10.4.1 A secondary malignancy is a cancer caused by treatment for a 
previous malignancy (e.g., treatment with investigational 
agent/intervention, radiation, or chemotherapy). A secondary 
malignancy is not considered a metastasis of the initial neoplasm. 
10.4.2 Three options are available to describe the event:  
10.4.2.1 
Leukemia secondary to oncology chemotherapy (e.g., 
acute myelocytic leukemia [AML])  
10.4.2.2 
Myelodysplastic syndrome (MDS)  
10.4.2.3 
Treatment-related secondary malignancy  
10.4.3 Any malignancy possibly related to cancer treatment (including 
AML/MDS) should also be reported via the routine reporting 
mechanisms outlined in each protocol.  
10.5 Second Malignancy 
10.5.1 A second malignancy is one unrelated to the treatment of a prior 
malignancy (and is NOT a metastasis from the initial malignancy).  
Second malignancies require ONLY routine AE reporting unless 
otherwise specified. 
10.6 Adverse Event Reporting  
10.6.1 All SAEs should be reported by the Treating Physician in the eCRF 
within 24 hours of awareness. 
10.6.2 All SAEs must be reported with Treating Physician’s assessment of 
the event’s seriousness, severity, and relatedness to asciminib. 
10.6.3 All AEs must be reported in routine study data submissions. Adverse 
event data collection and reporting, which are required as part of every 
clinical trial, are done to ensure the safety of patients enrolled in the 
studies as well as those who will enroll in future studies using similar 
agents.  AEs are reported in a routine manner at scheduled times 
during the trial. 
10.6.4 Collection by sponsor 
10.6.4.1 
All SAEs 
10.6.4.2 
All reports of drug exposure during pregnancy 
10.6.4.3 
All non-serious AEs 
10.6.4.4 
All reports of misuse and abuse of investigational drug, 
other medication errors and uses outside of what is foreseen in 
protocol (irrespective if a clinical event has occurred) 
10.6.5 Transfer to Novartis within 15 days of awareness 
10.6.5.1 
All collected SAEs in subjects exposed to the Novartis 
investigational drug 
10.6.5.2 
All collected pregnancy reports in subjects exposed to 
the Novartis investigational drug 
10.6.5.3 
All collected reports of abuse and misuse of the Novartis 

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investigational drug 
 
 
11. STATISTICAL CONSIDERATIONS 
11.1 Study populations 
11.1.1 Screen failures 
11.1.1.1 
 Subjects who give informed written consent but are not 
eligible to study treatment and are noted as screen failures in 
the CRF are considered screen failures. Reasons for screen 
failure will be summarized using this population. 
11.1.2 Intent-to-treat population 
11.1.2.1 
 The intent-to-treat (ITT) population is defined as all 
enrolled subjects, regardless of whether study treatment was 
administered. This population will be the primary population for 
efficacy analyses.  
11.1.3 Safety population 
11.1.3.1 
 The safety population is defined as all subjects who 
receive at least 1 dose of study drug. This population will be 
used for all analyses of accountability, demographics, and 
safety. Data will be analyzed according to the actual treatment 
received at first dose for all subjects. 
11.1.4 Per protocol population 
11.1.4.1 
 The per-protocol (PP) population is defined as all 
subjects who did not violate key protocol inclusion or exclusion 
criteria, received the study drug, and did not have any protocol 
deviations or violations that would affect analysis. This 
population will be used for a sensitivity analysis of the primary 
efficacy analysis.  
11.1.5 Completers population 
11.1.5.1 
 The subset of subjects in the ITT population who 
complete the study. This population will be used for a sensitivity 
analysis of the primary efficacy analysis.  
11.2 General consideration for data analysis 
11.2.1 In general, descriptive summaries will include n, mean, standard 
deviation, median, minimum, and maximum for continuous variables 
and n and percent for categorical variables. Summaries will be 
presented by treatment and study visit. All individual subject data will 
be listed as measured.  
11.3 Subject Demographic and Disposition Data 
11.3.1 Demographic data and baseline characteristics including age, gender, 
race or ethnicity, height, body weight, BMI, and CML history will be 
summarized by treatment and overall. The following baseline 
measures will be summarized using descriptive statistics: dose, type, 
and duration of TKIs. Subject disposition will be presented by 
treatment and overall. The number of subjects who completed the 
study and those that discontinued from the study will be provided. The 

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reasons for early discontinuation will be presented. A tabulation of the 
number of subjects exposed to study drug and duration of exposure 
will also be presented for each treatment and overall. Treatment 
adherence, dose interruptions, and reason for dose interruptions will 
be provided as summaries or listed as appropriate.   
11.4 Analysis of Efficacy Variables  
11.4.1 The efficacy analyses will be based on the ITT population. The 
analyses of the PP population and completers population will be used 
to support the primary efficacy analyses. 
11.5 Sample Size Calculation 
11.5.1 The sample size is calculated based on Simon’s exact single-stage 
phase II design assuming that P0=0.25; P1=0.4; α-error=0.05 (one-
sided); β-error=0.2.  
11.5.2 The final number of patients required will be 69 with consideration of 
10% of drop-out rate. 
11.6 Statistical analysis  
11.6.1 Molecular response  
 
MMR 
MR4 
MR4.5 
MR5 
Minimum sum of 
reference gene 
transcripts 
10,000 ABL1a 
24,000 GUSBa 
10,000 ABL1 
24,000 GUSB 
32,000 ABL1 
77,000 GUSB 
100,000 ABL1 
240,000 GUSB 
BCR-ABL1 
transcript level on 
the ISb 
≤0.1% 
≤0.01% 
≤0.0032% 
≤0.001% 
aMinimal sensitivity for accurate quantification. 
bInternational Scale, IS. 
11.6.2 The cumulative incidence of MR3.0 or less continuously up to one 
year of TKI and TKI suspension is defined as the cumulative incidence 
of MR3.0 maintained for one year from the first day of suspension of 
administration of Aciminib and TKI. 
11.6.3 The rate of re-achievement of MR4.5 for adding an assiminib to a TKI 
is defined as the rate at which MR4.5 is re-acquired after adding an 
assiminib. 
11.6.4 The time to MR3.0/4.0/4.5 disappearance is calculated from the first 
day of discontinuation of administration of Aciminib and TKIs, 
respectively, when MR3.0/4.0/4.5 disappearance is confirmed. 
11.6.5 The molecular relapse free survival (MRFS) will be calculated from 
day 1 of stopping asciminib and TKIs till reoccurrence of BCR/ABL1 
RQ PCR.  
11.6.6 The treatment-free survival (TFS) will be calculated from day 1 of 
stopping asciminib and TKIs till loss of MR3.0 and subsequent restart 
of CML treatment.  
11.6.7 Overall survival will be calculated from day 1 of stopping asciminib and 
TKIs till death due to any causes.  
11.6.8 The survival curves will be constructed using the Kaplan-Meier 
method.  
11.6.9 The univariate analysis will be performed using Pearson’s chi-square, 

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Fisher’s exact test, or the log-rank test for survival curves. 
12. STUDY ADMINISTRATION 
12.1 Study Monitoring 
12.1.1 During study conduct, clinical research organization (CRO) or its 
designee will conduct periodic monitoring visits to ensure that the 
protocol and Good Clinical Practice (GCP) are being followed. The 
monitor(s) will review source documents to confirm that the data 
recorded on CRFs are accurate. The investigator and institution will 
allow the representative(s) of CRO or its designee direct access to 
source documents to perform this verification. 
12.1.2 It is important that the investigator(s) and relevant personnel are 
available during the monitoring visits and that sufficient time is devoted 
to the process.  
12.1.3 During the study, a representative(s) from CRO or its designee will 
have regular contacts with the investigational site personnel for the 
following: 
12.1.3.1 
Provide information and support to the investigator(s) 
12.1.3.2 
Confirm that facilities remain acceptable 
12.1.3.3 
Confirm that the investigational team is adhering to the 
protocol, that data are being accurately recorded in the CRFs, 
and that investigational product accountability checks are being 
performed 
12.1.3.4 
Perform source data verification. This includes a 
comparison of the data in the CRFs with the subject’s medical 
records at the hospital or practice, and other records relevant to 
the study. This will require direct access to all original records 
for each subject (e.g., clinic charts). 
12.1.3.5 
Record and report any protocol deviations not previously 
sent to CRO or its designee 
12.1.3.6 
Confirm AEs and SAEs have been properly documented 
on the CRFs and confirm any SAEs have been forwarded to 
BioCryst or its designee and those SAEs that met criteria for 
reporting have been forwarded to the ethics committee  
12.1.4 The representative(s) of CRO or its designee will be available between 
visits if the investigator(s) or other staff needs information or advice. 
12.2 Audits and Inspections 
12.2.1 Authorized representatives of CRO or its designee, Korean Food and 
Drug Administration (KFDA) and other regulatory authorities, and/or 
ethics committee may visit the site to perform audits or inspections, 
including source data verification.  
12.2.2 The purpose of CRO audit or inspection is to systematically and 
independently examine all study-related activities and documents to 
determine whether these activities were conducted, and data were 
recorded, analyzed, and accurately reported according to the protocol, 
standard operating procedures, ICH GCP guidelines, and any 

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applicable regulatory requirements.  
12.2.3 The investigator should contact CRO immediately if contacted by a 
regulatory agency about an inspection.  
12.2.4 It is important that the investigator and relevant personnel are 
available during the possible audits or inspections and that sufficient 
time is devoted to the process. 
12.3 Institutional review board (IRB) 
12.3.1 The investigator must obtain IRB approval for the investigation. Initial 
IRB approval, and all materials approved by the IRB committee, 
including the ICF and any recruitment materials, must be maintained 
by the investigator and made available for inspection. 
12.4 Serious Breaches of GCP 
12.4.1 It is the responsibility of the PI to notify the competent authority of any 
serious breach of GCP that is likely to affect, to a significant degree, 
the safety or mental integrity of the subjects of the study or the 
scientific value of the study.  
12.4.2 All serious breaches will be notified to the relevant competent authority 
in accordance with locally applicable regulations.  
12.4.3 The reporting to the PI will be performed by the party who suspects 
the serious breach. 
13. QUALITY CONTROL AND QUALITY ASSURANCE 
13.1 Quality control 
13.1.1 During study conduct, CRO or its designee will conduct periodic 
monitoring visits to ensure that the protocol and GCP are being 
followed as described in Section 12.1. 
13.2 Quality assurance 
13.2.1 To ensure compliance with GCP and all applicable regulatory 
requirements, CRO or its designee may conduct a quality assurance 
audit. Please see Section 12.2 for more details regarding the audit 
process. The investigator agrees to allow the auditors to inspect the 
drug storage area, study drug stocks, drug accountability records, 
subject charts and study source documents, and other records relative 
to study conduct. 
14. IRB 
14.1 IRB Review 
14.1.1 The final study protocol and the final version of the ICF must be 
approved or given a favorable opinion in writing by IRB committee, as 
appropriate.  
14.1.2 The investigator must submit written approval from the IRB committee 
to CRO before he or she can enroll any subject into the study. The IRB 
committee will be informed of any amendment to the protocol in 
accordance with local requirements. In addition, the IRB committee 
must approve any advertising used to recruit subjects for the study.  
14.1.3 The protocol must be re-approved by the IRB committee upon receipt 
of amendments and annually, as local regulations require. The IRB 
committee will be provided with reports of any reportable serious 

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adverse drug reactions from any other study conducted with the 
investigational product, in accordance with local regulations.  
14.1.4 CRO will provide this information to the investigator. Progress reports 
and notifications of serious adverse drug reactions will be provided to 
the ethics committee according to local regulations and guidelines. 
14.2 Ethical Conduct of the Study 
14.2.1 The study will be performed in accordance with ethical principles that 
have their origin in the Declaration of Helsinki and are consistent with 
ICH GCP, applicable regulatory requirements. 
14.3 Written Informed Consent 
14.3.1 In accordance with applicable national or local law, and current 
institutional practice, written informed consent to participate in the 
study will be obtained from each subject prior to conducting any study-
related assessments/procedures. 
14.3.2 A signed ICF must be obtained from each subject prior to performing 
any study-related procedures. Each subject should be given both oral 
and written information describing the nature, purpose, and duration of 
the study. Subjects will be informed that they are free not to participate 
in the study and that they may withdraw consent to participate at any 
time. They will be told that refusal to participate in the study will not 
prejudice future treatment. They will also be told that their records may 
be examined by competent authorities and authorized persons, but 
that personal information will be treated as strictly confidential and will 
not be publicly available. The informed consent process should take 
place under conditions where the subject has adequate time to 
consider the risks and benefits associated with participation in the 
study. 
14.3.3 Subjects must be given the opportunity to ask questions. Subjects will 
not be screened or treated until the subject has signed an approved 
ICF written in a language in which the subject is fluent. 
14.3.4 The ICF that is used must be approved by the governing IRB 
committee. The ICF should be in accordance with the current revision 
of the Declaration of Helsinki, current ICH and GCP guidelines. The 
investigator shall maintain a log of all subjects for whom consent was 
signed and indicate if the subject was enrolled into the study or reason 
for non-enrollment. 
14.3.5 The subject should receive a signed and dated copy of the ICF. The 
original signed ICF should be retained in the study files. 
15. DATA HANDLING AND RECORDKEEPING 
15.1 Inspection of Records 
15.1.1 CRO or designee will be allowed to conduct site visits to the 
investigation facilities for the purpose of monitoring any aspect of the 
study. The investigator agrees to allow the monitor to 
inspect the drug storage area, study drug stocks, drug accountability 
records, subject charts, and study source documents, and other 

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records relative to study conduct. 
15.2 Retention of Records 
15.2.1 To enable evaluations and/or audits from regulatory authorities or 
CRO, the investigator agrees to keep records, including the identity of 
all participating subjects (sufficient information to link records, eCRFs, 
and medical/hospital records), all original signed ICFs, all eCRFs, and 
detailed records of study drug accountability and treatment disposition. 
The records should be retained by the investigator according to local 
regulations or as specified in the Clinical Study Agreement, whichever 
is longer. 
15.2.2 If the investigator relocates, retires, or for any reason withdraws from 
the study, the study records may be transferred to an acceptable 
designee, such as another investigator, another institution, or to 
BioCryst. The investigator must obtain CRO’s written permission 
before disposing of any records and must notify CRO before 
transferring any records to another facility. All correspondence related 
to records retention, destruction, or transfer of study documents, 
should be sent directly to CRO study personnel. 
15.3 Confidentiality of Information and Data 
15.3.1 PI affirms the subject’s right to protection against invasion of privacy 
and secure maintenance of the confidential nature of his/her personal 
data. Only a subject identification number and subject identifiers 
permitted by local regulation will identify subject data retrieved by 
CRO. However, in compliance with Korean regulations, CRO requires 
the investigator to permit CRO’s representatives and, when necessary, 
representatives of the KFDA or other regulatory authorities to review 
and/or copy any medical records relevant to the study, maintaining 
pseudo-anonymity. 
15.3.2 All parties will abide by all applicable laws and regulations regarding 
subject privacy and confidentiality, where this rule is applicable. A valid 
authorization and consent must meet the specifications of the 
applicable laws and regulations relating to such personal data and 
health information.  
15.3.3 It is the responsibility of the investigator and institution to obtain such 
waiver/authorization in writing from the appropriate individual.  
16. PUBLICATION POLICY 
16.1 General policy 
16.1.1 All data generated from this study are the property of PI and shall be 
held in strict confidence along with all information furnished by PI.  
16.1.2 Except as provided through written agreement between PI, 
independent analysis and/or publication of these data by the 
investigator or any member of his/her staff is not permitted without 
prior written consent of PI.  
16.1.3 Such consent will not be withheld unreasonably.  
16.1.4 PI is in agreement with the principle of full disclosure of clinical study 

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results. 
17. REFERENCES 
1. 
Baccarani M, Deininger MW, Rosti G, et al. European LeukemiaNet 
recommendations for the management of chronic myeloid leukemia: 2013. Blood. 
2013;122(6):872-884. 
2. 
Cortes JE, Jones D, O'Brien S, et al. Nilotinib as front-line treatment for patients with 
chronic myeloid leukemia in early chronic phase. J Clin Oncol. 2010;28(3):392-397. 
3. 
Hochhaus A, O'Brien SG, Guilhot F, et al. Six-year follow-up of patients receiving 
imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia. 2009;23(6):1054-
1061. 
4. 
Kantarjian H, Shah NP, Hochhaus A, et al. Dasatinib versus imatinib in newly 
diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2010;362(24):2260-2270. 
5. 
Kwak JY, Kim SH, Oh SJ, et al. Phase III Clinical Trial (RERISE study) Results of 
Efficacy and Safety of Radotinib Compared with Imatinib in Newly Diagnosed Chronic Phase 
Chronic Myeloid Leukemia. Clin Cancer Res. 2017;23(23):7180-7188. 
6. 
O'Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-
dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 
2003;348(11):994-1004. 
7. 
Saglio G, Kim DW, Issaragrisil S, et al. Nilotinib versus imatinib for newly diagnosed 
chronic myeloid leukemia. N Engl J Med. 2010;362(24):2251-2259. 
8. 
Lee SE, Choi SY, Bang JH, et al. Predictive factors for successful imatinib cessation 
in chronic myeloid leukemia patients treated with imatinib. Am J Hematol. 2013;88(6):449-454. 
9. 
Mahon FX, Rea D, Guilhot J, et al. Discontinuation of imatinib in patients with chronic 
myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the 
prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol. 2010;11(11):1029-1035. 
10. 
Ross DM, Branford S, Seymour JF, et al. Safety and efficacy of imatinib cessation for 
CML patients with stable undetectable minimal residual disease: results from the TWISTER 
study. Blood. 2013;122(4):515-522. 
11. 
Legros L, Rousselot P, Giraudier S, et al. Second attempt to discontinue imatinib in 
CP-CML patients with a second sustained complete molecular response. Blood. 
2012;120(9):1959-1960. 
12. 
Qiang W, Antelope O, Zabriskie MS, et al. Mechanisms of resistance to the BCR-
ABL1 allosteric inhibitor asciminib. Leukemia. 2017;31(12):2844-2847. 
13. 
Schoepfer J, Jahnke W, Berellini G, et al. Discovery of Asciminib (ABL001), an 
Allosteric Inhibitor of the Tyrosine Kinase Activity of BCR-ABL1. J Med Chem. 
2018;61(18):8120-8135. 
14. 
Wylie AA, Schoepfer J, Jahnke W, et al. The allosteric inhibitor ABL001 enables dual 
targeting of BCR-ABL1. Nature. 2017;543(7647):733-737. 
15. 
Hughes TP, Mauro MJ, Cortes JE, et al. Asciminib in Chronic Myeloid Leukemia after 
ABL Kinase Inhibitor Failure. N Engl J Med. 2019;381(24):2315-2326. 
16. 
Rousselot P, Charbonnier A, Cony-Makhoul P, et al. Loss of major molecular 
response as a trigger for restarting tyrosine kinase inhibitor therapy in patients with chronic-
phase chronic myelogenous leukemia who have stopped imatinib after durable undetectable 
disease. J Clin Oncol. 2014;32(5):424-430. 
17. 
Bower H, Bjorkholm M, Dickman PW, Hoglund M, Lambert PC, Andersson TM. Life 
Expectancy of Patients With Chronic Myeloid Leukemia Approaches the Life Expectancy of the 
General Population. J Clin Oncol. 2016;34(24):2851-2857. 
18. 
Hochhaus A, Larson RA, Guilhot F, et al. Long-Term Outcomes of Imatinib 
Treatment for Chronic Myeloid Leukemia. N Engl J Med. 2017;376(10):917-927. 

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55 
19. 
Cortes JE, Saglio G, Kantarjian HM, et al. Final 5-Year Study Results of DASISION: 
The Dasatinib Versus Imatinib Study in Treatment-Naive Chronic Myeloid Leukemia Patients 
Trial. J Clin Oncol. 2016;34(20):2333-2340. 
20. 
Kantarjian HM, Hochhaus A, Saglio G, et al. Nilotinib versus imatinib for the 
treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, 
chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd 
trial. Lancet Oncol. 2011;12(9):841-851. 
21. 
Saussele S, Richter J, Guilhot J, et al. Discontinuation of tyrosine kinase inhibitor 
therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a 
prospective, multicentre, non-randomised, trial. Lancet Oncol. 2018;19(6):747-757. 
22. 
DeAngelo DJ. Clinical lymphoma, Myeloma & Leukemia. 2019;19:S290-S291. 
23. 
Talpas M. Clinical lymphoma, Myeloma & Leukemia. 2019;19:S287-S288. 
 
 

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APPENDIX A 
PERFORMANCE STATUS CRITERIA 
 
ECOG Performance Status Scale 
Karnofsky Performance Scale 
Grade 
Descriptions 
Percent 
Description 
0 
Normal activity.  Fully active, 
able to carry on all pre-disease 
performance without restriction. 
100 
Normal, no complaints, no 
evidence of disease. 
90 
Able to carry on normal activity; 
minor signs or symptoms of 
disease. 
1 
Symptoms, but ambulatory.  
Restricted in physically 
strenuous activity, but 
ambulatory and able to carry 
out work of a light or sedentary 
nature (e.g., light housework, 
office work). 
80 
Normal activity with effort; some 
signs or symptoms of disease. 
70 
Cares for self, unable to carry on 
normal activity or to do active 
work. 
2 
In bed <50% of the time.  
Ambulatory and capable of all 
self-care, but unable to carry 
out any work activities.  Up and 
about more than 50% of waking 
hours. 
60 
Requires occasional assistance 
but is able to care for most of 
his/her needs. 
50 
Requires considerable 
assistance and frequent medical 
care. 
3 
In bed >50% of the time.  
Capable of only limited self-
care, confined to bed or chair 
more than 50% of waking 
hours. 
40 
Disabled, requires special care 
and assistance. 
30 
Severely disabled, hospitalization 
indicated.  Death not imminent. 
4 
100% bedridden.  Completely 
disabled.  Cannot carry on any 
self-care.  Totally confined to 
bed or chair. 
20 
Very sick, hospitalization 
indicated. Death not imminent. 
10 
Moribund, fatal processes 
progressing rapidly. 
5 
Dead. 
0 
Dead. 
 
 
 

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APPENDIX B 
FORMULA TO ESTIMATE RENAL FUNCTION USING SERUM 
CREATININE 
 
Formulas to estimate renal function using serum creatinine provided by the NCI’s 
Investigational Drug Steering Committee (IDSC) Pharmacological Task Force in table 
below. 
 
1. Estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease 
Epidemiology Collaboration (CKD-EPI) (Levey et al., 2009). 
 
Formulae: 
 
Race and 
Sex 
Serum Creatinine (SCr), 
µmol/L (mg/dL) 
Equation 
Black 
 
 
Female 
≤62 (≤0.7) 
GFR = 166 × (SCr/0.7)−0.329 × 
(0.993)Age 
 
>62 (>0.7) 
GFR = 166 × (SCr/0.7)−1.209 × 
(0.993)Age 
Male 
≤80 (≤0.9) 
GFR = 163 × (SCr/0.9)−0.411 × 
(0.993)Age 
 
>80 (>0.9) 
GFR = 163 × (SCr/0.9)−1.209 × 
(0.993)Age 
 
 
 
White or 
other 
 
 
Female 
≤62 (≤0.7) 
GFR = 144 × (SCr/0.7)−0.329 × 
(0.993)Age 
 
>62 (>0.7) 
GFR = 144 × (SCr/0.7)−1.209 × 
(0.993)Age 
Male 
≤80 (≤0.9) 
GFR = 141 × (SCr/0.9)−0.411 × 
(0.993)Age 
 
>80 (>0.9) 
GFR = 141 × (SCr/0.9)−1.209 × 
(0.993)Age 
 
SCr in mg/dL; Output is in mL/min/1.73 m2 and needs no further conversions. 
 
2. eGFR using the Modification of Diet in Renal Disease (MDRD) Study (Levey et al., 2006). 
 
175 x SCr–1.154 × age–0.203 × 0.742 (if female) × 1.212 (if black) 
Output is in mL/min/1.73 m2 and needs no further conversions. 
3. Estimated creatinine clearance (ClCr) by the Cockcroft-Gault (C-G) equation (Cockcroft 
and Gault, 1976). 
 
 
Followed by conversion to a value normalized to 1.73 m2 with the patient’s body surface 
area (BSA). 
 
References 
1. Levey, A.S., L.A. Stevens, C.H. Schmid, et al.  (2009).  A new equation to 

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58 
estimate glomerular filtration rate.  Ann Inter Med.  150:604-612. 
2. Levey, A.S., J. Coresh, T. Greene, et al.  (2006).  Using standardized serum 
creatinine values in the modification of diet in renal disease study equation for 
estimating glomerular filtration rate.  Ann Intern Med.  145:247-254. 
3. Cockcroft, D.W. and M.H. Gault.  (1976).  Prediction of creatinine clearance from 
serum creatinine.  Nephron.  16:31-41.

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