A Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Profile of Single or Multiple Oral Doses of ABSK061 Mini-tablets and to Evaluate the Effect of Soft Food With ABSK061 Mini-tablets on Its Pharmacokinetic Profile in Healthy Adult Participants
Phase: PHASE1
Conditions: Healthy
Sponsor: Abbisko Therapeutics Co, Ltd

 
 
A study to evaluate the safety, tolerability, and 
pharmacokinetic profile of single or multiple oral doses of 
ABSK061 microt and to evaluate the effect of soft food 
with ABSK061 microchips on its pharmacokinetic profile 
in healthy adult participants 
 
Protocol No.: ABSK061-102 
Trial Phase: phase I 
Sponsor: 
shanghai 
Hezhu 
Biopharmaceutical 
Technology Co., Ltd. 
Building 3, No. 898 Halei Road, Pudong New District, 
Shanghai 201203 
Tel: + 86-021-68912098 
Version No.: 1.0 
Version Date: april 7, 2025 
 
The study will be conducted in strict compliance with the protocol and will be designed 
in compliance with GCP, the Declaration of Helsinki, and other applicable laws and 
regulations.  
 
Confidentiality Statement 
This protocol is intended for the use of clinical investigators only, and the information 
contained is confidential and may not be disclosed without written authorization from Shanghai 
Hezhu Biopharmaceutical Technology Co., Ltd., unless required by current laws or regulations. 
The investigator may disclose the contents of the document to the Ethics Committee and the study 
personnel directly involved in the implementation of the protocol. The above personnel shall sign a 
confidentiality agreement with Shanghai Hezhui Biopharmaceutical Technology Co., Ltd., and 
may not be copied or distributed to any third party.  
 

ABSK061-102 Version No. 1.0 Version Date April 7, 2025 
 
 
Sponsor Signature Page 
 
 
Jing Nie  
 
 
 
 
 
  
                    
Date 
Senior Director, Clinical Pharmacology 
 
 
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ABSK061-102 Version No. 1.0 Version Date April 7, 2025 
 
 
 
Investigator Signature Page 
I have understood that all study-related documents provided to me by Shanghai Hezhui 
Biopharmaceutical Technology Co., Ltd. or its designated third party will be kept strictly confidential, 
including the protocol, Investigator's Brochure, case report forms, and other scientific data.  
The study will not commence without written approval from the Institutional Review Board 
(IRB)/Ethics Committee (EC). No amendments to the protocol may be made without written approval 
from Shanghai Hezhui Biopharmaceutical Technology Co., Ltd. and the Ethics Committee, unless 
necessary to protect participants and eliminate direct hazards.  
I have read, understand and agree to comply with all the conditions and instructions in this 
clinical study protocol.  
 
 
 
 
Investigator Signature  
 
 
 
 
 
 
 
 
Date 
 
 
 
Site Name 
 
 
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ABSK061-102 Version No. 1.0 Version Date April 7, 2025 
 
 
Table of Contents 
Protocol Synopsis ...................................................................................................................... 8 
Study Flow Chart ..................................................................................................................... 16 
1 Study Background ................................................................................................................. 31 
1.1 Overview of ABSK061 ................................................................................................. 31 
1.2 Preclinical Study Results .............................................................................................. 31 
1.3 Clinical Study Results .................................................................................................. 32 
1.4 Risk/Benefit Assessment .............................................................................................. 33 
2 Study Objectives ................................................................................................................... 33 
2.1 Primary Objectives ....................................................................................................... 33 
2.2 Secondary Objectives ................................................................................................... 34 
3 Study Endpoints .................................................................................................................... 34 
3.1 Primary Endpoints ........................................................................................................ 34 
3.2 Secondary Endpoints .................................................................................................... 34 
4 Study Design ......................................................................................................................... 34 
4.1 Overall Design .............................................................................................................. 34 
4.2 Scientific Rationale for Study Design .......................................................................... 36 
4.3 Rationale for Dose Selection ........................................................................................ 37 
4.4 Dose Escalation Rules .................................................................................................. 38 
5 Study Population ................................................................................................................... 38 
5.1 Study Sample Size ........................................................................................................ 38 
5.2 Participant Selection Criteria ........................................................................................ 38 
5.2.1 Inclusion Criteria    ......................................................................................................... 38 
5.2.2 Exclusion Criteria    ........................................................................................................ 39 
5.3 Exercise and Dietary Restrictions ................................................................................. 41 
5.3.1 Dietary Restrictions    ................................................................................................ 41 
5.3.2 Motor Restrictions    .................................................................................................. 41 
5.4 Restrictions on beverages, caffeine, alcohol and tobacco    ......................................... 41 
5.5 Pregnancy Restriction    ................................................................................................ 42 
6 Investigational Medicinal Products, Medication History and Concomitant Medications    . 42 
6.1 PHYSICAL PROPERTIES OF THE INVESTIGATIONAL MEDICINAL PRODUCTS   
 
42 
6.2 Labeling of Investigational Product    .......................................................................... 42 
6.3 Packaging and Storage of Investigational Medicinal Products    ................................. 42 
6.4 Management, Dispensing and Recovery of Investigational Medicinal Products    ...... 43 
6.5Prior Medications and Concomitant Therapies    .......................................................... 43 
7 Study Procedures    ............................................................................................................... 44 
7.1 Study Procedures    ....................................................................................................... 44 
7.2 Participant Registration and Randomization    ............................................................. 44 
7.3 Blinding    ..................................................................................................................... 45 
7.4Screen Failure    ............................................................................................................. 45 
7.5 Investigational Product Dispensing    ........................................................................... 45 
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7.6 Administration of Investigational Medicinal Products    .............................................. 46 
7.7 Study Duration    ........................................................................................................... 46 
7.8 Study Compliance    ...................................................................................................... 46 
7.9Dose Modifications    ..................................................................................................... 47 
7.10 Participants lost to follow-up    ................................................................................... 47 
7.11 Participant Withdrawal    ............................................................................................ 47 
7.12 Early Termination of the Study    ................................................................................ 47 
7.12.1 Criteria for Study Suspension or Early Termination .................................................... 47 
7.12.2 Criteria for Site Suspension or Early Termination ....................................................... 48 
7.12.3 Procedures for Suspension or Early Termination of the Study .................................... 48 
7.13 End of Study    ............................................................................................................ 48 
8 Study Assessments    ............................................................................................................. 48 
8.1 Pharmacokinetic Evaluation    ...................................................................................... 48 
8.1.1 PK blood sampling    ...................................................................................................... 48 
8.1.2 Sample Analysis    .......................................................................................................... 48 
8.1.3 Sample Handling, Storage and Shipment    .................................................................... 48 
8.1.4 PK Parameter Analysis    ................................................................................................ 49 
8.2 Pharmacodynamic Assessments    ................................................................................ 49 
8.3Safety Assessments    ..................................................................................................... 49 
8.3.1Demographic and Disease History    ............................................................................... 50 
8.3.2 Vital Signs    ................................................................................................................... 50 
8.3.3 Physical Examination, Height and Weight    .................................................................. 50 
8.3.4   12Lead ECG ................................................................................................................. 51 
8.3.5 Blood pregnancy test    ................................................................................................... 51 
8.3.6Laboratory Tests    ........................................................................................................... 52 
8.3.7 Ophthalmic Examination    ............................................................................................. 52 
8.3.8Adverse Events    ............................................................................................................. 53 
8.3.9Serious Adverse Events    ................................................................................................ 53 
8.3.10 Suspected unexpected serious adverse reactions    ....................................................... 54 
8.3.11 Criteria for Determining the Severity of Adverse Events    .......................................... 54 
8.3.12 Criteria for Determining the Relationship between Adverse Events and Study Drug   
 
54 
8.3.13 Safety Reporting Period    ............................................................................................ 55 
8.3.14 Reporting Process of AEs and SAEs    ......................................................................... 55 
8.3.15 Pregnancy Exposure    .................................................................................................. 56 
8.3.16 Deaths    ........................................................................................................................ 57 
8.4 Overdose    .................................................................................................................... 57 
9 Statistical Methods    ............................................................................................................. 57 
9.1Sample Size Estimation    .............................................................................................. 57 
9.2 Datasets    ...................................................................................................................... 58 
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9.3 Statistical Analysis Methods    ...................................................................................... 58 
9.3.1 General Methods    ......................................................................................................... 58 
9.3.2Participant Disposition    ................................................................................................. 58 
9.3.3Demographic and Baseline Characteristics    .................................................................. 59 
9.3.4Dosing (Study Treatment, Concomitant Therapy, Compliance)    .................................. 59 
9.3.5 PK Data Analysis    ......................................................................................................... 59 
9.3.6 Safety Analysis    ............................................................................................................ 59 
9.3.7 Adverse Events    ............................................................................................................ 59 
9.3.8 Laboratory Abnormalities    ............................................................................................ 59 
9.3.9 Other Safety Data    ........................................................................................................ 60 
9.3.10 Interim Analyses    ........................................................................................................ 60 
10 Study Management    .......................................................................................................... 60 
10.1Good Clinical Practice    .............................................................................................. 60 
10.2 Ethics    ....................................................................................................................... 60 
10.3 Informed Consent    .................................................................................................... 60 
10.4 Clinical Monitoring    ................................................................................................. 60 
10.5Protocol Amendments    ............................................................................................... 61 
10.6 Data Quality Control    ............................................................................................... 61 
10.7Data Collection Tools/Source Data    .......................................................................... 61 
10.8 Participant Confidentiality Measures    ...................................................................... 61 
10.9 Record Retention    ..................................................................................................... 62 
10.10 Liability and Insurance    .......................................................................................... 62 
10.11 Publication of Study Results and Use of Information    ........................................... 62 
11 References    ........................................................................................................................ 63 
12 Appendices    ....................................................................................................................... 64 
12.1 Strong CYP3A inducers and inhibitors    ................................................................... 64 
 
 
 
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Table of Contents 
Table1 Part IStudy Design   9 
Table2 Part IIStudy Design   10 
Table3 Part IIIStudy Design   10 
Table4 Part IStudyPlanned(Single dose)   16 
Table5 Part IIStudyPlanned(Multiple dose)   20 
Table6 Part IIIStudy Plan   24 
Table7 Part I PKSampling time   28 
Table8  Part II PKSampling time   29 
Table9 Part III PKSampling time   30 
Table 10 PKParameters and their calculations   49 
 
 
 
List of Figures 
Figure 1 Overall Trial Design of Part I & II Study .........................................................................35 
Figure 2 Overall Trial Design of Part III Study ..............................................................................36 
 
 
 
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Protocol Synopsis 
Protocol 
Title 
A study to evaluate the safety, tolerability, and pharmacokinetic profile of 
single or multiple oral doses of ABSK061 microt and to evaluate the effect 
of soft food with ABSK061 microchips on its pharmacokinetic profile in 
healthy adult participants 
Protocol 
Number 
ABSK061-102 
Study 
Phase 
Phase 1 
Study drug 
ABSK061 
Number of 
samples 
Part I: 18 healthy participants enrolled (6/sequence) 
Part II: 12 healthy participants enrolled (6/sequence) 
Part III: 12 healthy participants enrolled (4/sequence) 
Study 
Objectives 
Primary Objective: 
 
Part I: to evaluate the pharmacokinetic profile (PK) and safety of a single 
oral dose of ABSK061 microchip in healthy adult participants;  
 
Part II: to evaluate the safety, tolerability, and PK profile of multiple oral 
doses of ABSK061 microt in healthy adult participants.  
 
Part III: to evaluate the effect of ABSK061 microt 5 mg administered with 
soft food on the PK profile of ABSK061.  
Secondary objectives: 
1. To assess the safety of ABSK061 microchips taken with soft food in 
healthy adult participants;  
2. To explore the dose-exposure proportionality of 1 to 35 mg of 
ABSK061 microchips in healthy adult participants.  
Study 
Endpoints 
Primary endpoint: 
• 
Safety and tolerability evaluation indicators, including adverse events 
(AEs), serious adverse events (SAEs), vital signs, physical examinations, 
electrocardiograms, laboratory tests, ophthalmic examinations, etc.;  
• 
Main PK parameters of ABSK061 micro-tablets, including maximum 
observed concentration (Cmax), time to reach maximum observed 
concentration (tmax), area under the plasma concentration-time curve 
(AUClast and AUC0- ∞), maximum observed concentration during the 
steady-state dosing interval (Cmax, ss), minimum observed concentration 
during the steady-state dosing interval (Cmin, ss), area under the 
concentration-time curve at steady-state dosing interval (AUCtau, ss), and 
accumulation index (AR);  
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• 
PK parameters, mainly including Cmax, AUC0- ∞, and AUClast, 
following a single dose of ABSK061 microt administration with or 
without soft food.  
Secondary endpoints: 
• 
Secondary PK parameters of ABSK061: including but not limited to 
terminal elimination half-life (t1/2), apparent clearance (CL/F), and 
apparent volume of distribution (Vz/F).  
Study 
Design 
The study consists of three parts: Part I, Part II and Part III. Part II and 
Part III will be performed in parallel after completion of Part I.  
Part I 
Part I is a single-dose PK study with the primary objective of evaluating 
the PK profile and safety of ABSK061 in healthy participants after a single 
dose. A total of 18 healthy participants were planned to be enrolled in Part I 
and randomized 1: 1: 1 to Sequences A, B, and C. Participants in three 
sequences received A single microchip dose of ABSK061 at doses of 1 mg, 10 
mg, and 35 mg, respectively, followed by A 7-day safety observation (until 
D8).  
All participants will take ABSK061 microchips with 180 mL of water 
under fasting conditions. The study design is shown in Table 1 Part I Test 
Design.  
Table 1 Part I Study Design 
 
D1 
D8 
Sequence A 
1 mg 
End of Safety 
Observations 
Sequence B 
10 mg 
Sequence C 
35 mg 
Part II 
Part II is a multiple dose escalation (MAD) study with the primary 
objective to evaluate the tolerability, safety and PK profile of ABSK061 
microchips in healthy participants after multiple doses. A total of 12 healthy 
participants were planned to be enrolled in Part II, with multiple dose 
escalation trials prespecified in Sequences D and E, with 6 healthy participants 
in each sequence. In this MAD study, participants in Sequence D received 
ABSK061 microchips 5 mg QD for 4 consecutive days with 14-day safety 
observations starting after the last dose (D5 to D18); the investigator and 
sponsor will decide whether to adjust the next dose level, Sequence E, based 
on the available safety data and PK data during the Sequence D trial. Healthy 
participants in Sequence E received ABSK061 microchips at 20 mg QD for 4 
consecutive days, as well as 14-day safety observations starting after the last 
dose (D5 to D18).  
All participants will take ABSK061 microchips with 180 mL of water 
under fasting conditions. The study design is shown in Table 2 Part II Study 
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Design Table 2 Part II Study Design.  
Table 2 Part II Study Design 
 
D1 
D2 
D3 
D4 
D18 
Sequen
ce D 
5 mg 
QD 
5 mg 
QD 
5 mg 
QD 
5 mg 
QD 
End of Safety 
Observations 
Sequen
ce E 
20 mg 
QD 
20 mg 
QD 
20 mg 
QD 
20 mg 
QD 
End of Safety 
Observations 
Part III 
Part III is a three-period, three-sequence crossover study with the primary 
objective to evaluate the effect of co-administration of soft food on the PK of 
ABSK061. Part III plans to include 12 healthy participants randomized 1: 1: 1 
to Sequence F, Sequence G, or Sequence H to receive a single oral dose of 
ABSK061 in triplicate doses of Treatment 1, Treatment 2, Treatment 3. 
Treatment 1 was 5 mg ABSK061 microchip taken with 180 mL of water, 
Treatment 2 was 5 mg ABSK061 microchip taken with a spoon of yogurt 
(approximately 15 mL), and Treatment 3 was administered with 5 mg 
ABSK061 microchip with a spoon of applesauce (approximately 15 mL). 
Participants in Sequence F will receive Treatment 1, Treatment 2, and 
Treatment 3 under fasting conditions in the morning on Cycle 1 Day 1 (D1), 
Cycle 2 Day 1 (D4), and Cycle 3 Day 1 (D7), respectively; participants in 
Sequence G will receive Treatment 2, Treatment 3, and Treatment 1 in the 
morning on D1, D4, and D7, respectively; participants in Sequence H will 
receive Treatment 3, Treatment 1, and Treatment 2 fasted in the morning on 
D1, D4, and D7, respectively. All participants were required to drink 180 mL 
of water immediately after swallowing the investigational drug. The washout 
period for each period was 3 days. The study design is shown in Table 3 Part 
III Study Design.  
Table 3 Part III Study Design 
 
Cycle 1 
Cycle 2 
Cycle 3 
Sequence 
F 
Treatment 1 
Treatment 2 
Treatment 3 
Sequence 
G 
Treatment 2 
Treatment 3 
Treatment 1 
Sequence 
H 
Treatment 3 
Treatment 1 
Treatment 2 
Note: Treatment 1: 5 mg ABSK061 micro-tablets were administered with 180 mL of water; 
treatment 2: 5 mg ABSK061 microchip + 1 tablespoon yogurt; treatment 3: 5 mg ABSK061 
microchips + 1 tablespoon of applesauce. The washout period of each cycle was 3 days.  
Investigati
onal 
Product 
ABSK061 capsules were manufactured and provided by the sponsor in 
two strengths: 0.2 mg/capsule, containing 4 0.05 mg tablets; 5 mg/capsule 
containing 10 0.5 mg tablets.  
Mode 
of 
The 1 mg dose corresponds to 5 capsules of the 0.2 mg strength, the 5 mg 
dose corresponds to 1 capsule of the 5 mg strength, the 10 mg dose 
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administra
tion 
corresponds to 2 capsules of the 5 mg strength, the 20 mg dose corresponds to 
4 capsules of the 5 mg strength, and the 35 mg dose corresponds to 7 capsules 
of the 5 mg strength. The ABSK061 cap was opened prior to dosing and the 
microt was poured out and swallowed. See Section 7.6 Investigational Product 
Administration for details.  
Part I&II: dosing was administered under fasting conditions and 
participants were required to fast overnight for at least 10 hours until the next 
morning. Water deprivation (except for water for drug administration) from 1 
hour before dosing to 1 hour after dosing. All participants received ABSK061 
microchips directly with 180 mL of water (see Table 1 Part I trial design and 
Table 2 Part II trial design), and no food was allowed for 4 hours after dosing.  
Part III: dosing was administered under fasting conditions, with 
participants fasting overnight for at least 10 hours until the next morning. 
Water deprivation (except for water for drug administration) from 1 hour 
before dosing to 1 hour after dosing. See Table 3 Part III Study Design.  
Participants receiving Treatment 1 received 10 0.5 mg ABSK061 
microchips directly with 180 mL of water, and no food was allowed within 4 
hours after dosing;  
Participants receiving Treatment 2 dispersed 10 0.5 mg tablets on 1 
tablespoon of yogurt (approximately 15 mL) and swallowed together, 
followed by 180 mL of water immediately, and no food was allowed for 4 
hours after dosing;  
Participants receiving Treatment 3 swallowed 10 0.5 mg tablets sprinkled 
on 1 tablespoon of applesauce (approximately 15 mL), followed by 180 mL of 
water immediately, and no food was allowed for 4 hours after dosing.  
PK 
blood 
sampling 
Plasma samples were collected from all participants in this study before 
and after dosing to determine the concentrations of ABSK061 and its 
metabolites (if applicable) for PK assessment. The specific collection times 
are detailed in Table 7 Part I PK sampling times, Table 8 Part II PK sampling 
times, and Table 9 Part III PK sampling times.  
The requirements for blood sampling and blood sample processing are 
provided in the Central Laboratory Manual.  
Inclusion/E
xclusion 
Criteria 
 
Inclusion criteria: 
1) Gender: male or female participants, both male and female;  
2) Age: 18 to 45 years (including 18 and 45 years);  
3) Weight: male participants weigh ≥ 50.0 kg, female participants weigh ≥ 
45.0 kg, and body mass index is in the range of 19.0-26.0 kg/m2 
(including cut-off value), and body mass index (BMI) = weight 
(kg)/height 2 (m2);  
4) Able to understand and willing to comply with the study procedures, 
voluntarily participate in this clinical trial and sign the informed consent 
form before screening;  
5) Male or female participants of childbearing potential must agree to use 
effective methods of contraception during the study and for 6 months after 
the last dose of investigational product (see Section 5.5 Pregnancy 
Restrictions for details) and that male participants do not donate sperm 
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during this period; female participants do not donate eggs during this 
period and must be non-pregnant, non-lactating female participants, 
defined as women after conception until termination of pregnancy, and 
human chorionic gonadotropin (β-HCG) is within the normal range.  
Exclusion criteria: 
1) 
History of bacterial, fungal, parasitic, viral (excluding nasopharyngitis), 
mycobacterial infection, COVID19 infection within 30 days prior to 
screening;  
2) 
Prolongation of QT interval corrected for heart rate at screening, QTcF > 
450 ms (Note: QTc interval corrected by Fridericia ’ s formula), or family 
history of long QT syndrome;  
3) 
Any of the following ophthalmic exclusion criteria: 
 
Current or past medical history of retinal pigment epithelial 
detachment (RPED)/central serous retinopathy (CSR) 
 
Previous laser therapy or intraocular injection for macular 
degeneration 
 
Current concomitant or past medical history of age-related macular 
degeneration 
 
Current concomitant or past medical history of retinal vein occlusion 
(RVO) 
 
Current concomitant or past medical history of retinal degenerative 
disease 
 
Diabetic retinopathy with macular edema 
 
Current concomitant or past medical history of any other clinically 
relevant retinal-choroidal defect 
 
Any symptoms of acute ophthalmic disease (within 4 weeks prior to 
the first dose) or active progression 
 
Current concomitant keratopathy (eg, keratitis, corneal abrasion, or 
ulceration) or conjunctivitis 
4) 
Subjects with a history of motor system, neuropsychiatric system, 
endocrine system, blood circulation system, respiratory system, digestive 
system, urinary system, reproductive system abnormalities, etc., or 
existing diseases, which may affect the assessment of study results;  
5) 
Prior history of gastric or intestinal surgery, or surgery affecting drug 
absorption, distribution, metabolism, excretion (except for appendicitis 
surgery); or plan to undergo surgery during the study;  
6) 
Donation of blood or massive blood loss (≥ 400 mL) within 3 months 
prior to screening or during screening (except for female physiological 
period); those who have received blood transfusion or blood products 
within 2 months prior to screening;  
7) 
History of drug abuse or positive urine drug screen (morphine, 
tetrahydrocannabinol 
acid, 
methamphetamine, 
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dimethyldioxyamphetamine, ketamine) within the past 5 years;  
8) 
Those who are allergic to drugs, environment or food or to ABSK061 
micro-tablets or its excipients [microcrystalline cellulose, mannitol, 
croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, 
film-coating premix (gastric soluble)]; those who are prone to allergic 
symptoms such as rash and urticaria; for Part III: previously known 
allergies to yogurt and applesauce foods;  
9) 
Previous chronic consumption of excessive tea, coffee, or caffeinated 
beverages (defined as ingestion of more than 6 units of caffeine per day, 
1 unit of caffeine equivalent to 177 mL of coffee, 355 mL of tea, 355 mL 
of cola, or 85 grams of chocolate) or who cannot stop drinking any 
caffeinated beverage during the trial;  
10) Those who consumed more than 14 units of alcohol per week (1 unit = 
360 mL of beer or 45 mL of spirits containing 40% alcohol or 150 mL of 
wine), or were unable to abstain from alcohol during the trial, or had an 
alcohol breath test result > 0 mg/100 mL within 3 months prior to signing 
the informed consent form;  
11) Smoking ≥ 5 cigarettes per day before signing the informed consent form; 
or cannot stop using any tobacco products during the trial;  
12) Those who have taken strong CYP3A4 inhibitors or inducers (including 
grapefruit juice, grapefruit hybrids, pomegranates, carambola, grapefruit, 
Seville oranges and fruit juices or other processed products within 14 
days prior to screening and during the screening period, as detailed in 
Appendix 12.1 Strong CYP3A inducers and inhibitors);  
13) Those who have special requirements for diet and cannot comply with 
the unified diet; specific dietary requirements were: (i) only meals 
provided by the study site during hospitalization, and (ii) avoidance of 
strong CYP3A4 inhibitors or inducers during the study;  
14) Dysphagia, inability to take the investigational product orally;  
15) Lactose intolerance (those who have had milk diarrhea);  
16) Those who have used any prescription drugs, over-the-counter drugs, 
Chinese herbal medicines or health products within 14 days prior to the 
first dose or plan to use them during the study;  
17) Those who have received vaccines (including COVID19 vaccine) within 
2 months prior to screening, or have planned vaccination throughout the 
study;  
18) Previous participation as a participant in any other ABSK061-related 
study and has taken any dosage form of ABSK061; those who have 
participated in other clinical trials and used other clinical investigational 
drugs or investigational devices within 3 months prior to screening or 
during screening, or who plan to participate in other clinical trials during 
this study, or who are not self-participating in clinical trials;  
19) Those with a history of needle sickness, blood sickness or intolerance to 
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venipuncture, or difficulty in blood collection;  
20) Abnormal physical examination, hematology, blood chemistry, 
coagulation function, urinalysis, 12-lead electrocardiogram, chest X-ray 
(anteroposterior), abdominal B-ultrasound, ophthalmic examination and 
judged by the investigator to be clinically significant;  
21) Vital signs outside the normal range, and the retest is still outside the 
normal range.  
22) Abnormal serum hepatitis B surface antigen (HBsAg), hepatitis C virus 
(HCV) antibody, human immunodeficiency virus (HIV) antibody, 
treponema pallidum antibody test and judged by the investigator to be 
clinically significant;  
23) Personnel involved in the design or implementation of this study project 
and their immediate family members (e.g., employees of Shanghai 
Hezhui Biopharmaceutical Technology Co., Ltd., CRO employees, and 
employees of the study site);  
24) Any other factor that, in the opinion of the investigator, is not suitable for 
enrollment, may affect the compliance of the participant with the 
protocol, affect the interpretation of the study results, or increase the 
participant's safety risk, or the participant withdraws from the trial for 
his/her own reasons.  
Statistical 
Methods 
No formal statistical hypothesis testing will be performed in this study. 
All analyses were mainly descriptive, and the primary analysis set included 
the PK concentration analysis set, the PK parameter analysis set, and the safety 
analysis set.  
Pharmacokinetic parameters of ABSK061 in capsules will be calculated 
and analyzed by a standard noncompartmental model. Results of PK 
parameters and summary data will be provided for each participant. 
Descriptive statistics (arithmetic mean, standard deviation, coefficient of 
variation, median, minimum, maximum, geometric mean, and geometric 
coefficient of variation) were calculated for all PK parameters except tmax, 
which will summarize the median, minimum, and maximum. Data listings for 
all PK parameters will be provided.  
The PK profile of single or multiple oral doses of ABSK061 microt was 
assessed based on the main PK parameters obtained, the effect of oral 
administration with soft food on the pharmacokinetics of ABSK061, and the 
dose-exposure proportionality of ABSK061 microt was explored. Specific PK 
parameters include, but are not limited to, total drug exposure (AUC0- ∞, 
AUClast), maximum concentration (Cmax), time to maximum concentration 
(tmax), elimination half-life (t1/2), apparent clearance (CL/F) and apparent 
volume of distribution (Vz/F), accumulation ratio (AR).  
Part III evaluated the effect of co-administration of soft food on the PK 
characteristics of ABSK061, and natural log-transformation was performed on 
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the main PK parameters (AUC0- ∞, AUClast, Cmax), and the Geometric Least 
Squares mean Ratio (Ratio in Geometric Least Squares Means, RGLSM, 
administered with soft food/water) was obtained by linear mixed model for 
statistical analysis and antilogarithmic transformation, and intra-individual 
coefficient of variation was calculated for each parameter.  
The dose-exposure proportionality of ABSK061 administered as capsules 
in fasted water will also be explored by graphical presentation of primary PK 
parameters (AUC0- ∞, AUClast, Cmax) and/or dose-normalized primary PK 
parameters. If applicable, the dose-exposure proportionality will be further 
explored through the Power model by natural log-transformation of the 
primary PK parameters.  
The safety analysis set will be used for safety analysis. Safety will be 
assessed based on AE reporting, clinical laboratory data, vital signs, and 
electrocardiograms. Missing safety data will not generally be imputed unless 
otherwise specified.  
End of Stu
dy Criteria 
A participant is considered to have completed the study if he/she has 
completed all visits to the study, including the last visit or last trial procedure 
shown in the flowchart.  
The end of study was defined as the completion of all procedures in the 
last visit or flowchart for the last participant (including safety telephone 
follow-up).  
Study Dura
tion 
Including screening period (and baseline period), trial period and safety 
observation period/follow-up period: 
Screening + Baseline: 14 days;  
Part I: the single-dose PK study included a single dose (1 day) and a 
safety observation period (7 days); part II: the multiple dose escalation PK 
study included multiple doses (4 days) and a safety observation period (14 
days);  
Part III consists of three cycles (3 days per cycle for a total of 9 days) and 
a safety observation period (7 days).  
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ABSK061-102 Version No. 1.0 Version Date April 7, 2025 
 
 
Study Flow Chart 
Table 4 Part I Study Plan (Single Dose) 
Study Procedures 
Screening 1 
Baseline 
Study Period 2 
Follow-up 3 
Early 
Withdrawal 
4 
D-14 ~D-2 
D-1 
D1 
D2 
D3 
D8 (+ 3 days) 
Signed informed consent 
× 
 
 
 
 
 
 
Eligibility Criteria 
× 
× 
 
 
 
 
 
Demographic Data 5 
× 
 
 
 
 
 
 
Medical history 6 
× 
 
 
 
 
 
 
Vital Signs 7 
× 
× 
× 
× 
× 
 
× 
Physical Examination 8 
× 
 
 
× 
 
× 
Height and weight 9 
× 
 
 
 
 
 
Hematology 10 
× 
× 
 
 
× 
 
× 
Urinalysis 11 
× 
× 
 
 
× 
 
× 
Blood Chemistry 12 
× 
× 
 
 
× 
 
× 
Coagulation 13 
× 
× 
 
 
× 
 
× 
Virology 14 
× 
 
 
 
 
 
Chest X-ray (anteroposterior) 15 
× 
 
 
 
 
 
Abdominal ultrasonography (liver, gallbladder, pancreas, spleen, 
kidney) 16 
× 
 
 
 
 
 
12-lead ECG 17 
× 
× 
× 
 
× 
 
× 
Blood pregnancy test 18 
× 
× 
 
 
× 
 
× 
Drug abuse screening 19 
 
× 
 
 
 
 
 
Alcohol breath screen 
 
× 
 
 
 
 
 
Ophthalmic Examination 20 
× 
 
 
 
× 
 
× 
Randomization 
 
× 
 
 
 
 
 
Admission to study ward 
 
× 
 
 
 
 
 
Taking ABSK06121 
 
 
× 
 
 
 
 
PK blood sampling 22 
 
 
× 
× 
× 
 
× 
Leave study ward 
 
 
 
 
× 
 
× 
Telephone follow-up 
 
 
 
 
 
× 
 
Adverse Events 23 
× 
Prior and concomitant medications 24 
× 
 
Abbisko Therapeutics Confidential Page 33 of 55 
 
 

ABSK061-102 Version No. 1.0 Version Date April 7, 2025 
 
 
Instructions: 
1. 
Screening: all assessments at screening should be completed within 14 days prior to the first dose of investigational product. If screening cannot be completed 
on time, the sponsor should be contacted to determine if the screening process performed prior to dosing is repeated. All screening examinations must be completed at this 
site. If a laboratory value at screening does not meet the participant selection criteria, only up to one retest that is judged by the investigator to be required during the 
screening period is allowed. If the retest value still does not match, the participant should be excluded.  
2. 
Study period: dosing on Day 1 (D1) and washout from D1 to D3 were included. Participants should be admitted to the clinical study ward of the study site on 
the day prior to dosing (i.e., D-1), eat uniformly, and undergo relevant visit examinations. Participants cannot leave the clinical study ward of the study site during the trial.  
3. 
Participants should be contacted by telephone follow-up on D8 (+ 3 days) 7 days after administration of ABSK061 and information on adverse events and 
concomitant medications should be collected.  
4. 
Early withdrawal applies to participants who have received ABSK061 and will no longer be followed for safety.  
5. 
Demographic data will include gender, ethnicity, and date of birth of the participant.  
6. 
Medical history inquiry: including past medical history and treatment history, smoking history, alcohol consumption history, drug allergy history, food allergy 
history, concomitant diseases and treatment. The inquiries are detailed in Protocol 8.3.1 Demographics and Disease History.  
7. 
Vital signs included ear temperature, sitting blood pressure, respiratory rate, and pulse rate. Vital signs are recommended after the participant has rested quietly 
for at least 5 minutes. Vital signs should be measured at 1 hour (± 1 hour) pre-dose, 2 hours (± 1 hour) post-dose, 6 hours (± 1 hour) post-dose, 24 hours (± 1 hour) post-
dose, 48 hours (± 1 hour) post-dose, and at the Early Withdrawal Visit. Vital signs should be performed prior to PK blood sampling or at least 20 min apart after PK blood 
sampling. Additional vital sign testing may be added during each study at the discretion of the investigator. If the vital signs test results at screening are not within the 
normal range, they may be repeated once, and if they are still not within the normal range, the screening fails; participants who have been assigned a random number may 
be retested once if their vital signs test results are not within the normal range prior to the first dose on D1, or drop out if they are still outside the normal range and judged 
by the investigator to be clinically significant.  
8. 
Physical examination: a complete physical examination is required at screening or baseline, and only a general physical examination will be performed during 
subsequent studies. A complete physical examination included mucocutaneous, lymph nodes, head, neck, chest, abdomen, spine, extremities, and nervous system. General 
physical examination, which may include head and neck, chest and abdomen, will be determined by the investigator as clinically indicated.  
9. 
Height and weight: collected at Screening or Baseline only. Investigators may perform more frequent tests if clinically indicated.  
10. Hematology: including red blood cell count (RBC), hemoglobin (HGB), hematocrit (HCT) and total platelet count (PLT), white blood cell count (WBC) with 
differential and proportion (including neutrophil percentage and absolute neutrophil percentage, lymphocyte percentage and absolute lymphocyte count, monocyte 
percentage and absolute monocyte count, eosinophil percentage and absolute eosinophil percentage, basophil percentage and absolute basophil percentage). If hematology 
at screening is performed within 7 days prior to the first dose, hematology will not be performed separately at baseline on D-1.  
11. Urinalysis: including specific gravity, glucose, protein, ketones, occult blood, and red blood cells. Participants with significant clinical findings should be further 
evaluated. If urinalysis at screening is performed within 7 days prior to the first dose, urinalysis will not be performed separately at baseline on D-1.  
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ABSK061-102 Version No. 1.0 Version Date April 7, 2025 
 
 
12. Blood chemistry: includes total bilirubin, direct bilirubin, total protein, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline 
phosphatase (ALP), glutamyl transpeptidase (GGT), lactate dehydrogenase, glucose, urea, creatinine, total cholesterol, triglycerides, potassium, sodium, chloride, calcium, 
phosphorus, magnesium, carbon dioxide. In the event of ≥ CT CA E2 transaminase elevations during the trial, more frequent liver function tests (at least twice weekly) 
will be required until recovery to Grade 1 or baseline. Additional laboratory tests may be performed if clinically indicated. If blood chemistry at screening is performed 
within 7 days prior to the first dose, blood chemistry will not be performed separately at baseline on D-1.  
13. Coagulation: includes prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), plasma fibrinogen (Fbg), and 
thrombin time (TT). If coagulation at screening is performed within 7 days prior to the first dose, coagulation tests will no longer be performed separately at baseline on 
D-1.  
14. Virology: including five tests for hepatitis B virus (HBV): hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B e antigen 
(HBeAg), hepatitis B e antibody (HBeAb), and hepatitis B core antibody (HBcAb); treponema pallidum antibody, hepatitis C virus antibody (HCV-Ab), human 
immunodeficiency virus antibody. If virology at screening is performed within 28 days prior to the first dose, virology will no longer be performed separately at Screening 
and Baseline.  
15. Chest X-ray (anteroposterior) will be performed only once at screening or baseline and results within 3 months prior to signing the informed consent form are 
acceptable.  
16. Abdominal B-ultrasound (liver, gallbladder, pancreas, spleen, kidney) will be performed only once at screening or baseline. If abdominal B-ultrasound at 
screening is performed within 28 days prior to the first dose, abdominal B-ultrasound will not be performed separately at screening and baseline.  
17. 12-lead ECG: a 12-lead ECG will be performed once at screening and once at baseline on D-1. If the 12-lead ECG at screening is performed within 7 days prior 
to the first dose, 12-lead ECG will not be performed separately at D-1 baseline. A single 12-lead electrocardiogram was performed 1 hour (± 1 hour) before dosing on the 
day of dosing (D1), the day of leaving the ward (D3), and early withdrawal. The 12-lead ECG prior to dosing on the day of dosing should be performed prior to PK blood 
sampling, and the remaining 12-lead ECGs should be performed at least 45 minutes apart if required after invasive tests (e.g., PK blood sampling, etc.). Additional ECGs 
may be performed by the investigator as clinically indicated. The 12-lead ECG should include heart rate, RR interval, PR interval, QT interval, and calculation of QTcF. 
The specific examination requirements of 12-lead ECG are detailed in Protocol 8.3.4 12-lead ECG.  
18. For female participants of childbearing potential, a blood pregnancy test is required at Screening, D-1 Baseline, and D3/Early Withdrawal. A blood pregnancy 
test is not required for women of non-childbearing potential. Women of non-childbearing potential were defined as postmenopausal (≥ 12 months postmenopausal) or had 
a documented bilateral tubal ligation, complete oophorectomy, or hysterectomy. If the blood pregnancy test at screening is performed within 2 days prior to the first dose, 
the blood pregnancy test will not be repeated at baseline on D-1.  
19. The drug screen included morphine, ketamine, methamphetamine, dimethylene dioxyamphetamine, and tetrahydrocannabinol acid.  
20. Ophthalmic Examination: participants were evaluated ophthalmologically by an ophthalmologist at Screening, D3/Early Withdrawal Visit. Each ophthalmologic 
assessment should be performed by the same ophthalmologist whenever possible. Specific examination requirements are detailed in 8.3.7 Ophthalmic Examination.  
21. Taking ABSK061: the drug should be taken in a fasted state on Day 1 (D1). Refer to Section 7.6 for details.  
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ABSK061-102 Version No. 1.0 Version Date April 7, 2025 
 
 
22. The time windows for PK blood sample collection are detailed in Table 7 Part I PK sampling times.  
23. Adverse events will begin when the participant signs the informed consent form until 7 days after administration of ABSK061 (i.e., D8), as detailed in 8.3.13 Safety 
Reporting Period.  
24. Concomitant medication information was collected from the start of ABSK061 administration until 7 days after administration of ABSK061. Medications up to 
14 days prior to dosing of ABSK061 until the end of dosing will be considered prior and will also be collected.  
Abbisko Therapeutics Confidential Page 33 of 55 
 
 

ABSK061-102 Version No. 1.0 Version Date April 7, 2025 
 
 
Table 5 Part II Study Plan (Multiple Doses) 
Study Procedures 
Screening 
1 
Baseline 
Study Period 2 
Follow-up 3 
Early 
Withdrawal 
4 
D-14 ~D-2 
D-1 
D1 
D2 
D3 
D4 
D5 
D6 
D18 (+ 3 days) 
Signed informed consent 
× 
 
 
 
 
 
 
 
 
 
Eligibility Criteria 
× 
× 
 
 
 
 
 
 
 
 
Demographic Data 5 
× 
 
 
 
 
 
 
 
 
 
Medical history 6 
× 
 
 
 
 
 
 
 
 
 
Vital Signs 7 
× 
× 
× 
× 
× 
× 
× 
× 
 
× 
Physical Examination 8 
× 
 
 
 
 
 
× 
 
× 
Height and weight 9 
× 
 
 
 
 
 
 
 
 
Hematology 10 
× 
× 
 
 
 
 
 
× 
 
× 
Urinalysis 11 
× 
× 
 
 
 
 
 
× 
 
× 
Blood Chemistry 12 
× 
× 
 
 
 
 
 
× 
 
× 
Coagulation 13 
× 
× 
 
 
 
 
 
× 
 
× 
Virology 14 
× 
 
 
 
 
 
 
 
 
Chest X-ray (anteroposterior) 15 
× 
 
 
 
 
 
 
 
 
Abdominal 
ultrasonography 
(liver, 
gallbladder, pancreas, spleen, kidney) 16 
× 
 
 
 
 
 
 
 
 
12-lead ECG 17 
× 
× 
× 
 
 
 
 
× 
 
× 
Blood pregnancy test 18 
× 
× 
 
 
 
 
 
× 
 
× 
Drug abuse screening 19 
 
× 
 
 
 
 
 
 
 
 
Alcohol breath screen 
 
× 
 
 
 
 
 
 
 
 
Ophthalmic Examination 20 
× 
 
 
 
 
 
 
× 
 
× 
Assign Enrollment Number 
 
× 
 
 
 
 
 
 
 
 
Admission to study ward 
 
× 
 
 
 
 
 
 
 
 
Taking ABSK06121 
 
 
× 
× 
× 
× 
 
 
 
 
PK blood sampling 22 
 
 
× 
× 
× 
× 
× 
× 
 
× 
Leave study ward 
 
 
 
 
 
 
 
× 
 
× 
Telephone follow-up 
 
 
 
 
 
 
 
 
× 
 
Adverse Events 23 
× 
Prior and concomitant medications 24 
× 
 
Abbisko Therapeutics Confidential Page 33 of 55 
 
 

ABSK061-102 Version No. 1.0 Version Date April 7, 2025 
 
 
 
Instructions: 
1. 
Screening: all assessments at screening should be completed within 14 days prior to the first dose of investigational product. If screening cannot be completed 
on time, the sponsor should be contacted to determine if the screening process performed prior to dosing is repeated. All screening examinations must be completed at this 
site. If a laboratory value at screening does not meet the participant selection criteria, only up to one retest that is judged by the investigator to be required during the 
screening period is allowed. If the retest value still does not match, the participant should be excluded.  
2. 
Study period: including 4 days of dosing (D1 to D4) and washout from D4 to D6. Participants should be admitted to the clinical study ward of the study site on 
the day prior to dosing (i.e., D-1), eat uniformly, and undergo relevant visit examinations. Participants cannot leave the clinical study ward of the study site during the trial.  
3. 
Participants should be contacted by telephone follow-up on D18 (+ 3 days) 14 days after the last dose of ABSK061, and information on adverse events and 
concomitant medications should be collected.  
4. 
Early withdrawal applies to participants who have received at least one dose of ABSK061 and will no longer be followed for safety.  
5. 
Demographic data will include gender, ethnicity, and date of birth of the participant.  
6. 
Medical history inquiry: including past medical history and treatment history, smoking history, alcohol consumption history, drug allergy history, food allergy 
history, concomitant diseases and treatment. The inquiries are detailed in Protocol 8.3.1 Demographics and Disease History.  
7. 
Vital signs included ear temperature, sitting blood pressure, respiratory rate, and pulse rate. Vital signs are recommended after the participant has rested quietly 
for at least 5 minutes. Vital signs should be measured at 1 hour (± 1 hour) pre-dose, 2 hours (± 1 hour) post-dose, 6 hours (± 1 hour) post-dose, D5, D6, and at the Early 
Withdrawal Visit on D1 to D4. Vital signs should be performed prior to PK blood sampling or at least 20 min apart after PK blood sampling. Additional vital sign testing 
may be added during each study at the discretion of the investigator. If the vital signs test results at screening are not within the normal range, they may be repeated once, 
and if they are still not within the normal range, the screening fails; participants who have been assigned enrollment numbers may be retested once if their vital signs test 
results are not within the normal range prior to the first dose on D1, or drop out if they are still outside the normal range and judged by the investigator to be clinically 
significant.  
8. 
Physical examination: a complete physical examination is required at screening or baseline, and only a general physical examination will be performed during 
subsequent studies. A complete physical examination included mucocutaneous, lymph nodes, head, neck, chest, abdomen, spine, extremities, and nervous system. General 
physical examination, which may include head and neck, chest and abdomen, will be determined by the investigator as clinically indicated.  
9. 
Height and weight: collected at Screening or Baseline only. Investigators may perform more frequent tests if clinically indicated.  
10. Hematology: including red blood cell count (RBC), hemoglobin (HGB), hematocrit (HCT) and total platelet count (PLT), white blood cell count (WBC) with 
differential and proportion (including neutrophil percentage and absolute neutrophil percentage, lymphocyte percentage and absolute lymphocyte count, monocyte 
percentage and absolute monocyte count, eosinophil percentage and absolute eosinophil percentage, basophil percentage and absolute basophil percentage). If hematology 
at screening is performed within 7 days prior to the first dose, hematology will not be performed separately at baseline on D-1.  
11. Urinalysis: including specific gravity, glucose, protein, ketones, occult blood, and red blood cells. Participants with significant clinical findings should be further 
Abbisko Therapeutics Confidential Page 33 of 55 
 
 

ABSK061-102 Version No. 1.0 Version Date April 7, 2025 
 
 
evaluated. If urinalysis at screening is performed within 7 days prior to the first dose, urinalysis will not be performed separately at baseline on D-1.  
12. Blood chemistry: includes total bilirubin, direct bilirubin, total protein, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline 
phosphatase (ALP), glutamyl transpeptidase (GGT), lactate dehydrogenase, glucose, urea, creatinine, total cholesterol, triglycerides, potassium, sodium, chloride, calcium, 
phosphorus, magnesium, carbon dioxide. In the event of ≥ CT CA E2 transaminase elevations during the trial, more frequent liver function tests (at least twice weekly) 
will be required until recovery to Grade 1 or baseline. Additional laboratory tests may be performed if clinically indicated. If blood chemistry at screening is performed 
within 7 days prior to the first dose, blood chemistry will not be performed separately at baseline on D-1.  
13. Coagulation: includes prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), plasma fibrinogen (Fbg), and 
thrombin time (TT). If coagulation at screening is performed within 7 days prior to the first dose, coagulation tests will no longer be performed separately at baseline on 
D-1.  
14. Virology: including five tests for hepatitis B virus (HBV): hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B e antigen 
(HBeAg), hepatitis B e antibody (HBeAb), and hepatitis B core antibody (HBcAb); treponema pallidum antibody, hepatitis C virus antibody (HCV-Ab), human 
immunodeficiency virus antibody. If virology at screening is performed within 28 days prior to the first dose, virology will no longer be performed separately at Screening 
and Baseline.  
15. Chest X-ray (anteroposterior) will be performed only once at screening or baseline and results within 3 months prior to signing the informed consent form are 
acceptable.  
16. Abdominal B-ultrasound (liver, gallbladder, pancreas, spleen, kidney) will be performed only once at screening or baseline. If abdominal B-ultrasound at 
screening is performed within 28 days prior to the first dose, abdominal B-ultrasound will not be performed separately at screening and baseline.  
17. 12-lead ECG: a 12-lead ECG will be performed once each at screening and at D-1 baseline, D6, and at the Early Withdrawal Visit. If the 12-lead ECG at 
screening is performed within 7 days prior to the first dose, a 12-lead ECG will not be performed separately at D-1 baseline. In Part II, serial 12-lead ECG measurements 
were performed at 1 hour (± 15 minutes), 30 minutes (± 15 minutes), and 15 minutes (± 15 minutes) before dosing and 30 minutes (± 15 minutes), 1 hour (± 15 minutes), 
and 1.5 hours (± 15 minutes) postdose on the first day of dosing (D1). Participants should remain supine or semi-recumbent for at least 10 minutes prior to each ECG 
examination. Triplicate measurements were performed at each time point ≥ 1 minute apart, and triplicate recordings at each time point should be completed within 10 
minutes. A total of 6 12-lead ECGs were required on D1. 12-lead ECGs should be performed prior to invasive tests (e.g., PK blood sampling, etc.). Additional ECGs may 
be performed by the investigator as clinically indicated. The 12-lead ECG should include heart rate, RR interval, PR interval, QT interval, and calculation of QTcF. The 
specific examination requirements of 12-lead ECG are detailed in Protocol 8.3.4 12-lead ECG.  
18. For female participants of childbearing potential, a blood pregnancy test is required at Screening, D-1 Baseline, D6, and Early Withdrawal Visit. A blood 
pregnancy test is not required for women of non-childbearing potential. Women of non-childbearing potential were defined as postmenopausal (≥ 12 months 
postmenopausal) or had a documented bilateral tubal ligation, complete oophorectomy, or hysterectomy. If the blood pregnancy test at screening is performed within 2 
days prior to the first dose, the blood pregnancy test will not be repeated at baseline on D-1.  
19. The drug screen included morphine, ketamine, methamphetamine, dimethylene dioxyamphetamine, and tetrahydrocannabinol acid.  
Abbisko Therapeutics Confidential Page 33 of 55 
 
 

ABSK061-102 Version No. 1.0 Version Date April 7, 2025 
 
 
20. Ophthalmic Examination: participants were evaluated ophthalmologically by an ophthalmologist at Screening, D6, Early Withdrawal Visit. Each ophthalmologic 
assessment should be performed by the same ophthalmologist whenever possible. Specific examination requirements are detailed in 8.3.7 Ophthalmic Examination.  
21. Taking ABSK061: the drug should be taken in a fasted state from D1 to D4. Refer to Section 7.6 for details.  
22. The time windows for PK blood sample collection are detailed in Table 8 Part II PK sampling times.  
23. Adverse events will begin when the participant signs the informed consent form until 14 days after the last dose of ABSK061 (i.e., D18), as detailed in 8.3.13 Safety 
Reporting Period.  
24. Concomitant medication information was collected from the first dose of ABSK061 until 14 days after the last dose of ABSK061. Medications up to 14 days 
prior to the first dose of ABSK061 until the end of the first dose will be considered prior and will also be collected.  
 
 
Abbisko Therapeutics Confidential Page 33 of 55 
 
 

ABSK061-102 Version No. 1.0 Version Date April 7, 2025 
 
 
Table 6 Part III Study Plan 
Study Procedures 
Screening 1 
Baseline 
Study Period Period 1 2 
Study Period Period 2 3 
Study Period Period 3 4 
Follow-up 5 
Early 
Withdrawal 
6 
D-14 ~D-2 
D-1 
D1 
D2 
D3 
D4 
D5 
D6 
D7 
D8 
D9 
D14 (+ 3 days) 
Signed informed consent 
× 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility Criteria 
× 
× 
 
 
 
 
 
 
 
 
 
 
 
Demographic Data7 
× 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 8 
× 
 
 
 
 
 
 
 
 
 
 
 
 
Vital Signs 9 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
 
× 
Physical Examination 10 
× 
 
 
× 
 
 
× 
 
 
× 
 
× 
Height and weight 11 
× 
 
 
 
 
 
 
 
 
 
 
 
Hematology 12 
× 
× 
 
 
× 
 
 
× 
 
 
× 
 
× 
Urinalysis 13 
× 
× 
 
 
× 
 
 
× 
 
 
× 
 
× 
Blood Chemistry 14 
× 
× 
 
 
× 
 
 
× 
 
 
× 
 
× 
Coagulation 15 
× 
× 
 
 
× 
 
 
× 
 
 
× 
 
× 
Virology 16 
× 
 
 
 
 
 
 
 
 
 
 
 
Chest X-ray (anteroposterior) 17 
× 
 
 
 
 
 
 
 
 
 
 
 
Abdominal 
ultrasonography 
(liver, 
gallbladder, pancreas, spleen, kidney) 
18 
× 
 
 
 
 
 
 
 
 
 
 
 
12-lead ECG 19 
× 
× 
× 
 
× 
× 
 
× 
× 
 
× 
 
× 
Blood pregnancy test 20 
× 
× 
 
 
 
 
 
 
 
 
× 
 
× 
Drug abuse screening 21 
 
× 
 
 
 
 
 
 
 
 
 
 
 
Alcohol breath screen 
 
× 
 
 
 
 
 
 
 
 
 
 
 
Ophthalmic Examination 22 
× 
 
 
 
 
 
 
 
 
 
× 
 
× 
Randomization 
 
× 
 
 
 
 
 
 
 
 
 
 
 
Admission to study ward 
 
× 
 
 
 
 
 
 
 
 
 
 
 
Taking ABSK06123 
 
 
× 
 
 
× 
 
 
× 
 
 
 
 
PK blood sampling 24 
 
 
× 
× 
× 
× 
× 
× 
× 
× 
× 
 
× 
Confirmation of Cycle 2 25 
 
 
 
 
× 
 
 
 
 
 
 
 
 
Confirmation of Cycle 3 26 
 
 
 
 
 
 
 
× 
 
 
 
 
 
Leave study ward 
 
 
 
 
 
 
 
 
 
 
× 
 
× 
Telephone follow-up 
 
 
 
 
 
 
 
 
 
 
 
× 
 
Adverse Events 27 
× 
Abbisko Therapeutics Confidential Page 33 of 55 
 
 

ABSK061-102 Version No. 1.0 Version Date April 7, 2025 
 
 
Study Procedures 
Screening 1 
Baseline 
Study Period Period 1 2 
Study Period Period 2 3 
Study Period Period 3 4 
Follow-up 5 
Early 
Withdrawal 
6 
D-14 ~D-2 
D-1 
D1 
D2 
D3 
D4 
D5 
D6 
D7 
D8 
D9 
D14 (+ 3 days) 
Prior and concomitant medications 28 
× 
Instructions: 
1. 
Screening: all assessments at screening should be completed within 14 days prior to the first dose of investigational product. If screening cannot be completed 
on time, the sponsor should be contacted to determine if the screening process performed prior to dosing is repeated. All screening examinations must be completed at this 
site. If a laboratory value at screening does not meet the participant selection criteria, only up to one retest that is judged by the investigator to be required during the 
screening period is allowed. If the retest value still does not match, the participant should be excluded.  
2. 
Cycle 1 of the study period: including the administration on Day 1 of Cycle 1 (D1) and the washout from D1 to D3. Participants should be admitted to the 
clinical study ward of the study site on the day prior to dosing (i.e., D-1), eat uniformly, and undergo relevant visit examinations.  
3. 
Period 2 of the study period: subjects who complete the relevant visit examinations on Day 3 of Cycle 1 (D3) and are judged as eligible by the investigator will 
conduct the study in Period 2, which includes dosing on D4 and washout from D4 to D6. Participants cannot leave the clinical study ward of the study site during the trial.  
4. 
Cycle 3 of the study period: subjects who complete the relevant visit examinations on Day 3 of Cycle 2 (D6) and are judged as eligible by the investigator will 
conduct the study in Cycle 3, which includes dosing on D7 and washout from D7 to D9. Participants cannot leave the clinical study ward of the study site during the trial.  
5. 
Should be taken last time Participants were contacted by telephone follow-up 7 days (+ 3 days) after ABSK061 to collect information on adverse events and 
concomitant medications.  
6. 
Early withdrawal applies to participants who have received at least one dose of ABSK061 and will no longer be followed for safety.  
7. 
Demographic data will include gender, ethnicity, and date of birth of the participant.  
8. 
Medical history inquiry: including past medical history and treatment history, smoking history, alcohol consumption history, drug allergy history, food allergy 
history, concomitant diseases and treatment. The inquiries are detailed in Protocol 8.3.1 Demographics and Disease History.  
9. 
Vital signs included ear temperature, sitting blood pressure, respiratory rate, and pulse rate. Vital signs are recommended after the participant has rested quietly 
for at least 5 minutes. Vital signs in each period should be measured at 1 hour (± 1 hour) pre-dose, 2 hours (± 1 hour) post-dose, 6 hours (± 1 hour) post-dose, 24 hours (± 
1 hour) post-dose, 48 hours (± 1 hour) post-dose, and at the Early Withdrawal Visit. Vital signs should be measured before or after at least a 20-minute interval after PK 
blood sampling. Additional vital sign testing may be added during each study at the discretion of the investigator. If the vital signs test results at screening are not within 
the normal range, they may be repeated once, and if they are still not within the normal range, the screening fails; participants who have been assigned a randomization 
number may be retested once if the vital signs test results prior to the first dose on D1 of Cycle 1 are not within the normal range or drop out if they are still not within the 
normal range and are judged by the investigator to be clinically significant.  
10. Physical examination: a complete physical examination is required at screening or baseline, and only a general physical examination will be performed during 
subsequent studies. A complete physical examination included mucocutaneous, lymph nodes, head, neck, chest, abdomen, spine, extremities, and nervous system. General 
physical examination, which may include head and neck, chest and abdomen, will be determined by the investigator as clinically indicated.  
Abbisko Therapeutics Confidential Page 33 of 55 
 
 

ABSK061-102 Version No. 1.0 Version Date April 7, 2025 
 
 
11. Height and weight: collected at Screening or Baseline only. Investigators may perform more frequent tests if clinically indicated.  
12. Hematology: including red blood cell count (RBC), hemoglobin (HGB), hematocrit (HCT) and total platelet count (PLT), white blood cell count (WBC) with 
differential and proportion (including neutrophil percentage and absolute neutrophil percentage, lymphocyte percentage and absolute lymphocyte count, monocyte 
percentage and absolute monocyte count, eosinophil percentage and absolute eosinophil percentage, basophil percentage and absolute basophil percentage). If hematology 
at screening is performed within 7 days prior to the first dose, hematology will not be performed separately at baseline on D-1.  
13. Urinalysis: including specific gravity, glucose, protein, ketones, occult blood, and red blood cells. Participants with significant clinical findings should be further 
evaluated. If urinalysis at screening is performed within 7 days prior to the first dose, urinalysis will not be performed separately at baseline on D-1.  
14. Blood chemistry: includes total bilirubin, direct bilirubin, total protein, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline 
phosphatase (ALP), glutamyl transpeptidase (GGT), lactate dehydrogenase, glucose, urea, creatinine, total cholesterol, triglycerides, potassium, sodium, chloride, calcium, 
phosphorus, magnesium, carbon dioxide. In the event of ≥ CTCAE Grade 2 transaminase elevations during the trial, more frequent liver function tests (at least twice 
weekly) will be required until recovery to Grade 1 or baseline. Additional laboratory tests may be performed if clinically indicated. If blood chemistry at screening is 
performed within 7 days prior to the first dose, blood chemistry will not be performed separately at baseline on D-1.  
15. Coagulation: includes prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), plasma fibrinogen (Fbg), and 
thrombin time (TT). If coagulation at screening is performed within 7 days prior to the first dose, coagulation tests will no longer be performed separately at baseline on 
D-1.  
16. Virology: including five tests for hepatitis B virus (HBV): hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B e antigen 
(HBeAg), hepatitis B e antibody (HBeAb), and hepatitis B core antibody (HBcAb); treponema pallidum antibody, hepatitis C virus antibody (HCV-Ab), human 
immunodeficiency virus antibody. If virology at screening is performed within 28 days prior to the first dose, virology will no longer be performed separately at Screening 
and Baseline.  
17. Chest X-ray (anteroposterior) will be performed only once at screening or baseline and results within 3 months prior to signing the informed consent form are 
acceptable.  
18. Abdominal B-ultrasound (liver, gallbladder, pancreas, spleen, kidney) will be performed only once at screening or baseline. If abdominal B-ultrasound at 
screening is performed within 28 days prior to the first dose, abdominal B-ultrasound will not be performed separately at screening and baseline.  
19. 12-lead ECG: a 12-lead ECG will be performed once at screening and once at baseline on D-1. If the 12-lead ECG at screening is performed within 7 days prior 
to the first dose, 12-lead ECG will not be performed separately at D-1 baseline. A single 12-lead electrocardiogram was performed 1 hour (± 1 hour) before dosing on the 
day of dosing (D1, D4, D7) of each period, the day of confirming whether to enter the next cycle (D3, D6), the day of leaving the ward (D9), and early withdrawal. The 
12-lead ECG before dosing on the day of dosing in each period should be performed before PK blood sampling, and the remaining 12-lead ECGs should be performed at 
least 45 minutes apart if required after invasive tests (e.g., PK blood sampling, etc.). Additional ECGs may be performed by the investigator as clinically indicated. The 
12-lead ECG should include heart rate, RR interval, PR interval, QT interval, and calculation of QTcF. The specific examination requirements of 12-lead ECG are detailed 
in Protocol 8.3.4 12-lead ECG.  
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20. For female participants of childbearing potential, a blood pregnancy test is required at Screening, D-1 Baseline, and D9/Early Withdrawal. A blood pregnancy 
test is not required for women of non-childbearing potential. Women of non-childbearing potential were defined as postmenopausal (≥ 12 months postmenopausal) or had 
a documented bilateral tubal ligation, complete oophorectomy, or hysterectomy. If the blood pregnancy test at screening is performed within 2 days prior to the first dose, 
the blood pregnancy test will not be repeated at baseline on D-1.  
21. The drug screen included morphine, ketamine, methamphetamine, dimethylene dioxyamphetamine, and tetrahydrocannabinol acid.  
22. Ophthalmic Examination: participants were evaluated ophthalmologically by an ophthalmologist. Each ophthalmologic assessment should be performed by the 
same ophthalmologist whenever possible. Specific examination requirements are detailed in 8.3.7 Ophthalmic Examination.  
23. Taking ABSK061: the drug should be taken in a fasted state on the first day of Cycle 1, Cycle 2, and Cycle 3, respectively. Refer to Section 7.6 for details.  
24. The time windows for PK blood sample collection are detailed in Table 9 Part III PK sampling times.  
25. On Day 3 of Cycle 1 (D3), the investigator will comprehensively determine whether the participant enters the study in Period 2 based on the participant ’ s 
physical condition and relevant visit test results.  
26. On Day 3 of Cycle 2 (D6), the investigator will comprehensively determine whether the participant enters the study in Cycle 3 based on the participant ’ s 
physical condition and relevant visit test results.  
27. Adverse events will begin when the participant signs the informed consent form until 7 days after the last dose of ABSK061 (i.e., D14), as detailed in 8.3.13 Safety 
Reporting Period.  
28. Concomitant medication information was collected from the first dose of ABSK061 until 7 days after the last dose of ABSK061. Medications up to 14 days prior to the 
first dose of ABSK061 until the end of the first dose will be considered prior and will also be collected.  
 
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Sampling Schedule 
Table 7Part I PK Sampling Times 
Visit 
Sampling time (window) 
D1 
Early Withdrawal 1 
Pre-dose (-60 minutes) 
× 
× 
30 minutes (± 5 minutes) 
× 
1 hour (± 10 minutes) 
× 
1.5 hours (± 10 minutes) 
× 
2 hours (± 10 minutes) 
× 
4 hours (± 10 minutes) 
× 
6 hours (± 15 minutes) 
× 
10 hours (± 15 minutes) 
× 
24 hours (± 1 hour) 2 
× 
48 hours (± 1 hour) 3 
× 
 
Instructions: 
1. 
PK sampling for "early withdrawal" participants should be completed within 24 hours of investigator decision;  
2. 
The PK sampling point of a single dose of Part I at 24 h occurred on D2;  
3. 
The PK sampling point of a single dose of Part I at 48 h occurred on D3;  
 
 
 
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Table 8Part II PK Sampling Times 
Visit 
Sampling time (window) 
D1 
D2 
D3 
D4 
Early 
Withdrawal 1 
Pre-dose (-10 minutes) 
× 
× 
× 
× 
× 
30 minutes (± 5 minutes) 
× 
 
 
× 
1 hour (± 10 minutes) 
× 
 
 
× 
1.5 hours (± 10 minutes) 
× 
 
 
× 
2 hours (± 10 minutes) 
× 
 
 
× 
4 hours (± 10 minutes) 
× 
 
 
× 
6 hours (± 15 minutes) 
× 
 
 
× 
10 hours (± 15 minutes) 
× 
 
 
× 
24 hours (-10 minutes) 2 
 
 
 
× 
48 hours (-10 minutes) 2 
 
 
 
× 
 
Instructions: 
1. 
PK sampling for "early withdrawal" participants should be completed within 24 hours of investigator decision;  
2. 
Since there was no dosing schedule on D5 of the MAD study, PK blood sampling at 24 and 48 hours after the last dose on D4 had to be completed within the 
first 10 minutes of the 24 hour and 48 hour time point after the last dose. If dosing was completed at 8 AM on D4, the corresponding 24 and 48 hour PK sampling times 
were 7 AM on D5, respectively：50 -8: 00 and D6 7 AM：50 -8
：00。
 
 
 
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Table 9Part III PK Sampling Times 
Visit 
Sampling time (window) 
Cycle 1 
Cycle 2 
Cycle 3 
Early Withdrawal 
1 
D1 
D4 
D7 
Pre-dose (-60 minutes) 
× 
× 
× 
× 
30 minutes (± 5 minutes) 
× 
× 
× 
1 hour (± 10 minutes) 
× 
× 
× 
1.5 hours (± 10 minutes) 
× 
× 
× 
2 hours (± 10 minutes) 
× 
× 
× 
4 hours (± 10 minutes) 
× 
× 
× 
6 hours (± 15 minutes) 
× 
× 
× 
10 hours (± 15 minutes) 
× 
× 
× 
24 hours (± 1 hour) 2 
× 
× 
× 
48 hours (± 1 hour) 3 
× 
× 
× 
 
Instructions: 
1. 
PK sampling for "early withdrawal" participants should be completed within 24 hours of investigator decision;  
2. 
PK sampling points at 24 h in Cycle 1, Cycle 2 and Cycle 3 of Part III occurred on D2, D5, and D8, respectively;  
3. 
The 48 h PK sampling points of Part III Cycle 1, Cycle 2 and Cycle 3 occurred on D3, D6, and D9, respectively.  
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1 Study Background 
1.1 Overview of ABSK061 
ABSK061 is a new molecular entity developed by Shanghai Hezhu Biopharmaceutical 
Technology Co., Ltd. It is a selective and potent inhibitor of fibroblast growth factor receptor 
2/3 (FGFR2/3) and is effective orally. In vitro and in vivo pharmacology data showed potent 
and selective inhibition of FGFR2/3 by ABSK061 and demonstrated significant antitumor 
effects in FGFR2/3-dependent xenograft mouse models. The drug metabolism and 
pharmacokinetic profile of ABSK061 is favorable for oral administration, and the risk of drug-
drug interaction DDIs is expected to be small.  
Preclinical study data for ABSK061 support the clinical development of this 
investigational medicinal product. The toxicity profile of ABSK061 has been confirmed by 
preclinical safety assessments to support clinical investigation of the investigational product in 
different tumor types with FGFR2/3 mutations/fusions. Please refer to the Investigator ’ s 
Brochure for more information on preclinical studies.  
achondroplasia (ACH) is the most common dwarfism in humans, which belongs to 
autosomal dominant disease. Mutations in the FGFR3 gene are the main cause of the disease. 
In recent years, drug development strategies targeting the overactive FGFR3 receptor and 
downstream signaling have begun to evolve. ABSK061 will also be planned for the 
development of this pediatric indication.  
1.2 Preclinical Study Results 
ABSK061 was shown to be moderately to highly permeable in vitro, suggesting that it 
may be a substrate for efflux transporters. In pharmacokinetic studies in rats and dogs, 
ABSK061 was moderately cleared and the volume of distribution following intravenous 
administration was close to or slightly higher than the total volume of body fluids. The absolute 
bioavailability was 50%, 72% and 72% after a single oral dose in male rats, 72% in female rats, 
and dogs, respectively. The elimination half-life was 1.2 h in rats and 0.9 h in dogs; cmax and 
AUClast increased proportionally with increasing dose. Pharmacokinetic and toxicokinetic 
results of repeated dosing showed no accumulation of ABSK061 in rats and dogs at any dose 
level for 28 consecutive days.  
After administration of ABSK061, its oxidative metabolites could be detected, and there 
were no species differences in its major metabolic pathways. ABSK061 is mainly metabolized 
by CYP3A4 enzymes. ABSK061 showed an extensive metabolic profile in rats following oral 
administration. The major metabolic pathways of ABSK061 were oxidative dehydrogenation, 
dealkylation, and sulfation.  
ABSK061 showed weak inhibitory effects on CYP2C8, CYP2C9, CYP2C19 and 
moderate inhibition on CYP3A4 (based on midazolam) and CYP3A4 (based on testosterone); 
no induction of cytochrome P450 enzymes such as CYP1A2, CYP2B6 and CYP3A4 was 
demonstrated.  
Other preclinical study results are detailed in the ABSK061 Investigator ’ s Brochure V3.0.  
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1.3 Clinical Study Results 
ABSK061 is currently conducting "An Open-Label Phase 1 Study to Evaluate the Safety, 
tolerability, and Pharmacokinetics of ABSK061 in Patients with Advanced Solid 
Tumors"(ABSK061-101). The study consists of a 28-day treatment cycle consisting of a dose 
escalation phase and an expansion phase to evaluate the safety and tolerability of the drug, as 
well as preliminary anti-tumor activity. A total of 198 participants are expected to be recruited.  
Safety Data 
As of 27 September 2024, ABSK061-101 has conducted dose escalation studies in a total 
of 9 cohorts of 5 mg BID/10 mg BID/20 mg BID/35 mg BID/50 mg BID/75 mg BID/100 mg 
BID/150 mg QD/200 mg QD, with a total of 47 adult patients with advanced solid tumors 
enrolled in the study. A total of 47 (47/47, 100.0%) patients experienced at least 1 TEAE, 
including 4 (4/47, 8.5%) deaths due to TEAEs (all due to disease progression and unrelated to 
study drug). Drug-related TEAEs of CT CAE Grade ≥ 3 were reported in 6 (6/47, 12.8%) 
patients and drug-related serious TEAEs were reported in 1 (1/47, 2.1%) patient. Drug-related 
TEAEs leading to treatment interruption were reported in 16 (16/47, 34%) patients, drug-
related TEAEs leading to dose reduction were reported in 8 (8/47, 17%) patients, and no drug-
related TEAEs led to treatment discontinuation. TEAEs leading to death were reported in 4 
(4/47, 8.5%) patients, none of which were due to drug-related TEAEs.  
As of 27 September 2024,Treatment-related adverse events (TRAEs) with frequency ≥ 
10% included aspartate aminotransferase increased (16/47, 34.0%), alanine aminotransferase 
increased (15/47, 31.9%), anemia (13/47, 27.7%), hyperphosphatemia (12/47, 25.5%), diarrhea 
(11/47, 
23.4%), 
blood 
alkaline 
phosphatase 
increased 
(9/47, 
19.1%), 
hypoalbuminemia/alopecia/rash (7/47, 14.9%), dry mouth/hypokalemia (6/47, 12.8%), and 
blood 
creatinine 
increased/blood 
lactate 
dehydrogenase 
increased/platelet 
count 
decreased/retinal pigment epithelium detachment/dry eye (5/47, 10.6%). Most of these hepatic 
function-related adverse events were Grade 1-2 and transiently increased, which may be more 
closely related to their own diseases. The potential for this product to cause severe 
hepatotoxicity in patients is low. This product had some effect on the patient's blood 
phosphorus laboratory values, but most were transient and did not require dose interruption. 
Retinal toxicity is highly relevant to individual patients, but safety is manageable, no serious 
events have occurred, and its incidence is similar to historical data for similar drugs of the same 
class.  
The above study results showed that ABSK061 was generally safe and well tolerated in 
patients with low safety risk, supporting further clinical studies.  
Efficacy data 
As of 27 September 2024, a total of 6 partial responses (PRs) were observed in 23 patients 
with FGFR2 fusion/amplification/mutation, FGFR3 fusion/mutation, with an objective 
response rate of 26.1%, of which 4 were confirmed partial responses with a confirmed objective 
response rate of 17.4%; eight stable disease (SD) and nine progressive disease (PD) were 
observed with a disease control rate of 60.9%.  
Clinical Pharmacology 
As of June 30, 2024, in the ongoing first-in-human study of ABSK061-101 in China and 
the United States, intensive PK sampling was performed in 41 patients, including 5 mg BID, 
10 mg BID, 20 mg BID, 35 mg BID, 50 mg BID, 75 mg BID, 100 mg BID, and 150 mg QD, 
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of which 33 patients had evaluable PK data: ABSK061 was rapidly absorbed after a single dose, 
with a median tmax interval of 0.5 to 1.5 hours across dose groups; the mean terminal t1/2 
values for each dose group ranged from 2.9 to 6.8 hours. The apparent volume of distribution 
of ABSK061 after oral administration ranged from 93 to 136 L, suggesting extensive 
distribution in vivo. No significant accumulation was observed after multiple doses, with mean 
accumulation ratios of 1.2 to 2.2 for AUC across dose groups following QD or BID dosing. 
The inter-individual differences among ABSK061 participants were small, with coefficients of 
variation of 20% to 43% and 5% to 42% for Cmax, ss and AUCtau, ss, respectively, after 
multiple doses.  
1.4 Risk/Benefit Assessment 
ABSK061 is a potent and selective inhibitor of the FGFR2/3 receptor. As of 27 SEP 2024, 
there were no important identified risks during the clinical development program. Important 
potential risks include tongue, bone, eye, thymus, and pancreatic abnormalities.  
Based on data from ABSK061-101,Drug-related TEAEs with frequency ≥ 10% were: 
aspartate aminotransferase increased (16/47, 34.0%), alanine aminotransferase increased 
(15/47, 31.9%), anemia (13/47, 27.7%), hyperphosphatemia (12/47, 25.5%), diarrhea (11/47, 
23.4%), blood alkaline phosphatase increased (9/47, 19.1%), hypoalbuminemia (7/47, 14.9%), 
alopecia (7/47, 14.9%), rash (7/47, 14.9%), dry mouth (6/47, 12.8%), hypokalaemia (6/47, 
12.8%), blood creatinine increased(5/47, 10.6%), blood lactate dehydrogenase increased (5/47, 
10.6%), platelet count decreased (5/47, 10.6%), detachment of retinal pigment epithelium (5/47, 
10.6%), dry eye (5/47, 10.6%). Since the drug is still being studied in Phase 1, close attention 
should be paid to possible adverse reactions. In order to reduce the overall risk of participants, 
an appropriate subject population was included through the inclusion/exclusion criteria, close 
monitoring measures were established during the trial, the effects of the drug on liver, kidney 
and gastrointestinal systems were closely observed, a strict pharmacovigilance system was 
established to effectively handle adverse events, and the safety and rights of participants were 
safeguarded.  
Healthy participants were recruited in this study to evaluate the PK profile of a single oral 
dose of ABSK061 microchip under fasting conditions and the effect of administration with soft 
food on the PK of ABSK061. Therefore, participation in this study will not bring clinical 
benefit to healthy participants. Further information on known and expected benefits, risks, 
SAEs, and reasonably expected AEs of ABSK061 can be found in the Investigator ’ s Brochure.  
2 Study Objectives 
2.1 Primary Objective 
• 
Part I: to evaluate the pharmacokinetic (PK) characteristics and safety of a single oral 
dose of ABSK061 microchip in healthy adult participants;  
• 
Part II: to evaluate the safety, tolerability and PK profile of multiple oral doses of 
ABSK061 microchips in healthy adult participants;  
• 
Part III: to evaluate the effect of ABSK061 microt 5 mg administered with soft food on 
the PK profile of ABSK061.  
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2.2 Secondary Objective 
• To assess the safety of ABSK061 microchips taken with soft food in healthy adult 
participants;  
• To explore the dose-exposure proportionality of 1 to 35 mg of ABSK061 
microchips in healthy adult participants.  
3 Study Endpoints 
3.1 Primary endpoint 
• 
Safety and tolerability evaluation indicators, including adverse events (AEs), serious 
adverse events (SAEs), vital signs, physical examinations, electrocardiograms, 
laboratory tests, ophthalmic examinations, etc.;  
• 
Main PK parameters of ABSK061 micro-tablets, including maximum observed 
concentration (Cmax), time to reach maximum observed concentration (tmax), area under 
the plasma concentration-time curve (AUClast and AUC0- ∞), maximum observed 
concentration during the steady-state dosing interval (Cmax, ss), minimum observed 
concentration during the steady-state dosing interval (Cmin, ss), area under the 
concentration-time curve at steady-state dosing interval (AUCtau, ss), and accumulation 
index (AR); 
• 
PK parameters, mainly including Cmax, AUC0- ∞, and AUClast, following a single dose 
of ABSK061 microt administration with or without soft food.  
3.2 Secondary endpoints 
• 
Secondary PK parameters of ABSK061: including but not limited to terminal elimination 
half-life (t1/2), apparent clearance (CL/F), and apparent volume of distribution (Vz/F).  
4 Study Design 
This study is divided into three parts: Part I, II and III. Part I is a single dose study and 
Part II is a multiple dose escalation (MAD) study with the primary objective to evaluate the 
tolerability, safety and PK profile of single or multiple ABSK061 microchips in healthy adult 
participants. Part III is a three-period, three-sequence crossover study with the primary 
objective to evaluate the effect of ABSK061 microchips taken with soft food on PK. Part II and 
Part III will be performed in parallel after completion of Part I.  
4.1 Overall design 
Part I plans to include 18 participants randomized 1: 1: 1 to Sequences A to C for A 
parallel single-dose trial. Participants in Sequences A, B, C will receive 1 mg, 10 mg, and 35 
mg ABSK061 microchips on the first day (D1), respectively, followed by A 7-day safety 
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observation period. The preset dosing of Parts II and III may be adjusted based on the results 
of Part I trials.  
Part II plans to include 12 participants, prespecified for MAD trials in Sequences D, E. 
Participants in Sequence D will receive 5 mg ABSK061 microchips orally once daily from D1 
to D4, with a 14-day safety observation period after the end of dosing. If the dose escalation 
criteria are met (see Section 4.4 Dose Escalation Rules), the 20 mg multiple dose group of 
Sequence E will be conducted, with the same 4-day QD dosing and 14-day safety observation. 
The dose of Sequence E may be adjusted based on the results of Sequence D. Other doses may 
be explored based on the test results.  
The study design is shown in Figure 1, Part I & II Study Overall Trial Design.  
 
Figure 1 Overall Trial Design of Part I & II Study 
Part III plans to include 12 healthy participants randomized 1: 1: 1 to Sequence F, 
Sequence G, or Sequence H to receive three single doses of Treatment 1, Treatment 2, and 
Treatment 3. Original pure yogurt (hereinafter referred to as "yogurt", raw milk > 90%, the 
main ingredients include protein, fat, carbohydrate, sodium, calcium) and applesauce (the main 
ingredients include carbohydrate and sodium) will be used as two different soft foods to help 
swallow microchips. Treatment 1 was 5 mg ABSK061 microchip, Treatment 2 was 5 mg 
ABSK061 microchip taken with a spoon of yogurt (approximately 15 mL), and Treatment 3 
was 5 mg ABSK061 microchip taken with a spoon of applesauce (approximately 15 mL). 
Participants in Sequence F will receive Treatment 1, Treatment 2, and Treatment 3 under fasting 
conditions in the morning on Cycle 1 Day 1 (D1), Cycle 2 Day 1 (D4), and Cycle 3 Day 1 (D7), 
respectively; participants in Sequence G will receive Treatment 2, Treatment 3, and Treatment 
1 in the morning on D1, D4, and D7, respectively; participants in Sequence H will receive 
Treatment 3, Treatment 1, and Treatment 2 fasted in the morning on D1, D4, and D7, 
respectively. All participants were required to drink 180 mL of water immediately after taking 
the investigational drug or with food. A washout period of 3 days per cycle.  
The study design is shown in Figure 2, Part III Study Overall Trial Design.  
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Figure 2 Overall Trial Design of Part III Study 
Pre-dose and post-dose plasma samples were collected from all participants for 
concentration determination of ABSK061 and its potential high proportion of metabolites, if 
applicable, and PK assessments were performed.  
Drug safety will be assessed by recording adverse events, clinical laboratory tests, and 
follow-up of vital signs, etc.  
Whether or not a participant completing the current period of the study enters the next 
cycle of the study will be determined comprehensively by the investigator based on the 
participant's physical condition and relevant visit examination results. For participants who 
interrupt or permanently discontinue the study due to an adverse event or clinically significant 
laboratory abnormality, the frequency of visits will be determined comprehensively as required 
by the Testing Facility or as clinically indicated until the AE resolves or stabilizes, whichever 
occurs first.  
4.2 Scientific Rationale for Study Design 
ABSK061 is planned to be used to explore the treatment of ACH in the pediatric 
population. The formulation was changed from capsules in ABSK061-101 to microcapsulated 
microparticles given that the target population for treatment was children 3 to 12 years of age 
and the therapeutic dose was low. Pharmacokinetic experiments with single gavage doses of 
25 mg ABSK061 capsules and ABSK061-NX microt in Beagle dogs showed no significant 
difference in PK behavior between the two formulations, with mean Cmax and AUC0-inf of 
1510 ng/mL, 2490 ng ∙ h/mL (ABSK061 capsules), and 1300 ng/mL, 2460 ng ∙ h/mL 
(ABSK061-NX microt), respectively. In ABSK061-101, there was a linear relationship 
between drug exposure and dose over a single dose of 35 mg. The effective dose of ABSK061 
for ACH is expected to be below the dose-linear range of this investigational drug, where a 
dose range of 1 mg to 20 mg may cover the majority of the ACH pediatric population. In order 
to better understand the drug exposure of ABSK061 at low doses and the pharmacokinetic 
characteristics of microchips, referring to the Technical Guidelines for Clinical 
Pharmacokinetic Studies of Chemical Drugs issued by the Center for Drug Evaluation of the 
National Medical Products Administration in March 2005, Part I of this study plans to conduct 
single-dose pharmacokinetic studies at three doses of 1 mg, 10 mg and 35 mg, and multiple 
dose escalation PK studies of 5 mg and 20 mg will be conducted in Part II to further explore 
the safety and tolerability of the study drug.  
Based on the ABSK061-101 study, no Grade ≥ 2 drug-related adverse events were 
reported in any of the 6 patients in the 5 to 35 mg BID dose groups, and the three dose groups 
(1, 10, 35 mg) of a single dose of Part I will be conducted in parallel with a 7-day safety 
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observation.  
The Part II Multiple Dose Escalation (MAD) study will evaluate the safety and tolerability 
of ABSK061 at this dose by conducting repeat dose trials of 5 mg and 20 mg successively 
based on the results of the single dose study. The placebo group will not be included in this 
study. Since most ABSK061-related TEAEs in ABSK061-101 are abnormalities such as 
laboratory tests and ophthalmic examinations, relevant monitoring items have been included 
in this study as the primary and objective evaluation indicators of safety, and whether the 
placebo group is set up will not have an impact on objective results such as laboratory 
parameters and PK. The trial was small in size and limited in sample size, and the addition of 
placebo significantly reduced the efficiency of the trial. Based on the half-life (median 5.4 h in 
adult oncology patients) and dosing frequency (QD) of the study drug, it can be stable after 
approximately 3.3 consecutive days of dosing, so it is proposed to test steady-state PK after 4 
consecutive days of dosing in this MAD trial. Finally, the safety observation period for this 
MAD study is proposed to be 14 days due to the short half-life of the investigational drug, 
which can be completely eluted from the body within 3 days.  
The PK of 5 mg ABSK061 was performed in Part III and the effect on the PK of the 
investigational drug at this dose when the microchip was taken with soft food, since dysphagia 
may still be present in young children, and 5 mg fell within the effective dose interval for 
children with ACH at that age based on the estimated effective dose. Common pure yogurt and 
applesauce 2,3 will be used in this study as soft foods to help swallow. Participants in the 
control group took the tablets directly with 180 mL of water, and participants in the test group 
were required to take 180 mL of water immediately after helping swallow the tablets with 
yogurt or applesauce to evaluate the effect of a soft meal on PK. A washout period of 3 days 
(more than 7 half-lives) was set between the two doses of the participants, minimizing the 
potential carryover of the study drug in the previous cycle. The last blood sampling point 48 h 
after administration also covers 7 half-lives, which can ensure the AUC0- ∞ of the extrapolated 
drug.  
4.3 Rationale for Dose Selection 
The doses of ABSK061 in this study were selected as single doses at 1 mg, 10 mg, and 35 
mg, multiple dose escalations at 5 mg and 20 mg, and the effect of soft food at 5 mg on PK 
based on the following reasons: 
a. Based on data from Study ABSK061-101, doses of 35 mg and below were 
safe and well tolerated in patient studies: a total of one participant experienced 
treatment-related TEAEs (sinus bradycardia, electrocardiogram T-wave abnormality, 
constipation, proteinuria, all of which were CT CA E Grade 1 in the 10 mg BID dose 
group); there were no events of drug dose reduction or discontinuation due to any 
treatment-related TEAEs.  
b. The effective dose of ABSK061 for the treatment of ACH is expected to be 
0.1 to 0.5 mg/kg, whereas the median weight of children with ACH aged 3 to 12 years 
is 12 to 31 kg4. For the target population with ACH, doses ranging from 1 to 35 mg 
are potential therapeutic doses for children with ACH.  
c. Given that the PK results in ABSK061-101 show an accumulation index of 
approximately 2 after repeated dosing of the study drug, single doses (10 mg and 35 
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mg) of the high dose will be initiated in this study and the Part II dose escalation study 
will be conducted after the end of the Part I safety observation period, and PK and 
safety data from Part I can support systemic exposure of 5 mg/20 mg in subsequent 
multiple dose groups.  
4.4 Dose Escalation Rules 
The prespecified starting dose in Part II and 5 mg in Part III will be tested in Part II and 
III by the investigator and the sponsor after adequate assessment of safety data and available 
PK data for all participants in Part I.  
In the Part II multiple dose escalation PK study, interruption of dose escalation will be 
considered if any of the following occurs in the first dose group (Sequence D). The investigator 
and sponsor will decide to continue escalation to a preset dose or an intermediate dose (E.g., a 
dose lower than the preset dose, such as 10 mg or 15 mg) based on safety data and PK data 
from Sequence D (Sequence E) if the following does not occur: 
1. Grade 3 adverse events assessed by the investigator as at least possibly related 
to ABSK061 in ≥ 2 participants 
2. Grade 4 adverse events assessed by the investigator as at least possibly related 
to ABSK061 in ≥ 1 participant 
3. Serious adverse events assessed by the investigator as at least possibly related 
to ABSK061 in ≥ 1 participant 
If any of the above occurred in the second dose group (Sequence E), the investigator 
discussed with the Sponsor whether to explore a lower dose based on available safety and PK 
data.  
5 Study Population 
5.1 Study Sample Size 
Part I: 18 healthy participants (6 per sequence) were enrolled;  
Part II: enrollment of 12 healthy participants (6 per sequence);  
Part III: twelve healthy participants (4/sequence) were enrolled.  
5.2 Participant Selection Criteria 
5.2.1 Inclusion Criteria 
1) Gender: male or female participants, both male and female;  
2) Age: 18 to 45 years (including 18 and 45 years);  
3) Weight: male participants weigh ≥ 50.0 kg, female participants weigh ≥ 45.0 kg, and body 
mass index is in the range of 19.0-26.0 kg/m2 (including cut-off value), and body mass 
index (BMI) = weight (kg)/height 2 (m2);  
4) Able to understand and willing to comply with the study procedures, voluntarily 
participate in this clinical trial and sign the informed consent form before screening;  
5) Male or female participants of childbearing potential must agree to use effective methods 
of contraception during the study and for 6 months after the last dose of investigational 
product (see Section 5.5 Pregnancy Restrictions for details) and that male participants do 
not donate sperm during this period; female participants do not donate eggs during this 
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period and must be non-pregnant, non-lactating female participants, defined as women 
after conception until termination of pregnancy, and human chorionic gonadotropin (β-
HCG) is within the normal range.  
5.2.2 Exclusion Criteria 
1) 
History of bacterial, fungal, parasitic, viral (excluding nasopharyngitis), mycobacterial 
infection, COVID19 infection within 30 days prior to screening;  
2) 
Prolongation of QT interval corrected for heart rate at screening, QTcF > 450 ms (Note: 
QTc interval corrected by Fridericia ’ s formula), or family history of long QT syndrome;  
3) 
Any of the following ophthalmic exclusion criteria: 
 
Current or past medical history of retinal pigment epithelial detachment 
(RPED)/central serous retinopathy (CSR) 
 
Previous laser therapy or intraocular injection for macular degeneration 
 
Current concomitant or past medical history of age-related macular degeneration 
 
Current concomitant or past medical history of retinal vein occlusion (RVO) 
 
Current concomitant or past medical history of retinal degenerative disease 
 
Diabetic retinopathy with macular edema 
 
Current concomitant or past medical history of any other clinically relevant retinal-
choroidal defect 
 
Any symptoms of acute ophthalmic disease (within 4 weeks prior to the first dose) or 
active progression 
 
Current concomitant keratopathy (eg, keratitis, corneal abrasion, or ulceration) or 
conjunctivitis 
4) 
Subjects with a history of motor system, neuropsychiatric system, endocrine system, 
blood circulation system, respiratory system, digestive system, urinary system, 
reproductive system abnormalities, etc., or existing diseases, which may affect the 
assessment of study results;  
5) 
Prior history of gastric or intestinal surgery, or surgery affecting drug absorption, 
distribution, metabolism, excretion (except for appendicitis surgery); or plan to undergo 
surgery during the study;  
6) 
Donation of blood or massive blood loss (≥ 400 mL) within 3 months prior to screening 
or during screening (except for female physiological period); those who have received 
blood transfusion or blood products within 2 months prior to screening;  
7) 
History of drug abuse or positive urine drug screen (morphine, tetrahydrocannabinol acid, 
methamphetamine, dimethyldioxyamphetamine, ketamine) within the past 5 years;  
8) 
Those who are allergic to drugs, environment or food or to ABSK061 micro-tablets or its 
excipients [microcrystalline cellulose, mannitol, croscarmellose sodium, colloidal silicon 
dioxide, magnesium stearate, film-coating premix (gastric soluble)]; those who are prone 
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to allergic symptoms such as rash and urticaria; for Part III: previously known allergy to 
yogurt and applesauce;  
9) 
Previous chronic consumption of excessive tea, coffee, or caffeinated beverages (defined 
as ingestion of more than 6 units of caffeine per day, 1 unit of caffeine equivalent to 177 
mL of coffee, 355 mL of tea, 355 mL of cola, or 85 grams of chocolate) or who cannot 
stop drinking any caffeinated beverage during the trial;  
10) Those who consumed more than 14 units of alcohol per week (1 unit = 360 mL of beer or 
45 mL of spirits containing 40% alcohol or 150 mL of wine), or were unable to abstain 
from alcohol during the trial, or had an alcohol breath test result > 0 mg/100 mL within 3 
months prior to signing the informed consent form;  
11) Smoking ≥ 5 cigarettes per day before signing the informed consent form; or cannot stop 
using any tobacco products during the trial;  
12) Those who have taken strong CYP3A4 inhibitors or inducers (including grapefruit juice, 
grapefruit hybrids, pomegranates, carambola, grapefruit, Seville oranges and fruit juices 
or other processed products within 14 days prior to screening and during the screening 
period, as detailed in Appendix 12.1 Strong CYP3A inducers and inhibitors);  
13) Those who have special requirements for diet and cannot comply with the unified diet; 
specific dietary requirements were: (i) only meals provided by the study site during 
hospitalization, and (ii) avoidance of strong CYP3A4 inhibitors or inducers during the 
study;  
14) Dysphagia, inability to take the investigational product orally;  
15) Lactose intolerance (those who have had milk diarrhea);  
16) Those who have used any prescription drugs, over-the-counter drugs, Chinese herbal 
medicines or health products within 14 days prior to the first dose or plan to use them 
during the study;  
17) Those who have received vaccines (including COVID19 vaccine) within 2 months prior 
to screening, or have planned vaccination throughout the study;  
18) Previous participation as a participant in any other ABSK061-related study and has taken 
any dosage form of ABSK061; those who have participated in other clinical trials and 
used other clinical investigational drugs or investigational devices within 3 months prior 
to screening or during screening, or who plan to participate in other clinical trials during 
this study, or who are not self-participating in clinical trials;  
19) Those with a history of needle sickness, blood sickness or intolerance to venipuncture, or 
difficulty in blood collection;  
20) Abnormal physical examination, hematology, blood chemistry, coagulation function, 
urinalysis, 12-lead electrocardiogram, chest X-ray (anteroposterior), abdominal B-
ultrasound, ophthalmic examination and judged by the investigator to be clinically 
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significant;  
21) Vital signs outside the normal range, and the retest is still outside the normal range.  
22) Abnormal serum hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, 
human immunodeficiency virus (HIV) antibody, treponema pallidum antibody test and 
judged by the investigator to be clinically significant;  
23) Personnel involved in the design or implementation of this study project and their 
immediate family members (e.g., employees of Shanghai Hezhui Biopharmaceutical 
Technology Co., Ltd., CRO employees, and employees of the study site);  
24) Any other factor that, in the opinion of the investigator, is not suitable for enrollment, may 
affect the compliance of the participant with the protocol, affect the interpretation of the 
study results, or increase the participant's safety risk, or the participant withdraws from 
the trial for his/her own reasons.  
5.3 Exercise and dietary restrictions 
Participants were required to comply with the following restrictions on exercise and diet 
throughout the study.  
5.3.1 Dietary restriction 
Participants consumed only meals provided by the study site during their hospitalization.  
All participants should be fasted for at least 10 hours during the night before study drug 
administration, drinking water (except water for drug administration) is prohibited from 1 hour 
before dosing to 1 hour after dosing, and no food is allowed for 4 hours after dosing. 
Participants received a standardized diet throughout the study.  
5.3.2 Motor restriction 
Participants should refrain from strenuous physical activity from one week prior to the 
first dose and throughout the study.  
5.4 Restrictions on beverages, caffeine, alcohol and tobacco 
Beverages: grapefruit, pomegranate, carambola, grapefruit, Seville oranges, Seville 
orange jam, or beverages and products containing these fruits will be prohibited within 14 days 
prior to the first dose and throughout the study.  
Alcohol: participants are prohibited from heavy alcohol consumption (i.e., greater than 14 
units of alcohol per week, approximately 360 mL of beer per unit of 1 unit of alcohol or 45 mL 
of spirits containing 40% alcohol or 150 mL of wine) within 3 months prior to screening and 
throughout the study, and during admission to the study ward.  
Caffeine/Methylxanthine: participants are prohibited from consuming foods and 
beverages containing caffeine or methylxanthine, such as coffee, tea, cola, energy drinks, and 
chocolate, from the time of signing the informed consent form until the end of the study 
(overdose is defined as intake of more than 6 units of caffeine per day, one unit of caffeine 
equivalent to 177 mL of coffee, 355 mL of tea, 355 mL of cola, or 85 grams of chocolate).  
Smoking: smoking or use of nicotine-containing products is prohibited from the time of 
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signing the informed consent form until the end of the study.  
5.5 Pregnancy restriction 
No studies have been conducted on possible side effects of ABSK061 in fetuses or infants. 
Participants may not participate in this study if they are preparing for pregnancy. Male or 
female participants of childbearing potential who decide to participate in this study must agree 
to use appropriate contraception from the time of signing the informed consent form until 6 
months after the last dose of the investigational product. Appropriate contraceptive measures 
include vasectomy (male sterilization), use of condoms, use of contraceptive membranes with 
spermicidal gel (Pure), contraceptive rings, and surgical birth control.  
If a participant ’ s partner becomes pregnant at any time during the study, or if the 
participant believes that her partner may become pregnant, the study doctor must be notified 
immediately.  
6 
Investigational Medicinal Products, Medication History and 
Concomitant Medications 
6.1 Physical Properties of Investigational Product 
The chemical name of this compound (ABSK061-NX) 3- (2,6-dichloro-3,5-
dimethoxyphenyl) -1-methyl-7- (1- (2-morpholinethyl) -1H-pyrazol-4-yl) -1,6-naphthyridin-2 
(1H) -one is the free base form of ABSK061.  
The formulations provided in this study were ABSK061 capsules in the strengths of 0.2 
mg/capsule and 5 mg/capsule, the 0.2 mg strength capsule contained 4 ABSK061 micro-tablets 
containing 0.05 mg active ingredient, and the 5-mg capsule contained 10 ABSK061 micro-
tablets containing 0.5 mg active ingredient. Each tablet contains the following inactive 
pharmaceutical excipients: microcrystalline cellulose, mannitol, croscarmellose sodium, 
colloidal silicon dioxide, magnesium stearate, film-coating premix (gastric soluble, where the 
0.05 mg microt film-coating premix is pink and the 0.5 mg microt film-coating premix is white).  
6.2 Labeling of Investigational Product 
The label of the investigational product will include the sponsor name, protocol number, 
drug name, drug dosage form, drug batch number, dosage unit, dosage and administration, 
duration of use, storage conditions, etc., and indicate that the drug is "for clinical trial use only". 
The labeling of the investigational medicinal product will contain information that complies 
with applicable regulatory requirements. The investigational product may not be relabeled 
without prior approval from the sponsor.  
In addition, the labeling or labeling of the investigational product should be in accordance 
with local and national regulations and will not in any way carry any false or misleading 
statement and will not indicate that the investigational product is safe or effective for the 
purposes of the study.  
6.3 Packaging and Storage of Investigational Medicinal Products 
The shells used for the ABSK061 microt are empty hydroxypropylmethylcellulose 
capsules (Vcaps Plus 0 #, white opaque cap/white opaque body, Sprinkle). The packaging 
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materials used for microspheres in ABSK061 capsules are high-density polyethylene (HDPE) 
bottles for oral solid pharmaceutical use, polyolefin functional combination caps for oral solid 
pharmaceutical use, and high-density polyethylene desiccant tank (1 g/tank) for oral solid 
pharmaceutical use. Packed in 75 mL HDPE bottle in 30 capsules per bottle, 1 canister of 
desiccant.  
The investigational product should be stored in accordance with the relevant requirements 
in the drug label.  
6.4 Management, Dispensing and Recovery of Investigational Medicinal Products 
The investigator is responsible for the investigational product at the study site. The 
investigator should ensure that the investigational product is used in compliance with protocol 
requirements. The investigator may designate a pharmacist or other appropriate person to be 
responsible for drug management and dispensing. The warehousing information, inventory 
quantity, distribution, return to the sponsor (or destruction after approval by the sponsor) of the 
investigational product should be fully documented and kept at the study site. These records 
will be used to demonstrate that the participant has obtained sufficient investigational product 
from the sponsor to be administered at the dose specified in the protocol. Drug records will 
include date, quantity, batch/serial number, expiration time (if applicable), and participant 
number. Records will be reconciled by the sponsor or its designee at the time of monitoring, 
and the sponsor must be notified immediately if a dispensing error or record mismatch is found. 
All used and unused investigational product (s) should be retained at the study site until the 
monitor accountability is completed or the sponsor authorizes destruction. All unused or 
expired investigational products should be returned to the sponsor or its designated third party, 
or destroyed and documented with the authorization of the sponsor. The relevant procedures of 
drug application, distribution, storage, accountability and destruction are detailed in the 
Investigational Drug Management Manual.  
6.5 Prior Medications and Concomitant Therapies 
Medications that ended 14 days prior to the first dose of ABSK061 to the end before the 
first dose of ABSK061 were considered prior medications. Medications taken from the first 
dose of ABSK061 to 7 days after the last dose were considered concomitant medications in the 
single-dose PK study of Part I and the soft food co-administration study in Part III. In the MAD 
study of Part II, medications taken from the first dose of ABSK061 to 14 days after the last 
dose were considered concomitant medications. Any other medication other than the protocol 
is prohibited from 14 days prior to the first dose until the entire study unless an AE requiring 
treatment or other sudden illness (including viral respiratory tract infections such as COVID-
19) occurs. If treatment of an AE or other disease is required, the investigator is encouraged to 
discuss it with the sponsor or the clinical study doctor. Any medication considered necessary 
for the safety and health of the participant may be administered at the discretion of the 
investigator and documented in the study medical record. All medications (except study drug) 
and important non-drug therapies received by the participant during the study must be recorded.  
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7 Study Procedures 
7.1 Study flow 
Refer to Table 4 Part I study plan, Table 5 Part II study plan, and Table 6 Part III study 
plan for specific study procedures. Of these, the study schedule describes the contents and 
specific times of each study plan throughout the study flow, and the sampling schedule 
describes the time of PK sample collection. Participants may be asked by the investigator to 
perform additional safety assessments to determine the relationship between the occurrence or 
duration of the clinical event and the investigational product, as required by clinical practice.  
7.2 Participant Registration and Randomization 
Participants will be strictly screened and assessed by the investigator. Once the participant ’ 
s eligibility for participation in the clinical study is confirmed, the investigator or his/her 
designated study personnel will complete the participant registration form.  
After signing a written informed compassionate letter and completing the necessary 
screening assessments, participants in Parts I and III were assigned to different study sequences 
according to randomization codes and Part II participants entered different study sequences 
according to the enrollment number. If a participant withdraws from the study, his/her screening 
number, randomization number, or enrollment number will not be reused. No participant will 
be enrolled or initiated with the investigational product until the screening number is registered 
and assigned.  
Assignment of Screening Number 
The entire study will consist of three study parts, and participants who sign the informed 
consent form will be assigned a unique screening number in the format of "S + 3 digit sequential 
number" in the chronological order of signing the informed consent form. For example: 
screening number S001 represents the first informed consenting participant at the study site, 
screening number S002 represents the second informed consenting participant at the study site, 
and so on.  
Assignment of Enrollment Number 
Participants who are screened successfully in Part II will be sequentially assigned 
enrollment numbers in the order of screening numbers in the format of "2000 + 3 digits", e.g., 
enrollment number 2001 indicates the first participant who has successfully entered Part II 
according to the order of screening numbers, enrollment number 2002 indicates the second 
participant who has successfully been screened into Part II according to the order of screening 
numbers, and so on.  
Randomization Number Assignment 
Part I: participants screened successfully (i.e. those who meet the inclusion criteria and do 
not meet the exclusion criteria after screening) will be randomized in A 1: 1: 1 ratio to 
Sequences A, B, and C. According to the Randomization Plan and/or the Randomization 
Coding Form (provided by Shanghai Hezhui Biopharmaceutical Technology Co., Ltd.), 
participants will sequentially assign randomization numbers according to the order of screening 
numbers. Based on the setting of sample size in this protocol, the proposed range of 
randomization number is: 1001 ~ 1018.  
Part III: participants screened successfully (i.e. participants who meet the inclusion criteria 
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and do not meet the exclusion criteria after screening) will be randomized in a 1: 1: 1 ratio to 
Sequence F, Sequence G, or Sequence H. According to the Randomization Plan and/or the 
Randomization Coding Form (provided by Shanghai Hezhui Biopharmaceutical Technology 
Co., Ltd.), participants will sequentially assign randomization numbers according to the order 
of screening numbers. Based on the setting of sample size in this protocol, the proposed range 
of randomization number is: 3001-3012.  
Participant Replacement 
Participants who have been randomized to Part I and Part III but fail to receive the first 
dose for any reason will be replaced and the replacement participant will be consistent with the 
study sequence of the replaced participant. The random number of the replacement participant 
will be the random number of the replaced participant plus 100. For example, a participant with 
a random number of 1001 will be replaced with 1101, a participant with a random number of 
3002 will be replaced with 3102, and so on.  
Participants who have been assigned an enrollment number to Part II but fail to receive 
the first dose for any reason will be replaced and the replacement participant will be consistent 
with the study sequence of the replaced participant. The replacement participant enrollment 
number will be the replacement participant enrollment number plus 100. For example, a 
participant with an enrollment number of 2001 will be replaced with 2101, and so on.  
Participants who have been dosed are not allowed to be replaced.  
7.3 Blinding 
This study is an open-label study.  
7.4 Screening failure 
Participants who have signed informed consent but fail to start dosing for any reason will 
be considered screening failures. The reason for failure to start dosing will be entered in the 
Screening Inclusion Form and recorded on the eCRF as required by the eCRF completion 
guidelines.  
7.5 Investigational Product Assignment 
Part I: participants were screened to meet eligibility criteria and were randomized 1: 1: 1 
to receive A single microchip dose of 1 mg, 10 mg, and 35 mg of ABSK061 in Sequences A to 
C, respectively.  
Part II: participants in Sequence D received once daily oral administration of 5 mg 
ABSK061 microchips for 4 consecutive days; participants in Sequence E received once daily 
oral administration of 20 mg ABSK061 microchips for 4 consecutive days.  
Part III: after screening and meeting the eligibility criteria, participants were randomly 
assigned 1: 1: 1 to Sequences F, G, and H to receive Treatment 1 (5 mg ABSK061 microchip 
fasted), Treatment 2 (5 mg oral ABSK061 microchips sprinkled on a spoon of yogurt under 
fasting conditions), and Treatment 3 (5 mg ABSK061 microchip was sprinkled on a spoon of 
applesauce under fasted state). Wherein, participants in Sequence F will receive Treatment 1, 
Treatment 2, and Treatment 3 in the morning on D1 of Cycle 1 Day 1, D4 on Day 1 of Cycle 
2, and D7 on Day 1 of Cycle 3, respectively; participants in Sequence G will receive Treatment 
2, Treatment 3, and Treatment 1, respectively, on Cycle 1 Day 1 D1, Cycle 2 Day 1 D4, and 
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Cycle 3 Day 1 D7 in the morning; participants in Sequence H will receive Treatment 3, 
Treatment 1, and Treatment 2 in the morning on Cycle 1 Day 1 D1, Cycle 2 Day 1 D4, and 
Cycle 3 Day 1 D7, respectively.  
7.6 Investigational Product Administration 
The drug was administered under fasting conditions. All participants were fasted 
overnight for at least 10 hours before dosing, drinking water was prohibited from 1 hour before 
dosing to 1 hour after dosing, and no food was allowed for 4 hours after dosing. The 
investigational product must be swallowed completely and cannot be chewed. When the 
number of microchips is large, dosing may be divided into multiple doses, but participants must 
complete swallowing of all microchips at the prescribed dose within 3 minutes.  
After removal of the ABSK061 capsules, open the cap and pour out the corresponding 
number of microt: 5 0.2 mg capsules for 1 mg ABSK061, 10 microt for 5 mg ABSK061, 2 5 
mg capsules for 10 mg ABSK061, 4 5 mg capsules for 20 mg ABSK061, and 70 microt for 7 
5 mg 35 mg ABSK061.  
Part I & II: all participants received the corresponding number of microchips directly with 
180 mL of water.  
Part III: participants receiving Treatment 1 took 10 0.5 mg tablets directly with 180 mL 
of water; participants receiving Treatment 2 dispersed 10 0.5 mg tablets on 1 tablespoon of 
yogurt (approximately 15 mL) and swallowed together, followed by 180 mL of water 
immediately; participants receiving Treatment 3 sprinkled 10 0.5 mg tablets on 1 tablespoon 
of applesauce (approximately 15 mL) and swallowed them together, followed by 180 mL of 
water immediately.  
7.7 Study Duration 
Including screening period (and baseline period), trial period and safety observation 
period/follow-up period.  
Screening + Baseline: 14 days.  
Part I: the single dose PK study consisted of a single dose (1 day) and a safety observation 
period (7 days).  
Part II: the multiple-dose escalation PK study included multiple doses (4 days) and a 
safety observation period (14 days).  
Part III consists of three cycles (3 days per cycle for a total of 9 days) and a safety 
observation period (7 days). Whether or not a participant completing the current period of the 
study enters the next cycle of the study will be determined comprehensively by the investigator 
based on the participant's physical condition and relevant visit examination results.  
For participants who interrupt or permanently discontinue the study due to an adverse 
event or clinically significant laboratory abnormality, the frequency of visits will be determined 
comprehensively as required by the Testing Facility or as clinically indicated until the AE 
resolves or stabilizes, whichever occurs first.  
7.8 Study Compliance 
Dosing will be performed under the supervision of the investigator. After administration, 
the investigator must examine the oral cavity of the participant to ensure that the investigational 
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product can be swallowed completely and correctly.  
7.9 Dose Modification 
No dose modifications were allowed during this study.  
7.10 
Participants lost to follow-up 
A participant will be considered lost to follow-up if he/she fails to return for a visit 
examination multiple times at the scheduled visit time and the site is unable to contact the 
participant or the participant explicitly refuses to follow-up. The specific criteria for not being 
able to contact are: telephone calls twice daily (morning and afternoon), unconnected/hung 
up/shutdown/shutdown/empty for three consecutive days, which will be recorded as lost to 
follow-up, each time by the notifier.  
7.11 
Participant Withdrawal 
Participants may withdraw voluntarily from the trial at any time without giving reasons 
and without any penalty or discrimination. The investigator may also ask the participant to 
withdraw from the study based on the actual clinical situation of the participant. Reasons for 
discontinuation or withdrawal from the study may include: 
• Adverse events;  
• Death;  
• Protocol violation;  
• Lost to follow-up;  
• Withdrawal of consent by participants;  
• Pregnancy 
• Study termination by the sponsor;  
• Participants were considered unsuitable for participation in the study by the 
investigator.  
If a participant experiences vomiting within 2 hours of dosing, the investigator may 
determine whether the participant needs to withdraw from the study early based on the severity 
of vomiting.  
If a participant voluntarily withdraws from the study, an attempt should be made to contact 
the participant to determine the reason for discontinuation. For any reason, premature 
withdrawal should complete all study procedures and assessments required for "early 
withdrawal". All participants who interrupt the study due to an AE will be followed until the 
AE resolves or stabilizes, as detailed in 8.3.13 Safety Reporting Period.  
7.12 
Early termination of the study 
The investigator or sponsor may choose to terminate the study prematurely if he/she 
believes there is sufficient reasonable cause. The party discontinuing the study will provide 
written notice to the investigator or sponsor stating the reason for discontinuation of the study.  
7.12.1 Criteria for Study Suspension or Early Termination 
Criteria for study suspension or early termination include: 
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1. New information on the safety of the investigational product indicates a 
change in the pre-existing risk profile of the investigational medicinal product, 
resulting in an unacceptable risk to participants participating in the study.  
2. A serious GCP violation occurred that seriously affected the achievement of 
the primary study objectives or jeopardized the safety of participants.  
3. The sponsor may suspend or prematurely discontinue the study for reasons 
unrelated to the study process.  
7.12.2 Criteria for Site Suspension or Early Termination 
If a site (including the investigator) is found to be in serious violation of GCP, protocol, 
contractual agreements, or is unable to ensure the proper conduct of the study, the site may be 
suspended or prematurely terminated.  
7.12.3 Procedures for Suspension or Early Termination of the Study 
If the sponsor chooses to suspend or terminate the study itself or a study center, the sponsor 
will provide instructions for specific procedures for study suspension or early termination; 
during the suspension or termination of the study, applicable sites will follow this procedure 
for subsequent operations.  
7.13 
End of study 
A participant is considered to have completed the study if he/she has completed all visits 
to the study, including the last visit or last trial procedure shown in the flowchart. The end of 
study was defined as the completion of all procedures in the last visit or flowchart for the last 
participant (including safety telephone follow-up).  
8 Study Assessments 
8.1 Pharmacokinetic assessment 
8.1.1 PK blood sampling 
PK blood samples should be collected according to Table 7 Part I PK sampling times, 
Table 8 Part II PK sampling times, and Table 9 Part III PK sampling times, and plasma samples 
of all participants in this study before and after dosing to determine the concentrations of 
ABSK061 and its metabolites (if applicable) for PK assessment. The actual date and time of 
each sampling (24-hour clock) will be recorded. The consumables used for blood sample 
collection are provided in the Laboratory Manual.  
8.1.2 Sample analysis 
Approximately 2 mL of venous blood samples will be collected at each sampling time 
point to determine plasma concentrations of ABSK061 and its potential high proportion of 
metabolites, if applicable.  
8.1.3 Sample Handling, Storage and Shipment 
PK samples will be analyzed at a central laboratory and plasma sample processing, storage, 
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labeling, and shipping details will be referenced in a separate laboratory manual.  
8.1.4 PK Parameter Analysis 
The PK parameters of ABSK061 for each participant under different dosing conditions 
will be calculated and subjected to descriptive statistical analysis based on individual 
pharmacokinetic time-concentration profiles and actual sampling times.  
The following PK parameters will be reported. Additional PK parameters will be reported 
if needed.  
Table 10 PK parameters and their calculations 
 
Parameters Definition 
Single dose 
tmax 
Time to peak, i.e. the actual sampling time to reach the peak concentration 
Cmax 
Peak concentration, i.e. observed peak concentration 
tlast 
Actual time of last quantifiable observed concentration (non-BQL) 
AUClast 
Area under the ABSK061 plasma concentration-time curve from 0 to the last 
measurable (non-BQL) concentration time point (calculated using the 
Linear Up Log Down trapezoidal method) 
AUC0-∞ 
The area under the ABSK061 drug concentration-time curve from time 0 
to infinity was calculated as follows: AUC0- ∞ = AUClast + Clast/λz;  
Clast refers to the actual last measurable (non-BQL) plasma concentration 
of ABSK061.  
kel 
Terminal elimination rate constant, calculated by linear regression after 
logarithmic transformation from the end of the drug concentration-time 
curve.  
t1/2 
Apparent elimination half-life, calculated as follows: t1/2, λ = ln2/λz, 
CL/F 
Total apparent clearance of drug after single oral administration: CL/F = 
Dose/AUC0- ∞ 
Vz/F 
Apparent volume of distribution of the drug after single oral administration: 
Vz/F = Dose/(AUC0- ∞ · λz) 
Multiple 
dose 
tmax,ss 
Actual time of maximum observed concentration during the dosing interval 
at steady state 
Cmax,ss 
Maximum concentration during the dosing interval at steady state 
Cmin,ss 
Trough concentrations over the dosing interval at steady state 
AUCtau,ss 
Area of the concentration-time curve over the dosing interval at steady state 
ARAUC 
Accumulation index based on AUC calculation as follows: ARAUC = 
AUCtau, ss/AUCtau, sd 
ARCmax 
When AUC is not available, the accumulation index will be calculated as 
Cmax instead of AUC. The accumulation index based on Cmax was 
calculated as follows: ARcmax = Cmax, ss/Cmax, sd 
t1/2,eff 
Effective half-life, calculated as follows: t1/2, eff = Ln (2) * tau/Ln 
((AR/(AR-1))), where AR is ARAUC 
CLss/F 
CLss/F = Dose/AUCtau,ss 
8.2 Pharmacodynamic assessment 
This section does not apply to this study.  
8.3 Safety assessment 
The safety of ABSK061 will be evaluated during the trial by recording adverse events, 
laboratory tests, vital signs, electrocardiograms, and physical examinations. During the study, 
the symptoms and signs of the participants after administration should be closely observed. 
Adverse events or adverse drug reactions should be handled promptly and effectively to ensure 
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the safety and rights and interests of participants. The type, symptoms, time of onset, degree 
(or grade), symptomatic treatment and outcome of adverse events should be recorded, and then 
the adverse events should be analyzed, assessed and statistically analyzed.  
8.3.1 Demographic and Disease History 
Demographic and medical history information will be collected for all participants at the 
times indicated in Table 4 Part I study plan, Table 5 Part II study plan, and Table 6 Part III study 
plan. Demographic information will include participant gender, ethnicity, and date of birth.  
Participants will be carefully asked about past medical history and treatment information, 
food allergy, drug allergy, concomitant diseases and treatments, and smoking and alcohol 
consumption during the screening period. Past medical history and concomitant diseases 
should record the disease name, time of onset and drug use in detail; history of drug and food 
allergy should document drug or food name and allergy symptoms.  
8.3.2 Vital signs 
For each participant, vital signs including ear temperature, sitting blood pressure, 
respiratory rate, and pulse rate will be measured according to Table 4 Part I study plan, Table 
5 Part II study plan, and Table 6 Part III study plan. Vital signs are recommended after the 
participant has rested quietly for at least 5 minutes. Vital signs should be performed prior to 
PK blood sampling or at least 20 min apart after PK blood sampling. Additional vital sign 
testing may be added during each study at the discretion of the investigator. If the vital signs 
test results at screening are not within the normal range, they may be repeated once, and if they 
are still not within the normal range, the screening fails; participants who have been assigned 
a randomization number/enrollment number may be retested once if the vital signs test results 
before the first dose on D1 are not within the normal range, or drop out if they remain within 
the normal range and are judged by the investigator to be clinically significant.  
Normal Vital Sign Range: 
• 35.9 °C ≤ ear temperature ≤ 37.5 °C 
• 90 mmHg ≤ systolic blood pressure < 140 mmHg, 60 mmHg ≤ diastolic blood 
pressure < 90 mmHg 
• 12 beats/min ≤ respiratory rate ≤ 22 beats/min 
• 55 beats/min ≤ pulse rate ≤ 100 beats/min 
Additional vital sign assessments may be added at scheduled visit timepoints as clinically 
indicated. Additional orthostatic vital sign assessments should be performed for any AE 
associated with dizziness, an AE in which differences in body posture may cause symptoms. If 
an upright measurement is required, the participant should stand for at least 3 minutes first. If 
the participant feels unable to stand, only supine vital signs will be recorded.  
8.3.3 Physical examination, height and weight 
The physical examination, which includes a complete physical examination at screening 
and a general physical examination during the subsequent study, will be performed at the times 
indicated in Table 4 Part I study plan, Table 5 Part II study plan, and Table 6 Part III study plan. 
A complete physical examination including mucocutaneous, lymph nodes, head, neck, chest, 
abdomen, spine, extremities, and nervous system will be performed at screening. General 
physical examination, which may include head and neck, chest and abdomen, will be 
determined by the investigator as clinically indicated. Height and weight were collected only 
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during the screening examination period. Investigators may perform more frequent tests if 
clinically indicated.  
8.3.4 12-lead ECG 
The 12-lead ECG will be measured according to Table 4 Part I study plan, Table 5 Part II 
study plan, and Table 6 Part III study plan.  
A 12-lead ECG will be performed once at screening and once at baseline on D-1. If the 
12-lead ECG at screening is performed within 7 days prior to the first dose, 12-lead ECG will 
not be performed separately at baseline on D-1.  
The single-dose PK study of Part I will undergo a single 12-lead ECG 1 hour (± 1 hour) 
before dosing on the day of dosing (D1), the day of leaving the ward (D3), at the safety follow-
up visit, and early withdrawal.  
A total of 6 12-lead electrocardiograms were required on the day of dosing in the multiple 
dose escalation PK study of Part II. Serial 12-lead electrocardiograms were performed at 1 hour, 
30 minutes, and 15 minutes before dosing on the day of dosing (D1), and at 30 minutes, 1 hour, 
and 1.5 hours after dosing, with a window of 15 minutes before and after the selected time 
point. Participants in Part II should remain supine or semi-recumbent for at least 10 minutes 
prior to each ECG collection. Recordings were performed in triplicate at each time point, at 
least 1 minute apart, and ECG collection at that time point was completed within 10 minutes. 
ECG collection for all participants in Part II must be completed prior to PK sampling.  
Part III will perform a single 12-lead ECG 1 hour (± 1 hour) prior to dosing on the day of 
dosing (D1, D4, and D7) of each period, on the day of confirming whether to enter the next 
cycle (D3 and D6), on the day of leaving the ward (D9), and on the day of early withdrawal.  
The 12-lead ECG should include heart rate, RR interval, PR interval, QT interval, and 
calculation of QTcF. Additional ECGs may be performed by the investigator as clinically 
indicated.  
All ECGs are recommended after the participant has rested quietly for at least 5 minutes. 
Keep supine and awake during ECG collection. A 12-lead electrocardiogram prior to dosing on 
the day of dosing should be performed prior to PK blood sampling. In studies in Parts I and III, 
at least 45 minutes apart is required if the test is performed after an invasive test (e.g., PK blood 
sampling, etc.).  
All abnormal ECGs should be identified as clinically significant by the investigator or 
designee. The number of examinations may be increased for safety purposes. If a clinically 
significant abnormal ECG is found after enrollment, the investigator will determine whether 
the participant can continue the study and confirm whether it is recorded as an adverse event 
based on 8.3.8 Adverse Events.  
8.3.5 Blood pregnancy test 
For female participants of childbearing potential, blood pregnancy tests will be performed 
according to Table 4 Part I study plan, Table 5 Part II study plan, and Table 6 Part III study plan 
(if blood pregnancy test during the screening examination is performed within 2 days prior to 
the first dose, blood pregnancy test will not be repeated at baseline on D-1). Blood pregnancy 
tests are not required for women of non-childbearing potential, defined as postmenopausal (≥ 
12 months postmenopausal) or documented bilateral tubal ligation, complete oophorectomy, or 
hysterectomy.  
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8.3.6 Laboratory tests 
For each laboratory test, it should be performed according to Table 4 Part I study plan, 
Table 5 Part II study plan, and Table 6 Part III study plan and analytical testing should be 
completed at the study site. Additional laboratory tests may be performed if clinically indicated.  
Laboratory Tests 
Hematology: 
Red blood cell count (RBC), 
hemoglobin 
(HGB), 
hematocrit (HCT) and total 
platelet count (PLT), white 
blood cell count (WBC) with 
differential and proportion 
(including 
neutrophil 
percentage 
and 
absolute 
neutrophil 
count, 
lymphocyte percentage and 
absolute lymphocyte count, 
monocyte percentage and 
absolute monocyte count, 
eosinophil percentage and 
absolute 
eosinophil 
percentage, 
basophil 
percentage 
and 
absolute 
basophil 
percentage 
and 
absolute basophil count) 
Urinalysis: 
Specific gravity, glucose, 
protein, 
ketones, 
occult 
blood and erythrocytes 
Blood chemistry: 
Total bilirubin, direct 
bilirubin, total protein, 
albumin, 
alanine 
aminotransferase 
(ALT), 
aspartate 
aminotransferase 
(AST), 
alkaline 
phosphatase 
(ALP), 
glutamine 
transpeptidase (GGT), 
lactate dehydrogenase, 
glucose, 
urea, 
creatinine, 
total 
cholesterol, 
triglycerides, 
potassium, 
sodium, 
chloride, 
calcium, 
phosphorus, 
magnesium, 
carbon 
dioxide 
Infectious Disease 
Screening: 
Five tests for hepatitis B 
virus (HBV): hepatitis B 
surface antigen (HBsAg), 
hepatitis B surface antibody 
(HBsAb), hepatitis B e 
antigen (HBeAg), hepatitis 
B e antibody (HBeAb) and 
hepatitis B core antibody 
(HBcAb); 
treponema 
pallidum antibody, hepatitis 
C virus antibody (HCV-
Ab), 
human 
immunodeficiency 
virus 
antibody 
Coagulation: 
Prothrombin 
time 
(PT), 
international 
normalized 
ratio (INR), activated partial 
thromboplastin 
time 
(APTT), plasma fibrinogen 
(Fbg), and thrombin time 
(TT) 
Drug abuse screening: 
Morphine, 
ketamine, 
methamphetamine, 
dimethyldioxyamphetamine, 
and 
tetrahydrocannabinol 
acid 
Pregnancy test: 
Blood pregnancy 
Alcohol Screening: 
Alcohol breath test 
8.3.7 Ophthalmic examination 
Participants were evaluated ophthalmologically by an ophthalmologist as indicated in 
Table 4 Part I study plan, Table 5 Part II study plan, and Table 6 Part III study plan. Each 
ophthalmologic assessment should be performed by the same ophthalmologist whenever 
possible.  
The following assessments will be performed: 
 
Visual acuity assessments (best corrected), including near and far vision, were 
performed separately for each eye 
 
Slit lamp inspection according to local practice 
 
Intraocular pressure and ophthalmoscopy 
 
Optical coherence tomography (OCT) of the macular area of both eyes should be 
performed at each ophthalmic examination and should be performed once in the 
event of any clinical symptoms or signs suggestive of RPED. Sites should retain 
duplicate OCT scans. If OCTs are not included in local clinical practice, similar 
alternative diagnostic methods should be used to screen for RPED 
 
Add additional tests as clinically indicated as needed 
At any other time, participants will undergo a full ophthalmic assessment if abnormal 
visual symptoms or signs occur.  
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8.3.8 Adverse Events 
An adverse event (AE) is any untoward medical occurrence that occurs in a patient or 
clinical study participant that is temporally related to the study intervention. It is not necessarily 
causally related to the study intervention. Adverse events may include, but are not limited to, 
the following: 
1) worsening of the original (before entering the clinical trial) medical condition/disease 
(including symptoms, signs, laboratory abnormalities and/or increased frequency);  
2) Any new adverse medical condition (including symptoms, signs, newly diagnosed 
diseases);  
3) Abnormal and clinically significant laboratory test results (e.g., blood biochemistry, 
urinalysis) or other tests (e.g., radiological examination, electrocardiogram, vital signs), 
including those that worsen from baseline and are considered clinically significant according 
to the investigator's medical and scientific judgment.  
The following are not considered adverse events: 
Clinically significant laboratory variables or test abnormalities related to the underlying 
disease are not considered adverse events unless judged by the investigator to be more severe 
than expected.  
Abnormal Laboratory Findings: 
Not all abnormal laboratory results were consistent with adverse events. However, 
abnormal laboratory results must be reported as adverse events if any of the following criteria 
are met: 
 With symptoms;  
 Requires clinical intervention or further investigation or additional diagnostic 
tests;  
 Leading to drug dose modification or discontinuation of study intervention.  
If a clinically significant laboratory abnormality is not a sign of a disease or syndrome, 
the abnormal laboratory test itself should be recorded as an adverse event. If laboratory 
abnormalities can be described by more precise clinical terms according to standard definitions, 
clinical terms should be recorded as adverse events.  
8.3.9 Serious Adverse Events 
A serious adverse event (SAE) is an adverse event occurring at any dose that meets any 
of the following conditions, regardless of causality: 
• Leading to death.  
• Life-threatening. Life-threatening refers to an event in which the participant 
was immediately at risk of death at the time of the event, i.e., excluding an event that 
hypothetically might have caused death if the event was more severe.  
• Requires participant hospitalization or prolongation of hospitalization. A 
planned hospitalization and/or surgery prior to enrollment of a participant in the study 
will not be considered an adverse event provided there is no unexpected worsening 
during the study (e.g., surgery performed earlier than scheduled). Hospitalization for 
sociality and/or convenience without an untoward medical occurrence is not an 
adverse event.  
• Resulting in permanent or severe disability/incapacity.  
• Congenital anomaly/birth defect.  
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• Important medical event. Important medical events are those that may not 
result in death or be life-threatening or require hospitalization, but may jeopardize the 
participant or may require medical or surgical intervention to prevent the occurrence 
of any of the outcomes listed in the definition of an SAE, based on appropriate 
medical judgment, which are also considered SAEs. Such medical events include 
allergic bronchospasm requiring intensive treatment in the emergency room or at 
home, blood cachexia or convulsions that do not require hospitalization, or 
development of drug dependence or drug abuse.  
8.3.10 Suspected unexpected serious adverse reaction 
Suspected unexpected serious adverse reaction (SUSAR) refers to a suspected and 
unexpected serious adverse reaction in which the nature and severity of the clinical 
manifestation exceeds the available information such as the Investigator's Brochure of the 
investigational Product, the package insert of a marketed drug, or a summary of product 
characteristics.  
8.3.11 Criteria for Severity of Adverse Events 
The investigator will assess the severity of AEs according to the toxicity grades described 
in the Common Adverse Event Evaluation Criteria NCI-CT CA E 5.0. For AEs not listed in CT 
CA E 5.0, the following standard grades may be used: 
Grade 1: mild; asymptomatic or mild; clinical or diagnostic findings only; no treatment 
required.  
Grade 2: moderate; requires small, local, or noninvasive treatment; age-appropriate 
instrumental activities of daily living (ADL) limitation *.  
Grade 3: serious or medically significant but not immediately life-threatening; resulting 
in hospitalization or prolongation of hospitalization; disabling; self-Rational ADL Limited * *.  
Grade 4: life-threatening; urgent treatment is required.  
Grade 5: deaths related to AEs.  
* Instrumental ADLs refer to cooking, shopping for clothing, using the telephone, 
managing money, etc.  
* * Self-care ADL refers to bathing, dressing and undressing, eating, washing, taking 
medications, etc., and not bedridden.  
8.3.12 Criteria for Relationship between Adverse Events and Study Drug 
The investigator is obligated to make a medical judgment as to the causal relationship 
between each AE/SAE and the study intervention.  
Investigators should consider and investigate other possible etiologies, temporal 
associations, and use clinical judgment to determine causality. The investigator will determine 
the relationship to study drug using the following criteria: 
Definitely 
related: 
Events or laboratory abnormalities with a reasonable temporal relationship 
to drug intake; cannot be explained by disease or other drugs; reasonable response 
after discontinuation (pharmacology, pathology); events identified from a 
pharmacological or phenomenological perspective (i.e., objective and specific 
medical conditions or recognized pharmacological phenomena); rechallenge 
results (if necessary) passed.  
Probably 
related: 
Events or laboratory abnormalities with a reasonable temporal relationship 
to drug intake; not likely attributable to disease or other drugs; reasonable clinical 
response after discontinuation; rechallenge testing is not required.  
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Possibly 
related: 
Events or laboratory abnormalities with a reasonable temporal relationship 
to drug intake; it can also be explained by disease or other drugs; discontinuation 
information may be missing or equivocal.  
Unlikely 
related: 
Events or laboratory abnormalities that are unlikely (but not impossible) 
temporally related to drug intake; the disease or other medication may provide a 
reasonable explanation.  
Not related: 
The adverse event was not related to study drug. There is no or little 
likelihood that the study drug causes an adverse event; other conditions, including 
intercurrent illness, progression or presentation of the condition condition, or 
response to concomitant medications, provided a good explanation for the event.  
For safety reporting purposes, in general, all adverse events classified as "definitely 
related", "probably related" or "possibly related" will be considered treatment related, and 
adverse events "unlikely related" and "unrelated" will be considered as treatment-unrelated 
unless specifically specified by the local drug regulatory authority.  
The investigator must make a causality determination for each adverse event before 
reporting to the sponsor, even if the investigator has limited information in the initial report.  
The investigator may change the causality determination based on the information 
obtained at follow-up and update the causality determination in the follow-up report.  
8.3.13 Safety Reporting Period 
The reporting period for adverse events in this study begins with the signing of informed 
consent by the participant (prior to any study-related procedures and/or receipt of study drug) 
until the last Safety Follow-up Visit (7 days after the last dose of the investigational product in 
Parts I and III; 14 days after the last dose of the investigational product in Part II). Any serious 
adverse event occurring after the reporting period must also be reported immediately if a causal 
relationship to the study drug is suspected.  
If a participant fails due to laboratory abnormalities, no AEs will be recorded; however, if 
an SAE or AE possibly related to the study procedure is screened, the corresponding AE/SAE 
should be recorded. No AE/SAE is required to be recorded after screening failure, i.e., 
"AE/SAE report is terminated when screening failure status is determined".  
If a participant withdraws from the study and withdraws informed consent for future 
information collection, the AE/SAE reporting period is terminated at the time of withdrawal of 
consent.  
8.3.14 Reporting Process for AEs and SAEs 
Each participant must be carefully monitored for any adverse events. This information 
should be obtained in the form of non-leading questions (e.g., "How do you feel?"), as well as 
from signs and symptoms detected during each examination, observations by researchers, and 
spontaneous reports from participants.  
All AEs (serious and nonserious) reported spontaneously by the participant and/or 
determined by answering open-label questions raised by the study personnel or by observation, 
physical examination, or other diagnostic procedures must be recorded. Whenever possible, 
signs and symptoms with common pathological features should be considered a composite 
event. Concomitant signs or symptoms (eg, abnormal laboratory values) should not be reported 
as additional adverse events. If the diagnosis is unknown, one or more symptoms may be 
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reported as separate adverse events. If the subsequently reported symptom is confirmed, the 
reported symptom term must be modified to "attributable" or "due to" the diagnosis.  
All adverse events should be followed until resolution, stable disease, or until the 
investigator decides that follow-up is not required. After the safety reporting period, AEs 
determined to be unrelated to the investigational product will no longer be followed up.  
For all SAEs occurring during the reporting period, whether initial or follow-up, 
regardless of causality, the investigator must report the SAE to the sponsor within 24 hours of 
awareness. SAEs must be followed until resolution, stable disease, or until the investigator 
decides that follow-up is not required. For study analysis, if the event is not resolved by the 
end of the study reporting period, it must be recorded as ongoing (not recovered/resolving). 
For regulatory safety monitoring purposes, a follow-up report should be sent as soon as more 
information becomes available.  
The follow-up report should contain sufficient information required for a complete 
medical assessment and independent causality determination. All relevant information, such as 
concomitant medications and disease information, must be provided. For fatal cases, available 
summaries of necropsy or other death examinations must be submitted as soon as possible.  
SAE initial and follow-up reports were submitted via email (contact details below).  
All SAEs must be reported regardless of whether or not considered causally related to 
study drug. The sponsor may request the investigator to provide follow-up information on 
SAEs.  
Contact Information 
Sponsor Email: drugsafety@abbisko.com 
In the event of a suspected unexpected serious adverse reaction (SUSAR), the sponsor or 
its authorized representative will comply with the requirements of local regulatory authorities 
to ensure that the relevant regulatory authorities and all personnel involved in the study are 
notified as soon as possible. In accordance with local regulations and institutional policies, 
ethics committees (ECs)/institutional review boards (IRBs) and hospital facilities need to be 
notified of SUSARs or other required information.  
8.3.15 Pregnancy Exposure 
Participants are obligated to inform the investigator of any pregnancy that occurs during 
study treatment and up to 6 months after the last dose of study drug. Pregnancies occurring 6 
months after the last dose of study drug or due to sperm donation/sperm preservation prior to 
study drug exposure are not reported.  
Female participants who become pregnant during the clinical trial must immediately 
discontinue study drug and complete the Early Withdrawal Visit and the Safety Follow-up Visit. 
If the female partner of a male participant becomes pregnant during the study, the participant 
must immediately notify the investigator, and the male participant may continue the clinical 
study. Male participants must commit to use an acceptable method of contraception (to avoid 
or prevent fetal exposure to study drug) for the duration of the study until 6 months after the 
last dose of study drug. The investigator must notify the sponsor within 1 working day of 
becoming aware of the pregnancy of the participant (or his/her partner).  
The participant or his/her spouse must be followed up until the end of pregnancy and the 
infant must be followed up to 1 month of birth, if informed consent is available. A separate 
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informed consent form (ICF) must be provided to explain these follow-up behaviors. Infant 
deaths after 1 month of life should also be reported as SAEs if assessed by the investigator as 
possibly related to study drug exposure. Pregnancy per se does not constitute an AE. Any 
adverse pregnancy outcome, such as stillbirth, spontaneous abortion, fetal malformation, is 
considered an SAE and needs to be reported as required for an SAE. The SAE Report Form 
and Pregnancy Report Form need to be completed separately for the same time limit as the 
SAE.  
8.3.16 Death 
All deaths occurring during the adverse event reporting period, whether related to study 
treatment or not, must be immediately reported to the sponsor as SAEs.  
Deaths considered related to this study drug outside of the safety reporting period are 
required to be reported as SAEs.  
8.4 Overdose 
Any ABSK061 above the indicated dose will be considered an overdose. There is no 
specific antidote for ABSK061 and in the event of an overdose, participants should receive 
appropriate supportive care and record any AEs.  
9 
Statistical Methods 
9.1 Sample Size Estimation 
The objective of this study was to evaluate the PK profile of ABSK061 capsules in single 
or multiple oral doses, to assess the effect of soft food on the pharmacokinetics of ABSK061, 
and to explore the dose-exposure proportionality of ABSK061 microt. The sample size was 
estimated based on actual considerations and feasibility, and no hypothesis testing was 
performed.  
The study was planned to enroll 18 participants in Part I and to be randomized in A 1: 1: 
1 ratio to three different study sequences, A, B, and C.  
Part II plans to enroll 12 participants and preset 2 study sequences (sequences D and E, 
6/sequence).  
Part III planned to enroll 12 participants and were randomized in a 1: 1: 1 ratio to three 
different study sequences: F, G, and H. Based on the data from the Phase 1 trial in patients with 
solid tumors of ABSK061-101, the weighted mean of the geometric coefficient of variation 
(CVw%) of each dose group was obtained for AUC0- ∞, AUClast and Cmax. Considering that 
this was the inter-patient coefficient of variation, the intra-individual coefficient of variation 
(CVw%) in healthy participants in this study was estimated as 70% of the above-mentioned 
weighted mean, I.e. 27.272%, 27.384%, 21.966%. Although the sample size for this trial is not 
based on statistical testing, as a reference, it is assumed that there is no difference between the 
drug taken with water and with soft food. The two-sided 90% confidence intervals for the 
estimated precision (90% confidence interval half-width) and the Ratio of the Geometric 
Means Ratio (GMR) of the log-transformed PK parameters (taken with soft food-water) at 
different sample sizes are presented below.  
Table of Estimated Accuracy of Primary PK Parameters at Different Sample Sizes (GMR = 
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1) 
Part III 
Three-
sequence, 
three-period 
crossover 
design 
AUC0-∞ 
AUClast 
Cmax 
Evaluable 
Participants 
Accuracy 
GMR 
90% 
confidence 
interval 
Accuracy 
GMR 
90% 
confidence 
interval 
Accuracy 
GMR 
90% 
confidence 
interval 
9 
0.222 
0.801, 
1.249 
0.223 
0.800, 
1.250 
0.180 
0.835, 
1.198 
12 
0.189 
0.828, 
1.208 
0.189 
0.828, 
1.208 
0.153 
0.858, 
1.165 
15 
0.167 
0.846, 
1.182 
0.167 
0.846, 
1.182 
0.135 
0.874, 
1.145 
9.2 Dataset 
The Screening Analysis Set includes all participants who signed informed consent. For 
participant disposition summaries and listings only.  
The PK Concentration Analysis Set (PCS) includes all participants who have received at 
least one dose of ABSK061 in capsules and are able to provide at least one evaluable postdose 
PK blood sample. It will be the primary analysis set for all PK concentration data analyses.  
The PK Parameters Analysis Set (PPS) includes all participants who are included in the 
PK concentration Analysis Set and have at least one PK parameter available for Analysis. It 
will be the primary analysis set for data analysis of all PK parameters.  
The Safety Analysis Set (SST) includes all participants who received at least one dose of 
ABSK061 in capsules. Summary statistics and/or listings will be performed by treatment group 
actually received by the participant, primarily for safety analysis.  
9.3 Statistical Analysis Methods 
The statistical analysis of this study will be the responsibility of Shanghai Hezhui 
Biopharmaceutical Technology Co., Ltd. or its designee. Where applicable, data will be listed 
and summarized in accordance with Shanghai Hezhui Biopharmaceutical Technology Co., Ltd. 
or designee reporting criteria. Full details will be documented in the Statistical Analysis Plan 
(SAP).  
9.3.1 General Methods 
Descriptive statistics (mean, standard deviation, median, minimum, maximum) will be 
performed for continuous variables. Frequency distributions and percentages will be 
summarized for discrete variables. All available data will be included in the data listings.  
Specific analyses of all endpoints will be detailed in the Statistical Analysis Plan (SAP).  
9.3.2 Participant Disposition 
Descriptive statistical analyses will be performed on the number of participants enrolled, 
received with study drug, reason for discontinuation by study sequence and overall, and the 
date and reason for discontinuation will be presented at the individual participant level.  
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9.3.3 Demographic and Baseline Characteristics 
Demographic and other baseline data will be summarized descriptively by study sequence 
and overall based on the Safety Analysis Set.  
9.3.4 Administration (study treatment, concomitant therapy, compliance) 
All information related to drug management will be listed. Concomitant medications and 
important non-drug therapies prior to and after administration of study drug ABSK061 will be 
listed using the Safety Analysis Set.  
9.3.5 PK Data Analysis 
ABSK061 pharmacokinetic parameters will be calculated and analyzed by a standard 
noncompartmental model. The PK profile of single or multiple oral doses of ABSK061 microt 
was assessed based on the primary pharmacokinetic parameters obtained.  
Results of PK parameters and summary data will be provided for each participant. 
Descriptive statistics (arithmetic mean, standard deviation, coefficient of variation, median, 
minimum, maximum, geometric mean, and geometric coefficient of variation) were calculated 
for all PK parameters of oral ABSK061 in each treatment group except for tmax, which will be 
summarized as median, minimum, and maximum. Data listings for all PK parameters will be 
provided.  
Part III assessed the effect of coadministration with soft food on the PK profile of 
ABSK061. The main PK parameters (Cmax, AUC0- ∞, AUClast) were log-transformed and 
statistically analyzed using a linear mixed-effects model. The dosing sequence and period in 
the model served as fixed effects and participants (in sequence) served as random effects. The 
magnitude of the difference between the Least Squares Means (and their 90% confidence 
intervals and the Ratio of the Geometric Least Squares Means (RGLSM, taken with soft 
food/water) and their 90% confidence intervals were estimated by logarithmic transformation, 
and the intra-individual coefficient of variation was calculated for each parameter. 
In addition, the dose-exposure proportionality of ABSK061 microchips was explored by 
graphical presentation of different doses by primary PK parameters (Cmax, AUC0- ∞, AUClast) 
and/or dose-normalized primary PK parameters for each treatment group. If applicable, the 
dose-exposure proportionality will be further explored through the Power model by natural 
log-transformation of the primary PK parameters.  
The detailed analysis plan will be further described in the Statistical Analysis Plan (SAP).  
9.3.6 Safety Analysis 
Adverse events, clinical laboratory data, vital signs, and electrocardiograms will be 
assessed using the Safety Analysis Set, with descriptive statistical analysis as the main. Missing 
safety data will not generally be imputed unless otherwise specified.  
9.3.7 Adverse Events 
Adverse events occurring in each participant were coded by system organ class and 
MedDRA preferred term in the Medical Dictionary for Regulatory Activities (MedDRA). The 
incidence of treatment-emergent AEs, TEAEs (new or pre-dose but worsening after the first 
dose to the last safety follow-up visit) will be summarized. All adverse events, study drug-
related adverse events, serious adverse events (SAEs), and adverse events leading to death will 
be listed.  
9.3.8 Laboratory abnormalities 
Laboratory measurements and changes from baseline will be summarized descriptively 
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(mean, median, standard deviation, maximum, minimum) by treatment group. Listings with 
abnormal values will be provided.  
The results of hematology, blood chemistry, urinalysis, and clinical significance as judged 
by the investigator included in the CRF will be summarized according to the scheduled visit. 
The number and percentage of participants with measurements judged high, low, or normal 
compared to the normal laboratory range will be summarized by treatment group using a 
crossover table, if applicable.  
9.3.9 Other safety data 
Data from other tests (e.g., electrocardiograms or vital signs) will be listed and flagged 
with abnormal values. Summary tables of additional safety data will also be provided.  
9.3.10 Interim Analysis 
Not applicable for this study.  
10 Study Management 
10.1 
Good Clinical Practice 
This study will be conducted in strict compliance with the regulatory requirements of 
ICH-GCP. The investigator needs to be fully familiar with the protocol and the rational use of 
the investigational product. Necessary clinical documents will be retained to demonstrate 
compliance with the study and the reliability of the data. Study main body documents should 
be established at the start of the study and maintained throughout the study as required by 
regulations.  
10.2 
Ethical norms 
The study will strictly follow the ethical principles of the Declaration of Helsinki. The 
IRB/IEC/REB will review all study documents to safeguard the rights, safety and welfare of 
participants. The study will be conducted only at sites approved by the IRB/IEC/REB. 
Amendments to the protocol, informed consent form, written information given to participants 
(including diary cards), and other documents will be submitted by the investigator to the 
IRB/IEC/REB.  
10.3 
Informed Consent 
Participants should fully understand the contents of the study and sign the informed 
consent form before participating in this study. The method of obtaining and documenting 
informed consent and its contents will comply with the requirements of ICH-GCP and all 
applicable regulations.  
10.4 
Clinical Monitoring 
Shanghai Hezhui Biopharmaceutical Technology Co., Ltd. will conduct inspections and 
reviews during the study to ensure that the study complies with GCP guidelines. Monitoring 
activities will be conducted by Shanghai Hezhui Biopharmaceutical Technology Co., Ltd., or 
designated third party designated monitors, including on-site review of eCRF integrity and 
clarity, cross-validation with source documents, reconciliation of other matters required by 
regulatory requirements, etc. The review of medical records will be conducted in a manner that 
ensures participant privacy.  
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The monitor will ensure that the investigator complies with the protocol design and 
regulatory requirements by frequent correspondence (letter, telephone, fax). Regulatory 
authorities, IRBs/IECs/REBs, and/or sponsors (or designated third parties) have access to all 
source documents, CRFs, and other study documents at the time of on-site verification. 
Sponsors need to ensure that these documents are readily accessible to support these activities.  
10.5 Protocol Amendment 
The investigator will conduct the clinical study in accordance with the protocol provided 
by Shanghai Hezhui Biopharmaceutical Technology Co., Ltd. The protocol will be approved 
by the IRB/IEC/REB and the corresponding regulatory authorities. The protocol contents may 
not be modified without the consent of the sponsor and the investigator. Protocol amendments 
need to be approved by the IRB/IEC/REB, unless they directly threaten the rights and interests 
of participants. Shanghai Hezhui Biopharmaceutical Technology Co., Ltd. will ensure 
compliance with regulatory requirements and submit all protocol amendments to regulatory 
authorities. Substantial amendments to the protocol can be made only after approval by 
regulatory authorities and the IRB/IEC/REB. When protocol deviations that pose a direct 
hazard to participants need to be immediately eliminated, the investigator should contact 
Shanghai Hezhui Biopharmaceutical Technology Co., Ltd. as circumstances permit to discuss 
the action plan. All deviations from the protocol need to be fully documented.  
10.6 
Data Quality Control 
To ensure the accuracy, completeness and reliability of the data, Shanghai Hezhui 
Biopharmaceutical Technology Co., Ltd. or its designated third party will perform the 
following: 
 Provide guidance materials to sites as needed;  
 Provide training as needed to guide investigators and clinical coordinators. 
Specific training content will involve the protocol, CRFs and study procedures;  
 Regular visits to the study site;  
 Maintain contact with site staff by mail, telephone, and/or fax;  
 Review and assess CRF data and/or use standard computer editing to detect 
errors in data collection;  
 Perform a quality review of the database.  
In addition, Shanghai Hezhui Biopharmaceutical Technology Co., Ltd. or its 
representatives will be inspected based on participant data samples recorded in the site source 
documents. Shanghai Hezhui Biopharmaceutical Technology Co., Ltd. and/or regulatory 
authorities may review the study at any time.  
10.7 
Data Collection Tools/Source Data 
The CRF Data for this study will be completed using an Electronic Data Capture (EDC) 
system, and all source records will be defined and retained by the site, and all records of source 
Data entered into the EDC system will be retained.  
10.8 
Participant Confidentiality Measures 
To maintain participant privacy, all CRFs, investigational product records, study reports, 
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and correspondence will identify participants by designated participant numbers. The study 
personnel will grant monitors and inspectors access to the participant ’ s original medical 
records to Shanghai Hezhui Biopharmaceutical Technology Co., Ltd. or its designees and 
regulatory authorities to verify the data collected on the CRFs and review the data collection 
process. To the extent permitted by applicable laws and regulations, the privacy of participants 
will be strictly protected from disclosure.  
10.9 Record Retention 
The investigator will retain all study records as required by ICH-GCP and other applicable 
regulations. If the investigator is no longer responsible for the retention of study records, 
regulatory authority needs to be transferred to other persons willing to assume responsibility. 
Shanghai He Gloria Biopharmaceutical Technology Co., Ltd. shall be notified in writing of any 
change in custody.  
10.10 
Liability and Insurance 
Shanghai Hezhu Biopharmaceutical Technology Co., Ltd. has signed the coverage scope 
of the insurance strategy in the terms of the study, and the legal liability for injury to the 
participants will be scientifically verified in strict accordance with applicable laws and 
professional standards.  
10.11 
Publication of Study Results and Use of Information 
All ABSK061-related information provided to the investigator by the sponsor is 
confidential. The investigator may use this information to complete the study and may not be 
used for other purposes without the consent of the sponsor. The investigator is obligated to 
provide the sponsor with complete data obtained during the study. Information obtained during 
the clinical study will be used for the development of ABSK061 and may be disclosed to 
regulatory authorities, other investigators, business partners, and consultants as needed.  
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11 References 
 
 
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12 Appendix 
12.1 Strong CYP3A inducers and inhibitors 
Listed below are strong inducers or inhibitors of the CYP3A family and concomitant use 
with ABSK061 should be prohibited, except for non-systemic use.  
Strong CYP3A inducers a 
Apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. 
John's wort 
Strong CYP3A inhibitors b 
Boceprevir, clarithromycin, cobicistat, danoprevir and ritonavir, etegravir and 
ritonavir, grapefruit, idelaris, indinavir and ritonavir, itraconazole, ketoconazole, 
lopinavir and ritonavir, nefazodone, nelfinavir, palitonavir and ritonavir and 
(obinasabuvir and/or dasabuvir), posaconazole, ritonazole, ritonavir, saquinavir and 
ritonavir, telaprevir, telithromycin, telithromycin and ritonavir, troleandomycin, 
voriconazole 
CYP = cytochrome P450 
This list does not list all cases in detail. Similar restrictions apply to other drugs known to potently 
modulate CYP3A activity. Please contact the Sponsor on your own initiative if you have any questions.  
(a) fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-
substrates-inhibitors-andinducers#table3-3 (Accessed 25 August 2020). 
(b) fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-
substrates-inhibitors-andinducers#table3-2 (Accessed 25 August 2020). 
 
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