A Single-Arm, Multicenter, Phase II Clinical Trial of CS1001 in Subjects With Relapsed or Refractory Extranodal Natural Killer/ T Cell Lymphoma(ENKTL)
Phase: PHASE2
Conditions: Extranodal Natural Killer/T-Cell Lymphoma
Sponsor: CStone Pharmaceuticals

Clinical Protocol CS1001-201 
ClinicalTrials.gov Document Cover Page 
Clinical Protocol 
Study CS1001-201 
Study Title: A Single-Arm, Multicenter, Phase II Clinical Trial of CS1001 in Subjects with 
Relapsed or Refractory Extranodal Natural Killer/ T Cell Lymphoma 
Document Date: 25 Feb 2021 
NCT Number: NCT03595657 

CS1001-201, Version: 3.0 
CS1001 
 
 
 
 
Clinical Trial Protocol 
 
Protocol Title:  
A Single-Arm, Multicenter, Phase II Clinical Trial 
of CS1001 in Subjects with Relapsed or Refractory 
Extranodal Natural Killer/ T Cell Lymphoma 
Protocol No.:  
CS1001-201 
Current Version Number:  
25 Feb 2021, Version 3.0  
Previous Version Number:  
01 Jul 2020, Version 2.0 
Study Phase:  
II 
Sponsor:  
CStone Pharmaceuticals (Suzhou) Co., Ltd. 
CStone Pharmaceuticals (Shanghai) Co., Ltd. 
E168, 2nd Floor, 218 Xinghu Str., A1 Building, North 
Block, BioBay, Suzhou Industrial Park, Suzhou, 
China 
211-20, 2nd Floor, 38 Debao Rd., Free Trade Zones, 
Shanghai, China 
 
 
 
 
 
 
  
  
 
 
 
Confidentiality Statement 
This confidential information in this document is provided to investigators, consultants, members of the 
study team, and the applicable Institutional Review Board/Independent Ethics Committee for review. 
Your acceptance of this document constitutes an agreement that you will not disclose the information 
contained herein to others without written authorization from the sponsor. 

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Signature Page for Sponsor 
Protocol Title: 
A Single-Arm, Multicenter, Phase II Clinical Trial of 
CS1001 in Subjects with Relapsed or Refractory 
Extranodal Natural Killer/ T Cell Lymphoma 
Protocol No.: 
CS1001-201 
Version Number: 
3.0 
Date of Current Version: 
25 Feb 2021 
 
 
CStone Pharmaceuticals will carefully fulfill the duties of sponsors according to current 
Good Clinical Practice of relevant countries and regions and be responsible for the initiating, 
submitting, organizing, sponsoring and monitoring this clinical study. Patients with serious 
adverse events during the clinical study will be provided with active intervention and the 
corresponding treatment expense will be covered by sponsor according to applicable national 
regulatory requirements. Adequate financial compensation will be offered to patients who 
experience damage confirmed to be consequence of investigational product-induced serious 
adverse effect. 
I have participated in the development of and discussion on this study protocol and agree to 
its contents. I have fully understood sponsor’s duties related with this trial protocol and agree 
to conduct clinical study per this protocol and applicable regulatory requirements. 
 
 
Sponsor:  
CStone Pharmaceuticals (Suzhou) Co., Ltd. 
CStone Pharmaceuticals (Shanghai) Co., Ltd. 
 
__________________                                                                        _____________ 
 
 
 
 
 
 
 
  
 
 
 
 
 
 

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Signature Page for Investigator 
Protocol Title: 
A Single-Arm, Multicenter, Phase II Clinical Trial of 
CS1001 in Subjects with Relapsed or Refractory Extranodal 
Natural Killer/ T Cell Lymphoma 
Protocol No.: 
CS1001-201 
Version Number: 
3.0 
Date of Current Version: 
25 Feb 2021 
 
 
This protocol is a confidential document of CStone Pharmaceuticals (Suzhou) Co., Ltd. 
and CStone Pharmaceuticals (Shanghai) Co., Ltd. for confidential circulation. I confirm 
I have read through and understand this protocol and will follow the protocol in the study. 
Furthermore, I will abide by the ethics principles in Declaration of Helsinki, Good Clinical 
Practice and applicable regulatory requirements during the study. By signing for this 
document, I agree that I will not make public or disclose any non-public information herein 
without prior written permission from CStone Pharmaceuticals (Suzhou) Co., Ltd. and 
CStone Pharmaceuticals (Shanghai) Co., Ltd. 
 
Note to investigator: Please sign your name and date on this signature page. Fill in printed names of 
you and your site to conduct this trial. A copy of this signature page will be returned to CStone 
Pharmaceuticals (Suzhou) Co., Ltd. and CStone Pharmaceuticals (Shanghai) Co., Ltd. 
 
I have read through the full text of the protocol and agree to follow it in the study. 
 
  
 
  
  
 
 
 
 
 
 

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SYNOPSIS 
Version 3.0 
Date: 25 February 2021 
Protocol No.: CS1001-201 
Experimental Drug: CS1001 
Title of Study: 
A Single-Arm, Multicenter, Phase II Clinical Trial of CS1001 in Subjects with Relapsed or Refractory 
Extranodal Natural Killer/ T Cell Lymphoma (R/R ENKTL) 
Number of Sites: Multiple sites 
Study Phase: Phase II 
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary objectives 
Primary endpoints 
To evaluate the efficacy of 
CS1001 in subjects with R/R 
ENKTL 
Objective response rate (ORR) assessed by the independent 
radiological review committee (IRRC) according to Criteria for 
Response Assessment of Lymphoma: Lugano 2014 Classification 
Secondary objectives 
Secondary endpoints 
To evaluate the efficacy of 
CS1001 in subjects with R/R 
ENKTL 
ORR assessed by investigators; 
Complete response rate (CRR), partial response rate (PRR), time 
to response (TTR), duration of response (DoR) assessed by IRRC 
and investigators 
To evaluate the safety of CS1001 
in subjects with R/R ENKTL 
Frequency and severity of adverse events (AEs) and frequency of 
serious adverse events (SAEs) 
To characterize the 
pharmacokinetics (PK) of 
CS1001  
To determine the peak and trough serum concentration of CS1001 
To evaluate the immunogenicity 
of CS1001 
Number and percentage of subjects with anti-drug antibody (ADA) 
Exploratory objectives 
Exploratory endpoints 
To evaluate the progression-free 
survival (PFS) and overall 
survival (OS) of R/R ENKTL 
subjects  
6-months PFS rate, 6-month OS rate 
To evaluate genetic aberrations 
in R/R ENKTL by whole-exome 
sequencing test of tumor tissues 
The association between genetic aberrations and efficacy 

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Study design and methods:  
This is a multicenter, single-arm phase II study to evaluate the efficacy and safety of CS1001 monotherapy 
in R/R ENKTL.  
Eighty eligible patients with R/R ENKTL who failed prior asparaginase-based treatment regimen(s) are 
assigned to receive CS1001 1200 mg intravenous (IV) infusion every three weeks (Q3W) until disease 
progression, intolerable to study treatment, consent withdrawal, death, or other causes specified in the 
protocol. The duration of treatment will be up to 24 months. 
 
For immune therapies such as CS1001, pseudo-progression may occur due to immune cell infiltration 
and other mechanisms as manifested by an apparent increase of existing tumor masses or appearance of 
new tumor lesions. Thus, for progressive disease (PD) suspected by the investigator as pseudo-
progression, treatment may continue until confirmation of PD with repeated imaging at least 4 weeks later 
(or preferred at the next scheduled regular imaging time point). All of the following criteria must be met 
to continue the treatment: 
a. 
Absence of clinically significant symptoms and signs of PD (including worsening laboratory 
values) 
b. 
Stable Eastern Cooperative Oncology Group Performance Status (ECOG PS) 
c. 
Absence of rapid progression of disease or PD at critical anatomical sites that necessitates 
urgent medical intervention 
The primary endpoint of this trial is ORR, defined as the percentage of subjects whose best overall 
response (BOR) is either CR or PR, as assessed by IRRC based on Criteria for Response Assessment of 
Lymphoma: Lugano 2014 Classification (hereinafter referred to as ‘Lugano 2014 classification’). The 
final efficacy analysis of the primary endpoint will be performed when the last subject completes the 
efficacy assessment of up to 24 weeks. 
Safety follow-up visits should be conducted 30, 60, 90 days after the last dose of study treatment. Safety 
follow-up period refers to the 90 days after the last dose of the investigational treatment or the start of new 
anti-cancer treatment, whichever occurs earlier. Survival follow-up should be conducted every 12 weeks 
after the last dose of study treatment. Apart from subjects who discontinue treatment due to disease 
progression assessed by tumor imaging, radiological assessment should be performed at scheduled time 
points until radiological disease progression, the start of new anti-cancer treatment, death, or the end of 
this trial, whichever occurs first. 
 
 

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Key Inclusion/Exclusion Criteria: 
Inclusion Criteria: 
1. Subjects who are willing to participate in this trial; fully understand and are fully informed of this 
trial, and are able to provide written informed consent form (ICF); are willing and able to follow 
all study procedures. 
2. Subjects are ≥ 18 years and ≤ 75 years of age on the day of signing informed consent.  
3. Subjects must have a histologically confirmed ENKTL at the study site. Both nasal and non-nasal 
ENKTL are allowed. 
4. Subjects must have relapsed or refractory ENKTL failing asparaginase-based chemotherapy or 
chemoradiotherapy. (Relapse: disease progression after response to the last treatment; refractory: 
no response to the last treatment.)  
5. ECOG PS of 0 or 1. 
6. Life expectancy ≥ 12 weeks. 
7. Subjects must have at least one evaluable or measurable lesion per Lugano 2014 classification 
[An evaluable lesion is a lymph node or extranodal lesion with radioactive uptake higher than 
liver on 18F-Fluorodeoxyglucose/ Positron Emission Tomography (18FDG/PET) and with typical 
lymphoma characteristics on PET and (or) computed tomography (CT); Measurable lesion: 
the longest diameter (LDi) is of > 15 mm for nodal lesion or >10 mm for extranodal lesion (if the 
only measurable lesion has received prior radiotherapy, the subject must have evidence of 
radiological progression after radiotherapy), and concurrent elevated uptake of 18FDG]. Absence 
of measurable lesion with diffuse 18FDG uptake increase in the liver should be ruled out first. 
8. Subjects must provide stained tumor tissue sections and corresponding pathological reports or 
unstained tumor tissue sections (or tissue block) for central pathology review. Investigators may 
enroll subjects before the result of central pathology review. 
9. Subjects must have adequate organ function and bone marrow function without severe 
hematopoietic disorder, or heart, lung, liver or kidney dysfunction or immune deficiency (no 
blood transfusion, granulocyte colony-stimulating factor or other relevant medical supporting 
care within 14 days before the first dose of study treatment): 
a) 
Absolute neutrophil count ≥ 1.0 × 109 /L; 
b) 
Platelets ≥ 50 × 109 /L; 
c) 
Hemoglobin ≥ 8 g/dL; 
d) 
Creatinine clearance ≥ 40 mL/min (according to Cockcroft-Gault equation); 
e) 
Serum total bilirubin ≤ 1.5 × ULN, unless considered to be due to Gilbert’s disease, where 
it must be ≤3 × ULN 
f) 
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 × ULN; 
g) 
Coagulation: International normalized ratio (INR) ≤ 1.5 × ULN; prothrombin time (PT) and 
activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (unless the subject is on anti-
coagulant therapy and PT and APTT at screening are within the expected range for patients 
on anti-coagulant). 
10. Subjects with prior anti-cancer treatment can only be enrolled when the toxicity of prior anti-
cancer treatment has recovered to baseline or ≤ Grade 1 according to Common Terminology 
Criteria for Adverse Events (CTCAE) v4.03. For patients with irreversible Grade 2 toxicities (e.g. 
thrombocytopenia, anemia, neurotoxicity, alopecia, and hearing impairment) that is anticipated 
to be unlikely to worsen during study treatment, the subject can be enrolled after approval by the 
medical monitor of the sponsor. 
11. Women of childbearing potential (WOCBP, as defined in Section 4.1.4) must have a negative 
serum pregnancy test ≤7 days before the first dose of investigational product. WOCBP or fertile 

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men and their WOCBP partners must agree to use an effective contraceptive method from 
providing signed ICF through 6 months after the last dose of the investigational product. (Refer 
to Section 4.1.5 for details.) 
Exclusion Criteria: 
1. Aggressive natural killer-cell leukemia or ENKTL patients who have any degree of leukemic 
involvement will be excluded. 
2. Concomitant with hemophagocytic lymphohistiocytosis. 
3. Current or historical primary central nervous system lymphoma (PCNSL) or secondary CNS 
involvement. 
4. Prior allogeneic organ transplantation. 
5. Allogenic hematopoietic stem cell transplantation (HSCT) ≤ 5 years before the first dose of 
investigational product. (Patients are permitted to enroll if they received allogenic HSCT more 
than 5 years before the first dose of investigational product and without any current graft-versus-
host reaction.) 
6. Current participation in another clinical study or use of any investigational drug within 4 weeks 
before the first dose of investigational product in this trial. 
7. Autologous HSCT within 90 days before the first dose of investigational product. 
8. Subjects with an active autoimmune disease that requires systemic treatment in the past two years. 
(Hormone replacement therapy is not considered as systemic therapy such as the patient has type 
I diabetes mellitus, hypothyroidism that can be managed with thyroid hormone replacement only, 
or adrenal insufficiency or pituitary insufficiency that requires a physiological dose of 
corticosteroid replacement). Subjects are permitted to enroll if they have an autoimmune disease 
that didn’t require any systemic treatment in the past two years. 
9. Subjects received systemic corticosteroid or any other immunosuppressive therapy within 14 days 
before the first dose of the investigational product; subjects are permitted to use topical, ocular, 
intra-articular, intranasal and inhaled corticosteroids (with minimal systemic absorption); a short 
course (≤ 7 days) of corticosteroids for prophylaxis (e.g., hypersensitivity to contrast media) or 
for treatment of non-autoimmune conditions (e.g., delayed hypersensitivity caused by contacting 
allergens).] 
10. A known additional malignancy within 5 years prior to the first dose of investigational product. 
Subjects with locally curable malignancies (including basal cell carcinoma of skin, squamous cell 
carcinoma of skin, breast cancer in situ or cervical cancer in situ, etc.) that have undergone 
curative therapy are permitted to enroll. 
11. Subjects who have had prior chemotherapy, immunotherapy, biological therapy (including cancer 
vaccine, cytokine therapy or growth factors to treat cancer) used as a systemic treatment for 
cancer, within 28 days before the first dose of investigational product. 
12. Subjects who underwent a major surgical procedure within 28 days before the first dose of 
investigational product or radiotherapy within 90 days before the first dose of investigational 
product. 
13. Any use of traditional Chinese medicines or herbal preparations with anti-tumor indications 
within 7 days before the first dose of investigational product. 
14. Has received a live vaccine within 28 days before the first dose of investigational product. 
(Attenuated influenza vaccine is allowed). 
15. Known history of human immunodeficiency virus (HIV) infection and/or acquired immune 
deficiency syndrome (AIDS). 
16. Subjects at the active phase of chronic hepatitis B or with active hepatitis C. Subjects who are 
hepatitis B surface antigen (HBsAg) positive or hepatitis C virus (HCV) antibody-positive at 
screening must not be enrolled until further definitive testing with hepatitis B virus (HBV) DNA 
titers (≤ 2500 copies/mL or 500 IU/mL) and HCV RNA tests (≤ the lower limit of detection) can 

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conclusively rule out the presence of active hepatitis B or C that requires treatment, respectively. 
Subjects that carry the hepatitis B virus, with stable hepatitis B (HBV DNA titer ≤ 2500 
copies/mL or 500 IU/mL) after medical treatment or with cured hepatitis C are permitted to enroll. 
17. History of interstitial lung disease (except for those induced by radiation therapies and are 
asymptomatic). 
18. Active tuberculosis infection. 
19. Any active infection requiring systemic anti-infection therapy within 14 days before the first dose 
of investigational product. 
20. Subjects who have received prior therapy with an anti-programmed cell death protein-1 
monoclonal antibody (anti-PD-1 monoclonal antibody), anti-programmed cell death-ligand 1 
monoclonal antibody (anti PD-L1 monoclonal antibody) or anti cytotoxic T-lymphocyte-
associated protein 4 monoclonal antibody (anti-CTLA-4 monoclonal antibody). 
21. Subjects with a known severe allergy to monoclonal antibodies (≥ Grade 3 per CTCAE v 4.03) 
or uncontrolled allergic asthma. 
22. Women in pregnancy or lactation. 
23. Subjects with active alcohol or drug dependence.  
24. Subjects with uncontrollable concomitant diseases including but not limited to symptomatic 
congestive heart failure, uncontrolled hypertension, unstable angina, active gastrointestinal ulcer 
or hemorrhagic disorders. 
25. Subjects with a history of psychiatric disease; or subjects with incapacity or limited capacity. 
26. Underlying condition that in the investigator's opinion would increase the risk of investigational 
product administration or confound the assessment for its toxicity. 
27. Subjects in the investigator’s opinion are not suitable for participating in this trial. 
Number of Subjects: 
Approximately 80 subjects with R/R ENKTL will be enrolled 
Study Treatment: 
CS1001 1200 mg, intravenous infusion for no less than 60 minutes, every 3 weeks (Q3W; 21 days). 
Duration of Study: 
This trial will be divided into three periods: screening period (28 days before the first dose of 
investigational product), treatment period (up to 2 years), and the follow-up period. 
Study Evaluation:  
Safety: 
Safety assessments will include vital signs, physical examinations, electrocardiograms (ECG), ECOG PS, 
radiology, and incidence and severity of adverse events (AEs) and serious adverse events (SAEs). 
AEs will be coded using the preferred term (PT) and system organ class (SOC) in Medical Dictionary for 
Regulatory Activities (MedDRA), International Conference for Harmonization (ICH). 
The safety of the investigational product will be assessed according to CTCAE v4.03. 
Efficacy: 
Efficacy evaluation will be performed by investigators and IRRC based on Lugano 2014 classification. 
Contrast-enhanced CT will be performed at screening and every 12 weeks after the first dose of 
investigational product. Examined sites include head and neck region (that must include nasal cavity, 
palatum durum, anterior cranial fossa, and nasopharynx), chest, abdomen, and pelvis. For patients allergic 
to CT contrast media, enhanced magnetic resonance imaging (MRI) will be used as an alternative. Positron 
emission tomography / computed tomography (PET/CT) will be performed at screening, Week 12, and 

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Week 24. Only enhanced CT will be used for follow-up tumor imaging after first radiological CR or Week 
24, whichever comes first. For patients without any measurable lesion, follow-up with PET/CT will be 
performed until radiological confirmation of CR or progression if the patient hasn’t reached CR in the first 
24 weeks. Additional PET/CT will be performed if follow-up enhanced CT reveals residual lesion or 
suspected progression. 
If contrast media for CT can be injected when PET/CT is performed and meet requirements on PET/CT 
and contrasted CT, additional enhanced CT can be skipped. View Central Radiology Manual for details. 
Apart from subjects who discontinue treatment due to radiological disease progression, tumor assessment 
should be performed at pre-specified regular time points until radiological disease progression, the start 
of new anti-cancer treatment, death, or the end of this trial, whichever occurs first. 
Pharmacokinetics and Immunogenicity: 
Samples will be analyzed for serum CS1001 concentrations and anti-drug antibody (ADA) using a 
validated immunoassay. The neutralizing antibody of CS1001 will be tested as needed if the neutralizing 
antibody assay method is established. 
Statistical Methods: 
Population: 
Efficacy analysis set (EAS) consists of all subjects who receive any dose of CS1001 and have the disease 
under study confirmed by central pathology. 
Safety analysis set (SAS) consists of all subjects who receive any dose of CS1001.  
Primary efficacy analyses: 
The primary efficacy endpoint is ORR assessed by IRRC, defined as the proportion of subjects who 
achieve CR or PR as the best overall response in all subjects with evaluable or measurable lesions in 
EAS. 
The 95% confidence interval (CI) of ORR will be calculated using the exact binomial (Clopper-Pearson) 
method to evaluate the precision of the ORR estimate. 
The statistical analysis will be performed by 24 weeks after the first dose of last subject.   
Secondary efficacy analyses: 
Proportions of subjects who achieve CR, PR, SD, and PD per IRRC evaluation and their 95% CIs will be 
summarized. This analysis will be performed in EAS subjects with evaluable or measurable lesion at 
baseline judged by IRRC. Proportions of subjects with responses per investigator’s evaluation and their 
95% CIs will be summarized. This analysis will be performed in EAS subjects with evaluable or 
measurable lesion at baseline judged by investigators. 
Duration of response (DoR) is defined as the time from the date of the first documented CR or PR 
(whichever comes first) to the date of the first documented disease progression or death, whichever 
comes first. DoR will be evaluated in subjects with objective responses per investigator’s or IRRC’s 
assessment, respectively. 
Time to response (TTR) is defined as the time from the date of the first study dose to the date of the first 
documented CR or PR, whichever comes first. TTR will only be evaluated for subjects who achieve 
ORR. TTR will be summarized according to the investigator's and IRRC’s assessment, respectively. 
Kaplan-Meier method will be used to analyze DoR; KM plots will be provided. DoR analysis will only 
be performed in subjects with objective responses. 
Exploratory efficacy analyses: 
Progression-free survival (PFS) is defined as the time from the date of the first study dose to the date of 
first documented disease progression or death, whichever comes first. 
Overall survival (OS) is defined as the time from the date of the first study dose to the date of death 
irrespective of its cause. 

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Kaplan-Meier method will be used to analyze PFS and OS. 
Sample size: 
The primary efficacy endpoint is ORR assessed by IRRC according to Criteria for Response Assessment 
of Lymphoma: Lugano 2014 Classification. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pharmacokinetic analysis: 
Descriptive statistics will be summarized for the serum concentration of CS1001 for blood samples taken 
at pre-specified time points. 
Safety analysis: 
All adverse events will be described according to MedDRA and graded according to the NCI CTCAE 
v4.03. All adverse events that occurred during or after investigational product administration will be 

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summarized by NCI CTCAE grade. Besides, SAEs, severe AEs (Grade 3, 4, or 5 events), drug-related 
AEs, and AEs causing discontinuation of or changes in investigational product administration will each be 
summarized. Multiple occurrences of the same event will only be counted once for the most severe event. 
The proportion of subjects with at least one AE will be reported. 
All deaths that occur during the study or within the follow-up period after the last dose/discontinuation of 
investigational product will be reported. 
Specific laboratory tests, vital signs, physical examinations, and 12-lead ECGs and their changes from 
baseline will be summarized. The values at baseline and each time point following baseline will be 
presented by crosstabs, when appropriate. 
Immunogenicity: 
Immunogenicity evaluation results will be reported for the following parameters. Number and percentage 
of subjects who have positive ADA at baseline; number and percentage of subjects with at least one 
positive ADA test result in any time point following the first dose of the investigational product; number 
and percentage of subjects who develop treatment-induced ADA any time after the first dose of the 
investigational product; number and percentage of subjects with treatment-enhanced ADA any time after 
the first dose of investigational product. 
Biomarkers: 
Biomarker measurements will be presented for available data. Graphical and/or tabular forms will be used 
to describe genetic aberrations and their relationship with the efficacy of anti-cancer treatment. 
The statistical method will be described in detail in the statistical analysis plan. 
 

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SCHEDULE OF STUDY ACTIVITIES 
Table 1 Schedule of Activities 
Trial Period 
Screening 
Treatment 
Follow-up 
Treatment cycles 
or visits 
Screening 
1 
2 
3 
4 
N 
End-of-
treatment 
Visit1 
Safety follow-
up2 
Radiology 
follow-up3 
Survival 
follow-up4 
Time of visit and 
time window  
Day -28 to 
Day -1 
± 3 days 
± 3 days 
± 3 days 
± 3 days 
± 3 days 
+7 days 
After the last 
dose 
30, 60, 90 days 
± 3 days 
 
After the last 
dose 
Every 12 weeks 
(± 7 days) 
Study Procedures 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
 
 
 
 
 
 
 
 
 
Demographics and 
medical history 
X 
 
 
 
 
 
 
 
 
 
Prior medications 
and 
concomitant 
medications5 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Clinical procedures/assessments 
Adverse events6 
X 
X 
X 
X 
X 
X 
X 
X 
 
 

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12-Lead ECG7 
X 
 
 
 
 
 
X 
X 
 
 
Height, 
weight, 
and vital signs8 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Physical 
examination 
and 
ECOG 
performance 
status9 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Subsequent 
anti-
cancer treatment 
 
 
 
 
 
 
 
 
X 
X 
Survival status 
 
 
 
 
 
 
 
 
 
X 
Study treatment 
CS100110 
 
X 
X 
X 
X 
X 
 
 
 
 
Laboratory procedures/assessments (at study sites) 
Pregnancy test11 
X 
 
 
 
 
 
X 
X 
 
 
Hematology, 
serum chemistry, 
urinalysis12 
X 
 
X 
X 
X 
X 
X 
X 
 
 
Coagulation 
functions13 
X 
 
 
 
 
 
 
 
 
 
Virology14 
X 
 
 
 
 
 
 
 
 
 

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Thyroid 
functions15 
X 
 
 
X 
 
X 
X 
X 
 
 
EBV DNA16 
X 
 
X 
X 
X 
X 
 
 
 
 
Laboratory procedures/assessments (performed by central laboratory) 
Central 
pathology17 
X 
 
 
 
 
 
 
 
 
 
PK18 
 
X 
X 
X 
X 
X 
X 
X 
 
 
ADA19 
 
X 
X 
X 
X 
X 
X 
X 
 
 
Efficacy evaluation 
Radiology 
examinations20 
X 
 
 
 
 
X 
 
 
X 
 
Bone marrow 
aspiration and 
biopsy21 
X 
 
 
 
 
 
 
 
 
 
Sample collection for biomarkers 
Blood sample 
collection22 
X 
 
 
 
 
 
 
 
 
 
Tumor tissue23 
X 
 
 
 
 
 
 
 
 
 
1. 
End-of-treatment (EOT) follow-up: EOT date will be the decision-making date for discontinuing the study treatment by investigators. EOT visit should occur 0-7 
days after the EOT date. 

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2. 
Safety follow-up: Safety follow-up visit should be conducted at 30, 60, 90 days (± 3 days) after the last dose of investigational product. If the EOT visit occurs in 
the time window of the first safety follow-up visit (30± 3 days), the same tests and examinations don't need to be repeated. It is recommended to complete all 
protocol required follow-up evaluations for the safety follow-up at 60 ± 3days and 90± 3 days after the last dose, or AEs and concomitant medications can be 
collected through phone call. Safety follow-up period refers to the 90 days after the last dose of the investigational treatment or the start of new anti-cancer 
treatment, whichever occurs earlier. 
3. 
Radiology follow-up: Apart from subjects who discontinue treatment due to radiological disease progression, tumor assessment should be performed at pre-
specified regular time points until radiological disease progression, the start of new anti-cancer treatment, death, or the end of this trial, whichever occurs first. 
4. 
Survival follow-up: Survival status will be assessed every 12 weeks by telephone after the last dose of investigational product.  
5. 
Concomitant medications: All concomitant medications received from 30 days before the screening will be recorded until 90 days after the last dose of study 
treatment or the start of new anti-cancer treatment, whichever occurs first. 
6. 
Adverse events (AEs): All AEs will be recorded from signing informed consent to 90 days after the last dose of investigational product or starting new anti-
cancer therapy, whichever comes first. Thereafter only study treatment-related SAEs need to be recorded. AEs that occur after the safety follow-up visit can be 
recorded by telephone follow-up 60 days and 90 days after the last dose. 
7. 
Electrocardiogram (ECG): ECG will be performed at screening, EOT visit, and safety follow-up visit. The frequency of ECGs may be increased if clinically 
indicated. 
8. 
Height, weight, and vital signs: Height will only be measured at screening, weight at screening, EOT visit, and safety follow-up visit. Vital signs include 
temperature, pulse, respiratory rate, and blood pressure. 
9. 
Physical examination and ECOG performance status: Overall physical examination will be performed at screening, EOT visit, and safety follow-up visit. The 
lymphoma-specific physical examination will be performed during the treatment period. 
10. Study treatment: The study treatment is CS1001 1200 mg, IV, Q3W, administered on the first day of each cycle after completing all the clinical and laboratory 
procedures/assessments. 
11. Pregnancy test: Blood human chorionic gonadotrophin test is performed as a pregnancy test only in women of childbearing potential at screening (within 7 days 
before the first dose), EOT visit, and safety follow-up visit. An additional urine pregnancy test may be performed if clinically indicated. A serum pregnancy test 
is needed if the urine test reveals a positive result. 
12. Hematology, serum chemistry, and urinalysis: Hematology includes complete blood count with differentials and hemoglobin. Serum chemistry tests include 
blood urea/urea nitrogen, creatinine, sodium, potassium, magnesium, chloride, calcium, phosphate, fasting blood glucose, total bilirubin, direct bilirubin, ALT, 
AST, alkaline phosphatase, lactate dehydrogenase, total cholesterol, total protein, and albumin. Urinalysis includes specific gravity, pH, urine glucose, urine 
protein, urine casts, ketones, and blood cells. These tests will be performed at screening (within 7 days before the first dose of investigational product), 3 days 
before each dosing starting from Cycle 2, EOT visit, and safety follow-up visit. 
13. Coagulation function: Coagulation function tests including PT, APTT, and INR will be performed at screening. 

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14. Virology: Tests for HBsAg, HCV antibody, and HIV antibody will be performed at screening. Subjects who are HBsAg positive must receive further HBV DNA 
test. Subjects who are HCV antibody positive must receive further HCV RNA test. 
15. Thyroid function: Thyroid function test including free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) tests will be 
performed at screening (within 7 days before the first dose of investigational product), thereafter 3 days before investigational product administration every other 
cycle (Cycle 3, 5, 7 and so on), EOT visit and safety follow-up visit. 
16. EBV DNA: EBV DNA test will be performed at screening and 3 days before each dosing starting from Cycle 2. For subjects who achieve radiological CR, the 
EBV DNA test will be performed every other cycle thereafter. 
17. Central pathology: Stained tumor tissue sections and corresponding pathological report or unstained tumor tissue sections (or tissue block) must be collected at 
screening for central pathology review. Both fresh and archival biopsies are accepted and can be used by central pathology. Investigators may enroll subjects 
before obtaining the result of the central pathology review. For subjects whose diagnosis is not ENKTL per central pathology laboratory’s evaluation, 
investigators in consultation with sponsor medical monitors will determine whether to continue or discontinue the subject from treatment. View Central 
Pathology Manual for detailed instructions. 
18. Pharmacokinetics (PK): Blood samples will be collected within 60 minutes before infusion as pre-treatment samples at Cycle 1, 2, 3, 4, and 8, and within 30 
minutes after infusion at Cycle 1 and 4 in the treatment period. Blood samples for PK testing will be collected at the EOT visit and safety follow-up visit at 30 
days, and 90 days after the last dose of study treatment. View Central Laboratory Manual for detailed instructions. 
19. Immunogenicity: Pre-treatment blood samples are collected (within 60 minutes before dosing) at Cycle 1, 2, 3, 4, and every 4 cycles thereafter (e.g., Cycle 8, 12, 
16, and so on). Blood samples for ADA testing will be collected at the EOT visit and safety follow-up visit at 30 days, and 90 days after the last dose of study 
treatment. View Central Laboratory Manual for detailed instructions. 
20. Radiology assessment: Efficacy evaluations will be performed by investigators and IRRC based on Lugano 2014 classification. Contrast-enhanced CT will be 
performed at screening and every 12 weeks after the first dose of investigational product. Examined sites include head and neck region (that must include nasal 
cavity, palatum durum, anterior cranial fossa, and nasopharynx), chest, abdomen, and pelvis. For subjects allergic to CT contrast media, enhanced MRI will be 
used as an alternative. Systemic PET/CT examination will be performed at screening, Week 12, and Week 24. Only enhanced CT will be used for follow-up after 
first radiological CR or Week 24, whichever comes first. For subjects without any measurable lesion, follow-up with PET/CT will be performed until 
radiological confirmation of CR or progression if the subject hasn’t reached CR in the first 24 weeks. Additional PET/CT will be performed if follow-up 
enhanced CT reveals residual lesion or suspected progression. If contrast media for CT can be injected when PET/CT is performed and meet requirements on 
PET/CT and contrasted CT, additional enhanced CT can be skipped. View Central Radiology Manual for details. Apart from subjects who discontinue treatment 
due to radiological disease progression, tumor assessment should be performed at pre-specified regular time points until radiological disease progression, the 
start of new anti-cancer treatment, death, or the end of this trial, whichever occurs first. 
21. Bone marrow aspiration and biopsy: Bone marrow aspiration and biopsy should be performed at screening for all subjects. Subjects with positive bone marrow 
aspiration/biopsy result or indeterminate overall bone marrow assessment at screening will undergo bone marrow aspiration and biopsy when achieving 
CR/CMR based upon radiology for confirmation. Immunohistochemistry (IHC) analyses should be performed under a microscope no matter bone marrow 
involves or not  (Suggest detecting CD56、TIA-1、CD3、GrB、perforin, and EBER hybridization in situ, etc.). 

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22. Blood sample for biomarker testing: A total amount of 2 mL whole blood sample will be collected as germline control in whole-exome sequencing for tumor 
tissue. The whole blood can be collected at screening or retrospectively after study entry. View Central Laboratory Manual for details. 
23. Tumor tissue for biomarker testing: Seven (7) unstained Formalin-Fixed, Paraffin-Embedded (FFPE) tumor tissue slides should be collected at screening for 
whole-exome sequencing of tumor tissue. If samples are not available at screening, a retrospective collection of 7 archival FFPE tumor tissue slides is allowed. 
View Central Laboratory Manual for details. 
 

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TABLE OF CONTENTS 
 
SYNOPSIS ............................................................................................................................. 3 
SCHEDULE OF STUDY ACTIVITIES .............................................................................. 11 
TABLE OF CONTENTS ..................................................................................................... 17 
1. INTRODUCTION ........................................................................................................... 22 
1.1 
DISEASE OVERVIEW ............................................................................................. 22 
1.2 
MECHANISM OF ACTION ..................................................................................... 23 
1.2.1 
Pre-Clinical Studies ............................................................................................... 24 
1.2.2 
Clinical Studies ...................................................................................................... 25 
1.2.3 
Risk/Benefit Assessment ....................................................................................... 25 
2. OBJECTIVES AND ENDPOINTS ................................................................................. 27 
3. STUDY DESIGN ............................................................................................................ 28 
3.1 
OVERALL DESIGN ................................................................................................. 28 
3.1.1 
Screening ................................................................................................................ 28 
3.1.2 
Treatment Period .................................................................................................... 28 
3.1.3 
Follow-up ............................................................................................................... 29 
3.1.4 
End of Study .......................................................................................................... 29 
3.1.5 
Treatment Beyond End of Study ............................................................................ 29 
3.2 
RATIONALE FOR STUDY DESIGN ...................................................................... 30 
3.2.1 
Rationale for Single-Arm Design .......................................................................... 30 
3.2.2 
Rationale for Primary Endpoint Analysis for Treatment of Up to 24 Weeks ........ 30 
3.2.3 
Rationale for Setting ORR as the Primary Endpoint with Historical Control ....... 30 
3.2.4 
Rationale for Treatment Beyond Disease Progression .......................................... 30 
3.2.5 
Rationale for Exploratory Biomarker Investigation .............................................. 31 
4. STUDY POPULATION .................................................................................................. 32 
4.1 
Inclusion Criteria ....................................................................................................... 32 
4.2 
Exclusion Criteria ...................................................................................................... 33 
4.3 
Discontinuation and Withdrawal ............................................................................... 35 
4.3.1 
Discontinuation of Study Treatment ...................................................................... 35 
4.3.2 
Follow-up After Discontinuation ........................................................................... 35 
4.3.3 
Consent Withdrawal ............................................................................................... 35 
4.4 
Definition of WOCBP ............................................................................................... 36 
4.5 
Definition of Effective Contraception ....................................................................... 36 
5. STUDY TREATMENT................................................................................................... 38 

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5.1 
INVESTIGATIONAL PRODUCT............................................................................ 38 
5.1.1 
Dosage Form and Specifications............................................................................ 38 
5.1.2 
Packaging and Labeling ......................................................................................... 38 
5.1.3 
Management of Investigational Product ................................................................ 38 
5.1.4 
Preparation and Administration ............................................................................. 39 
5.2 
TREATMENT COMPLIANCE ................................................................................ 39 
5.3 
INVESTIGATIONAL PRODUCT DOSING MODIFICATION ............................. 40 
5.3.1 
Overall Principle for Investigational Product Dosing Modification ...................... 40 
5.3.2 
Criteria for Dose Modification of Investigational Product .................................... 40 
5.3.3 
Criteria for Permanent Discontinuation of Investigational Treatment................... 41 
5.3.4 
Infusion-Related Reaction ..................................................................................... 42 
5.4 
CONCOMITANT THERAPY .................................................................................. 43 
5.4.1 
Prohibited Therapy ................................................................................................. 43 
5.4.2 
Permitted Therapy .................................................................................................. 43 
6. STUDY PROCEDURES AND ASSESSMENTS .......................................................... 45 
6.1 
STUDY PROCEDURES ........................................................................................... 45 
6.1.1 
Screening ................................................................................................................ 45 
6.1.2 
Treatment Period .................................................................................................... 47 
6.1.3 
Follow-up Period ................................................................................................... 49 
6.1.4 
Unplanned Visit ..................................................................................................... 49 
6.2 
SAFETY ASSESSMENTS ....................................................................................... 49 
6.2.1 
Vital signs .............................................................................................................. 49 
6.2.2 
Physical Examination and ECOG Performance Status .......................................... 50 
6.2.3 
Electrocardiogram (ECG) ...................................................................................... 50 
6.2.4 
Laboratory Tests .................................................................................................... 50 
6.3 
PATHOLOGICAL ASSESSMENTS ........................................................................ 50 
6.4 
EFFICACY ASSESSMENTS ................................................................................... 51 
6.5 
PHARMACOKINETICS AND IMMUNOGENICITY ............................................ 51 
6.6 
BIOMARKERS ......................................................................................................... 52 
7. REPORTING OF ADVERSE EVENTS ......................................................................... 53 
7.1 
ADVERSE EVENTS ................................................................................................. 53 
7.1.1 
Definition of an Adverse Event ............................................................................. 53 
7.1.2 
Adverse Event Monitoring ..................................................................................... 53 
7.1.3 
Recording of Adverse Events ................................................................................ 53 
7.2 
SERIOUS ADVERSE EVENTS ............................................................................... 56 

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7.2.1 
Definition of A Serious Adverse Event ................................................................. 56 
7.2.2 
Serious Adverse Event Reporting .......................................................................... 57 
7.3 
ASSESSMENT OF ADVERSE EVENTS AND SERIOUS ADVERSE 
EVENTS .......................................................................................................................... 57 
7.3.1 
Causality Assessment ............................................................................................. 58 
7.3.2 
Assessment of Severity .......................................................................................... 58 
7.4 
HANDLING OF ADVERSE EVENTS .................................................................... 59 
7.5 
REPORTING OF SPECIAL SITUATIONS ............................................................. 59 
7.5.1 
Definition of a Special Situation ............................................................................ 59 
7.5.2 
Reporting of Special Situations ............................................................................. 60 
7.6 
LIVER FUNCTION TEST FINDINGS .................................................................... 61 
7.7 
OTHER SAFETY CONSIDERATIONS .................................................................. 61 
8. STATISTICAL CONSIDERATIONS AND ANALYSIS PLANS ................................ 62 
8.1 
SAMPLE SIZE DETERMINATION ........................................................................ 62 
8.2 
SUMMARY OF CONDUCT OF STUDY ................................................................ 63 
8.2.1 
Analysis Sets .......................................................................................................... 63 
8.2.2 
Demographics and Baseline ................................................................................... 63 
8.3 
Efficacy Analyses ...................................................................................................... 63 
8.3.1 
Primary Efficacy Endpoints ................................................................................... 63 
8.3.2 
Secondary Efficacy Endpoints ............................................................................... 63 
8.4 
SAFETY ANALYSES .............................................................................................. 64 
8.5 
PHARMACOKINETIC ANALYSES ....................................................................... 64 
8.6 
IMMUNOGENICITY ANALYSES.......................................................................... 64 
8.7 
EXPLORATORY ANALYSES ................................................................................ 65 
8.8 
HANDLING OF MISSING DATA ........................................................................... 65 
9. ETHICAL CONSIDERATIONS .................................................................................... 66 
9.1 
ETHICS COMMITTEE ............................................................................................. 66 
9.2 
ETHICS INSTRUCTIONS FOR THE STUDY ........................................................ 66 
9.3 
SUBJECT INFORMED CONSENT FORM ............................................................. 66 
10. STUDY MANAGEMENT ........................................................................................... 67 
10.1 DATA MANAGEMENT .......................................................................................... 67 
10.1.1 
Completion and Submission of Case Report Forms .............................................. 67 
10.1.2 
Data Entry and Modification ................................................................................. 67 
10.1.3 
Data Review ........................................................................................................... 68 
10.1.4 
Archival .................................................................................................................. 68 

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10.2 INSPECTION PROCEDURES (QUALITY ASSURANCE) ................................... 68 
10.2.1 
Routine Monitoring ................................................................................................ 69 
10.2.2 
Audits and Inspections ........................................................................................... 69 
10.3 STUDY MANAGEMENT AND MATERIALS ....................................................... 69 
10.3.1 
Data Collection ...................................................................................................... 69 
10.3.2 
Archival of Source Data and Records .................................................................... 69 
10.3.3 
Confidentiality ....................................................................................................... 70 
10.4 APPLICATION PROCEDURES .............................................................................. 70 
10.4.1 
Ethics Approval ..................................................................................................... 70 
10.4.2 
Changes to the Protocol ......................................................................................... 71 
10.4.3 
Protocol Adherence and Deviations ....................................................................... 71 
10.4.4 
Publication of Study Results .................................................................................. 71 
10.4.5 
Clinical Study Report ............................................................................................. 71 
10.4.6 
Insurance, Reimbursement, and Compensations ................................................... 71 
10.4.7 
Termination of Study ............................................................................................. 72 
10.4.8 
Document Management at Sites ............................................................................ 72 
11. LIST OF ABBREVIATIONS ....................................................................................... 73 
12. REFERENCES .............................................................................................................. 77 
13. APPENDICES .............................................................................................................. 79 
13.1 CRITERIA FOR RESPONSE ASSESSMENT OF LYMPHOMA: LUGANO 
2014 CLASSIFICATION1 .............................................................................................. 79 
13.2 CRITERIA FOR ECOG PERFORMANCE STATUS ASSESSMENT ................... 82 
13.3 RESPONSIBILITY FOR MEDICATION MANAGEMENT .................................. 83 
13.4 IMMUNE-RELATED ADVERSE REACTIONS MANAGEMENT 
GUIDANCE FOR INVESTIGATORS ........................................................................... 84 
13.5 PROTOCOL AMENDMENT ................................................................................... 90 
 
 
 

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List of Tables 
Table 1 Schedule of Activities ............................................................................................. 11 
Table 2 Treatment Modification for Symptoms of Infusion-Related Reactions .................. 42 
Table 3 Visit procedures in the screening phase .................................................................. 45 
Table 4 Visit procedures in the treatment phase .................................................................. 47 
Table 5 Procedures in the End-of-Treatment Visit .............................................................. 48 
Table 6 Laboratory tests ....................................................................................................... 50 
Table 7 Summary of Recording and Follow-up for Adverse Events and Deaths ................ 54 
 
 
 

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1. INTRODUCTION 
1.1 DISEASE OVERVIEW 
ENKTL is a subtype of mature T cell and NK cell lymphomas. Its incidence varies by 
geography, higher in Asia than in Europe and North America (22% vs. 5% in mature T cell 
and NK cell lymphoma, respectively)[2, 3]. In a multi-center pathology classification survey 
of 10,002 lymphoma patients in 2012 in China, ENKTL accounted for about 6% of all 
lymphomas and 28% of all mature T cell and NK cell lymphomas[4]. Anthracycline-based 
chemotherapy is not recommended as the high expression of multidrug-resistant p-
glycoprotein in ENKTL. Current systemic chemotherapy regimens for ENKTL are 
asparaginase-based regimens, including SMILE, AspMetDex, and P-Gemox, etc. The ORR 
and CR of first-line treatment are approximately 80% and 50%, respectively[5]. High-dose 
chemotherapy combined with autologous or allogeneic hematopoietic stem cell 
transplantation is used as consolidation/intensification therapy or second-line salvage 
therapy but not considered as a standard of care, because of the limited data. 
There has not been any large prospective randomized control trial of medical treatment 
specifically targeting at R/R ENKTL population. A portion of R/R ENKTL patients 
enrolled in clinical studies for salvage combination chemotherapy have not received 
asparaginase in the first-line therapy and were treated with the asparaginase-based regime 
as salvage therapy, who have a better clinical outcome than those who have relapsed or are 
refractory after receiving asparaginase-based therapy. For now, the salvage combination 
chemotherapy showed significant toxicity and did not improve the OS significantly, with 
the median OS being less than 6.4 months[6-8]. As a targeted therapy, chidamide, a histone 
deacetylase inhibitor, has also been approved to treat R/R peripheral T-cell lymphoma 
(including R/R ENKTL) in China. It is reported to have a manageable safety profile and a 
CR rate of 6.3% (1/16) and an ORR of 18.8% (3/16) in the pivotal phase II trial[1]. And the 
post-marketing real-world data showed a CR rate of 6.1% (2/33) and an ORR of 15.2% 
(5/33)[9]. Furthermore, a phase II clinical study of anti-CD38 antibody daratumumab in 
R/R ENKTL reported an ORR of 25% (8/32) and a CR rate of 0%. The median duration of 
response (DoR) was short (55 days) and the survival benefit was limited (median OS: 130 
days)[10]. In summary, there is a significant unmet medical need for patients with R/R 
ENKTL. 
EBV infection is a primary mechanism and characteristic of ENKTL, which is highly 
correlated with tumor burden and its response to treatment[11, 12]. EBV infection induces 
immune tolerance of ENKTL by upgrading PD-L1 expression in tumor cells[13, 14]. Around 
80% of ENKTL tumor cells express PD-L1[15]. All of these studies have provided a 
theoretical foundation for treating ENKTL by inhibiting the PD-1/PD-L1 pathway. 
A small retrospective study published in Blood in February 2017 reported the results of 
pembrolizumab treatment in 7 R/R ENKTL patients after failure of asparaginase-based 
chemotherapy. Five patients achieved CR (including1 patient had pseudo-progression 
before achieving CR) and 2 achieved PR. The 5 CR patients were still in remission at a 6-
month follow-up, indicating durable response and good tolerability with PD-1/PD-L1 
inhibition[16]. Another retrospective study reported pembrolizumab treatment in 7 R/R 
ENKTL patients. Two patients achieved CR and 2 patients achieved PR[17]. A French study 
was conducted in 13 R/R ENKTL patients failing asparaginase-based chemotherapy. Three 
patients achieved CR, and 1 achieved PR[18]. A single-center retrospective study in Korea 
reported the outcome of 14 R/R ENKTL patients treated with pembrolizumab. Five 
patients achieved CR and 1 patient achieved PR[19]. Sintilimab, an anti-PD1 antibody 
developed in China, was explored in 28 R/R ENKTL patients failing asparaginase-based 

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regimens in a multicenter, single-arm, phase II trial (ORIENT-4). The CR rate and ORR 
were 7.1% (2/28) and 53.6% (15/28), respectively. Median DoR was 4.1 months[8]. 
Although the data of pembrolizumab in the treatment of R/R ENKTL were from small 
retrospective case studies, and no anti-PD1 antibody (including pembrolizumab and 
sintilimab) was approved in the treatment of R/R ENKTL, compared with other drugs, the 
anti-PD-1 antibody is demonstrated to be an effective treatment with mild adverse effects 
in R/R ENKTL. All of these data suggest great potential of significant efficacy and better 
tolerance of anti-PD-1 monoclonal antibody in R/R ENKTL patients who have failed 
multiple treatment lines. 
In summary, R/R ENKTL is a rare disease that lacks effective therapy. Existing clinical 
data showing the efficacy of anti-PD-1 monoclonal antibody in R/R ENKTL indicate 
inhibiting the PD-1/PD-L1 pathway to be a potentially effective treatment for R/R 
ENKTL. 
1.2 MECHANISM OF ACTION 
Immune checkpoints are a group of immunosuppressive molecules. Their physical function 
is to prevent normal cells from damage or injury by modulating the intensity and extent of 
immune reaction. While tumor cells often utilize this feature of immune checkpoints to 
avoid the attack by immune cells. Clinically validated immune checkpoints include CTLA-
4 and PD-1/PD-L1, in which PD-1/PD-L1 has greater clinical potential because of its 
favorable safety and wide indication. 
PD-L1 is primarily expressed on the surface of tumor cells and antigen-presenting cells 
and is the main ligand of T-cell inhibitory receptor PD-1[20]. The binding of PD-L1 
expressed on tumor cells and PD-1 on T cells triggers a signaling cascade that inhibits T 
cell proliferation and cytokine secretion by activated T cells, reduces the activity of T cells, 
and decreases the killing of tumor cells by T cells. Drugs that block the interaction between 
PD-1 and PD-L1 may restore T cell activity and its ability to kill tumor cells[21]. 
Up to 20 March 2020, the anti-PD-L1 monoclonal antibodies approved by the Food and 
Drug Administration (FDA) include atezolizumab, avelumab, and durvalumab. Anti-PD-1 
monoclonal antibodies approved by the FDA include pembrolizumab, nivolumab, and 
cemiplimab. The indications include advanced urothelial carcinoma, advanced non-small 
cell lung cancer (NSCLC), advanced melanoma, relapsed or refractory classical Hodgkin 
lymphoma, advanced renal cell carcinoma, and advanced head and neck squamous cell 
carcinoma, etc. Besides, many more indications are in the phase of pivotal registration 
trials or submission for approval. The approval of these drugs demonstrates the key 
position of PD-1/PD-L1 immune checkpoint inhibitors in cancer immunotherapy. The PD-
L1 inhibitors approved in China are durvalumab and atezolizumab. The New Drug 
Application of CS1001 for the treatment of stage IV NSCLC has been accepted by China 
Center for Drug Evaluation in Nov 2020. The PD-1 inhibitors approved in China include 
pembrolizumab, nivolumab, toripalimab, sintilimab, camrelizumab, and tislelizumab. The 
indications are unresectable stage III NSCLC, small cell lung cancer, unresectable or 
metastatic melanoma, relapsed or refractory classical Hodgkin lymphoma, advanced 
NSCLC, and recurrent or metastatic head and neck squamous cell carcinoma, etc. 
However, there has not been any PD-1/PD-L1 inhibitors approved for the treatment of 
ENKTL worldwide. The significance of actively developing these inhibitors is to offer 
patients with advanced cancer more and better treatment options. 

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1.2.1 Pre-Clinical Studies 
1.2.1.1 Pharmacodynamic Studies 
The in vitro activity of CS1001 was examined by various methods at both protein and cell 
levels. The results showed that CS1001 effectively bound to PD-L1 protein expressed on the 
cell surface, blocked PD-L1/PD-1 ligation, and effectively induced the proliferation of 
CD4+ T lymphocytes and the production of interferon-γ (IFN-γ) and interleukin-2 (IL-2). In 
addition, CS1001 employs IgG4 isotype and lacks antibody-dependent cellular mediated 
cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC), thus avoids direct 
damaging of PD L1(+) immune cells. In addition, in an in vitro assay, CS1001 in 
combination with a Poly ADP-ribose polymerase (PARP) inhibitor IMP4297 enhanced T 
cell-mediated tumor killing compared to IMP4297 or CS1001 alone. 
Furthermore, the in vivo efficacy of CS1001 in inhibiting tumor growth was demonstrated 
in the subcutaneous MC38-B7H1 murine colon carcinoma (murine MC38 cells expressing 
human PD L1) in PD-1 humanized mouse (Biocytogen’s B-hPD-1 mouse) model. When 
combined with lenvatinib (VEGFR1/2/3 inhibitor), CS1001 can enhance the tumor growth 
inhibition compared to each of the monotherapy agents in subcutaneous MC38-B7H1 
murine colon carcinoma (murine MC38 cells expressing human PD-L1) in PD-1 humanized 
mouse (Biocytogen’s B-hPD-1 mouse) model. 
1.2.1.2 Pharmacokinetic Studies 
Cynomolgus monkeys were given a single intravenous injection of CS1001 at 10, 30, 90 
mg/kg, respectively, and pharmacokinetic (PK) characteristics and anti-drug antibody (ADA) 
were evaluated. No significant PK differences were found between male and female 
cynomolgus monkeys; serum concentration at time 0 (C0) of CS1001 increased in a dose-
dependent manner in both genders as the dose increased from 10 mg/kg to 90 mg/kg and the 
ratio of area under the concentration-time curve from time 0 to the time of the last 
quantifiable concentration (AUC0-last) increase was greater than the ratio of dose increase. 
ADA data showed that the number of monkeys which were ADA positive in the high-dose 
group (no ADA was observed in 90 mg/kg group) was lower than that in the low-dose group 
(ADA positive rate in the 10 mg/kg group was 22.2% for both male and female; ADA 
positive rate in the 30 mg/kg group was 22.2% for the male and 11.1% for the female).  
The toxicokinetic analysis was incorporated into 29-day and 26-week monkey repeated dose 
toxicity studies. The results showed that all median time to maximum concentration 
appeared between 0.3-8.0 and 0.6-1.7 hours after administration for 29-day and 26-week 
studies, respectively. The systemic exposure increased in a dose-proportional manner and 
there were no significant gender differences. There was an increase in systemic exposure 
after repeated doses of CS1001, indicating the accumulation of drugs. 
1.2.1.3 Safety Studies 
Administration of CS1001 to cynomolgus monkeys by a single intravenous infusion at dose 
levels of 100, 300, or 1000 mg/kg followed by a 14-day observation period was well 
tolerated and did not result in any treatment-related effects on mortality, clinical signs, body 
weight, food consumption, or gross pathology. Under the conditions of the study, the 
maximum tolerated dose (MTD) was ≥ 1000 mg/kg. 
Administration of CS1001 to cynomolgus monkeys at dose levels of 30, 75, or 200 mg/kg 
once weekly for 29 days (a total of 5 doses) followed by a 4-week recovery period was well 
tolerated and did not result in any treatment-related effects on mortality, clinical signs, body 

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weight, food consumption, local irritation, body temperature, clinical pathology, safety 
pharmacology, immunology, or pathology. Consequently, under the conditions of the study, 
the no adverse effect level (NOAEL) was considered to be 200 mg/kg, the corresponding 
systemic exposure (expressed by Cmax and observed area under the concentration-time curve 
from time 0 to 168 hours [AUC0-168h]) on Day 22 were 15,100 μg/mL and 55,800 day•μg/mL 
in males, and 12,200 μg/mL and 51,800 day•μg/mL in females, respectively. No animals 
were detected as positive for the anti-CS1001 antibody during this study.  
In a 26-week toxicity study, similar to the results of the 29-day study, the dose level of 200 
mg/kg was well tolerated in cynomolgus monkeys and did not result in any test article related 
changes. No animals were detected as positive for the anti-CS1001 antibody during this 
study. Consequently, the NOAEL was 200 mg/kg, the corresponding systemic exposure 
(expressed by Cmax and AUC0-168h) on Day 176 was 14,600 μg/mL and 69,600-day•μg/mL. 
In the in vitro hemolysis test, CS1001 at concentrations of 6 and 30.8 mg/mL did not show 
any hemolytic potential. 
In the active systemic anaphylaxis test in guinea pigs, there were no test article-related 
changes in body weight and clinical signs during the induction and challenge phases. There 
were no unscheduled deaths during the study. CS1001 did not produce any indication of 
anaphylactic response. 
An immunohistochemistry staining method was applied to determine the binding activity of 
CS1001 in normal fresh frozen human, monkey, and rat tissues. CS1001 had tissue cross 
activity in the human placenta. 
1.2.2 Clinical Studies 
The clinical program with CS1001 currently includes 10 ongoing trials in patients. Study 
CS1001-101, a Phase Ia/Ib, open-label, first-in-human (FIH) study conducted in Mainland 
China in patients with advanced solid tumors or lymphoma; CS1001-102, a Phase I, open-
label, dose-escalation study of single-agent CS1001 conducted in the US in patients with 
advanced solid tumors; CS1001/Regorafenib-101, Phase Ib/II, multi-center and open-label 
study of CS1001 in combination with regorafenib in patients with advanced or refractory 
solid tumors; CS3008(BLU-554)-101, Phase Ib/II, multi-center, open-label, multi-dose 
study to evaluate CS1001 in combination with CS3008 (BLU 554) in patients with locally 
advanced or metastatic hepatocellular carcinoma (HCC);  CS1001-201/202, Phase II, single-
arm, multicenter studies conducted in patients with relapsed or refractory extranodal NK/T 
lymphoma and relapsed or refractory classical Hodgkin lymphoma, respectively; CS1001-
301/302/303/304, Phase II, multicenter, randomized, double-blind study conducted in China 
in patients with locally advanced/unresectable non-small cell lung cancer (NSCLC), Stage 
IV NSCLC, gastric/gastro-esophageal junction (GC/GEJ) adenocarcinoma, and advanced 
esophageal squamous cell carcinoma (ESCC), respectively. 
In Study CS1001-101 Ia, no DLT was observed in Study CS1001-101, and MTD was not 
reached. The recommended Phase II dose was determined as 1200 mg fixed-dose, once every 
3 weeks (Q3W), and was continued its dose expansion in various tumor types in Phase Ib of 
the study and in Phase II and III trials. The details refer to the investigator’s brochure 
(version 6.0, 10 July 2020).  
1.2.3 Risk/Benefit Assessment 
According to the mechanism of action of this investigational product and the clinical safety 
information of products with the same mechanism of action, expected possible adverse 
events in this trial are all kinds of inflammation caused by immune system activation, such 

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as pneumonitis, colitis, hepatitis, nephritis, and endocrine inflammation, etc. According to 
available clinical data of the investigational product, although the incidence of adverse 
effects is high, the drugs are well tolerated with only a small number of subjects 
discontinuing study due to adverse effects, and the majority of the adverse effects can well 
resolve after treatment. Early symptoms of immune-related adverse effects are quite 
heterogeneous. Therefore, investigators should pay special attention to early symptoms and 
signs of immune-related reactions to make accurate and timely judgments to dose 
modification and adequate intervention on time. Meanwhile, investigators should avoid 
enrolling patients with autoimmune diseases, which could get worse when the immune 
system is activated. 
According to the clinical reports on pembrolizumab in treating R/R ENKTL, PD-1/PD-L1 
pathway inhibition is shown to be an effective treatment with a manageable safety profile. 
In summary, this trial is planned to evaluate the efficacy and safety of CS1001 monotherapy 
in R/R ENKTL. 

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2. OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary objectives 
Primary endpoints 
To evaluate the efficacy of 
CS1001 in subjects with R/R 
ENKTL; 
Objective response rate (ORR) assessed by IRRC according to 
Lugano 2014 classification 
Secondary objectives 
Secondary endpoints 
To evaluate the efficacy of 
CS1001 in subjects with R/R 
ENKTL; 
ORR assessed by investigators; 
CRR, PRR, TTR, DoR assessed by IRRC and investigators; 
To evaluate the safety of CS1001 
in subjects with R/R ENKTL 
Severity and frequency of AEs, and frequency of SAEs 
To evaluate the PK of CS1001 
To determine the peak and trough serum concentration of CS1001 
To evaluate the immunogenicity 
of CS1001 
Number and percentage of subjects who develop ADA 
Exploratory objectives 
Exploratory endpoints 
To evaluate the progression-free 
survival (PFS) and overall 
survival (OS) of R/R ENKTL 
subjects  
6-months PFS rate,  6-month OS rate 
To evaluate genetic aberrations 
in R/R ENKTL by whole-exome 
sequencing test of tumor tissues 
The association between genetic aberrations and efficacy 
 

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3. STUDY DESIGN 
3.1 OVERALL DESIGN 
This study is a single-arm, multicenter, Phase II trial to evaluate CS1001 monotherapy in 
R/R ENKTL. This study consists of three periods: screening, treatment, and follow-up period. 
⚫ The screening period consists of 28 days before the first dose of investigational product. 
⚫ Treatment period: enrolled subjects will receive investigational product CS1001 1200 
mg intravenous infusion every 21 days up to 2 years until disease progression, 
intolerance, consent withdrawal, death, or other reasons specified in the protocol. 
Lugano 2014 classification (Appendix 13.1) will be used for efficacy assessment in the 
treatment period. 
⚫ Following study treatment discontinuation or two years of treatment, whichever comes 
first, subjects will enter into the follow-up period. 
The Schedule of study activities is shown in Table 1. 
3.1.1 Screening 
Subjects must sign the informed consent and complete the screening visit to determine 
whether they are eligible for study enrollment. 
Stained tumor tissue sections and corresponding pathological reports or unstained tumor 
tissue sections (or tissue block) must be collected at screening for central pathology review. 
Both fresh and archival biopsies are accepted and can be used by central pathology.  
Investigators may enroll subjects before obtaining the result of the central pathology review. 
Seven (7) unstained FPPE tumor slides should be collected at screening for whole-exome 
sequencing of tumor tissue. A total amount of 2 mL whole blood should be collected at 
screening as germline control of whole-exome sequencing. If the tumor tissue and whole 
blood samples were not available at screening,  retrospective collections of 7 archival FFPE 
tumor tissue slides and collection of 2 mL whole blood are allowed for whole-exome 
sequencing. 
The baseline tumor assessment will be completed within 28 days before the enrollment. 
3.1.2 Treatment Period 
All of the laboratory tests and vital sign measurements should be performed within 72 hours 
before dosing at each cycle. (For Cycle 1, pregnancy test, hematology, serum chemistry, 
urinalysis, and thyroid function can be assessed 7 days before dosing. AEs will be recorded 
at each visit. 
All subjects will receive CS1001 1200 mg once every 3 weeks up to 2 years until disease 
progression, intolerable to study treatment, consent withdrawal, death, or other reasons 
specified in the protocol. 
Efficacy will be assessed according to Lugano 2014 classification. 
Blood samples for pharmacokinetic and immunogenicity assays are collected at the time 
points specified in Table 1. 
Subjects must receive end-of-treatment (EOT) visit when permanently discontinue the study 
treatment. (The EOT date will be the decision making date for discontinuing the study 
treatment by investigators.) 

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3.1.2.1 Treatment Beyond Disease Progression 
For subjects who have PD according to Lugano 2014 classification, if it is suspected by the 
investigator as pseudo-progression, treatment may continue until confirmation of PD with 
repeated imaging at least 4 weeks later (or preferred at the next scheduled regular imaging 
time point). But all of the following criteria must be met to continue the treatment: 
a. Absence of clinically significant symptoms and signs of PD (including worsening 
laboratory values) 
b. Stable ECOG PS performance 
c. Absence of rapid progression of disease or PD at critical anatomical sites that 
necessitates urgent medical intervention 
In special situations, a subject with disease progression confirmed by radiology or other 
clinical examinations who will possibly benefit from further investigational treatment may 
continue the treatment at the discretion of the investigator in consultation with the sponsor. 
Written consent from the subject must be obtained before any treatment beyond disease 
progression (including suspected pseudo-progression and confirmed disease progression). 
3.1.2.2 Study Discontinuation Criteria for Clinical Deterioration 
Clinical events considered by the investigator as a result of disease progression that will 
probably not recover even if treatment continues will be judged to be a clinical deterioration. 
The subject will be determined to continue or discontinue treatment by the investigator in 
consultation with the medical monitor, and the process will be recorded in the study file. 
3.1.3 Follow-up 
Following study treatment discontinuation or two years of treatment, whichever comes first, 
subjects will enter into the follow-up period, which consists of three parts: 
⚫ 
Safety follow-up: A safety follow-up visit should be conducted 30, 60, 90 days after the 
last dose of the investigational product. Safety follow-up period refers to the 90 days 
after the last dose of the investigational treatment or the start of new anti-cancer 
treatment, whichever occurs earlier. 
⚫ 
Tumor assessment follow-up: For all subjects other than those who discontinue 
treatment due to radiological disease progression, tumor assessment should be 
performed at pre-specified regular time points until radiological disease progression, the 
start of new anti-cancer treatment, death, or the end of this trial, whichever occurs first. 
⚫ 
Survival follow-up: Subjects will receive a follow-up visit every 12 weeks after the last 
dose of investigation product and survival data collection will continue until lost to 
follow-up, death, consent withdrawal, or the end of the study, whichever comes first. 
Telephone follow-up is acceptable. 
AEs that occur during the follow-up period will be reported as per Section 7. 
3.1.4 End of Study 
The date of the end of the study is defined as the date of the last follow-up. The final analysis 
for the primary endpoint will be conducted up to 24 weeks after enrollment of the last subject. 
The study will continue until the last data point of the last subject has been collected (when 
the last subject completes the safety follow-up). The study can be terminated at any time by 
the sponsor.  
3.1.5 Treatment Beyond End of Study 
Subjects with clinical benefit (without disease progression and with good tolerance) when 
they have been on CS1001 treatment for 2 years or this clinical study ends may continue 

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treatment with the investigational product. These subjects must provide written ICF and be 
willing and able to continue to follow all study procedures in order to remain on treatment. 
The investigational product may be offered in another extension study or by means 
determined by the sponsor. 
3.2 RATIONALE FOR STUDY DESIGN 
3.2.1 Rationale for Single-Arm Design 
Given the rarity of R/R ENKTL and the lack of standard of care after the failure of 
asparaginase-based treatment, there is a significant unmet medical need in this population. 
Existing clinical data showing the efficacy of anti-PD-1 monoclonal antibody in R/R 
ENKTL demonstrates the potential of inhibition of the the PD-1/PD-L1 pathway as an 
effective treatment for R/R ENKTL. Therefore, this trial is designed as a single-arm study. 
3.2.2 Rationale for Primary Endpoint Analysis for Treatment of Up to 24 Weeks 
According to data reported for pembrolizumab, the response was primarily achieved at 6-
12 weeks of treatment. It’s expected that each of the disease responses will be observed by 
24 weeks after each of the subjects receives the drug. ORR analysis will be performed up 
to 24 weeks after the first dose in the last subject. The efficacy and safety will be evaluated 
via ORR in combination with PFS, DoR, and will use historical data as the reference. 
3.2.3 Rationale for Setting ORR as the Primary Endpoint with Historical 
Control 
In a report of pembrolizumab in 7 patients with R/R ENKTL who failed prior asparaginase-
based regimen, 5 patients achieved CR and 2 patients achieved PR. The 5 CR patients were 
still in remission at a 6-month follow-up[16]. Another study of pembrolizumab in 7R/R 
ENKTL patients reported that 2 patients achieved CR and 2 patients achieved PR [17]. A 
French study was conducted in 13 R/R ENKTL patients failing asparaginase-based 
chemotherapy. Three patients (3/13, 23%) achieved CR, and one (1/13,8%) achieved PR[18]. 
A single-center retrospective study in Korea reported the outcome of 14 R/R ENKTL 
patients treated with pembrolizumab, with a CR rate of 35.7% (5/14) and ORR of 42.9% 
(6/14)[19]. These results indicated anti-PD-1/PD-L1 pathway inhibition could lead to a 
durable objective response, which correlates with clinical benefit. Therefore, ORR is used 
as the primary endpoint in this trial. While the ORR was encouraging, these were small 
retrospective case studies, and pembrolizumab is not approved for this indication. So, these 
data were not appropriate to be referenced as historical control. As a targeted therapy, 
chidamide has been approved to treat R/R peripheral T-cell lymphoma (including R/R 
ENKTL) in China. For the R/R ENKTL indication, it is reported to have a CR rate of 6.3% 
(1/16) and an ORR of 18.8% (3/16) in the pivotal phase II trial[1]. Taking into consideration 
of chidamide registration study ORR in R/R ENKTL, the historical control is proposed as 
20% in this study. 
3.2.4 Rationale for Treatment Beyond Disease Progression 
Clinical data of other immune checkpoint inhibitors showed that a minority of subjects may 
derive clinical benefit from treatment beyond initial progression (manifesting as enlarged 
original lesion or occurrence of a new lesion) that occurs before clinical objective response 
and/or stable disease in some patients[22]. Currently, two mechanisms are believed to be 
responsible for this phenomenon. Firstly, intra-tumor inflammation aggravation may lead to 
an increase in tumor masses as manifested by an enlarged measurable lesion or new, visible 
unmeasurable lesion. Secondly, the anti-tumor immune response occurs at a later time in 
some patients who have a smaller tumor-inhibitory effect than the tumor growth kinetics in 

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the early stage. Therefore, for the subjects on CS1001 treatment who are considered to have 
clinical benefit and are well tolerated to the investigational product, they are allowed to 
continue treatment despite initial PD assessed by the investigator according to Lugano 2014 
classification. 
3.2.5 Rationale for Exploratory Biomarker Investigation 
Few clinical trials investigated anti-PD-1/PD-L1 monoclonal antibody treatment in 
ENKTL patients, and biomarkers for predicting whether ENKTL patients can benefit from 
anti-PD-1/PD-L1 monoclonal antibody have not been reported yet. ENKTL-associated 
genetic aberration data such as single nucleotide variation, nucleotide insertion, and 
deletion can be found by whole-exome sequencing assay on tumor tissues. By matching 
the featured genetic aberrations and the efficacy of CS1001 in patients with ENKTL, we 
may find genetic aberrations that are associated with the efficacy of anti-PD-L1 
monoclonal antibodies. These genetic aberrations may be used as biomarkers to guide 
patient selection and predict CS1001 efficacy in clinical practice. 

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4. STUDY POPULATION 
It’s planned to enroll approximately 80 subjects with R/R ENKTL in this trial. 
The detailed inclusion and exclusion criteria are listed below. 
4.1 Inclusion Criteria 
1. Subjects who are willing to participate in this trial; fully understand and are fully 
informed of this trial, and are able to provide written ICF; are willing and able to 
follow all study procedures. 
2. Subjects are ≥ 18 years and ≤ 75 years of age on the day of signing informed consent. 
3. Subjects must have a histologically confirmed ENKTL at the study site. Both nasal 
and non-nasal ENKTL are allowed. 
4. Subjects must have relapsed or refractory ENKTL failing asparaginase-based 
chemotherapy or chemoradiotherapy. (Relapse: disease progression after response to 
the last treatment; refractory: no response to the last treatment.)  
5. ECOG PS of 0 or 1. 
6. Life expectancy ≥ 12 weeks. 
7. Subjects must have at least one evaluable or measurable lesion per Lugano 2014 
classification [An evaluable lesion is a lymph node or extranodal lesion with 
radioactive uptake higher than liver on 18FDG/PET and with typical lymphoma 
characteristic on PET and/or CT; Measurable lesion: the longest diameter (LDi) is 
of > 15 mm for nodal lesion or >10 mm for extranodal lesion (if the only measurable 
lesion has received prior radiotherapy, the subject must have evidence of radiological 
progression after radiotherapy), and concurrent elevated uptake of 18FDG]. Absence 
of measurable lesion with diffuse 18FDG uptake increase in the liver should be ruled 
out first. 
8. Subjects must provide stained tumor tissue sections and corresponding pathological 
reports or unstained tumor tissue sections (or tissue block) for central pathology 
review. Investigators may enroll subjects before the result of the central pathology 
review. 
9. Subjects must have adequate organ function and bone marrow function without 
severe hematopoietic disorder, or heart, lung, liver or kidney dysfunction or immune 
deficiency (no blood transfusion, granulocyte colony-stimulating factor or other 
relevant medical supporting care within 14 days before the first dose of study 
treatment): 
a) Absolute neutrophil count ≥ 1.0 × 109 /L; 
b) Platelets ≥ 50 × 109 /L; 
c) Hemoglobin ≥ 8 g/dL; 
d) Creatinine clearance ≥ 40 mL/min (according to Cockcroft-Gault equation); 
e) Serum total bilirubin ≤ 1.5 × ULN, unless considered to be due to Gilbert’s 
disease, where it must be ≤3 × ULN 
f) 
AST and ALT ≤ 2.5 × ULN; 

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g) Coagulation functions: INR ≤ 1.5 × ULN; PT and APTT ≤ 1.5 × ULN (unless 
the subject is on anti-coagulant; and PT and APTT at screening are as expected 
in patients on anti-coagulant). 
10. Subjects with prior anti-cancer treatment can only be enrolled when the toxicity of 
prior anti-cancer treatment has recovered to baseline or ≤ Grade 1 according to 
CTCAE v4.03. For patients with irreversible Grade 2 toxicities (e.g. 
thrombocytopenia, anemia, neurotoxicity, alopecia, and hearing impairment) that is 
anticipated to be unlikely to worsen during study treatment, the subject can be 
enrolled after approval by the medical monitor of the sponsor. 
11. WOCBP must have a negative serum pregnancy test ≤7 days before the first dose of 
investigational product. WOCBP or fertile men and their WOCBP partners must 
agree to use an effective contraceptive method from providing signed ICF through 6 
months after the last dose of the investigational product (Refer to Section 4.1.5 for 
details). 
4.2 Exclusion Criteria 
1. Aggressive natural killer-cell leukemia or ENKTL patients who have any degree of 
leukemic involvement will be excluded. 
2. Concomitant with hemophagocytic lymphohistiocytosis. 
3. Current or historical primary central nervous system lymphoma (PCNSL) or 
secondary CNS involvement. 
4. Prior allogeneic organ transplantation. 
5. Allogenic hematopoietic stem cell transplantation (HSCT) ≤ 5 years before the first 
dose of investigational product. (Patients are permitted to enroll if they received 
allogenic HSCT more than 5 years before the first dose of investigational product 
and without any current graft-versus-host reaction.) 
6. Current participation in another clinical study or use of any investigational drug 
within 4 weeks before the first dose of investigational product in this trial. 
7. Autologous HSCT within 90 days before the first dose of CS1001. 
8. Subjects with an active autoimmune disease that requires systemic treatment in the 
past two years. (Hormone replacement therapy is not considered as systemic therapy 
such as the patient has type I diabetes mellitus, hypothyroidism that can be managed 
with thyroid hormone replacement only, or adrenal insufficiency or pituitary 
insufficiency that requires a physiological dose of corticosteroid replacement.) 
Subjects are permitted to enroll if they have an autoimmune disease that didn’t 
require any systemic treatment in the past two years. 
9. Subjects received systemic corticosteroid or any other immunosuppressive therapy 
within 14 days before the first dose of the investigational product. [Subjects are 
permitted to use topical, ocular, intra-articular, intranasal and inhaled corticosteroids 
(with minimal systemic absorption); a short course (≤ 7 days) of corticosteroids for 
prophylaxis (e.g., hypersensitivity to contrast media) or for treatment of non-
autoimmune conditions (e.g., delayed hypersensitivity caused by contacting 
allergens).] 
10. A known additional malignancy within 5 years prior to the first dose of 
investigational product. Subjects with locally curable malignancies (including basal 

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cell carcinoma of skin, squamous cell carcinoma of skin, breast cancer in situ or 
cervical cancer in situ, etc.) that have undergone curative therapy are permitted to 
enroll. 
11. Subjects who have had prior chemotherapy, immunotherapy, biological therapy 
(including cancer vaccine, cytokine therapy or growth factors to treat cancer) used 
as a systemic treatment for cancer, within 28 days before the first dose of 
investigational product. 
12. Subjects who underwent a major surgical procedure within 28 days prior to the first 
dose of investigational product or radiotherapy within 90 days before the first dose 
of investigational product. 
13. Any use of traditional Chinese medicines or herbal preparations with anti-tumor 
indications within 7 days before the first dose of investigational product. 
14. Has received a live vaccine within 28 days before the first dose of investigational 
product. (Attenuated influenza vaccine is allowed.) 
15. Known history of (HIV infection and/or acquired immune deficiency syndrome 
(AIDS). 
16. Subjects at the active phase of chronic hepatitis B or with active hepatitis C. Subjects 
who are HBsAg positive or HCV antibody positive at screening must not be enrolled 
until further definitive testing with HBV DNA titers (≤ 2500 copies/mL or 500 
IU/mL) and HCV RNA tests (≤ the lower limit of detection) can conclusively rule 
out the presence of active hepatitis B or C that requires treatment, respectively. 
Subjects that carry the hepatitis B virus, with stable hepatitis B (HBV DNA titer ≤ 
2500 copies/mL or 500 IU/mL) after medical treatment or with cured hepatitis C are 
permitted to enroll. 
17. History of interstitial lung disease (except for those induced by radiation therapies 
and are asymptomatic). 
18. Active tuberculosis infection. 
19. An active infection requiring systemic anti-infection therapy within 14 days before 
the first dose of investigational product. 
20. Subjects who have received anti-PD-1, anti-PD-L1, or anti-CTLA-4 monoclonal 
antibody treatment. 
21. Subjects with a known severe allergy to monoclonal antibodies (≥ Grade 3 per 
CTCAE v 4.03) or uncontrolled allergic asthma. 
22. Women in pregnancy or lactation. 
23. Subjects with active alcohol or drug dependence.. 
24. Subjects with uncontrollable concomitant diseases including but not limited to 
symptomatic congestive heart failure, uncontrolled hypertension, unstable angina, 
active gastrointestinal ulcer or hemorrhagic disorders. 
25. Subjects with a history of psychiatric disease; or subjects with incapacity or limited 
capacity. 
26. Underlying condition that in the investigator's opinion would increase the risk of 
investigational product administration or confound the assessment for its toxicity. 
27. Subjects in the investigator’s opinion are not suitable for participating in this trial. 

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4.3 Discontinuation and Withdrawal 
4.3.1 Discontinuation of Study Treatment 
Subjects must discontinue study treatment if any of the following criteria are met: 
1. Any AE that meets the treatment discontinuation criteria specified in the protocol 
(refer to Section 5.3). 
2. Disease progression. (Subject who meets the criteria for treatment beyond 
progression may continue treatment until confirmation of progressive disease by 
tumor assessment. Refer to Section 3.1.2.1.) 
3. Subjects who receive any prohibited treatment during the trial that compromises 
the assessment of safety and efficacy may be determined to discontinue study 
treatment by the investigator in consultation with the sponsor medical monitor. 
4. Any intercurrent condition that compromises the subject's ability to continue study 
treatment. 
5. Pregnancy of female subjects. 
6. Subjects and/or their legal guardian who decide to discontinue the study treatment 
may inform the subject's doctor at any time and then discontinue study treatment. 
According to the Deceleration of Helsinki and other applicable regulatory 
requirements, all subjects have the right to withdraw from the study at any time 
and for any reason. The doctor and the study site must not hold bias in their future 
treatment. 
7. Subject with poor compliance who doesn't receive treatment at the right dose and 
the right time despite the investigator’s effort in communication and coordination, 
which may lead to significant uncorrectable bias in the study results may be 
determined to discontinue study treatment by the investigator in consultation with 
the sponsor medical monitor. 
8. Other conditions that make study treatment continuation inappropriate judged by 
the investigator. 
In any case, the primary reason for study treatment discontinuation will be recorded in the 
original medical record. For subjects who discontinue study treatment for any reason, the 
investigator should try every effort to have the subject complete end of study visit if the 
subject has received at least one dose of the investigational product, and continue to follow 
up subjects with unresolved AE. 
4.3.2 Follow-up After Discontinuation 
Subjects who discontinue study treatment must be followed up. Outcome and/or survival 
follow-up data will be collected per protocol requirements until the subject dies or this 
study ends. Apart from subjects who discontinue treatment due to radiological disease 
progression assessed by imaging, tumor assessment should be performed at pre-specified 
regular time points until radiological disease progression, the start of new anti-cancer 
treatment, death, or the end of this trial, whichever occurs first. 
Study sites will contact subjects who are lost to follow-up, if possible, determine the reason 
for lost to follow-up, and rearrange follow-up visits. The date of contacting the subject and 
contact method will be recorded in the study file. 
4.3.3 Consent Withdrawal 
If a subject that requires study treatment discontinuation would continue the study, he/she 
must follow the follow-up procedures specified in the study protocol. The only exception 

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allowed is that the subject clearly withdraws the informed consent and himself/herself or 
other authorized personnel who provides this information cannot be contacted. The subject 
shall inform the investigator by a written notice about the decision to withdraw the consent 
to future follow-up, if possible. The investigator should record the details in the subject's 
medical record, including whether the consent withdrawal refers to study treatment 
discontinuation only or no more study procedures and/or post-discontinuation follow-up. 
Only data that allowed to be disclosed in compliance with legal and applicable regulatory 
requirements can be used for survival evaluation. 
4.4 Definition of WOCBP 
Women of childbearing potential (WOCBP) refer to women that have had menarche, 
haven't received any sterilization operation (such as hysterectomy or bilateral 
oophorectomy), and haven't reached menopause. Menopause is defined as amenorrhea for 
over 12 months without any biological or physiological cause in women aged >45 years. 
Furthermore, the documented follicular stimulating hormone (FSH) level of women aged 
<55 years must be > 40 mIU/mL to confirm menopause. 
* The FSH level of women on hormone replacement therapy (HRT) may be artificially 
suppressed. These women may need a washout period to obtain a physiological FSH level. 
The duration of the washout period is determined by the type of HRT. Guidelines 
recommend the following duration of the washout period. Investigators should determine 
the washout period at their own discretion when testing for serum FSH levels. Women 
whose serum FSH level is > 40 mIU/mL at any time during the washout period can be 
considered as menopause. 
• 
At least one week for vaginal contraception products (such as vaginal ring, contraceptive 
jelly, and gel) 
• 
At least 4 weeks for transdermal products 
• 
At least 8 weeks for oral contraceptive agents 
May need at least 6 months for other parenteral products. 
4.5 Definition of Effective Contraception 
Subjects must be willing to use at least two methods of contraception; one is a highly 
effective method and the other highly or less effective method as listed below. If total 
abstinence is used as a highly effective method, other methods will not be needed. 
Highly effective contraception methods 
WOCBP subjects or WOCBP partners of male subjects may use hormonal methods of 
contraception, for example, compound oral contraceptives, vaginal ring, injections, 
implant, or intrauterine device. The female partners of male subjects enrolled in this study 
may use hormonal contraceptive pills as an acceptable method of contraception because 
they don't receive investigational product administration. 
Intrauterine device 
Tubal ligation 
Vasectomy 
Total abstinence* 

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* Total abstinence defined as total avoidance of heterosexual intercourse is an acceptable 
method of contraception for all investigational products. Female subjects must continue to 
receive a pregnancy test. When a subject is no longer in total abstinence, other acceptable 
highly effective methods of contraception must be considered. 
Less effective contraception methods 
Male condom that contains spermicide 
Contraceptive diaphragm that contains spermicide 
Cervical cap that contains spermicide 
Vaginal sponge 
Male condom that doesn't contain spermicide 
WOCBP subject or WOCBP partner of a male subject takes pills that only contain 
progesterone 
Female condom* 
* Male condom and female condom should not be used at the same time. 
 

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5. STUDY TREATMENT 
5.1 INVESTIGATIONAL PRODUCT 
The investigational product in this protocol is CS1001, 
 
 
The investigational treatment regimen is CS1001, 1200 mg, IV infusion Q3W. 
5.1.1 Dosage Form and Specifications 
Dosage form: injection 
Specifications: 90 mg/3 mL/vial and 600 mg/20 mL/vial 
Excipients: histidine/histidine hydrochloride, mannitol, sodium chloride, Polysorbate 80; pH 
5.5 
Period of validity: 36 months, tentatively. 
Storage condition: 2 ℃ to 8 ℃ 
5.1.2 Packaging and Labeling 
CS1001 is for injection with specifications of 90 mg/3 mL/vial and 600 mg/20 mL/vial. All 
investigational products will be labeled in compliance with Good Clinical Practice (GCP) 
requirements. The label content will be designed according to the sponsor’s standards. All 
drugs will be dispatched as the main trial-specific materials. 
A uniform format will be applied to the drug labels. The labeling will contain the following 
information: protocol number, name of the investigational product (and “For clinical trial 
use” labeled), specification, storage, batch number, expiry date, and sponsor. 
All the records of batch number and expiry date as well as labels for all investigational 
products will be kept in the study file. 
5.1.3 Management of Investigational Product 
The investigational product handling liability will be executed as per requirements in 
Appendix 13.3. 
5.1.3.1 Dispensing of Investigational Products 
The investigational product is provided by the sponsor, dispatched to the study sites as per 
the plan. The investigational product must be kept and dispensed by a designated person at 
the study site. The investigational product will be stored in a locked cabinet as required. 
5.1.3.2 Storage of Investigational Product 
The investigational product will be kept, handled, and dispensed by a designated person at 
the study site. The responsible person at the study site will confirm the receipt of 
investigational product in writing and use the investigational product within the framework 
specified in the protocol. An accurate record of the shipment, dispensing, and return of the 
investigational product will be maintained. Meanwhile, the sponsor will retrieve the 
packages of investigational product at the end of this trial. The storage temperature of 
investigational products will also be recorded in corresponding documents. 
The investigational product will be dispensed by a member of the study team. The personnel 
should ensure and record the dispensing of the investigational product as planned; the 
quantity of dispensed and returned drugs and corresponding dates will be recorded in the 
source medical record. 

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5.1.3.3 Return of Investigational Product 
The investigational product will be returned in the study. All unused and/or partially used 
investigational product(s) will be returned to and destroyed by a third party designated by 
the sponsor following the accountability work at the study site.  
5.1.3.4 Destruction of Investigational Product 
The investigational product will be destroyed at a third party designated by the sponsor. 
Study personnel should ensure, develop, and record an adequate process of investigational 
product handling in compliance with applicable regulations, guidelines, and policies. The 
investigational product will be destroyed per sponsor’s approval. 
5.1.4 Preparation and Administration 
CS1001 is to be administered as an IV infusion in compliance with local clinical guidelines. 
(Infusion using a device through a 0.2 micrometer in-line or with an additional filter is 
recommended.) See the Drug Handbook for additional information on preparation and other 
special requirements. 
Dilution: 
 
Dilute the total dose of CS1001 to be administered with 250 mL of sterile normal 
saline (0.9% sodium chloride solution). 
Administration Instructions 
 
CS1001 is to be administered as an IV infusion, not an IV bolus injection. 
 
Ensure that the investigational product is clear, colorless, and free from any 
particulate matter on visual inspection. 
 
Withdraw a total of 40 mL (13.33 vials of 90 mg/3 mL/vial product, or 2 vials of 
600 mg/20 mL/vial product) of CS1001 solution into a syringe. The solution of the 
two specifications should not be mixed for a single infusion. Inject CS1001 solution 
withdrawn into a 250-mL infusion bag of normal saline. Do not insert a syringe into 
a vial to withdraw investigational products more than once. Do not use a glass 
syringe to withdraw investigational products. 
 
Mix by gently inverting several times. Do not shake. 
 
Visually inspect the final solution. If the solution is not clear or the contents appear 
to contain precipitate, the solution should be discarded and record in the drug 
management log. 
 
Record time and dose (in mg) of CS1001 preparation in the preparation sheet. 
 
The investigational product is administered over 60 minutes. For subjects who have 
an infusion-related reaction, the infusion duration can be extended appropriately, 
according to Section 5.3.4. The infusion line should not be used for other 
medication infusions. 
 
The infusion line should undergo flush with sufficient normal saline at the end of 
the infusion. 
 
The investigational product is recommended to be administered to subject 
immediately after preparation, avoiding exposing the prepared solution under room 
temperature for more than the recommended 6-hour limit. In which, the 6 hours 
include the time for CS1001 storage under room temperature, solution storage in 
the infusion bag, and infusion time. If the administration of the prepared drug is to 
be postponed, it should be stored under refrigeration at 2 ℃ to 8 ℃ for no more 
than 24 hours. 
5.2 TREATMENT COMPLIANCE 

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The dosing of the investigational product will be monitored by the principal investigator or 
his/her assistant for ensuring treatment compliance. The exact time of dosing (starting and 
ending of infusion) and dose administered should be recorded. For infusion interruption, the 
cause of interruption should be recorded in eCRF. 
5.3 INVESTIGATIONAL PRODUCT DOSING MODIFICATION 
5.3.1 Overall Principle for Investigational Product Dosing Modification 
The mechanism of CS1001 is to promote T-cell activation and proliferation. As a result, 
CS1001 may induce autoimmune hyperactivity which will further cause autoimmune 
diseases involving multiple organ systems. Immune-related AEs (irAEs), for example, 
pneumonitis, diarrhea/enterocolitis, renal impairment, rash, hepatitis, endocrine disorders, 
and peripheral or central neuropathy have occurred in the clinical use of other immune 
checkpoint inhibitors including ipilimumab, nivolumab, pembrolizumab, and atezolizumab. 
Once a subject develops any of the above AEs in this trial, the subject should be monitored 
for symptoms and signs. Appropriate tests and examinations may be conducted for 
differentiating etiology. If no other cause (for example disease progression, concomitant 
medication, or infection) is found while the subject requires corticosteroid and/or other 
immunosuppressive treatment, the AE is considered as related to the immune system 
hyperactivity caused by CS1001, and thus is an irAE. (This rule doesn't apply to 
endocrinology events, for example, hyperthyroidism/hypothyroidism, hypophysitis, type I 
diabetes mellitus, and adrenal insufficiency, which will still be considered as related to 
autoimmune hyperactivity caused by CS1001 treatment although they may not require 
immunosuppressive treatment). Identification, diagnosis, management, and dose 
modification for irAEs are detailed in Appendix 13.4. 
5.3.2 Criteria for Dose Modification of Investigational Product 
Dose increase or reduction of CS1001 is not permitted in this trial. The investigational 
product will be withheld for any of the following investigational drug-related adverse 
reactions: 
1. Grade 2 pneumonitis 
2. Grade 2 or 3 colitis; Grade 3 diarrhea or persistent Grade 2 diarrhea 
3. Grade 2 hepatitis (elevation of ALT, AST, or total bilirubin levels) 
4. Grade 2 hypophysitis without adrenal crisis 
5. Grade 2 nephritis 
6. Grade 3-4 hypothyroidism 
7. Grade 3 hyperthyroidism lasting for 6 weeks or more despite proper management 
8. Grade 3 dermatitis 
9. Grade 2 neuromuscular toxicity 
10. Grade 2 ocular toxicity 
11. Other Grade 2 AEs (for example arthritis, pancreatitis, hemolytic anemia, adrenal 
insufficiency, myasthenic syndrome, and rhabdomyolysis) 
12. Grade 4 hematologic toxicity 
13. Any Grade 3 abnormal laboratory test results except for the following situations: 
– Grade 3 hematologic toxicity. 

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– Study treatment will be delayed when Grade 2 hepatitis occurs. 
14. Any AE, abnormal laboratory test result, or intercurrent condition that in the 
investigator’s opinion requires postponing study treatment. 
Subjects may resume investigational treatment when the above AE(s) resolve(s) to Grade 
0/1 or baseline and the dose of systemic corticosteroid for treating the AE(s) have been 
tapered to 10 mg daily prednisone equivalents or less. 
The investigational treatment will not be resumed for dosing delay due to any cause for more 
than 9 weeks (12 weeks after the last dose). (Subject may continue treatment if he/she still 
benefits clinically at the discretion of investigator in consultation with the sponsor's medical 
monitor.) 
5.3.3 Criteria for Permanent Discontinuation of Investigational Treatment 
The investigational product will be permanently discontinued after consultation with the 
sponsor’s medical monitor for any of the following drug-related adverse events: 
⚫ Grade 3-4 pneumonitis 
⚫ Grade 4 colitis, recurrent Grade 3 colitis, or colitis with symptom suggestive of 
intestinal perforation 
⚫ Grade 3 hepatitis (elevation of ALT, AST, or total bilirubin levels) 
⚫ Grade 4 abnormal laboratory test results except for the following situations: 
–Grade 4 neutropenia lasting for ≤ 5 days  
–Grade 4 lymphocytopenia or leukopenia 
– Solitary Grade 4 electrolyte disorder/imbalance that can be corrected by 
electrolyte supplementation/adequate treatment in 72 hours without any clinical 
consequence. 
⚫ Grade 3-4 hypophysitis or adrenal crisis 
⚫ Grade 3-4 nephritis 
⚫ Grade 4 hyperthyroidism 
⚫ Grade 4 dermatitis 
⚫ Grade 3-4 neuromuscular toxicity 
⚫ Grade 3-4 ocular toxicity 
⚫ Other Grade 3-4 AEs (for example arthritis, pancreatitis, hemolytic anemia, adrenal 
insufficiency, myasthenic syndrome, and rhabdomyolysis) except for Grade 3/4 
hypothyroidism 
⚫ Grade 4 infusion-related reactions 
Permanent discontinuation of investigational product will be considered for recurrence of 
any of the following Grade≥2 irAEs: pneumonitis, ocular toxicity, cardiac toxicity, and at 
the discretion of the investigator. 
For subjects who meet any of the above criteria although benefiting from investigational 
treatment, the sponsor’s medical monitor and the investigator will discuss and make the final 
decision in the subject's best interest. 

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5.3.4 Infusion-Related Reaction 
The symptoms of infusion-related reactions include fever, chills, nausea, pruritus, 
angioedema, hypotension, headache, bronchospasm, urticaria, rash, vomiting, myalgia, 
dizziness, or hypertension. Severe reactions may include acute respiratory distress syndrome, 
myocardial infarction, ventricular fibrillation, and cardiogenic shock. Subjects should be 
closely monitored for such reactions. Treatment modification for symptoms of infusion-
related reactions due to CS1001 is presented in Table 2. 
Immediate access to an Intensive Care Unit (ICU) or equivalent environment and appropriate 
medical care (including epinephrine, corticosteroids, IV antihistamines, bronchodilators, and 
oxygen) must be available to treat infusion-related reactions in the study sites. Infusion of 
CS1001 will be discontinued in case of Grade ≥2 infusion-related, allergic, or anaphylactoid 
reactions. Subjects must be closely monitored for infusion-related reactions continuously for 
2 hours after the first two doses of CS1001. 
Table 2 Treatment Modification for Symptoms of Infusion-Related Reactions 
CTCAE Grade 
Treatment Modification for CS1001 
Grade 1  
Mild transient reaction; infusion interruption not 
indicated; intervention not indicated. 
CS1001 infusion rate is decreased by 50% and 
any worsening of the reaction is closely 
monitored until its resolution. 
Grade 2  
Therapy or infusion interruption indicated but 
responds promptly to symptomatic treatment (e.g., 
antihistamines, NSAIDs, narcotics, IV fluids); 
treatment of prophylactic medications ≤24 hours.  
CS1001 infusion is interrupted. Infusion is 
resumed at 50% of the previous rate once 
infusion-related reactions have resolved or 
decreased to Grade ≤1 in severity and any 
worsening is closely monitored.  
Grade 3 
Prolonged (e.g., not rapidly responsive to 
symptomatic treatment and/or brief interruption of 
infusion); recurrence of symptoms following 
initial improvement; hospitalization for clinical 
sequelae or cause clinical consequences (for 
example kidney injury or pulmonary infiltration). 
CS1001 infusion is immediately discontinued. 
Continuation of study therapy is at the 
discretion of the investigator. 
Grade 4 
Life-threatening consequences; urgent 
intervention (for example mechanical ventilation) 
indicated. 
Subjects must permanently discontinue CS1001 
treatment. 
NSAIDs, non-steroidal anti-inflammatory drugs. 
Once the CS1001 infusion rate has been decreased by 50% or suspended due to an infusion-
related reaction, it must remain decreased for all subsequent infusions. If the subject has a 
second infusion-related reaction (Grade ≥ 2) on the slower infusion rate, the infusion should 
be stopped, and the subject should be permanently discontinued from CS1001 treatment. 
CTCAE Grade 1 or 2 infusion reaction: Proper medical management should be instituted, 
as indicated per type of the reaction. This includes but is not limited to an antihistamine (e.g., 
diphenhydramine or equivalent), antipyretic (e.g., paracetamol or equivalent), and oral or IV 
corticosteroids, epinephrine, bronchodilators, and oxygen on demand. The subject should 
receive bedside monitoring until symptoms resolve. In the following cycles, subjects should 

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receive oral prophylactic treatment with an antihistamine (e.g., diphenhydramine or 
equivalent) and an antipyretic (e.g., paracetamol or equivalent) at least 30 minutes before 
the start of the infusion, and they should be closely monitored for clinical signs and 
symptoms of an infusion-related reaction. 
CTCAE Grade 3 or 4 infusion reaction: Immediately stop the infusion. Proper medical 
management should be instituted immediately, per type and severity of the reaction. This 
includes but is not limited to oral or IV anti-histamine, anti-pyretic, corticosteroids, 
epinephrine, bronchodilators, and oxygen. 
If a subject experiences a Grade 4 infusion-related reaction at any time, CS1001 must be 
discontinued permanently. 
In the event of a Grade 3 infusion-related reaction, the continuation of study therapy is at the 
discretion of the investigator after consultation with the sponsor’s medical monitor. If 
continued, the infusion time of CS1001 in the next cycle should be at least 2 hours. Subjects 
should receive oral prophylactic treatment with an anti-histamine (e.g., 50 mg 
diphenhydramine or equivalent) and an antipyretic (e.g., paracetamol, NSAIDs or equivalent) 
30-60 minutes before the start of the infusion. Subjects should be closely monitored for 
clinical signs and symptoms of an infusion-related reaction. 
5.4 CONCOMITANT THERAPY  
5.4.1 Prohibited Therapy 
Treatments that the investigator considers necessary for a subject’s medical needs may be 
administered except for the following prohibited therapies. If any of the following therapies 
is required by a subject as per the investigator's assessment, the subject's eligibility for 
continuing investigational treatment will be determined at the investigator’s discretion in 
consultation with the sponsor medical monitor. 
1. Anti-tumor therapies: no other anti-tumor therapy than the investigational product 
is permitted. This includes but is not limited to chemotherapy, immunotherapy, 
biologically targeted therapy, and traditional Chinese medicines with anti-tumor 
indications; and radiation therapy. 
2. Concurrent investigational agent (unapproved medications) other than CS1001.  
3. Immunosuppressant (unless for treating AEs). 
4. Systemic corticosteroids (of dose higher than 10 mg prednisone or equivalent per 
day), unless for conditions specified in Section 5.4.2 Item 2, or for treating AEs. 
5. Live vaccines are prohibited during the study. 
6. Other prohibited treatment as specified in the inclusion/exclusion criteria. 
5.4.2 Permitted Therapy 
1. Inactivated or attenuated influenza vaccine that doesn't require wash-out. The use 
of other inactivated or attenuated preventive vaccines will be determined according 
to the actual condition after discussion with the investigator and sponsor’s medical 
monitor. 
2. Topical, ophthalmic, intra-articular, and nasal and inhaled corticosteroids (with 
very little systemic absorption) are permitted. Adrenal replacement with ≤10 mg 
corticosteroid per day or equivalent is permitted. Short-course (<3 weeks) of 
corticosteroid as prophylaxis (for contrast allergy) or treatment for non-
autoimmune diseases (for example delayed-type hypersensitivity caused by 
allergen contact). 

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3. Symptomatic and supportive treatment for AEs during the study treatment is 
permitted. 
4. Other permitted treatment as specified in the inclusion/exclusion criteria. 

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6. STUDY PROCEDURES AND ASSESSMENTS 
Study procedures and assessments should be performed at the planned time points (refer to 
Table 1). Refer to Section 6.1 for details. 
Once a subject is included in this trial, the subject must be informed of the study's nature and 
procedures, and a signed, written informed consent must be obtained before any study-
related procedure. 
6.1 STUDY PROCEDURES 
6.1.1 Screening 
The screening period is from D-28 to D-1. The assessments to be completed during screening 
are listed in Table 3: 
Table 3 Visit procedures in the screening phase 
Items 
Note 
Study Management Procedures 
Inclusion/exclusion criteria 
Assess the subject's eligibility according to the inclusion/exclusion 
criteria 
Demographics and medical 
history 
⚫ 
Age, sex, ethnicity, smoking and alcohol use history 
⚫ 
Pathohistology, clinical stage, tumor-related symptoms 
Prior medications and 
concomitant medications 
⚫ 
Treatment regimens with administration methods, starting time 
and ending time, best response and cause for discontinuation for 
prior local or systemic anti-cancer therapies 
⚫ 
Concomitant medications within 28 days before the first 
investigational product dosing 
Clinical Procedures and Assessments 
Adverse events 
AEs that occur after obtaining informed consent and before the 
administration of the investigational product 
Electrocardiogram (ECG) 
Standard 12-lead ECG will be used 
Height, weight, and vital signs 
The vital signs include temperature, blood pressure, pulse, and 
respiratory rate 
Physical examination and 
ECOG performance status 
⚫ 
Conduct Physical examination 
⚫ 
Score ECOG PS 
Laboratory Procedures/Assessments (at site) 
Pregnancy test 
Blood human chorionic gonadotrophin test is performed as a 
pregnancy test within 7 days before the first dose of study treatment 
Hematology, serum chemistry, 
urinalysis 
Hematology, serum chemistry, and urinalysis tests are performed 
within 7 days before the first dose 
⚫ 
Hematology: complete blood count (CBC) and hemoglobin 
⚫ 
Serum chemistry: blood urea/urea nitrogen, creatinine, sodium, 

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Items 
Note 
potassium, magnesium, chloride,  calcium, phosphate, fasting 
glucose, total bilirubin, direct bilirubin, ALT, AST, alkaline 
phosphatase, lactate dehydrogenase, total cholesterol, total 
protein, and albumin 
⚫ 
Urinalysis: specific gravity, pH, glucose, protein, cast, ketones, 
and blood cells 
Coagulation 
PT, APTT, and INR 
Virology 
All subjects must receive anti-HIV antibody, HBsAg, and anti-HCV 
antibody tests 
⚫ 
Subjects with positive HBsAg must further undergo HBV DNA 
test 
⚫ 
Subjects with positive anti-HCV antibody must further undergo 
HCV RNA test 
Thyroid function 
Thyroid function tests including FT3, FT4, and TSH will be performed 
within 7 days before the first dose of study treatment 
EBV DNA 
Blood sample collection 
Laboratory Procedures/Assessments (by central laboratory) 
Central pathology 
Stained tumor tissue sections and corresponding pathological reports 
or unstained tumor tissue sections (or tissue block) must be collected 
at screening for central pathology review. Both fresh and archival 
biopsies are accepted and can be used by central pathology. 
Investigators may enroll subjects before obtaining the result of central 
pathology review 
Efficacy Evaluation 
Radiology 
⚫ 
Baseline radiology assessment methods include contrast-
enhanced CT [for head and neck region (that must include nasal 
cavity, palatum durum, anterior cranial fossa and nasopharynx), 
chest, abdomen, and pelvis; for patients allergic to CT contrast 
media, enhanced MRI will be used as an alternative] and systemic 
PET/CT 
⚫ 
Tumor assessment performed with the same machine and method 
in the same hospital within 28 days before the first dose can be 
used as the baseline tumor evaluation 
Bone marrow aspiration and 
biopsy 
Bone marrow aspiration and biopsy should be performed. 
Immunohistochemistry (IHC) analyses should be performed under a 
microscope no matter bone marrow involves or not (Suggest detecting 
CD56、TIA-1、CD3、GrB、perforin, and EBER hybridization in 
situ, etc.) 
Sample Collection for Biomarkers 
Blood samples 
Collect 2 mL of whole blood 

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Items 
Note 
Tumor tissue 
Seven (7) unstained FFPE tumor tissue slides 
 
6.1.2 Treatment Period 
Subjects will receive CS1001 1200 mg IV infusion every 21 days (3 weeks ± 3 days). All 
visits will be conducted at the planned time points specified in the protocol. 
The items to be completed during the treatment phase are listed in Table 4: 
Table 4 Visit procedures in the treatment phase 
Items 
Note 
Study Management Procedures 
Prior 
medications 
and 
concomitant medications 
Concomitant medications are documented 
Clinical Procedures and Assessments 
Adverse events 
Adverse events are recorded 
Height, weight, and vital signs 
Vital signs only; within 3 days before dosing in each cycle starting 
from Cycle 2 
Physical examination and ECOG 
performance status 
Lymphoma-specific physical examination and ECOG performance 
status evaluation within 3 days before dosing in each cycle starting 
from Cycle 2 
Laboratory Procedures/Assessments (at site) 
Hematology, serum chemistry, 
urinalysis 
Within 3 days before dosing in each cycle starting from Cycle 2 
Thyroid function tests 
Within 3 days before dosing every other cycle starting from Cycle 3 
(Cycles 3, 5, 7, and so on) 
EBV DNA 
Blood sample for EBV DNA test will be collected at each cycle starting 
from Cycle 2 and every other cycle after radiological CR 
Laboratory Procedures/Assessments (by central laboratory) 
PK 
⚫ 
Blood samples will be collected within 60 minutes before dosing 
as pre-treatment samples at Cycles 1, 2, 3, 4, and 8, and within 30 
minutes after completion of infusion at Cycles 1 and 4  
ADA 
⚫ 
Pre-treatment blood samples are collected (within 60 minutes 
before dosing) at Cycle 1, 2, 3, 4 and every 4 cycles thereafter 
(e.g., Cycle 8, 12, 16, and so on) 
Efficacy Evaluation 
Radiology 
⚫ 
Contrast-enhanced CT will be performed every 12 weeks after the 
first dose of investigational product. Examined sites include head 

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Items 
Note 
and neck region (that must include nasal cavity, palatum durum, 
anterior cranial fossa, and nasopharynx), chest, abdomen, and 
pelvis. For patients allergic to CT contrast media, enhanced MRI 
will be used as an alternative. 
⚫ 
Systemic PET/CT examination will be performed at Week 12 and 
Week 24. Only enhanced CT will be used for follow-up after first 
radiological CR or Week 24, whichever comes first. For patients 
without any measurable lesion, follow-up with PET/CT will be 
performed until radiological confirmation of CR or progression if 
the patient hasn’t reached CR in the first 24 weeks. 
⚫ 
Additional PET/CT will be performed if follow-up enhanced CT 
reveals residual lesion or suspected progression. 
Bone marrow aspiration and 
biopsy 
If bone marrow aspiration/biopsy was/were positive or overall bone 
marrow assessment was indeterminate at screening, bone marrow 
aspiration and biopsy should be performed when CR is achieved 
according to radiology. Immunohistochemistry (IHC) analyses should 
be performed under a microscope no matter bone marrow involves or 
not (Suggest detecting CD56、TIA-1、CD3、GrB、perforin, and 
EBER hybridization in situ, etc.) 
 
6.1.2.1 End-of-Treatment Visit 
The date of end-of-treatment (EOT) visit will be the decision making date for discontinuing 
the study treatment by investigators. EOT visit should be the EOT date + 7 days. The items 
to be completed at the EOT visit are listed in the table below: 
Table 5 Procedures in the End-of-Treatment Visit 
Items 
Observation items 
Study Management Procedures 
Prior 
medications 
and 
concomitant medications 
Concomitant medications are documented 
Clinical Procedures and Assessments 
Adverse events 
Adverse events are recorded 
Electrocardiogram (ECG) 
ECG is performed 
Height, weight, and vital signs 
Height, weight, and vital signs are measured 
Physical examination and ECOG 
performance status 
Systemic physical examination and ECOG performance status 
evaluation is performed 
Laboratory Procedures/Assessments (at site) 
Pregnancy test 
Blood human chorionic gonadotrophin test is performed as a 
pregnancy test 

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Items 
Observation items 
Hematology, serum chemistry, 
urinalysis 
Hematology, serum chemistry, and urinalysis tests are performed 
Thyroid function tests 
Thyroid function tests are performed 
Laboratory Procedures/Assessments (by central laboratory) 
ADA 
Blood sample for ADA test is collected 
PK 
Blood sample for PK test is collected 
6.1.3 Follow-up Period 
6.1.3.1 Safety Follow-up 
Safety follow-up period refers to the 90 days after the last dose of the investigational 
treatment or the start of new anti-cancer treatment, whichever occurs earlier. The safety 
follow-up visit is at 30 days (± 3 days) after the last investigational treatment, which has the 
same items as the EOT visit (refer to Section 6.1.2.1). If the EOT visit occurs in the time 
window of safety follow-up visit, the same tests and examinations do not need to be repeated. 
It is recommended to complete all protocol required follow-up evaluations for the safety 
follow-up at 60± 3 days and 90± 3 days after the last dose, or AEs and concomitant 
medications can be collected through phone call. Concomitant medications are recorded until 
90 days after the last dose or the start of new anti-cancer treatment, whichever occurs earlier. 
6.1.3.2 Radiology Follow-up 
Apart from subjects who discontinue treatment due to radiological disease progression, 
tumor assessment should be performed at pre-specified regular time points if possible until 
radiological disease progression, the start of new anti-cancer treatment, death, or the end of 
this trial, whichever occurs first; follow up with subsequent anti-cancer treatment. 
6.1.3.3 Survival Follow-up 
Survival status and the following anti-cancer treatment will be assessed every 12 weeks by 
telephone after the last dose of investigational product. 
6.1.4 Unplanned Visit 
If an additional follow-up visit is needed, all procedures (including laboratory test results) 
taken by the investigator should be recorded in the source medical record and unplanned 
visit page in the eCRF. 
6.2 SAFETY ASSESSMENTS 
Vital signs, physical examinations, ECOG performance status, laboratory tests, frequency, 
and severity of AEs and SAEs will be evaluated for safety assessment. 
AEs are coded according to PT and SOC in ICH MedDRA. 
The safety of investigational products will be assessed according to CTCAE v4.03. 
6.2.1 Vital signs 
Vital signs include temperature, blood pressure, pulse, and respiratory rate. Additional vital 
sign monitoring will be performed at the discretion of the investigator according to standard 
practice or as clinically indicated. 

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6.2.2 Physical Examination and ECOG Performance Status 
Physical examination includes height, weight, overall physical examination, and lymphoma-
specific examination. Abnormal changes in the physical examination will be assessed by the 
investigator. Changes of clinical significance (CS) should be reported as AEs by the 
investigator. 
6.2.3 Electrocardiogram (ECG) 
An electrocardiograph will be used to record the 12-lead ECG. ECGs must be recorded after 
5 minutes of rest in the supine position. ECG parameters including heart rate, PR interval, 
QRS interval, QT interval, QTc interval, QRS wave, and T wave evaluation, and 
investigator's evaluation on ECG should be recorded. Clinically significant ECG findings 
should be reported as AEs by the investigator. 
6.2.4 Laboratory Tests 
Blood and urine samples for laboratory tests will be collected as per this protocol. 
Table 6 Laboratory tests 
Tests 
Items 
Pregnancy test 
Blood human chorionic gonadotrophin pregnancy test 
Urinary human chorionic gonadotrophin pregnancy test (as clinically 
indicated) 
Hematology 
Complete blood count (CBC) and hemoglobin 
Serum chemistry 
Blood urea/urea nitrogen, creatinine, sodium, potassium, magnesium, 
chloride, calcium, phosphate, glucose, total bilirubin, direct bilirubin, 
ALT, AST, alkaline phosphatase, lactate dehydrogenase, total 
cholesterol, total protein, and albumin 
Urinalysis 
Specific gravity, pH, glucose, protein, cast, ketones, and blood cells 
Coagulation 
PT, APTT, and INR 
HBV, HCV, and HIV 
Anti-HIV antibody, HBsAg, anti-HCV antibody, HBV DNA test (only 
for HBsAg positive subjects), HCV RNA test (only for anti-HCV 
antibody positive subjects) 
Thyroid function 
FT3, FT4, and TSH 
EBV DNA 
EBV DNA 
 
For clinical laboratory test findings with unknown cause or unexpected results, if clinically 
significant judged by the investigator, the tests are recommended to be retaken in 24 hours 
and followed up until test results return to normal range and/or cause found. Clinically 
significant ECG findings should be reported as AEs by the investigator. 
6.3 PATHOLOGICAL ASSESSMENTS 
Stained tumor tissue sections and corresponding pathological reports or unstained tumor 
tissue sections (or tissue block) must be collected at screening for central pathology review. 
Both fresh and archival biopsies are accepted and can be used by central pathology. 

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Investigators may enroll subjects before obtaining the result of central pathology review. For 
subjects whose diagnosis is not ENKTL per central pathology laboratory’s judgment, 
investigators in consultation with sponsor medical monitors will determine whether to 
continue or discontinue the subject from treatment. See Central Pathology Manual for 
detailed instructions. 
In the screening and treatment periods, lesion biopsy may be performed at the discretion of 
the investigator for pathological examination to confirm radiological findings. 
6.4 EFFICACY ASSESSMENTS 
Efficacy evaluation will be performed by investigators and IRRC based on Lugano 2014 
classification. 
Contrast-enhanced CT will be performed at screening and every 12 weeks after the first dose 
of investigational product. Examined sites include head and neck region (that must include 
nasal cavity, palatum durum, anterior cranial fossa, and nasopharynx), chest, abdomen, and 
pelvis. For patients allergic to CT contrast media, enhanced MRI will be used as an 
alternative. Systemic PET/CT examination will be performed at screening, Week 12, and 
Week 24. Only enhanced CT will be used for follow-up after first radiological CR or Week 
24, whichever comes first. For patients without any measurable lesion, follow-up with 
PET/CT will be performed until radiological confirmation of CR or progression if the patient 
hasn’t reached CR in the first 24 weeks. Additional PET/CT will be performed if follow-up 
enhanced CT reveals residual lesion or suspected progression. 
If contrast media for CT can be injected when PET/CT is performed and meet requirements 
for PET/CT and contrasted CT, additional enhanced CT can be skipped. See Radiology 
Manual for Study Sites for details. 
Apart from subjects who discontinue treatment due to radiological disease progression, 
tumor assessment should be performed at pre-specified regular time points until radiological 
disease progression, the start of new anti-cancer treatment, death, or the end of this trial, 
whichever occurs first. 
Bone marrow aspiration and biopsy should be performed at screening. Subjects with positive 
bone marrow aspiration/biopsy result or indeterminate overall bone marrow assessment at 
screening will undergo bone marrow aspiration and biopsy when achieving CR/CMR based 
upon radiology. Immunohistochemistry (IHC) analyses should be performed under a 
microscope no matter bone marrow involves or not (Suggest detecting CD56、TIA-1、CD3、
GrB、perforin, and EBER hybridization in situ, etc.). 
6.5 PHARMACOKINETICS AND IMMUNOGENICITY 
All subjects will receive pharmacokinetic and immunogenicity assessments Neutralizing 
antibody of CS1001 will be tested if the neutralizing antibody testing method is established. 
Pharmacokinetics (PK): Blood samples will be collected within 60 minutes before infusion 
as pre-treatment samples at Cycle 1, 2, 3, 4, and 8, and within 30 minutes after infusion at 
Cycle 1 and 4 in the treatment phase. Blood samples for PK testing will be collected at the 
EOT visit, and safety follow-up visit at 30 days, and 90 days after the last dose of study 
treatment. 
Immunogenicity: Pre-treatment blood samples are collected (within 60 minutes before 
dosing) at Cycle 1, 2, 3, 4, and every 4 cycles thereafter (e.g., Cycle 8, 12, 16, and so on). 
Blood samples for ADA testing will be collected at the EOT visit and safety follow-up visit 
at 30 days, and 90 days after the last dose of study treatment. 

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See Laboratory Manual for detailed instructions. 
6.6 BIOMARKERS 
The whole-exome sequencing of tumor tissue and immune repertoire test of peripheral 
monocytes will be performed if permitted by the Ethics Committee. 
Whole exome sequencing of tumor tissue: seven (7) unstained FFPE tumor tissue slides 
should be collected at screening for whole-exome sequencing of tumor tissue; a total amount 
of 2 mL whole blood should be collected at screening as germline control of whole-exome 
sequencing. 
If the tumor tissue and whole blood samples were not available at screening,  retrospective 
collections of  7 archival FFPE tumor tissue slides and collection of 2 mL whole blood are 
allowed for whole-exome sequencing. 
Subjects must provide tumor tissue and whole blood sample for biomarker analysis. 
However, if tumor tissue is not available or the subject is unwilling to participate in the 
biomarker study, the subject enrollment will be determined by the investigator in 
consultation with the sponsor’s medical monitor. 

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7. REPORTING OF ADVERSE EVENTS 
7.1 ADVERSE EVENTS 
7.1.1 Definition of an Adverse Event 
An AE is any untoward medical occurrence or any worsening of existing medical conditions 
after the subject signs the informed consent in a study, regardless of its relationship with the 
investigational treatment. An AE can, therefore, be any unfavorable and unintended sign, 
symptom, or disease temporally associated with the use of a medication, whether or not 
related to the medication. An AE can also be a pre- or post-treatment complication resulting 
from protocol-specified procedure, overdose, drug abuse/misuse, or occupational exposure. 
Any occurrence with a worsening or changing nature in the study or resulting from 
participation is also considered as an AE. All AEs should be recorded on the Adverse Events 
page on the subject's eCRF. All AEs are graded according to CTCAE v4.03. 
The following conditions are not considered as AEs: 
 
Pre-existing or detected disease, condition, or laboratory finding before the 
screening visit that doesn’t get worse during the study; 
 
Occurrence without any untoward medical event (for example elective operation, 
hospitalization due to social reason or for personal convenience); 
 
Any clinically significant medical occurrence or laboratory finding occurs before 
the subject signing the informed consent and is unrelated to any protocol-defined 
procedure. This is considered as a preexisting occurrence and should be recorded 
in the Medical History page on eCRF. 
7.1.2 Adverse Event Monitoring 
In the whole study course, AEs will be closely monitored before and after medication 
administration and reported by the medical staff. Subjects receive a general physical 
examination, hematology, urinalysis, hepatic and renal function and chemistry tests, and 12-
lead ECG before and after the trial treatment. Vital signs will be monitored at various time 
points before and after investigational product administration on the dosing day. 
7.1.3 Recording of Adverse Events 
All AEs (including clinical symptoms, signs, or conditions) will be recorded in the eCRF, 
regardless of their relationship with the investigational treatment. 
Time Period for Collection of Adverse Events 
Adverse events will be collected from the time of signature of informed consent, throughout 
the treatment period and including the safety follow-up period of 90 days after the last dose 
of investigational product or the start of new anti-cancer treatment, whichever occurs earlier. 
After the safety follow-up visit (30 ± 3 days after the last investigational treatment), AEs can 
be collected by telephone follow-up 60±3 days and 90±3 days after the last dose. SAEs 
during the safety follow-up period will also be reported to the sponsor within a prespecified 
time frame. 
For subjects with treatment discontinuation for any reason but still in the trial: 
 
Ongoing AEs should be followed up with data collection in the survival follow-up 
period 

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 
Investigational product-related SAEs will still be collected during the survival 
follow-up period and reported to the sponsor according to the standard time frame 
and process of SAE reporting 
All deaths after disease progression and during the survival follow-up period will be 
collected and recorded in the eCRF. 
Refer to Table 7 for details. 
Table 7 Summary of Recording and Follow-up for Adverse Events and Deaths 
 
Treatment 
phase 
Safety follow-up 
Survival follow-
up 
Collection of all newly occurred AEs in 
eCRF 
Yes 
Yes 
No 
Collection of all ongoing AEs in eCRF 
Yes 
Yes 
Yes 
Collection of all drug-related SAEs in eCRF 
Yes 
Yes 
Yes 
Collection of all non-drug-related SAEs in 
eCRF 
Yes 
Yes 
No 
 
Any AE that is unresolved at the subject’s last visit in the study will be followed up by the 
investigator, but without further recording in the eCRF. The sponsor retains the right to 
request additional information for any subject with ongoing AE(s) at the end of the study if 
judged necessary. 
If an investigator learns of any SAE, including death, at any time after the subject has been 
discontinued from the study, and he/she considers there is a reasonable possibility that the 
event is related to the investigational product, the investigator should notify the sponsor. 
Variables 
The following variables will be collected for each AE: 
 
Diagnosis/description of AE 
 
The date when the AE started and stopped 
 
Change of CTCAE grade 
 
Whether the AE is serious or not 
 
Investigator causality attribution against the investigational product (yes or no) 
 
Investigator causality attribution against the investigational product 
 
Outcome 
In addition, additional variables including intervention will be collected for SAEs. 
It is important to distinguish between serious and severe AEs. Severity is to describe the 
intensity, while the definition of SAEs is listed in Section 7.2.1. An AE of severe intensity 
need not necessarily be considered serious. For example, nausea that persists for several 
hours may be considered severe nausea, but not an SAE. On the other hand, a stroke that 
results in only a limited degree of disability may be considered a mile stroke but would be 
an SAE. 

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Events will be assessed and graded based upon the NCI CTCAE v4.03. For events of 
uncoded CTCAE grade, mild, moderate, and severe events will be converted to CTCAE 
level as recommended by the NCI CTCAE guideline. The latest version of CTCAE can be 
downloaded from the web of cancer treatment and evaluation plan (http://ctep.cancer.gov). 
Causality Assessment 
The investigator will assess the causal relationship between the investigational product and 
each event, and answer ‘definitely related’, ‘possibly related’, ‘unlikely related’, 
‘definitely unrelated’ and ‘not evaluable’ to the question ‘Do you consider that there is a 
possibility that the event may have been caused by the investigational product?’ 
Refer to Section 7.3.1 for the causality assessment guideline. 
Adverse Events Based on Signs and Symptoms 
All AEs spontaneously reported by subjects or caregivers and AEs found through 
observation will be recorded in the eCRFs. The subject's symptoms and signs will be 
recorded in the Diagnosis record (if possible) during the collection of AEs. If the diagnosis 
is confirmed, however, with symptoms and signs that are unlikely to be caused by the 
diagnosis should be recorded separately. 
Adverse Events Based on Laboratory Tests and Examinations 
All results of the protocol mandatorily required laboratory tests, vital sign measurements, 
ECG and other safety assessments will be summarized in the Clinical Study Report (CSR). 
If a parameter is worsened than the baseline level and meets the SAE criteria, or it leads to 
subject withdrawal apart from disease progression (see Disease Progression), it will be 
reported as an AE. 
Worsened laboratory test results, vital signs, ECG, or other safety assessments with 
accompanying clinical symptoms and signs should be reported as supplementary 
information while the signs or symptoms reported as an AE. Reporting investigators should 
use clinical terminology whenever possible instead of laboratory terminology (for example 
anemia instead of low hemoglobin level). Non-mandatory test result that worsens with no 
accompanying clinical sign or symptom should be reported as an AE. 
Worsening of laboratory test which is unequivocally due to disease progression will not be 
reported as an AE. 
A newly found abnormal clinical test finding during physical examination or test results 
worse than the baseline level will be reported as an AE. 
Disease Progression 
Disease progression can be considered as deterioration of the subject’s condition attributable 
to the disease under study. It may be an increase in the severity of the disease under study 
and/or increases in the symptoms of the disease. The development of new, or progression of 
existing metastasis to the primary tumor under study should be considered as disease 
progression and not an AE. Events, which are unequivocally due to disease progression, 
should not be reported as an AE during the study. Refer to Section 7.5.2 for a detailed 
explanation. 
New Cancers 
The development of new cancer should be regarded as an AE, and under most circumstances, 
they meet at least one criterion of SAE. New primary cancers are those that are not the 
primary reason for the administration of the investigational product and have been identified 

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after the subject’s inclusion in this study. Metastasis of the primary tumor is not considered 
new cancer. 
Deaths 
All deaths that occur during the study, or within the protocol-defined follow-up period after 
the administration of the last dose of the investigational product, must be reported as follows: 
 
Death clearly the result of disease progression should be reported to the study 
monitor at the next monitoring visit and should be documented in the eCRF but 
should not be reported as an SAE. 
 
Where death is not clearly due to PD under study, the AE causing the death must 
be reported to the study monitor as an SAE within 24 hours. The report should 
contain a comment regarding the co-involvement of PD, if appropriate, and should 
assign main and contributory causes of death. 
 
Deaths with an unknown cause should always be reported as an SAE. Every effort 
should be made to identify the cause of death. An autopsy may be helpful in the 
assessment of the cause of death, and if performed a copy of the autopsy results 
should be forwarded to the representative of the sponsor in an expedited way within 
the predetermined timeframe. 
7.2 SERIOUS ADVERSE EVENTS 
7.2.1 Definition of A Serious Adverse Event 
According to the definition from ICH (International Council for Harmonisation), SAE is 
any adverse medical event that meets any of the following criteria: 
 
Results in death; 
 
Is life-threatening (Note: life-threatening in the context of an SAE refers to a 
reaction in which the patient was at risk of death at the time of the reaction; it does 
not refer to a reaction that hypothetically might have caused death if more severe); 
 
Requires in subject hospitalization or prolongation of existing hospitalization 
(except for hospitalization due to medical insurance reimbursement issue or 
hospitalization without approval by the study doctor); 
 
Results in persistent or significant disability/incapacity; 
 
Is a congenital anomaly/birth defect; 
 
Other medically significant events. 
These medically significant events that may not result in death, be life-threatening or require 
hospitalization may be considered serious when they jeopardize the participant and may 
require intervention to prevent one of the outcomes listed above. Medical and scientific 
judgment should be exercised in deciding whether the event should be reported in the light 
of expedited reporting rules. Examples of medically significant events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in subject hospitalization, or the development of 
drug dependency or drug abuse. For the avoidance of doubt, infection resulting from drug 
deterioration is considered as a medically significant event and should be reported according 
to the expedited reporting rules. 
The following hospitalizations that occur during the course of study should not be considered 
as SAEs: 

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 
Admission into an emergency room, outpatient, or other departments for <24 hours 
and not hospitalized (unless is considered “medically significant event” or life-
threatening event); 
 
Planned optional operation before ICF signing;  
 
Protocol-specified admission for medical/surgical treatment or monitoring; 
 
Admission for physical assessment; 
 
Admission for a Grade 1 AE, including overnight hospitalization due to non-
medical reasons after investigational product administration; 
 
Hospitalization for changing living conditions, which doesn’t affect health 
conditions and doesn’t involve medical/surgical intervention (for example for 
homeless, financial difficulty, family reasons, or management need). 
7.2.2 Serious Adverse Event Reporting 
Any SAE occurring from the time of ICF signing to 90 days after the last dose of 
investigational product or the start of new anti-cancer therapy, whichever occurs earlier,  
must be reported to the designated representative of CRO or the sponsor no later than 24 
hours when it gets learned of, regardless of causality with the investigational product. After 
the safety follow-up period, only treatment-related SAEs need to be recorded and reported. 
Once an SAE occurs, the investigator should: 
 
Immediately take appropriate treatment measures for the subject and report to the 
sponsor as described above, and to drug regulatory authorities, health 
administrative authorities, and the Ethics Committee according to the local 
requirements.  
Complete the SAE module in the EDC system, after which an automated email will 
be sent to the designated sponsor representative. In case EDC is down, all applicable 
modules of the sponsor’s SAE form will be completed by the investigator/site staff. 
The investigator must assess the relationship of each SAE to each specific 
component of study treatment, complete and sign the SAE Report Form, and submit 
the completed form within 24 hours to the sponsor pharmacovigilance 
representative. Follow-up information is submitted in a new SAE report form and 
marked as the follow-up information of a previously reported SAE. 
Any SAE that is unresolved at the end of study or subject withdrawal must be followed up 
until any of the following condition occurs: 
 
Event resolves; or 
 
Event stabilizes; or 
 
Event returns to baseline level (if baseline level available); or 
 
The event can be attributable to factors related with a medication other than the 
investigational product or unrelated with the investigator's behavior, or further 
information is unable to be obtained (when the subject or medical staff refuses to 
provide more information or when there’s evidence showing the subject is lost to 
follow-up despite every effort made). 
7.3 ASSESSMENT OF ADVERSE EVENTS AND SERIOUS ADVERSE 
EVENTS 
The investigator or study doctor is responsible for the causality and severity assessments of 
AEs and SAEs, and the final review and confirmation of the accuracy of data and 
assessments. 

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Any non-clinically significant laboratory finding is not recorded as an AE or SAE. Clinically 
significant (documented as ‘Abnormal finding with clinical significance’) laboratory 
findings (for example clinical laboratory, hematology, or urinalysis) and any other abnormal 
assessment result (for example ECG and vital signs) must be recorded as an AE or SAE. 
Events in compliance with the definition of AE or SAE must be recorded as an AE or SAE. 
If the laboratory finding is a component of a syndrome, the syndrome or diagnosis (for 
example anemia) instead of the laboratory finding (decreased hemoglobin) should be 
recorded. 
7.3.1 Causality Assessment 
The investigator should determine the relationship between the AE and the investigational 
product based on the following criteria: 
 
Definitely related: there is a rational temporal relationship of the occurrence of an 
AE including clinical laboratory finding to the administration of the investigational 
product. The investigational product can explain the AE more than any other reason 
(for example the underlying disease, environmental or toxic factors, or other 
treatment received by the subject); the reaction after discontinuation of 
investigational treatment is clinically reasonable. 
 
Possibly related: there is a rational temporal relationship of the occurrence of an 
AE including clinical laboratory finding to the administration of the investigational 
product. The investigational product can explain the AE with equal rationality with 
any other reason (for example the underlying disease, environmental or toxic 
factors, or other treatment received by the subject); information on post-
discontinuation reaction is unavailable or unclear. 
 
Unlikely related: other reasons (for example the underlying disease, 
environmental or toxic factors, or other treatment received by the subject) explain 
the AE (including laboratory findings) more than the investigational product 
 
Definitely unrelated: there is no rational temporal relationship of the occurrence 
of an AE to the administration of the investigational product. The AE has other 
more remarkable reasons (for example the underlying disease, environmental or 
toxic factors, or other treatment received by the subject). 
 
Not determined: the above information is not available and with no 
complementary data, making causality not determined. 
Definitely related, possibly related, and not determined events are counted as related 
adverse events when statistical analyses for adverse events are performed. 
7.3.2 Assessment of Severity 
For any AE, whether it is fatal or life-threatening, whether it leads to persistent or permanent 
disability, requires or prolongs hospitalization, or causes congenital anomaly will be 
recorded and graded based upon CTCAE v4.03. For an AE that is related to abnormal 
laboratory test finding(s), the event will be graded according to the clinical severity of the 
underlying condition; the grade is not necessarily in line with the grade of laboratory test 
finding. 
Intensity will be graded based upon the following rules: 
Grade 
Description 

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Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; or intervention not indicated 
Grade 2 
Moderate; minimal, local, or non-invasive intervention indicated; or limiting 
age appropriate instrumental activities of daily living* 
Grade 3 
Severe or medically significant, but not immediately life threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; or 
limiting self care activities of daily living** 
Grade 4 
Life-threatening consequences or urgent intervention indicated 
Grade 5 
Death related to adverse event 
* Instrumental activities of daily living refer to preparing meals, shopping for groceries or clothes, using the telephone, 
financial management, etc. 
** Examples of self-care activities of daily living include bathing, dressing, and undressing, taking food, using the toilet, 
and taking medications, as performed by patients who are not bedridden. 
 
7.4 HANDLING OF ADVERSE EVENTS 
All clinical events and clinically significant laboratory AEs will be handled based upon the 
guideline in CTCAE v4.03. 
The investigator will record AEs resulting from the treatment, remind the sponsor medical 
monitor to pay attention, and take appropriate actions in consultation with the sponsor’s 
medical monitor. Subjects with AEs must be followed up regularly if possible, regardless of 
the AEs' relationship with the treatment, until resolution of the symptoms, all the abnormal 
laboratory values return to normal or baseline values or are confirmed irreversible, or the 
observed changes can be properly explained.  
For Grade 3 or 4 laboratory test finding with clinical significance, the test should be repeated 
to confirm the finding, if possible. Every effort should be made to have the subject revisit 
the site within 3 days of obtaining the initial test result for repeating the test and taking 
appropriate actions. 
7.5 REPORTING OF SPECIAL SITUATIONS 
7.5.1 Definition of a Special Situation 
Reporting of special situations includes reporting of a medication error, drug abuse, misuse, 
overdose, and pregnancy (regardless of its relationship with any AE). Reports of adverse 
infant reaction post breast milk exposure and Reports of adverse drug effects associated with 
product complaints or tip-offs due to occupational exposure are also included. 
The Pregnancy Report is used to report any pregnancy after maternal or paternal exposure. 
Medication error refers to any unintended error in the prescription, dispensing, or 
administration of medications made by healthcare providers, subjects, or consumers. 
Drug abuse is defined as persistent or occasional intended overuse of medication by a subject. 
Misuse is defined as intended, improper use of medication that is not in line with the protocol 
or prescribing information. 

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Medication overdose is defined as: occasional or intended use/injection of the investigational 
product in a dose exceeding the prescribed one. Overdose is defined as: the subject has taken 
(accidentally or intentionally) a dose exceeding the dose prescribed in the protocol by 20%.  
A product complaint is a complaint due to potential bias in the manufacturing, packaging, or 
distribution of medication. 
7.5.2 Reporting of Special Situations 
7.5.2.1 Reporting of Pregnancy 
If any pregnancy occurs in a female subject in the course of the study, the investigational 
product should be discontinued immediately and report the pregnancy to the sponsor. Any 
pregnancy that occurs after the subject first agrees to participate (by signing the ICF) and 
during the clinical study (including post-treatment follow-up period and 6 months after the 
last dose) must be reported to the sponsor using the pregnancy report form by the 
investigational staff no later than 24 hours of when he/she becomes aware of it. 
Pregnancy itself is not regarded as an AE. Induced abortion for pregnancy termination is 
unnecessary unless there’s a medical reason. Early pregnancy termination (for example 
spontaneous abortion due to complication or other medical reasons, or therapeutic induced 
abortion) must be reported within 24 hours as an SAE. The medical reason during this course 
should be recorded as the AE term. Spontaneous abortion is always regarded and reported 
as an SAE. The subject will be appropriately monitored and taken care of until the end of 
pregnancy. However, subjective induced abortion for pregnancy termination without 
medical reason does not need to be reported as an SAE of pregnancy termination. 
For male subjects, the pregnancy of their female partners must be reported as an SAE. Their 
partners will be monitored until the end of pregnancy. Refer to Section 4.1.5 for effective 
contraceptive measures. 
7.5.2.2 Progression of Cancers 
The progression of underlying malignancies will not be reported as an AE. 
Hospitalization or death merely resulting from the progression of the underlying 
malignancies will not be reported as an SAE. If the symptom is not exclusively attributable 
to the underlying malignancy or the symptom is not an expected result of the progression of 
the investigational disease, the symptom will be reported as an AE. 
Some subjects may experience deterioration of clinical symptoms. In this case, the subject’s 
clinical symptom is a typical manifestation of PD but it’s not supported by the change in 
tumor lesion size; or the disease progression is substantial enough that the investigator may 
consider it unnecessary to perform any further assessments of disease. And as such, clinical 
progression will be determined based upon the clinical symptom deterioration. Such cases 
are rare, and the investigator, therefore, should make every effort to record the objective 
progression of the underlying malignancy. 
An AE that cannot be determined as exclusively resulting from the investigational product 
will be reported as an AE or SAE. 
7.5.2.3 Reporting of Other Special Situations 
All other special situations must be recorded by the investigator within 24 hours when he/she 
becomes aware of it. A special situation that constitutes an AE or SAE, will be reported as 
an AE or SAE. All reports must contain information regarding the involved investigational 
product, but not for the concomitant medications. Concomitant medications will not be 
reported unless it results in an AE. Any improper use of prohibited medication should not 

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be reported as ‘misuse’ but appropriately recorded as protocol deviation. All clinical 
sequelae related to these special situations should be reported as AEs using the AE report 
form. If a special situation results in an SAE, it should be reported using the SAE report 
form. The report will contain information regarding symptoms, signs, clinical intervention, 
and outcome. 
Overdose 
If an overdose occurs, symptomatic and supportive care should be given to the subject. If 
the dose of the investigational product exceeds that specified in the protocol and has an 
accompanying AE, the AE will be recorded using the Adverse Event Form. Any of the above 
situations leading to an SAE should be reported as an SAE. 
7.6 LIVER FUNCTION TEST FINDINGS 
If ALT or AST > 3 x ULN with elevation in total bilirubin (>2 x ULN), it will be considered 
as a marker of severe liver injury after ruling out Cholelithiasis or other clinical jaundices 
that may lead to bilirubin. Therefore, any of the following events must be reported as an AE 
by the investigator: 
 
During the course of treatment, ALT or AST > 3 x baseline level; or ALT or 
AST >2 x baseline level and total bilirubin > 2 x ULN (direct bilirubin 35%) in a 
subject with baseline transaminase elevation; 
 ALT or AST > 3 x baseline level with clinical jaundice during the course of treatment. 
The most appropriate diagnosis or clinical test finding (if diagnosis unestablished) will be 
recorded in the eCRF and reported to the sponsor within 24 hours when the investigator gets 
aware of it, whether it’s an SAE or not. 
7.7 OTHER SAFETY CONSIDERATIONS 
Any significant worsening of interim or final physical examination, ECG, or other safety 
assessments (no matter it's required by the protocol or not) must be recorded and reported. 

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8. STATISTICAL CONSIDERATIONS AND ANALYSIS 
PLANS 
8.1 SAMPLE SIZE DETERMINATION  
The primary efficacy endpoint is ORR assessed by IRRC according to Criteria for 
Response Assessment of Lymphoma: Lugano 2014 Classification. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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8.2 SUMMARY OF CONDUCT OF STUDY  
8.2.1 Analysis Sets  
Efficacy analysis set (EAS) consists of all subjects who received at least one dose of 
investigational product and confirmed by central pathology. 
Safety analysis set (SAS) consists of all subjects who received at least one dose of 
investigational product. The distribution of subjects, their demographics, other baseline 
characteristics, and the safety analyses will be based upon the SAS. 
Pharmacokinetics analysis set (PKAS) consists of subjects who received at least one dose of 
investigational product and have available plasma drug concentration data. 
Anti-drug antibody analysis set (ADAAS) consists of subjects who received at least one dose 
of investigational product and have available ADA data. 
Biomarker analysis set (BAS) consists of subjects who received at least one dose of 
investigational product and have available biomarker data. 
All analysis sets will be determined prior to database lock. 
8.2.2 Demographics and Baseline 
Patient demographics and baseline characteristics, for example, age, sex, baseline disease 
characteristics, ECOG PS, and prior anti-cancer treatment, will be summarized for the SAS. 
Baseline measurement refers to the last measurement obtained before the first dose of 
investigational product in a subject. 
Continuous variables will be summarized using descriptive statistics (mean, median, 
standard deviation, minimum, and maximum) and categorical variables will be summarized 
in terms of the number and percentage of patients in each category. 
8.3 Efficacy Analyses 
8.3.1 Primary Efficacy Endpoints 
The primary efficacy endpoint, objective response evaluated by IRRC, refers to CR or PR 
determined by IRRC based upon Lugano 2014 classification. For subjects who fail to meet 
the above criteria or fail to receive any tumor assessment after baseline will be considered 
as non-responder. 
ORR is the rate of objective responders. The population involved in the IRRC-ORR analysis 
are EAS subjects with evaluable or measurable lesion at baseline confirmed by IRRC. 
The 95% confidence interval (CI) of ORR will be calculated using the exact binomial 
(Clopper-Pearson) method to evaluate the precision of the ORR estimate. 
The statistical analysis will be performed by 24 weeks after the first dose of the last 
subject.  
8.3.2 Secondary Efficacy Endpoints 
Proportions of subjects who achieve CR, PR, SD, and PD per IRRC evaluation and their 95% 
CIs will be summarized. This analysis will be performed in EAS subjects with evaluable or 
measurable lesion at baseline judged by IRRC. Proportions of subjects with responses per 
investigator’s evaluation and their 95% CIs will be summarized. This analysis will be 
performed in EAS subjects with evaluable or measurable lesion at baseline judged by 
investigators. 

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Duration of response (DoR) is defined as the time from the first documented CR or PR 
(whichever comes first) to the first documented disease progression or death, whichever 
comes first. DoR will be evaluated in subjects with objective responses per investigator’s or 
IRRC’s assessment, respectively. At analysis, subjects without event (disease progression or 
death) as of data cutoff will be censored at the date of “last tumor assessment”. If no tumor 
assessment is performed after the first occurrence of CR or PR, DoR will be censored at the 
date when CR or PR first occurs. Kaplan-Meier method will be used to analyze DoR; the 
KM curve will be constructed. 
Time to response (TTR) is defined as the time from the first study dose to the first 
documented CR or PR, whichever comes first. TTR will only be evaluated for subjects who 
achieve ORR. TTR will be summarized according to the investigator's and IRRC’s 
assessments, respectively. 
8.4 SAFETY ANALYSES  
The safety analysis will be performed for the SAS population. 
Descriptive statistics will be performed to summarize the exposure of the investigational 
product, which may contain number of cycles, administrations and dose levels, etc.  
All adverse events will be described according to MedDRA and graded according to the NCI 
CTCAE v4.03. All adverse events that occurred during or after investigational product 
administration will be summarized by NCI CTCAE grade. In addition, serious adverse 
events, severe adverse events (Grade 3, 4, or 5 events), drug-related AEs, and AEs causing 
discontinuation or dose modification of the investigational product will each be summarized. 
Multiple occurrences of the same event will be only counted once for the most severe event. 
The proportion of subjects with more than one adverse event will be reported. 
All deaths that occur during the study or within the defined follow-up period after the last 
dose/discontinuation of investigational product will be reported. 
Specific laboratory tests, vital signs, physical examinations, and 12-lead ECGs and their 
changes compared with baseline will be summarized. The values at baseline and each time 
point post-baseline will be presented by crosstabs, when appropriate.  
8.5 PHARMACOKINETIC ANALYSES 
Descriptive analysis will be performed for serum concentration of CS1001 in samples taken 
planned sampling time points. The data in this study will be pooled with that from other 
CS1001 trials to develop a population PK model. This model will be used to evaluate internal 
and external covariates and their influence on the PK of CS1001. Furthermore, the exposure-
response analysis will be performed on specific efficacy and safety endpoints. Results of the 
above group PK and exposure-response analyses will be recorded in separate reports. 
8.6 IMMUNOGENICITY ANALYSES 
Immunogenicity evaluation results will be reported for the following parameters. Number 
and percentage of subjects who have positive ADA at baseline; number and percentage of 
subjects with at least one positive ADA test result in any time point following the first dose 
of the investigational product; number and percentage of subjects who develop treatment-
induced ADA anytime after the first dose of the investigational product; number and 
percentage of subjects with treatment-enhanced ADA anytime after the first dose of 
investigational product. The treatment-induced ADA will also be analyzed by computing 
and reporting duration of an induced ADA response which will be classified as transient-
positive ADA or persistent-positive ADA. 

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8.7 EXPLORATORY ANALYSES  
Progression-free survival (PFS) and overall survival (OS) will be explored. PFS is defined 
as the time from the first study dose to the date of first documented disease progression or 
death, whichever comes first. The investigators and IRRC will assess the progression of 
disease based upon the Lugano 2014 classification. At the analysis, subjects without event 
(disease progression or death) will be censored at the date of “last tumor assessment”. 
Subjects without tumor assessment after baseline will be censored at the date of the first dose. 
Six-month PFS rate refers to the proportion of subjects who are alive without any 
progression at 6 months after the first dose of investigational product. Six-month PFS rate 
will be calculated using the Kaplan-Meier method and the Greenwood formula was used to 
derive the variance regarding its 95% CI calculation. 
OS is defined as the time from the first study dose to the date of death irrespective of its 
cause. Subjects without death reports as of data cutoff will be censored at the date of the last 
survival confirmation. Subjects without any data after baseline will be censored at the date 
of the first dose. The same analysis method is used for PFS. 
Exploratory biomarker analysis will be performed to identify the relationship between tumor 
genetic aberrations and the efficacy of the investigational product. Subjects will be sub-
grouped based upon their demographics (for example age, sex) and baseline characteristics 
(for example ECOG PS, prior treatment lines) for evaluating the consistency among all 
subgroups. 
The consistency of ORR (yes or no) between IRRC evaluation and investigator's evaluation 
will also be assessed. 
8.8 HANDLING OF MISSING DATA  
Subjects without any assessment after baseline will be regarded as non-responders at ORR 
analysis. 
Subjects without available data on the date of disease progression or death when calculating 
PFS will be censored at the date of the last tumor assessment. Subjects without any tumor 
assessment after the baseline will be censored at the date of the first dose. 
Subjects without death report at OS analysis will be censored at the date of the last survival 
confirmation. For OS analysis, subjects without any data after baseline will be censored at 
the date of the first dose. 
For DoR analysis, subjects without event (no disease progression or death) by database 
locking will be censored at the date of “last tumor assessment”. If no tumor assessment is 
performed after the first occurrence of CR or PR, DoR will be censored at the date of the 
first occurrence of CR or PR first occurs. 
 

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9. ETHICAL CONSIDERATIONS 
9.1 ETHICS COMMITTEE 
Before initiating a trial, the clinical study protocol and informed consent form (ICF) are 
submitted to the Ethics Committee (EC) for review and approval. The Ethics Committee 
must be constituted in accordance with all applicable regulatory requirements and 
International Conference on Harmonization (ICH) E6 Good Clinical Practice (GCP) 
guidelines. 
The investigator will inform the EC of the progress of the trial in accordance with the 
requirements from the EC. All changes in the study activities and unanticipated questions 
involved in the subject's risks must be reported to the EC immediately. If the risk of 
participation in a study significantly outweighs the expected outcome, the investigators 
should inform the subjects and the EC about it. During the further review by the EC, the trial 
may be suspended unless this suspension jeopardizes the health of subjects. Investigators 
should also ensure all subjects should be informed about such risks. 
The trial must not be changed before obtaining the approval from the EC unless it's necessary 
to eliminate immediate substantial harm to the human subjects. 
9.2 ETHICS INSTRUCTIONS FOR THE STUDY 
The study will be conducted in compliance with the ethical principles in the Declaration of 
Helsinki, the 18th World Medical Association (WMA) in Helsinki, Finland in June 1964, 
and the later amendments. 
The conduct of this study will also comply with the Committee for Proprietary Medicinal 
Products (CPMP) guidance and ICH E6 GCP guidelines (CPMP/ICH/135/95). 
As long as national laws are not violated, the ICH guidelines and other applicable 
international guidelines, recommendations, and requirements will be considered 
comprehensively to ensure the maximization of the subject's rights, safety, and health. 
9.3 SUBJECT INFORMED CONSENT FORM 
The investigator will give full and adequate oral and written information to each subject, 
their legal representative, or witness about the objectives, procedures, possible risk, and 
benefit of the study. Each subject must provide signed and dated informed consent before 
conducting any procedure specifically for the study. The ICF contains information about the 
purpose, procedures, possible risks and limitations of the trial, and specifically possible 
adverse effects of the investigational product and potential drug-drug interactions. 
Furthermore, the ICF also explains the range of insurance in the course of the study. 
Elements involved in the ICF are drawn up in accordance with ICH E6 GCP guidelines. 

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10. STUDY MANAGEMENT 
10.1 DATA MANAGEMENT 
Data Management will be performed by the sponsor delegated CRO. 
10.1.1 Completion and Submission of Case Report Forms  
All eCRFs will be completed by the investigator or the designated personnel according to 
the original medical record. Changes to the data in eCRF will be recorded as audit tracking. 
The reason for changes, the name of the staff who makes the changes, and the time and date 
of changes will be recorded in the audit tracking log. 
10.1.2 Data Entry and Modification 
Before the initiation of a site or any data entry, the investigators and delegated site personnel 
will receive appropriate training and take proper safety measures. 
The data entry in eCRF should be completed as soon as possible during or after each visit 
and kept updated to ensure the eCRF can reflect the latest status of the subject. Investigators 
should review data in the eCRF to verify they are authentic and accurate. Any assessment 
not conducted in the study or any information that is unavailable, inapplicable, or unknown 
should be recorded in the eCRF by the investigator. 
The eCRF is only used as forms to collect data instead of the source documents unless 
otherwise specified. The source documents are subject-related documents used by the 
investigators or hospitals, which can prove the existence and eligibility of a subject. The 
source data include laboratory test results, ECG results, notes, dispensing log of the 
pharmacy and subject file, etc. 
The investigator is responsible for maintaining all source documents and provide them to be 
reviewed by CRA at each visit. In addition, the investigator must submit the complete eCRF 
for all the subjects, regardless of their duration of study participation. All supportive 
documents (for example laboratory record or hospital record) submitted together with the 
eCRF must be verified carefully for the protocol number and subject number, and all 
personal information (including the subject’s name) should be deleted or unidentifiable to 
protect the privacy of subjects. 
eCRF records will be automatically appended with the identification of the creator, by means 
of their unique User ID. By entering his/her electronic signature, the investigator confirms 
that all recorded data have been verified as accurate. The e-signing process will be done by 
entering the user ID and password. The system will automatically append the date and time 
of the signature. Investigators must not share user ID or password with others. 
AEs and diseases will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA). Medications will be coded using the World Health Organization Drug 
Dictionary (WHO-Drug). 
To ensure the accuracy, completeness, and reliability of the data, the sponsor or the 
designated representative will take the following measures: 
 
Instructions for each site at the appropriate time. 
 
Initiation training for the investigators and coordinators (on the protocol, 
completion of eCRF, and study procedures). 
 
Routine site visits. 

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 
Offer counseling service and maintain contact with the site staff by email, 
telephone, and/or fax. 
 
Review and evaluate eCRF data and use standard computerized editing to check 
for errors in the data collection. 
 
Quality checks for the database. 
Furthermore, the sponsor or the designated representatives may conduct periodic audits to 
subject data samples recorded by the site personnel with reference to the source documents. 
The sponsor or the authorized representatives and/or regulatory authority may perform audits 
at any time, which will be notified to the investigator beforehand. 
To ensure the safety of participants and the accuracy, completeness, and reliability of the 
data, the laboratory test reports, clinical records, and subject’s medical record will be kept 
in the subject's file as the source documents of this study by the investigator. The 
investigators allow the sponsor, regulatory authorities, and the Ethics Committees, if 
applicable, direct access to the source documents per request. 
10.1.3 Data Review 
The data management personnel will perform data, range, and logic reviews for all the ranges 
and interactions of each parameter in the eCRF. A computer program may be coded to 
conduct checks, identify the cause of errors, and correct them. The content of all errors and 
corrections will be filed for reference. 
10.1.4 Archival 
Important study documents will be archived in a secure way and ensured their accessibility 
when requested by a regulatory authority. 
The archival of subject (hospital) files should comply with requirements of local regulations 
and be kept for the longest period allowed by the hospital and institutes. The 
investigator/institute must inform the sponsor of any changes to the archival arrangement 
(for example altered location or ownership). 
The Investigator Site File (ISF) must not be destroyed without the sponsor’s approval. 
The investigator's contract will cover all applicable regulatory requirements related to the 
sites. 
All trial data must be kept for at least 15 years after the study is completed. 
1. Storage of trial records: the source documents will be kept in each site. 
2. eCRF: 
a) eCRF will be completed in accordance with the GCP principles to ensure the 
accuracy of data. 
b) Delegated personnel will complete eCRF based upon the source record. 
c) Lastly, the PI will sign off the eCRF after review. 
10.2 INSPECTION PROCEDURES (QUALITY ASSURANCE) 
The sponsor and investigators will fulfill their duties, strictly follow the study protocol, and 
adopt a standard operation procedure (SOP) to ensure quality control and quality assurance 
are performed for the study. 

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10.2.1 Routine Monitoring 
The main responsibilities of a monitor are to supervise the process of the study and ensure 
that the study is conducted in compliance with the protocol and GCP principles, all records 
and reports are accurate and complete, and all the subjects sign ICF before entering the study. 
A monitor must report any occurrence inconsistent with the study protocol to the sponsor 
and responsible person for the project during the trial. 
10.2.2 Audits and Inspections 
A regulatory authority, an EC, and/or the sponsor may perform on-site audits or inspections 
at the site to ensure that the study process, completion of eCRF, and other reports are in 
compliance with the protocol, GCP, Declaration of Helsinki, and applicable regulatory 
requirements. The auditors/inspectors will conduct source data verification (SDV) to ensure 
the credibility of the data. Quality control will be performed at each stage of the study to 
ensure that the data are reliable and the whole study process is correct. The quality control 
will be performed in accordance with the Quality Management Manual of the sponsor. When 
an investigator receives notice of inspection from a regulatory authority, he/she should 
inform the sponsor immediately. 
10.3 STUDY MANAGEMENT AND MATERIALS 
10.3.1 Data Collection 
The participating doctors will record all major observations and findings in the subject’s 
medical record, which include: 
 
Actual date of visits, and the scheduled date or visit. 
 
Notes on the general condition and subject's conditions, including major medical 
findings. The severity, frequency, duration of any reported AE, resolution to the 
AE, and investigator’s assessment about the relationship between the reported AE 
and the investigational product. 
 
Changes to the concomitant medication or dosage. 
 
The signature or initials of the doctor. 
In addition, any contact with the subject on the major clinical information through telephone 
or other measures should also be recorded in medical records (progress note) as stated above. 
The data in the medical record (progress note) and other source documents will be 
transcribed into the appropriate sections in the eCRF in time. 
Changes to the information in the medical record (progress note), eCRF, and other source 
documents will be signed and dated by the investigator or the designated personnel. If the 
cause of change is not clear, a short note should be made alongside the change. 
10.3.2 Archival of Source Data and Records 
The source documents include original observations and all activities of the clinical study. 
They include but are not limited to, medical records (progress notes), printouts, screening 
diaries, and data recorded by automated devices. 
All source documents in this study will be maintained by the investigators, and authorized 
personnel is permitted access to these documents. The original, signed ICFs are stored 
together with the investigator’s records, with a copy provided to the subject. 
All data obtained from the study are the property of the CStone Pharmaceuticals (Shanghai) 
Co., Ltd., and CStone Pharmaceuticals (Suzhou) Co., Ltd. 

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The records will be stored in accordance with the latest version of ICH GCP guidelines. All 
necessary documents (including the subject records, source documents, eCRFs, and the 
investigational product dispensing and returning forms) must be kept. 
All these necessary documents must be kept until 15 years after the approval of the 
investigational product. However, the relevant documents will be kept for a longer time if 
required by the regulatory authority or sponsor. The sponsor will inform the investigators of 
the duration requirements of document storage. 
The investigator will not dispose of any document of this study without the written 
permission of the sponsor. The investigator will provide the sponsor with opportunities to 
collect relevant records. The investigator is responsible for ensuring the sufficiency and 
accuracy of the paper source documents for all reports of observations and data obtained 
during this trial. The sponsor, the designated representative, and regulatory authority may 
perform audits and inspections on these documents at any time. 
If an investigator has position changes, withdraws from the study, or retires, the 
responsibility of maintaining records will be transferred to other study personnel with sub-
responsibilities. This responsibility transfer must be notified and approved by the sponsor. 
10.3.3 Confidentiality 
Any subject’s health-related data obtained during this trial will be confidential. A written 
agreement must be obtained before disclosing any data. 
The investigators must ensure that subject’s identity is not disclosed. The subject’s name 
will not be used as an identifier in the eCRF and other documents submitted to the sponsor 
or the delegated CRO. In contrast, the enrollment No. of the subject will be used to ensure 
all of the study documents are confidential. This unique number will be used for the subject 
in the whole course of the study. The investigator will keep a separate log for each subject 
number. 
To comply with the regulatory requirements and to ensure the safety of subjects, the sponsor, 
representative of the sponsor, CRO personnel, local study review committee, or regulatory 
authorities may inspect the subject's medical record due to its correlation with the study. The 
unique enrollment number of subjects on eCRF is the only means of subject identification. 
The full name of a subject, however, may be released to the drug administrative authority or 
other authorized government organizations or healthcare officers, if necessary, and 
designated personnel of the sponsor. 
Documents (for example ICFs) not submitted to the sponsor or CRO will be held in strict 
confidentiality by the sponsor. But monitors from the sponsor or CRO and inspectors from 
a regulatory authority have the absolute privilege to review them. All documents in which a 
subject may be identified by his/her name must not leave the site, and the identity of subjects 
in all study-related publications will be kept confidential. 
10.4 APPLICATION PROCEDURES 
10.4.1 Ethics Approval 
According to national laws and regulations, CStone Pharmaceuticals (Shanghai) Co., Ltd., 
and CStone Pharmaceuticals (Suzhou) Co., Ltd., or the delegated agents will be responsible 
for obtaining approval of applicable regulatory authorities and the EC. 
Any subject must not enter the trial before the approval of the regulatory authorities. A copy 
of the approval (if available according to local regulations) will be provided to the 
investigators and ECs. 

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10.4.2 Changes to the Protocol 
According to ICH GCP E6 guidelines, an investigator must not deviate from or change the 
protocol before obtaining the written approval of the sponsor and EC, unless the protocol 
amendment is required to eliminate the immediate harm suffered by a subject, or it is a 
logistics or administrative change (for example altered monitor or telephone number). 
Any change to the study protocol must be handled as a protocol amendment. Any potential 
revision must be approved by the sponsor. A written amendment must be submitted to the 
regulatory authorities and the responsible EC. The protocol amendment will not be executed 
before the approval of EC unless the change is required to eliminate the immediate harm 
suffered by a subject. In this case, the change must be communicated to the EC within 5 days 
of execution. 
The regulatory authorities and ECs are to approve each protocol amendment except for the 
administrative change which is only to be communicated to but not approved by each 
regulatory authority or EC. Each approved amendment attached to the instructions on how 
to add it to the protocol will be distributed to all recipients of the original protocol. 
If a protocol amendment changes the study design, procedures, and/or increases the subject’s 
potential risks, judged by the local EC, investigators, and/or the sponsor, the current 
approved ICF will be revised. The regulatory authorities and ECs are to approve the revised 
ICF before the revised form is used. In this case, the enrolled subjects must resign a new ICF 
before further participating in the study. 
10.4.3 Protocol Adherence and Deviations 
Read through the whole study protocol and follow the instructions. A protocol deviation 
judged by the investigator or a reliable, well trained professional personnel (sub-investigator) 
designated by the investigator as a necessary immediate emergent intervention for the 
subject’s protection, safety, and health considerations may be regarded as an exception. 
However, the investigator or designated personnel must communicate any major protocol 
deviation due to an emergency, accident, or error to the medical monitor by telephone. And 
as such the decision regarding the subject’s eligibility to further participate in the trial will 
be jointly determined and recorded by the investigator, sponsor, and medical monitor. 
10.4.4 Publication of Study Results 
Upon study completion, the study results may be co-submitted by the investigators and 
sponsor for publication. Investigators must commit that any data obtained under this protocol 
will not be submitted for publication without prior permission from CStone Pharmaceuticals 
(Shanghai) Co., Ltd., and CStone Pharmaceuticals (Suzhou) Co., Ltd. 
10.4.5 Clinical Study Report 
A final clinical study report (CSR) will be prepared in accordance with ICH E3. A final CSR 
will be prepared regardless of whether this study is completed or early terminated. The 
sponsor will provide a copy of the final CSR to all investigators for archival. 
10.4.6 Insurance, Reimbursement, and Compensations 
CStone Pharmaceuticals (Shanghai) Co., Ltd. and CStone Pharmaceuticals (Suzhou) Co., 
Ltd. will execute the policy regarding insurance for the study. 
This is to prevent the situation when protocol deviation (especially unplanned dose, other 
methods of administration, other indications, or prolonged treatment period) is not covered 
by the subject's compulsory insurance. 

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10.4.7 Termination of Study 
The sponsor may terminate the study when it's in the best interest of the subjects and due to 
medical or ethical considerations. The study may be terminated at any time upon agreement 
of investigators and the sponsor. CStone Pharmaceuticals (Shanghai) Co., Ltd., CStone 
Pharmaceuticals (Suzhou) Co., Ltd., the CROs, and investigators must ensure the full 
consideration about protecting subjects’ rights at the study termination. 
Reasons for study termination may include but are not limited to: 
 Unanticipated, major or unacceptable risk occurred in enrolled subjects; 
 The sponsor determines to suspend or stop the development of the investigational 
product. 
10.4.8 Document Management at Sites 
The investigator is responsible for securing the storage of site documents. The site 
documents may include, but are not limited to the following data: 
1. Investigator's Brochure; 
2. Current version of the approved protocol and every previous version of protocol; 
3. Protocol amendments (if applicable); 
4. Operation manuals (if applicable); 
5. Current version of ICF (blank) and every previous version of ICF; 
6. The curriculum vitae of the investigator and sub-investigators, a copy of their 
licenses (if required by law); the investigators must also complete all regulatory 
documents required by ICH GCP and local or national regulations; 
7. EC approvals for the protocol, ICF, protocol amendments, and ICF revisions; 
8. Key communications on the conduct of study among investigators, the ECs, and 
sponsor/CROs; 
9. Laboratory accreditation certificates; 
10. Monitoring log; 
11. Record of investigational product management (including dispensing sheet, 
temperature record and accountability record, etc.); 
12. Study staff delegation form. 

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11. LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
ADA 
Anti-drug Antibody 
ADAAS 
Anti-drug Antibody Analysis Set 
ADCC 
Antibody-Dependent Cell-mediated Cytotoxicity 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
AIDS 
Acquired Immune Deficiency Syndrome 
ALT 
Alanine Transaminase 
APTT 
Activated Partial Thromboplastin Time 
AST 
Aspartate Transaminase 
auto-SCT 
Autologous Stem Cell Transplantation 
BAS 
Biomarker Analysis Set 
CDC 
Complement Dependent Cytotoxicity 
CMR 
Complete Metabolic Response 
CR 
Complete Response/Remission 
CRA 
Clinical Research Assistant 
CRO 
Contract Research Organization 
CRR 
Complete Remission Rate 
CS 
Clinical Significance 
CSR 
Clinical Study Report 
CT 
Computed Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTLA-4 
Cytotoxic T Lymphocyte-Associated Antigen-4 
DLT 
Dose-Limiting Toxicity 
DoR 
Duration of Response 
EBV 
Epstein-Barr Virus 
ECG 
Electrocardiogram 

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Abbreviation 
Definition 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic Case Report Form 
FAS 
Full Analysis Set 
18FDG/PET 
18F-Fluorodeoxyglucose/ Positron Emission Tomography 
FFPE 
Formalin-Fixed, Paraffin-Embedded 
FT3 
Free Triiodothyronine 
FSH 
Follicular Stimulating Hormone 
FT4 
Free Thyroxine 
GCP 
Good Clinical Practice 
HBsAg 
Hepatitis B Surface Antigen 
HBV 
Hepatitis B Virus 
HCV 
Hepatitis C Virus 
HIV 
Human Immunodeficiency Virus 
HRT 
Hormone Replacement Therapy 
HSCT 
Hematopoietic Stem Cell Transplantation 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation  
ICU 
Intensive Care Unit 
INR 
International Normalized Ratio 
irAE 
Immune-related Adverse Event 
IRRC 
Independent Radiological Review Committee 
IV 
Intravenous 
LDi 
Longest Diameter 
LY 
Lymphocyte 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
Magnetic Resonance Imaging 
NCS 
No Clinically Significant 

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Abbreviation 
Definition 
NOAEL 
No-Observed-Adverse-Effect-Level 
NSAID 
Nonsteroidal Anti-inflammatory Drug 
NSCLC 
Non-Small Cell Lung Cancer 
ORR 
Objective Response Rate 
OS 
Overall Survival 
PARP 
Poly ADP-Ribose Polymerase 
PCNSL 
Primary Central Nervous System Lymphoma 
PD-1 
Programmed Death-1 
PD-L1 
Programmed Death Ligand 1 
PET/CT 
Positron Emission Tomography/Computed Tomography 
PFS 
Progression-Free Survival 
PK 
Pharmacokinetics 
PKAS 
Pharmacokinetics Analysis Set 
PR 
Partial remission 
PRR 
Partial Remission Rate 
PT 
Prothrombin Time 
PT 
Preferred Term 
RP2D 
Recommended Phase II Dose 
R/R ENKTL 
Relapse or Refractory Extranodal Natural Killer / T cell lymphoma  
SAE 
Serious Adverse Event 
SAS 
Safety Analysis Set 
SD 
Stable Disease 
SDV 
Source Data Verification 
SMC 
Safety Monitoring Committee 
SOC 
System Organ Class 
TEAE 
Treatment-Emergent Adverse Event 
TSH 
Thyroid Stimulating Hormone 

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Abbreviation 
Definition 
TTR 
Time to Response 
ULN 
Upper Limit of Normal 
VEGFR 
Vascular Endothelial Growth Factor Receptor 
WOCBP 
Women of Childbearing Potential 

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12. REFERENCES 
1. 
Shi, Y., et al., Results from a multicenter, open-label, pivotal phase II study of chidamide in 
relapsed or refractory peripheral T-cell lymphoma. Ann Oncol, 2015. 26(8): p. 1766-1771. 
2. 
National Comprehensive Cancer Network. (NCCN) Clinical Practice Guidelines in Oncology. 
T-Cell Lymphomas, Version 2.2019. United States. 
3. 
Au, W.Y., et al., Clinical differences between nasal and extranasal natural killer/T-cell 
lymphoma: a study of 136 cases from the International Peripheral T-Cell Lymphoma 
Project. Blood, 2009. 113(17): p. 3931-7. 
4. 
李小秋，等, 中国淋巴瘤亚型分布_国内多中心性病例10002 例分析. 诊断学理论与实
践, 2012. 11(2). 
5. 
Yong, W., Clinical study of l-asparaginase in the treatment of extranodal NK/T-cell 
lymphoma, nasal type. Hematol Oncol, 2016. 34(2): p. 61-8. 
6. 
Ahn, H.K., et al., Gemcitabine alone and/or containing chemotherapy is efficient in 
refractory or relapsed NK/T-cell lymphoma. Invest New Drugs, 2013. 31(2): p. 469-472. 
7. 
Lim, S.H., et al., Beyond first-line non-anthracycline-based chemotherapy for extranodal 
NK/T-cell lymphoma: clinical outcome and current perspectives on salvage therapy for 
patients after first relapse and progression of disease. Ann Oncol, 2017. 28(9): p. 2199-
2205. 
8. 
Tao, R., et al., Presented at: ASCO Annual Meeting. May 31-June4, 2019; Chicago, IL. 
Abstract 7504. 
9. 
Shi, Y., et al., Chidamide in relapsed or refractory peripheral T cell lymphoma: a 
multicenter real-world study in China. J Hematol Oncol, 2017. 10(1): p. 69. 
10. 
Huang, H.Q., et al., Daratumumab Monotherapy for Patients with Relapsed or Refractory 
(R/R) Natural Killer/T-Cell Lymphoma (NKTCL), Nasal Type: Updated Results from an Open-
Label, Single-Arm, Multicenter Phase 2 Study. 2019, American Society of Hematology 
Washington, DC. 
11. 
Suzuki, R., et al., Prospective measurement of Epstein-Barr virus-DNA in plasma and 
peripheral blood mononuclear cells of extranodal NK/T-cell lymphoma, nasal type. Blood, 
2011. 118(23): p. 6018-22. 
12. 
Ito, Y., et al., Pretreatment EBV-DNA copy number is predictive of response and toxicities 
to SMILE chemotherapy for extranodal NK/T-cell lymphoma, nasal type. Clin Cancer Res, 
2012. 18(15): p. 4183-90. 
13. 
Chen, B.J., et al., PD-L1 Expression is Characteristic of a Subset of Aggressive B-Cell 
Lymphomas and Virus-Associated Malignancies. Clinical cancer research : an official 
journal of the American Association for Cancer Research, 2013. 19(13): p. 3462-3473. 
14. 
Quan, L., et al., PD-1 Blockade Can Restore Functions of T-Cells in Epstein-Barr Virus-
Positive Diffuse Large B-Cell Lymphoma In Vitro. PLoS One, 2015. 10(9): p. e0136476. 
15. 
Jo, J.C., et al., Expression of programmed cell death 1 and programmed cell death ligand 1 
in extranodal NK/T-cell lymphoma, nasal type. Ann Hematol, 2017. 96(1): p. 25-31. 
16. 
Kwong, Y.L., et al., PD1 blockade with pembrolizumab is highly effective in relapsed or 
refractory NK/T-cell lymphoma failing l-asparaginase. Blood, 2017. 129(17): p. 2437-2442. 
17. 
Li, X., et al., Activity of pembrolizumab in relapsed/refractory NK/T-cell lymphoma. J 
Hematol Oncol, 2018. 11(1): p. 15. 
18. 
Couronné, L., et al., PD-1 Blockade in a French Series of 13 Relapsed / Refractory Nk/T-Cell 
Lymphoma Patients. Hematological Oncology, 2019. 37(S2): p. 272-273. 
19. 
Kim, S.J., et al., Comparison of Efficacy of Pembrolizumab between Epstein-Barr 
VirusPositive and Negative Relapsed or Refractory Non-Hodgkin Lymphomas. Cancer Res 
Treat, 2019. 51(2): p. 611-622. 
20. 
Zou, W. and L. Chen, Inhibitory B7-family molecules in the tumour microenvironment. Nat 
Rev Immunol, 2008. 8(6): p. 467-77. 

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21. 
Chen, L. and X. Han, Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future. 
Journal of Clinical Investigation, 2015. 125(9): p. 3384-3391. 
22. 
Chiou, V.L. and M. Burotto, Pseudoprogression and Immune-Related Response in Solid 
Tumors. J Clin Oncol, 2015. 33(31): p. 3541-3. 
 

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13. APPENDICES 
13.1 CRITERIA FOR RESPONSE ASSESSMENT OF LYMPHOMA: 
LUGANO 2014 CLASSIFICATION1 
Response 
and Site 
PET-CT-Based Response 
CT-Based Response 
CR 
Complete metabolic response 
Complete radiologic response (all 
of the following) 
Lymph 
nodes and 
extralympha
tic sites 
Score 1, 2, or 3* with or without a residual mass 
on 5PS† 
It is recognized that in Waldeyer’s ring or 
extranodal sites with high physiologic uptake or 
with activation within spleen or marrow (eg, with 
chemotherapy or myeloid colony-stimulating 
factors), uptake may be greater than normal 
mediastinum and/or liver. In this circumstance, 
complete metabolic response may be inferred if 
uptake at sites of initial involvement is no greater 
than surrounding normal tissue even if the tissue 
has high physiologic uptake. 
Target nodes/nodal masses must 
regress to ≤ 1.5 cm in LDi 
No extralymphatic sites of disease 
Nonmeasur
ed lesion 
Not applicable 
Absent 
Organ 
enlargement 
Not applicable 
Regress to normal 
New lesions 
None 
None 
Bone 
marrow 
No evidence of FDG-avid disease in marrow 
Normal by morphology; if 
indeterminate, IHC negative 
PR 
Partial metabolic response 
Partial remission (all of the 
following) 
Lymph 
nodes and 
extralympha
tic sites 
Score 4 or 5 with reduced uptake compared with 
baseline  
and residual mass(es) of any size 
At interim, these findings suggest responding 
disease 
 
At end of treatment, these findings indicate 
residual disease 
≥ 50% decrease in SPD of up to 6 
target measurable nodes and 
extranodal sites 
When a lesion is too small to 
measure on CT, assign 5 mm × 5 
mm as the default value 
When no longer visible, 0 × 0 mm 
For a node ＞ 5 mm × 5 mm, but 
smaller than normal, use actual 
measurement for calculation 
Nonmeasur
ed lesion 
Not applicable 
Absent/normal, regressed, but no 
increase 
Organ 
enlargement 
Not applicable 
Spleen must have regressed by ＞ 
50% in length beyond normal 

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New lesions 
None 
None 
Bone 
marrow 
Residual uptake higher than uptake in normal 
marrow but reduced compared with baseline 
(diffuse uptake compatible with reactive changes 
from chemotherapy allowed). If there are 
persistent focal changes in the marrow in the 
context of a nodal response, consideration should 
be given to further evaluation with MRI or 
biopsy or an interval scan. 
Not applicable 
SD 
No metabolic response 
Stable disease 
Target 
nodes/nodal 
masses, 
extranodal 
lesions 
Score 4 or 5 with no significant change in FDG 
uptake from baseline at interim or end of 
treatment 
＜ 50% decrease from baseline in 
SPD of up to 6 dominant, 
measurable nodes and extranodal 
sites; no criteria for progressive 
disease are met 
Nonmeasur
ed lesion 
Not applicable 
No increase consistent with 
progression 
Organ 
enlargement 
Not applicable 
No increase consistent with 
progression 
New lesions 
None 
None 
Bone 
marrow 
No change from baseline 
Not applicable 
PD 
Progressive metabolic disease 
Progressive disease requires at 
least 1 of the following 
Individual 
target 
nodes/nodal 
masses 
Extranodal 
lesions 
Score 4 or 5 with an increase in intensity of 
uptake from baseline and/or 
New FDG-avid foci consistent with lymphoma at 
interim or end-of-treatment assessment 
PPD progression: 
An individual node/lesion must be 
abnormal with: 
LDi ＞ 1.5 cm and 
Increase by ≥ 50% from PPD 
nadir and 
An increase in LDi or SDi from 
nadir 
0.5 cm for lesions ≤ 2 cm 
1.0 cm for lesions ＞ 2 cm 
In the setting of splenomegaly, 
the splenic length must increase 
by ＞ 50% of the extent of its 
prior increase beyond baseline 
(eg, a 15-cm spleen must increase 
to ＞ 16 cm). If no prior 
splenomegaly, must increase by at 
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New or recurrent splenomegaly 
Nonmeasur
ed lesion 
None 
New or clear progression of 
preexisting nonmeasured lesions 
New lesions 
New FDG-avid foci consistent with lymphoma 
rather than another etiology (eg, infection, 
inflammation). If uncertain regarding etiology of 
new lesions, biopsy or interval scan may be 
considered 
Regrowth of previously resolved 
lesions 
A new node ＞ 1.5 cm in any axis 
(with an absolute increase of > 
0.5 cm compared to the nadir 
value) 
A new extranodal site ＞ 1.0 cm 
in any axis; if ＜ 1.0 cm in any 
axis, its presence must be 
unequivocal and must be 
attributable to lymphoma 
Assessable disease of any size 
unequivocally attributable to 
lymphoma 
Bone 
marrow 
New or recurrent FDG-avid foci 
New or recurrent involvement 
Abbreviations: 5PS, 5-point scale; CT, computed tomography; FDG, fluorodeoxyglucose; IHC, 
immunohistochemistry; LDi, longest transverse diameter of a lesion; MRI, magnetic resonance 
imaging; PET, positron emission tomography; PPD, cross product of the LDi and perpendicular 
diameter; SDi, shortest axis perpendicular to the LDi; SPD, sum of the product of the perpendicular 
diameters for multiple lesions. 
*A score of 3 in many patients indicates a good prognosis with standard treatment, especially if at the 
time of an interim scan. However, in trials involving PET where de-escalation is investigated, it may 
be preferable to consider a score of 3 as inadequate response (to avoid undertreatment). Measurable 
dominant lesions: Up to six of the largest dominant nodes, nodal masses, and extranodal lesions 
selected to be clearly measurable in two diameters. Nodes should preferably be from disparate 
regions of the body and should include, where applicable, mediastinal and retroperitoneal areas. Non-
nodal lesions include those in solid organs (eg, liver, spleen, kidneys, lungs), GI involvement, 
cutaneous lesions, or those noted on palpation. Nonmeasured lesions: Any disease not selected as 
measured, dominant disease and truly assessable disease should be considered not measured. These 
sites include any nodes, nodal masses, and extranodal sites not selected as dominant or measurable or 
that do not meet the requirements for measurability but are still considered abnormal, as well as truly 
assessable disease, which is any site of suspected disease that would be difficult to follow 
quantitatively with measurement, including pleural effusions, ascites, bone lesions, leptomeningeal 
disease, abdominal masses, and other lesions that cannot be confirmed and followed by imaging. In 
Waldeyer’s ring or in extranodal sites (eg, GI tract, liver, bone marrow), FDG uptake may be greater 
than in the mediastinum with complete metabolic response, but should be no higher than surrounding 
normal physiologic uptake (eg, with marrow activation as a result of chemotherapy or myeloid 
growth factors). 
†PET 5PS: 1, no uptake above background; 2, uptake ≤ mediastinum; 3, uptake ＞ mediastinum but 
≤ liver; 4, uptake moderately ＞ liver; 5, uptake markedly higher  
than liver and/or new lesions; X, new areas of uptake unlikely to be related to lymphoma. 
1Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of 
Hodgkin and non-Hodgkin lymphoma: The Lugano Classification. J Clin Oncol 2014;32(27):3059-3068. 
 
 

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13.2 CRITERIA FOR ECOG PERFORMANCE STATUS ASSESSMENT 
Grade 
ECOG Performance Status 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of 
a light or sedentary nature, e.g. light house work, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work activities; up 
and about more than 50% of waking hours 
3 
Capable of only limited selfcare; confined to bed or chair more than 50% of waking 
hours 
4 
Completely disabled; cannot carry on any selfcare; totally confined to bed or chair 
5 
Dead 
 
 
 

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13.3 RESPONSIBILITY FOR MEDICATION MANAGEMENT 
1. Each investigational product should have a label and package provided by CStone 
Pharmaceuticals (Shanghai) Co., Ltd. and CStone Pharmaceuticals (Suzhou) Co., 
Ltd. The sponsor will carry the qualification certificate, the inspection report of the 
investigational product and the investigational product to each site for handover 
procedure. The investigational product will be stored in a specific area; 
2. A delegated personnel at the site will manage the investigational product, receive, 
dispense and return the medication by strictly following applicable SOPs and drug 
administrative requirements. 
3. The investigational product is only for use in this trial, but not any other 
circumstance. 
4. The transport, receiving, dispensing and return of the investigational product must 
be recorded by a delegated personnel. The use of investigational product will be 
carefully recorded in the Investigational Product Use Log, signed and dated by the 
operator. 
5. The investigator must not destroy and package or label or the remaining unused 
medication without prior notification and permission of the sponsor. 
6. When the trial ends, the investigational product will be destroyed at a third party 
designated by the sponsor. Study personnel should ensure, develop and record 
adequate process of investigational product handling in compliance with applicable 
regulations, guidelines and policies. The investigational product will be destroyed 
per sponsor’s approval. 
 

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13.4 IMMUNE-RELATED ADVERSE REACTIONS MANAGEMENT GUIDANCE FOR INVESTIGATORS 
Identification, diagnosis, management and dose modification for irAEs are detailed below: 
Potential irAE 
Potential signs and 
symptoms 
Diagnosis and differential 
diagnosis 
Recommended management 
Dose modification 
Pneumonitis 
Symptomatic: dyspnea, cough, 
pleuritic chest pain, hypoxia 
Asymptomatic: lung infiltrates 
that mimic severe bacterial 
pneumonia 
• 
Radiographic imaging of 
chest 
• 
Tissue and lavage samples 
from bronchoscopy to rule 
out infectious pathogens 
and pathologic evaluation 
Moderate (Grade 2): administration of 
corticosteroids at a dose of 1-2 
mg/kg/day prednisone equivalents 
Withhold CS1001 until 
resolved to ≤ Grade 1 
 
≥ Severe (Grade 3): high dose 
corticosteroids (2-4 mg/kg/day IV 
methylprednisolone) along with 
antibiotics; in-subject hospitalization; 
consultation with a respiratory 
physician; additional 
immunosuppression with infliximab can 
be considered 
Permanent 
discontinuation from the 
study treatment 
Colitis 
Watery diarrhea, mucus or 
blood in stool, abdominal pain, 
nausea/vomiting, dehydration, 
peritoneal signs, bowel 
perforation 
• 
Stool cultures 
• 
Endoscopy or colonoscopy 
to rule out infection  
• 
Biopsy to rule out 
alternative etiology 
≤ Grade 2 diarrhea: antidiarrheal 
medication, oral hydration, electrolyte 
supplement 
Continue dosing 
Persistent Grade 2 diarrhea: 
administration of corticosteroids at a 
dose of 1-2 mg/kg/day prednisone 
equivalents 
Withhold CS1001 until 
resolved to ≤ Grade 1 

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Potential irAE 
Potential signs and 
symptoms 
Diagnosis and differential 
diagnosis 
Recommended management 
Dose modification 
≥ Severe (Grade 3) diarrhea: high dose 
corticosteroids (2-4 mg/kg/day IV 
methylprednisolone) along with 
antibiotics; infliximab can be considered 
for steroid refractory diarrhea 
Withhold CS1001 until 
resolved to ≤ Grade 1 
Recurrent severe (Grade 3) or life-
threatening (Grade 4) diarrhea: high 
dose corticosteroids (2-4 mg/kg/day IV 
methylprednisolone) along with 
antibiotics; infliximab can be considered 
for steroid refractory diarrhea; in-subject 
hospitalization 
Permanent 
discontinuation from the 
study treatment 
If bowel perforation is suspected, steroid 
should be withheld and surgical opinion 
should be explored; in-subject 
hospitalization; Infliximab should not be 
administered 
Permanent 
discontinuation from the 
study treatment 
Hepatitis 
Symptomatic: fever, fatigue, 
nausea, abdominal pain, 
jaundice, hepatomegaly 
Asymptomatic: elevation of 
liver function tests (hepatic 
transaminases, bilirubin) 
• 
Chemistry: elevated levels 
of hepatic transaminases 
• 
Serologic testing: should 
be performed to rule out 
viral hepatitis (including 
hepatitis A and B), 
cytomegalovirus, and 
Epstein-Barr virus 
• 
Ultrasonograms of the liver 
• 
Biopsy or radiologic 
imaging to distinguish 
• 
Moderate (Grade 2): administration 
of corticosteroids at a dose of 1-2 
mg/kg/day prednisone equivalents 
Withhold CS1001 until 
resolved to ≤ Grade 1 

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Potential irAE 
Potential signs and 
symptoms 
Diagnosis and differential 
diagnosis 
Recommended management 
Dose modification 
from other etiologies of 
hepatic injury, such as 
neoplastic disease 
progression in the liver, 
infections, and effects of 
other medications or 
alcohol intake 
• 
≥ Severe (Grade 3): administration 
of high dose corticosteroids (2-4 
mg/kg/day IV methylprednisolone); 
if not improved after 48-72 hours, 
alternative immunosuppression 
agents (mycophenolate mofetil) 
should be considered; in-subject 
hospitalization; consultation with a 
hepatologist 
• 
Total serum bilirubin >3 times 
upper limit of normal 
Permanent 
discontinuation from the 
study treatment 
Hypophysitis 
Headache refractory to 
nonsteroidal anti-
inflammatory drugs or other 
analgesics; weakness; fatigue, 
weight gain or weight loss; 
changes in mood or behavior; 
hypotension; electrolyte 
disturbances; abdominal pain; 
loss of libido; adrenal crisis; 
hypogonadism 
• 
Clinical chemistry tests 
• 
Endocrinologic laboratory 
test, ACTH, thyroid 
function test 
• 
Magnetic resonance 
imaging (MRI) of the 
brain: enlargement of the 
pituitary with variable 
contrast enhancement 
characteristics 
Moderate (Grade 2) without adrenal 
crisis: high-dose corticosteroids 
(methylprednisolone 1 to 2 mg/kg/day 
or the equivalent); initiate appropriate 
hormone replacement therapy; 
consultation with an endocrinologist 
Withhold CS1001 until 
resolved to ≤ Grade 1 
 
 
 
 
≥ Grade 3 or adrenal crisis: high-dose 
corticosteroids (methylprednisolone 1 to 
2 mg/kg/day or the equivalent); 
consultation with an endocrinologist 
Permanent 
discontinuation from the 
study treatment 
Nephritis 
Hematuria, peripheral edema, 
elevated serum creatinine 
• 
Clinical chemistry tests 
• 
Urine test 
• 
Biopsy if necessary 
Moderate (Grade 2): administration of 
corticosteroids at a dose of 1-2 
mg/kg/day prednisone equivalents 
Withhold CS1001 until 
resolved to ≤ Grade 1 

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Potential irAE 
Potential signs and 
symptoms 
Diagnosis and differential 
diagnosis 
Recommended management 
Dose modification 
≥ Severe (Grade 3): administration of 
corticosteroids at a dose of 1-2 
mg/kg/day prednisone equivalents 
Permanent 
discontinuation from the 
study treatment 
Hypothyroidism 
/hyperthyroidism 
Typically asymptomatic and is 
identified by lab tests 
Triiodothyronine (T3), 
thyroxine (T4) and thyroid 
stimulating hormone (TSH) test 
results 
Asymptomatic ≤ moderate (Grade 2) 
hypothyroidism: thyroxine replacement 
therapy 
Continue dosing 
Asymptomatic ≤ moderate (Grade 2) 
hyperthyroidism: consider beta blockade 
Continue dosing 
≥ Severe (Grade 3) hypothyroidism: 
replacement therapy 
Withhold CS1001 until 
resolved to ≤ Grade 1 or 
baseline 
Severe (Grade 3) hyperthyroidism 
lasting ≥ 6 weeks despite active 
management: administration of 
corticosteroids at a dose of 1-2 
mg/kg/day prednisone equivalents 
Withhold CS1001 until 
resolved to ≤ Grade 1 
Life-threatening (Grade 4) 
hyperthyroidism 
Permanent 
discontinuation from the 
study treatment 
Dermatitis 
Maculopapular rash or 
erythroderma, pruritus, skin 
ulceration, bullous dermatitis, 
Stevens-Johnson syndrome 
• 
Unless an alternative 
etiology is identified, it 
should be considered 
immune-related 
• 
Pathologic evaluation of 
skin biopsy can be 
≤ Moderate (Grade 2) (up to 30% of 
body surface area): topical 
corticosteroids and oral over-the-counter 
antihistamines and systemic 
corticosteroids if no improvement within 
7 days 
Continue dosing 

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Potential irAE 
Potential signs and 
symptoms 
Diagnosis and differential 
diagnosis 
Recommended management 
Dose modification 
performed to rule out 
alternative etiology 
Severe (Grade 3, > 30% of body surface 
area): administration of corticosteroids 
at a dose of 1-2 mg/kg/day prednisone 
equivalents 
Withhold CS1001 until 
resolved to ≤ Grade 2 
Life-threatening (Grade 4, for example 
Stevens-Johnson syndrome, toxic 
epidermal necrosis, full-thickness 
dermal ulceration, necrosis or 
hemorrhage): high dose corticosteroids 
(2-4 mg/kg/day IV methylprednisolone); 
in-subject hospitalization; consultation 
with a dermatologist 
Permanent 
discontinuation from the 
study treatment 
Neuromuscular 
toxicity 
Peripheral sensory neuropathy, 
muscle weakness, Guilliain-
Barre syndrome, transverse 
myelitis, myasthenia gravis 
• 
Physical exam of sensory 
change, loss of deep-
tendon reflexes 
• 
Neuroimaging, nerve 
conduction exam 
• 
Nerve/muscle biopsy 
≤ Moderate (Grade 2): administration of 
corticosteroids at a dose of 1-2 
mg/kg/day prednisone equivalents 
Withhold CS1001 until 
resolved to ≤ Grade 1 
≥ Severe (Grade 3): high dose 
corticosteroids (2-4 mg/kg/day IV 
methylprednisolone) 
Permanent 
discontinuation from the 
study treatment 

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Potential irAE 
Potential signs and 
symptoms 
Diagnosis and differential 
diagnosis 
Recommended management 
Dose modification 
Ocular toxicity 
Photosensitivity, pain or 
dryness of the eyes, blurred 
vision, uveitis, iritis, 
episcleritis 
• 
Ophthalmic exam  
 ≤ Moderate (Grade 2): topical steroids 
(1% prednisolone) 
Withhold CS1001 until 
resolved to ≤ Grade 1; if 
not resolved ≤ Grade 1 
within 14 days with 
topical steroids or 
initiation of systemic 
treatment, permanent 
discontinuation from the 
study treatment 
≥ Severe (Grade 3): high dose 
corticosteroids (2-4 mg/kg/day IV 
methylprednisolone) 
Permanent 
discontinuation from the 
study treatment 
Other irAEs, such as 
arthritis, pancreatitis, 
hemolytic anemia, 
adrenal insufficiency, 
myasthenic syndrome, 
and rhabdomyolysis 
 
 
Moderate (Grade 2) 
Withhold CS1001 until 
resolved to ≤ Grade 1 
≥ Severe (Grade 3) 
Permanent 
discontinuation from the 
study treatment 
 

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13.5 PROTOCOL AMENDMENT 
Major amendments in protocol Version 3.0 
Section(s) 
Title of section(s) 
Amendment details 
Amendment rationale 
SYNOPSIS 
Secondary endpoints 
Move 6 month PFS and 6 month OS rate from 
secondary endpoints to exploratory endpoints, 
details refer to Protocol Amendment 3.0 
 
 
In single-arm trials, time-to-event 
efficacy endpoints such as PFS and OS 
should be exploratory rather than 
secondary endpoints 
Secondary efficacy analyses 
Exploratory endpoints 
Exploratory efficacy analyses 
 
2．OBJECTIVES AND 
ENDPOINTS 
8.3.2 
8.7 
Secondary Efficacy Endpoints 
EXPLORATORY ANALYSES 
SYNOPSIS 
Inclusion Criteria / Exclusion Criteria 
Inclusion Criteria： 
“3. Subjects must have a histologically confirmed 
ENKTL at the study site。” is amended to 
“Subjects must have a histologically confirmed 
ENKTL at the study site. Both nasal and non-nasal 
ENKTL are allowed.” 
Add “ 6. Life expectancy ≥ 12 weeks.” 
“8. d) Serum creatinine ≤ 1.5 × upper limit of normal 
(ULN) or creatinine clearance ≥ 40 mL/min 
(according to Cockcroft-Gault equation); e) Serum 
total bilirubin ≤ 1.5 × ULN;” is amended to“8. d) 
Creatinine clearance ≥ 40 mL/min (according to 
Cockcroft-Gault equation); e) Serum total bilirubin ≤ 
 
 
 
4.1/4.2 
Inclusion Criteria / Exclusion Criteria 

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1.5 × ULN, unless considered to be due to Gilbert’s 
disease, where it must be ≤3 × ULN;” 
Exclusion Criteria： 
“ 1.Aggressive natural killer-cell leukemia. ”  is 
amended to “ 1. Aggressive natural killer-cell 
leukemia or ENKTL patients who have any degree of 
leukemic involvement will be excluded.” 
“3. Primary central nervous system lymphoma 
(PCNSL) or secondary CNS involvement” is 
amended to “3. Current or historical primary 
central nervous system lymphoma (PCNSL) or 
secondary CNS involvement.” 
“10. A known other malignancy within the past 5 
years. Subjects with basal cell carcinoma of the skin, 
squamous cell carcinoma of the skin, breast cancer 
in situ, or cervical cancer in situ that have undergone 
curative therapy are permitted to enroll” is amended 
to “10. A known additional malignancy within 5 
years piror to the first dose of investigational 
product. Subjects with locally curable malignancies 
(including basal cell carcinoma of skin, squamous 
cell carcinoma of skin, breast cancer in situ or 
cervical cancer in situ, etc.) that have undergone 
curative therapy are permitted to enroll” 
“23. Subjects with a known history of alcoholism 
or drug abuse.” is amended to “23. Subjects with 
active alcohol or drug dependence.” 
“25. Subjects with a history of psychiatric disease; 
subjects with incapacity or limited capacity ”  is 
amended to “ 25. Subjects with a history of 

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psychiatric disease; or subjects with incapacity or 
limited capacity.” 
SYNOPSIS 
Primary efficacy analyses 
“The statistical analysis will be performed by 24 
weeks after the first dose of last subject.  The median 
duration of follow-up of all responders since the 
time of first response is estimated to be around 23 
months by that time, under an assumed enrollment 
rate of 1.5 subjects per month.” is amended to  
“The statistical analysis will be performed by 24 
weeks after the first dose of last subject.” 
Update statistical methods 
8.3.1 
Primary efficacy endpoints 
SYNOPSIS 
Sample size 
The primary efficacy endpoint is ORR assessed by 
IRRC according to Criteria for Response 
Assessment of Lymphoma: Lugano 2014 
Classification. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.1 
SAMPLE SIZE DETERMINATION 

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. 
SCHEDULE OF STUDY 
ACTIVITIES 
Safety follow-up 
“2. Safety follow-up：Adverse events (AEs) and 
concomitant medications can be collected by 
telephone follow-up at 60 days and 90 days after the 
last dose.” is amended to“2. safety follow-up：It is 
recommended to complete all protocol required 
follow-up evaluations for the safety follow-up at 60 
± 3days and 90± 3 days after the last dose, or AEs 
and concomitant medications can be collected 
through phone call.” 
According to Protocol clarification letter 
dated 27 Jul 2020, clarify the safety 
follow-up 
6.1.3.1 
safety follow-up 
SCHEDULE OF STUDY 
ACTIVITIES 
Central pathology 
Add：“Both fresh and archival biopsies are accepted 
and can be used by central pathology.” 
clarify the request of sample for central 
pathology 
3.1.1 
Screening 
6.1.1 
Screening Central pathology 
6.3 
PATHOLOGICAL ASSESSMENTS 
 
SCHEDULE OF STUDY 
ACTIVITIES 
Bone marrow aspiration and biopsy 
“21.Bone marrow aspiration and biopsy: Bone 
marrow aspiration and biopsy should be performed 
at screening for all subjects. Subjects with positive 
bone marrow aspiration/biopsy result at screening 
will undergo bone marrow aspiration and biopsy 
when achieving CR/CMR based upon radiology for 
confirmation.” is amended to “21.Bone marrow 
aspiration and biopsy: Bone marrow aspiration and 
biopsy should be performed at screening for all 
subjects. Subjects with positive bone marrow 
aspiration/biopsy result or indeterminate overall 
bone marrow assessment at screening will undergo 
Clarify that  the bone marrow aspiration 
and biopsy should be performed when 
achieving CR/CMR, if the overall bone 
marrow assessment is  indeterminate at 
screening  
6.1.2 
Treatment Period, Bone marrow 
aspiration and biopsy 
 
6.4 
EFFICACY ASSESSMENTS 

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bone marrow aspiration and biopsy when achieving 
CR/CMR based upon radiology for confirmation.” 
SCHEDULE OF STUDY 
ACTIVITIES 
Blood sample/ tumor tissue for 
biomarker testing 
“22.Blood sample for biomarker testing: A whole 
blood sample of 2 mL will be taken as genetic 
control in whole-exome sequencing for tumor tissue. 
View Central Laboratory Manual for details. 
Tumor tissue for biomarker testing: Seven (7) 
unstained tumor tissue sections are collected at 
screening for whole-exome sequencing of tumor 
tissue. View Central Laboratory Manual for details.” 
is amended to  
“22.Blood sample for biomarker testing: A total 
amount of 2 mL whole blood sample will be 
collected as germline control in whole-exome 
sequencing for tumor tissue. The whole blood can be 
collected at screening or retrospectively after study 
entry. View Central Laboratory Manual for details. 
23.Tumor tissue for biomarker testing: Seven (7) 
unstained Formalin-Fixed, Paraffin-Embedded 
(FFPE) tumor tissue slides should be collected at 
screening for whole-exome sequencing of tumor 
tissue. If no samples were collected at screening, a 
retrospective collection of 7 archival FFPE tumor 
tissue slides is allowed. View Central Laboratory 
Manual for details.” 
To clarity that the samples for 
biomarker testing can be retrospective 
collected in study period. 
1.2.1.1 
Pharmacodynamic Studies 
 
Update the data of pharmacodynamic studies, details 
refer to Protocol Amendment 3.0 
Data from pre-clinical 
pharmacodynamic studies were updated 
according to CS1001 IB v6.0. 
1.2.2 
Clinical Studies 
 
Update the data of clinical studies, details refer to 
Protocol Amendment 3.0 
Data from clinical studies were updated 
according to CS1001 IB v6.0. 

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3.1.1 
Screening 
“At the screening phase, tumor tissue (7 evaluable 
unstained sections) and 2 mL of whole blood as 
genetic control in whole exome sequencing for 
tumor tissue” is amended to: 
 “Seven (7) unstained FPPE tumor slides should be 
collected at screening for whole-exome sequencing 
of tumor tissue. A total amount of 2 mL whole blood 
should be collected at screening as germline control 
of whole-exome sequencing. If the tumor tissue and 
whole blood samples were not available  at 
screening,  retrospective collections of 7 archival 
FFPE tumor tissue slides and collection of 2 mL 
whole blood are allowed for whole-exome 
sequencing” 
To clarity that the samples for 
biomarker testing can be retrospective 
collected in study period. 
3.1.5 
Treatment Beyond End of Study 
Add “These subjects must provide written ICF and 
be willing and able to continue to follow all study 
procedures for continuing treatment.” 
According to Protocol clarification letter 
dated 27 Jul 2020, clarify the treatment 
beyond end of study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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” 
5.3.2 
Criteria for Dose Modification of 
Investigational Product 
Add“13.Any Grade 3 abnormal laboratory test result 
except for the following situations : 
– Grade 3 hematologic toxicity. 
– Study treatment will be delayed when Grade 2 
hepatitis occurs. 
14. Any AE, abnormal laboratory test result or 
intercurrent condition that in the investigator’s 
opinion requires postponing study treatment.” 
Clarity the laboratory and other criteria 
for dose modification of investigational 
product 
5.3.3 
Criteria for Permanent Discontinuation 
of Investigational Treatment 
Add “Grade 4 abnormal laboratory test result except 
for the following situations: 
–Grade 4 neutropenia lasting for ≤ 5 days  
–Grade 4 lymphocytopenia or leukopenia  
–Solitary Grade 4 electrolyte disorder/imbalance that 
can be corrected by electrolyte 
supplementation/adequate treatment in 72 hours 
without any clinical consequence.” 
Clarity the laboratory and other criteria 
for permanent discontinuation of 
investigational product 
6.6 
Biomarkers 
“Whole exome sequencing of tumor tissue: seven (7) 
unstained tumor tissue sections are collected at 
screening for whole-exome sequencing of tumor 
tissue; 2 mL of whole blood collected as genetic 
control.” is amended to:  
“Whole exome sequencing of tumor tissue: seven (7) 
unstained FFPE tumor tissue slides should be 
collected at screening for whole-exome sequencing 
of tumor tissue; a total amount of 2 mL whole blood 
To clarity that the samples for 
biomarker testing can be retrospective 
collected in study period. 

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should be collected at screening as germline control 
of whole-exome sequencing. 
If the tumor tissue and whole blood samples were 
not available at screening,  retrospective collections 
of 7 archival FFPE tumor tissue slides and collection 
of 2 mL whole blood are allowed for whole-exome 
sequencing.” 
Throughout the document 
 
Administrative changes: 
 
Modifications to the heading and the texts 
 
Abbreviation list update  
 
Cross-reference update 
Typo and formatting update 
To increase protocol clarity, consistency 
and readability 
 
Major amendments in protocol Version 2.0 
Section(s) 
Title of section(s) 
Amendment details 
Amendment rationale 
SYNOPSIS 
Study design and methods 
The flow-chart: 
“safety follow-up: 30 days after the last dose of 
study treatment” is amended to “safety follow-up:30, 
60, 90 days after the last dose of study treatment，
Safety follow-up period refers to the 90 days after 
the last dose of the investigational treatment or the 
start of new anti-cancer treatment, whichever occurs 
earlier.” 
To clarify the safety follow-up 
timeframe.  
SYNOPSIS 
Exclusion Criteria (number 13) 
To clarify the criteria of Chinese 

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4.2 
“13. Any use of traditional Chinese medicines or 
herbal preparations within 7 days prior to the first 
dose of investigational product.” is amended to “13. 
Any use of traditional Chinese medicines or herbal 
preparations with anti-tumor indications within 7 
days before the first dose of investigational product” 
medicines or herbal preparations in prior 
treatment in exclusion criteria. 
SYNOPSIS 
 
 
 
 
 
 
  
SYNOPSIS 
Statistical Methods 
Update “Statistical Methods”, detail refer to Protocol 
Amendment 2.0 
Statistical methods were updated. 
SCHEDULE OF STUDY 
ACTIVITIES 
Safety follow-up (with footnote 2) 
“safety follow-up: 30 days after the last dose of 
study treatment” is amended to “safety follow-up:30, 
60, 90 days after the last dose of study treatment, 
Safety follow-up period refers to the 90 days after 
the last dose of the investigational treatment or the 
start of new anti-cancer treatment, whichever occurs 
earlier.” 
To clarify the safety follow-up 
timeframe. 
SCHEDULE OF STUDY 
ACTIVITIES 
Concomitant medications (with 
footnote 5) 
“All concomitant medications received from 30 days 
prior to the screening will be recorded until safety 
follow up is completed” is amended to “All 
concomitant medications received from 30 days 
prior to the screening will be recorded until 90 days 
after the last dose of study treatment or the start of 
new anti-cancer treatment, whichever occurs first” 
According to Protocol clarification letter 
dated 17 Apr 2019, clarify the period for 
collection of concomitant medications. 
SCHEDULE OF STUDY 
ACTIVITIES 
PK (with footnote 18) 
Add: “Blood samples for PK testing will be 
collected at the EOT visit, and safety follow-up visit 
at 30 days, and 90 days after the last dose of study 
treatment.” 
ADA sample should be always 
accompanying by PK sample 
simultaneously as reference of 
concentration data for justifying ADA 
result especially for negative result. 
6.1.2.1 
End-of-Treatment Visit 
6.5 
Pharmacokinetics and immunogenicity 

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SCHEDULE OF STUDY 
ACTIVITIES 
ADA (with footnote 19) 
“Blood samples for ADA testing will be collected at 
EOT visit and safety follow-up visit” is amended to 
“Blood samples for ADA testing will be collected at 
the EOT visit and safety follow-up visit at 30 days, 
and 90 days after the last dose of study treatment” 
Add ADA follow-up visit to follow 
ADA  until the serum titers revert to 
baseline 
6.5 
Pharmacokinetics and immunogenicity 
SCHEDULE OF STUDY 
ACTIVITIES 
Hematology, serum chemistry and 
urinalysis 
Delete “bicarbonate” 
According to Protocol clarification letter 
dated 07 Dec 2018, delete the collection 
of bicarbonate value 
6.1.1 
6.2.4 
SCHEDULE OF STUDY 
ACTIVITIES 
Bone marrow aspiration and biopsy 
“Bone marrow aspiration/biopsy should be 
performed at screening. Subjects with positive bone 
marrow aspiration/biopsy result at screening will 
undergo bone marrow aspiration/biopsy when 
achieving CR based upon radiology for 
confirmation. Flow cytometry or 
immunohistochemistry (IHC) analyses can be used 
per investigator’s judgment if bone marrow 
involvement cannot be determined under 
microscope.” is amended to “Bone marrow 
aspiration and biopsy should be performed at 
screening for all subjects. Subjects with positive 
bone marrow aspiration/biopsy result at screening 
will undergo bone marrow aspiration and biopsy 
when achieving CR/CMR based upon radiology for 
confirmation. Immunohistochemistry (IHC) analyses 
should be performed under microscope  no matter 
bone marrow involves or not (Suggest detecting 
CD56、TIA-1、CD3、GrB、perforin, and 
EBER hybridization in situ, etc.).” 
According to Protocol clarification letter 
dated 08 May 2018, clarify the 
requirements for bone marrow 
aspiration and biopsy 
6.1.1 

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1.1 
DISEASE OVERVIEW 
Update overview of indication, details refer to 
Protocol Amendment 2.0 
Update the disease overview to provide 
more background information 
1.2 
MECHANISM OF ACTION 
Update the information of approved anti-PD1/L1 
antibody products, details refer to Protocol 
Amendment 2.0 
Update the information about approved 
competitive products to provide more 
up-to-date information on the marketing 
status of these products 
1.2.1.2 
Pharmacokinetic Studies 
Update the data of PK studies, details refer to 
Protocol Amendment 2.0 
Data from pre-clinical PK studies were 
updated according to CS1001 IB v4.0. 
1.2.1.3 
Safety Studies 
Update the data of safety studies, details refer to 
Protocol Amendment 2.0 
Data from pre-clinical safety studies 
were updated according to CS1001 IB 
v4.0. 
1.2.2 
Clinical Studies 
Update the data of clinical studies, details refer to 
Protocol Amendment 2.0 
Data from clinical studies were updated 
according to CS1001 IB v4.0. 
3.1.3  
Safety follow-up 
“A safety follow-up visit should be conducted 30 
days after the last dose of the investigational 
product.” is amended to “A safety follow-up visit 
should be conducted 30, 60, 90 days after the last 
dose of the investigational product. Safety follow-up 
period refers to the 90 days after the last dose of the 
investigational treatment or the start of new anti-
cancer treatment, whichever occurs earlier.” 
To clarify the safety follow-up 
timeframe. 
3.2.3 
Rationale for Setting ORR as the 
Primary Endpoint 
Update the rationale of ORR as primary endpoint 
Update the references to support the 
selection of ORR as the primary 
endpoint 
4.5 
Definition of Effective Contraception 
Add “If total abstinence was used as highly effective 
method, other methods were no needed.” 
According to Protocol clarification letter 
dated 17 Apr 2019, clarify the definition 
of effective contraception 
5.4.2 
Permitted Therapy 
“Adrenal replacement with >10 mg corticosteroid 
per day or equivalent is permitted.” is amended to 
To correct a typo error. 

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“Adrenal replacement with ≤10 mg corticosteroid 
per day or equivalent is permitted.” 
6.1.2 
Treatment Period 
“Bone marrow aspiration/biopsy should be 
performed at screening and when CR is achieved 
according to radiology. Flow cytometry or 
immunohistochemistry can be used per 
investigator’s judgment if bone marrow involvement 
cannot be determined under microscope.” is 
amended to “Bone marrow aspiration and biopsy 
should be performed. Immunohistochemistry (IHC) 
analyses should be performed under microscope no 
matter bone marrow involves or not (Suggest 
detecting CD56、TIA-1、CD3、GrB、perforin, 
and EBER hybridization in situ, etc.)” 
According to Protocol clarification letter 
08 May 2018, clarify the requirements 
for bone marrow aspiration and biopsy 
6.4 
EFFICACY ASSESSMENTS 
6.1.3.1 
Safety Follow-up 
“Safety follow-up period refers to the 90 days after 
the last dose of the investigational treatment” is 
amended to “Safety follow-up period refers to the 90 
days after the last dose of the investigational 
treatment or the start of new anti-cancer treatment, 
whichever occurs earlier.” 
Add “Concomitant medications are recorded until 90 
days after the last dose or the start of new anti-
cancer treatment, whichever occurs first.” 
According to Protocol clarification letter 
dated 17 Apr 2019, clarify the collection 
period of concomitant medications and 
clarify the safety follow up period. 
7.1.3 
Recording of Adverse Events 
7.2.1 
Definition of A Serious Adverse Event 
“A SAE is defined as any adverse event that occurs 
from the time when subject signs the ICF to the time 
of end of post-treatment follow-up or PD (whichever 
occurs last), which meets any one of the following 
criteria:” is amended to “According to the definition 
from ICH (International Council for Harmonisation), 
SAE is any adverse medical event that meets any of 
the following criteria:” 
According to the requirement of ICH 
guideline, update the definition of SAE 
7.2.2 
Serious Adverse Event Reporting 
Update “Serious adverse event reporting” 
According to Protocol clarification letter 
dated 17 Apr 2019, clarify the 

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requirement of SAE reporting and 
update the information of 
pharmacovigilance 
7.5.2.1 
Reporting of Pregnancy 
Add “However, subjective induced abortion for 
pregnancy termination without medical reason does 
not need to be reported as a SAE of pregnancy 
termination.” 
Clarify the criterion for reporting of 
pregnancy 
8.1, 8.3 and 8.9 
Sample Size Determination (8.1); 
Efficacy Analyses (8.3); and Interim 
Analysis (8.9) 
Update statistical considerations and analysis plans, 
details refer to Protocol Amendment 2.0 
Update sample size determination and 
efficacy analyses sections. 
 
Remove Section 8.9 as no interim 
analysis will be performed. 
8.6 
Immunogenicity Anslysis 
Add “The treatment-induced ADA will also be 
analyzed by computing and reporting duration of an 
induced ADA response which will be classified as 
transient-positive ADA or persistent-positive ADA.” 
Clarify the analysis of transient-positive 
ADA or persistent-positive ADA 
9.1 
ETHICS COMMITTEE 
“The EC is constituted in accordance with China 
Food and Drug Administration (CFDA) 
recommendations and ….” Is amended to “The 
Ethics Committee must be constituted in accordance 
with all applicable regulatory requirements and ….” 
The constituent of  EC need to meet the 
request of all applicable regulatory 
requirements 
Throughout the document 
 
Administrative changes: 
 
Modifications to the heading and the texts 
 
Abbreviation list update  
 
Cross-reference update 
 
Typo and formatting update 
To increase protocol clarity, consistency 
and readability 
 
Major amendments in protocol Version 1.1 

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Section 
Title of section 
Amendment details 
Cause of amendment 
1.2.2 
Clinical Studies 
“Up to now, no dose-limiting toxicity was observed in the dose-
limiting toxicity study in a total of 6 subjects from 3 mg/kg and 10 
mg/kg dose groups. The study showed overall good safety and 
tolerability” is amended to “To date (up to 13 February, 2018), no 
dose-limiting toxicity or treatment related serious adverse event was 
observed in the dose-limiting toxicity study in a total of 14 subjects 
from 4 groups including 3 mg/kg, 10 mg/kg, 20 mg/kg and 1200 mg 
fixed dose group. The study showed good overall safety and 
tolerability." 
Data from phase I trial was updated. 
3.1 
Overall Design 
“At the screening phase, tumor tissue (7 evaluable unstained 
sections) and 9 mL of peripheral blood will be collected for 
biomarker investigation.” is amended to “At the screening phase, 
tumor tissue (7 evaluable unstained sections) and 2 mL of whole 
blood as genetic control in whole exome sequencing for tumor 
tissue.” 
The immune repertoire assay of peripheral monocytes is not 
required, and therefore there’s no need for taking peripheral 
blood sample of 7 mL. 
3.1.2.1 
Treatment Beyond 
Disease Progression 
The following paragraphs are added: 
"In special situations, a subject with disease progression confirmed 
by radiology or other clinical examinations who will possibly 
benefit from further investigational treatment may continue the 
treatment at the judge of investigator in consultation with the 
sponsor. 
A written consent from the subject must be obtained before any 
treatment beyond progression (including suspected 
pseudoprogression and confirmed disease progression)." 
According to feedback from investigators and clinical study 
results of drugs of a similar target, in special cases, a patient may 
continue to benefit from the investigational treatment despite 
disease progression confirmed by radiology or other clinical 
examinations. In the protocol, a written consent is required for a 
subject to receive treatment beyond definite disease progression. 
4.1.1 
Inclusion Criteria 
“With disease progression as the best response to the last line of 
therapy, or progression following response or stable disease 
achieved after the last line of therapy” is amended to “relapse: 
disease progression after response to the last treatment; refractory: 
no response to the last treatment”. 
According to input from clinicians and designs of similar 
studies, patients who are non-responders to the last treatment 
may be enrolled in the clinical trial. 

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7.1.3 
Recording of Adverse 
Events 
“…the safety follow-up period of 30 days after the last dose of 
investigational product” is amended to “...the safety follow-up 
period of 90 days after the last dose of investigational product. AEs 
that occur after the safety follow-up visit can be recorded by 
telephone follow-up 60 days and 90 days after the last dose."  
Adverse effects of an anti-PD-L1 or anti-PD-1 drug are primarily 
immune related events that last longer period of time. Prolonged 
period for AE collection will improve the safety management for 
subjects. Method of AE collection after the safety follow-up visit 
is defined. 
7.2.2 
Serious Adverse 
Events Reporting 
"Any SAE occurring from the time of ICF signing to 30 days after 
the last dose of investigational product…” is amended to "Any SAE 
occurring from the time of ICF signing to 90 days after the last dose 
of investigational product..." 
To correct a clerical mistake. “90 days” is in line with note 6 of 
Schedule of Study Activities. 
6.4 
Efficacy Assessment 
“Bone marrow aspiration/biopsy should be performed when CR is 
achieved according to radiology” is amended to “Bone marrow 
aspiration/biopsy should be performed at screening. Subjects with 
positive bone marrow aspiration/biopsy result at screening will 
undergo bone marrow aspiration/biopsy when achieving CR based 
upon radiology." 
According to Lugano classification, only subjects with positive 
baseline bone marrow need to have bone marrow test when CR 
is achieved according to radiology evaluation. 
6.4 
Efficacy Assessment 
The sentence “PET/CT should be performed first followed by 
enhanced CT at screening, week 12 and week 24” is deleted. 
The “PET/CT first and then enhanced CT” rule only applies to 
the situation where PET/CT and enhanced CT are performed on 
the same day. According to feedback from clinicians, PET/CT 
and enhanced CT are performed on separate dates in most cases. 
Therefore this requirement is deleted from the protocol, while a 
new requirement stating that “if PET/CT and enhanced CT are to 
be performed on the same day, PET/CT should be performed 
first followed by enhanced CT” is added in the Radiology 
Manual provided to the sites. 
13.1 
Criteria for Response 
Assessment of 
Lymphoma: Lugano 
2014 Classification 
In the “PD-New lesions” part, “A new node ＞ 1.5 cm in any axis” 
is amended to “A new node ＞ 1.5 cm in any axis (with an absolute 
increase of > 0.5 cm compared to the nadir value)" 
The radiology evaluation criteria is refined after agreement is 
achieved with the central radiologists.