Clinical trial NCT02395016
Conditions: Pancreatic Cancer
Sponsor: Biotech Pharmaceutical Co., Ltd.
Start date: 2015-04-01; Completion date: 2021-11-01
Enrollment: 90 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Nimotuzumab is a humanized monoclonal antibody against epidermal growth factor receptor (EGFR). Clinical trials are ongoing globally to evaluate Nimotuzumab in different indications. Nimotuzumab has been approved to treat squamous cell carcinoma of head and neck (SCCHN), glioma and nasopharyngeal carcinoma in different countries.The clinical phase Ⅲ trial designed to assess overall survival（OS）of the combination of Nimotuzumab administered concurrently with Gemcitabine in patients with RAS wild type of locally advanced or metastatic pancreatic cancer

Detailed description:
Nimotuzumab is a humanized monoclonal antibody against epidermal growth factor receptor (EGFR). Clinical trials are ongoing globally to evaluate Nimotuzumab in different indications. Nimotuzumab has been approved to treat squamous cell carcinoma of head and neck (SCCHN), glioma and nasopharyngeal carcinoma in different countries.The clinical phase Ⅲ trial designed to assess overall survival（OS）of the combination of Nimotuzumab administered concurrently with Gemcitabine in patients with RAS wild type of locally advanced or metastatic pancreatic cancer.Secondary objectives include time to progression（TTP）,progression-free survival（PFS）,Objective Response Rate（ORR）,Disease Control Rate（DCR）,Clinical Benefit Response（CBR）and safety.

Arms: arm 1: nimotuzumab,400mg/w，Intravenous infusion over 60 minutes,Until disease progression or intolerable toxicity or subjects ask to leave the test.

Gemcitabine，1000mg/m2，Intravenous infusion over 30 minutes,Once every three weeks, rest one week (d1,8,15; q28d), Every 4 weeks for a period,Until disease progression or intolerable toxicity or subjects ask to leave the test. arm 2: placebo,400mg/w，Intravenous infusion over 60 minutes,Until disease progression or intolerable toxicity or subjects ask to leave the test.

Gemcitabine，1000mg/m2，Intravenous infusion over 30 minutes,Once every three weeks, rest one week (d1,8,15; q28d), Every 4 weeks for a period,Until disease progression or intolerable toxicity or subjects ask to leave the test.
Interventions: intervention 1: nimotuzumab intervention 2: Gemcitabine intervention 3: Placebo
Intervention descriptions: intervention 1: nimotuzumab,400mg/w，Intravenous infusion over 60 minutes,Until disease progression or intolerable toxicity or subjects ask to leave the test. intervention 2: Gemcitabine，1000mg/m2，Intravenous infusion over 30 minutes,Once every three weeks, rest one week (d1,8,15; q28d), Every 4 weeks for a period,Until disease progression or intolerable toxicity or subjects ask to leave the test. intervention 3: Placebo，400mg/w，Intravenous infusion over 60 minutes,Until disease progression or intolerable toxicity or subjects ask to leave the test.

Protocol documents:
Prot_000.pdf: 
Protocol No. BPL-Nim-PC-1 
 Version date: June16, 2014 
 Version 1.1 
Drug clinical research approval No. of State Food and Drug Administration: 
2011l01239 
Prospective study of nimotuzumab combined with gemcitabine 
versus placebo plus gemcitabine in the treatment of K-RAS 
wild type locally advanced or metastatic pancreatic cancer 
Randomized controlled, double-blind, multicenter clinical 
trial Team leaders:
    The 81st Hospital of PLA
  and Shanghai Fudan University Cancer Hospital Researchers:       Qin Shukui and Jin Li 
Sponsor:            
   Biotech Pharmaceutical Co., Ltd 
Version number:  Version 1.1 
Version date:        16 June 2014 


Protocol No. BPL-Nim-PC-1 
 Version date: June16, 2014 
 Version 1.1 
Protocol title page 
Protocol No. 
BPL-Nim-PC-1 
Research topic 
A prospective, randomized, double-blind, multicenter 
registered clinical trial of nimotuzumab combined with 
gemcitabine versus placebo plus gemcitabine in the 
treatment of locally advanced or metastatic pancreatic 
cancer of K-RAS wild type 
Sponsor 
Biotech Pharmaceutical Co., Ltd located in the 2 
rongjingdong street, Beijing Economic and Technological 
Development Zone, 100176 
Study Drug 
Nimotuzumab  injection 
To increase  
the indication 
Locally advanced or metastatic pancreatic cancer 
Version date 
16 June 2014 
GCP statement 
The study was carried out in accordance with the 
provisions of the declaration of Helsinki and the good 
practice for quality management of clinical trials of drugs, 
and the required documents were filed according to the 
requirements of the state and local food and drug 
administration. 
Confidentiality 
statement 
This document is confidential and contains the property 
right information of Baitai biopharmaceutical Co., 
Ltd(Biotechplc.com). and is only used for review or 
execution trial of this study. Without the approval of 
Biotech Pharmaceutical Co., Ltd., other personnel and 
units are prohibited from spreading, copying, publishing 
or applying. 


Protocol No. BPL-Nim-PC-1 
 Version date: June16, 2014 
 Version 1.1 
CATALOG 
Protocol title page ..................................................................................................................................... 2 
Abbreviation list ....................................................................................................................................... 5 
Summary .................................................................................................................................................. 6 
1. 
Research background .................................................................................................................. 11 
2. 
Research purpose ......................................................................................................................... 14 
2.1 
Primary purpose ................................................................................................................... 14 
2.2 
Secondary purpose ................................................................................................................ 14 
3. 
Research overall design ............................................................................................................... 14 
3.1 
Multicenter research ............................................................................................................. 15 
3.2 
Central random ..................................................................................................................... 15 
3.3 
Control drug selection .......................................................................................................... 15 
3.4 
Blinding method .................................................................................................................... 15 
3.5 
Sample size ............................................................................................................................ 16 
4 
Study population .......................................................................................................................... 16 
4.1 
Inclusion criteria ................................................................................................................... 16 
4.2 
Exclusion criteria .................................................................................................................. 17 
4.3 
Exit criteria ........................................................................................................................... 18 
4.3.1 
Withdraw from research ..................................................................................................... 18 
4.3.2 
Treatment of withdrawal from study medication .................................................................. 18 
4.4 
Termination criteria .............................................................................................................. 18 
5 
Study drug and administration plan .......................................................................................... 19 
5.1 
Research drug ....................................................................................................................... 19 
5.2 
Grouping and administration scheme ................................................................................... 20 
5.3 
Dose adjustment .................................................................................................................... 21 
5.3.1 
Adjustment of trial drug (nimotuzumab / placebo) ........................................................... 21 
5.3.2 
Gemcitabine dose adjustment ........................................................................................... 23 
5.4 
Combination therapy............................................................................................................. 26 
6 
Research steps and evaluation .................................................................................................... 26 
6.1 
Research process .................................................................................................................. 26 
6.1.1 
Screening period check (I) ................................................................................................ 26 
6.1.2 
Screening period examination (II) .................................................................................... 26 
6.1.3 
Baseline visit ..................................................................................................................... 27 
6.1.4 
Treatment visit .................................................................................................................. 28 
6.1.5 
The efficacy evaluation visit was conducted every 8 weeks ............................................. 29 
6.1.6 
Final cancer assessment visit ............................................................................................ 29 
6.1.7 
Evaluation of early termination and withdrawal ............................................................... 29 
6.1.8 
Follow-up.......................................................................................................................... 30 


Protocol No. BPL-Nim-PC-1 
 Version date: June16, 2014 
 Version 1.1 
6.2 
Assessment ............................................................................................................................ 30 
6.2.1 
Demographic and other baseline characteristics ............................................................... 30 
6.2.2 
Efficacy evaluation ........................................................................................................... 31 
6.2.3 
Safety assessment ............................................................................................................. 35 
6.3 
Biomarkers ............................................................................................................................ 38 
7 
Blinding and randomization ....................................................................................................... 39 
7.1 
Blinding and blind base preservation ................................................................................... 39 
7.2 
Emergency envelope ............................................................................................................. 39 
7.3 
Emergency unblinding .......................................................................................................... 40 
7.4 
Unblinding requirements ...................................................................................................... 40 
8 
Drug management........................................................................................................................ 41 
8.1 
Drug specifications ............................................................................................................... 41 
8.2 
Drug packaging and labeling................................................................................................ 41 
8.3 
Drug delivery methods .......................................................................................................... 42 
8.4 
Management .......................................................................................................................... 42 
9 
Research progress and completion time .................................................................................... 43 
10 
Data management and statistical analysis ................................................................................. 43 
10.1 
Data management ................................................................................................................. 43 
10.1.1 
Electronic data management ........................................................................................ 43 
10.1.2 
Develop data management plan.................................................................................... 44 
10.2 
Statistical analysis................................................................................................................. 46 
10.2.1 
Sample size estimation ................................................................................................. 46 
10.2.2 
Analysis data set ........................................................................................................... 46 
10.2.3 
Statistical method ......................................................................................................... 47 
10.2.4 
Statistical software and general requirements .............................................................. 48 
11 
Quality control of clinical research ............................................................................................ 49 
12 
Ethical requirements and informed consent ............................................................................. 49 
13 
Data preservation ......................................................................................................................... 50 
14 
Researchers .................................................................................................................................. 50 
15 
References ..................................................................................................................................... 51 
APPENDIX 1: Schedule ....................................................................................................................... 53 
APPENDIX 2: KPS score..................................................................................................................... 56 
Karnofsky functional status scoring criteria .................................................................................. 56 
APPENDIX 3:Criteria for evaluating the efficacy of solid tumors (version 1.1) ............................ 57 
APPENDIX 4 Clinical benefit response (CBR) ................................................................................ 71 
APPENDIX 5: NYHA classification ................................................................................................... 72 


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
Abbreviation list 
 
AE 
adverse event 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
β-HCG 
Human chorionic gonadotropin 
CBR 
Clinical benefit response 
CR 
Complete remission or response 
CTCAE  
Common Terminology Criteria for Terminology of adverse events 
DCR 
Disease control rate 
DRQ 
Data Re Query 
EGF 
Epidermal Growth Factor 
EGFR 
Epidermal Growth Factor Receptor 
Hb 
Hemoglobin 
HIV 
HIV 
IgG 
Immunoglobulin 
mAb 
Monoclonal Antibody 
mg 
Milligram 
NCI  
National Cancer Institute 
Nimotuzumab 
Nimotuzumab 
NYHA 
New York Heart Association 
PD 
Progression Disease 
PFS 
Progression Free Survival 
PR 
Partial remission or response 
ORR 
Objective remission/response rate 
OS 
Overall Survival 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAE 
Serious adverse events 
SD 
Stable disease 
SOP 
Standard operating procedures 
SD 
Stable disease 
TKI 
Tyrosine kinase inhibitors 
TTP 
Time to disease progression 


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
Summary 
 
Name of study 
drug 
Nimotuzumab  injection 
Clinical trial 
topic 
A prospective study of nimotuzumab combined with gemcitabine 
versus placebo plus gemcitabine in the treatment of locally 
advanced or metastatic pancreatic cancer of wild type K-RAS, 
Randomized controlled, double-blind, multicenter clinical trial 
Purpose of  
the trial 
1. Primary purpose 
Objective to compare and evaluate the overall survival (OS) of 
nimotuzumab combined with gemcitabine versus placebo plus 
gemcitabine in the treatment of locally advanced or metastatic 
pancreatic cancer of wild type K-RAS 
2. Secondary purpose 
（1） Time to disease progression (TTP), progression free 
survival (PFS) 
（2） Objective response rate (ORR),Disease control rate(DCR) 
（3） Clinical benefit response (CBR) 
（4） Safety (according to NCI-CTCAE v4.03) 
Design 
Prospective, randomized, parallel controlled, double-blind, 
multicenter clinical trial 


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
Inclusion 
Criteria 
1. Age: 18-75 years old; 
2. Physical status KPS ≥ 60; 
3. Locally advanced pancreatic adenocarcinoma diagnosed by 
histopathology or cytology who is not suitable for radical 
radiotherapy or surgery, or recurrent and metastatic pancreatic 
adenocarcinoma (who should be ≥ 6 months before the last 
adjuvant chemotherapy); 
4. According to RECIST version 1.1 evaluation criteria, who 
should be at least one measurable and evaluable objective 
lesion (the longest diameter of target lesion detected by spiral 
CT is ≥ 10 mm; if there is only lymph node metastasis, the 
shortest diameter is ≥ 15 mm);  
5. The expected survival time was more than 12 weeks; 
6. K-RAS in tumor tissue was wild type; 
7. Serum AST / ALT ≤ 2.5 times the upper limit of normal value 
(ULN), with liver metastasis,  AST / ALT ≤ 5 times ULN; 
Total bilirubin ≤ 2 times ULN, if liver metastasis , less than 3 
times ULN; Absolute granulocyte count ≥ 1.5×109/L ;platelet 
≥100×109/L; Hemoglobin ≥ 90g / L; Creatinine clearance rate 
≥ 60ml / min; 
8. They voluntarily participated in the study, signed informed 
consent forms and had good compliance; 
9. The patients of childbearing age and their spouses are willing 
to take contraceptive measures. 


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
Exclusion 
criteria 
1. Prior to this study, the following treatments were received: 
a. Anti-tumor chemotherapy and molecular targeted therapy as 
palliative measures 
b. The target lesion had received radiotherapy without 
progression 
c. Within 4 weeks or participating in other therapeutic / 
intervention clinical trials 
2. Major surgery was performed within 4 weeks; 
3. There were brain metastasis or pia mater metastasis; 
4. Had a history of other malignancies other than pancreatic 
cancer (except for the cured cervical carcinoma in situ or skin 
basal cell carcinoma and other malignant tumors that had been 
cured for 5 years); 
5. Ascites with symptoms and requiring clinical treatment were 
complicated; 
6. Accompanied by other serious diseases, including but not 
limited to: 
a. 
Uncontrollable congestive heart failure (NYHA grade III 
or IV, see APPENDIX 5), unstable angina pectoris, poorly 
controlled arrhythmia, uncontrolled moderate or above 
hypertension (SBP > 160mmHg or DBP > 100mmHg) 
b. Active infection 
c. 
Uncontrolled diabetes 
d. Mental illness affecting informed consent forms and / or 
protocol compliance 
e. 
HIV infection 
f. 
There were serious diseases that other researchers 
considered unsuitable for this study 
7. Allergy to anti EGFR antibody preparations is known. 


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
Evaluating 
indicator 
1. Effectiveness evaluation: OS, TTP, PFS, DR, ORR, DCR and 
CBR evaluation time point: imaging examination (8,16,24 
weeks, etc., once every 8 weeks);For patients with CR or PR, 
the curative effect should be confirmed after 4 weeks. 
2. Safety evaluation: adverse events were evaluated according to 
NCI-CTC AE v4.03.All patients who had received at least one 
study drug treatment were included in the safety analysis. All 
adverse events were recorded and evaluated. Physical 
examination and ECG, Blood routine, urine routine, blood 
biochemistry, vital signs were monitored and evaluated 
regularly.  
Number of 
subjects 
A total of 276 cases were planned to be selected and randomly 
allocated according to the ratio of 1:1. 138 cases in the trial group 
and 138 cases in the control group. 
Case allocation Competitive enrollment among centers 


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
Administration 
regimen 
Trial group: treated with nimotuzumab combined with gemcitabine; 
Control group: received placebo (nimotuzumab simulant) combined 
with gemcitabine. 
1） Nimotuzumab injection / placebo: 400mg / w, intravenous 
drip, infusion time more than 60 minutes, once a week, 
until the disease progression or intolerable toxic reaction 
or the subject asked to withdraw from the trial. 
2） Gemcitabine: 1000mg /m2, intravenous drip for no less 
than 30 minutes, continuous use for 3 weeks, rest for 1 
week (D1, D8, D15; Q28 days), every 4 weeks as a cycle, 
until the disease progression or intolerable toxic reaction 
or the subject asked to withdraw. 
At the first treatment, nimotuzumab / placebo should be 
given on the same day as gemcitabine, and then gemcitabine 
should be given 1 hour after the end of nimotuzumab / placebo 
infusion. Since then, nimotuzumab / placebo and gemcitabine 
were treated on the same day in the same order as before. 
When 
intolerable 
chemotherapy 
toxicity 
occurs, 
chemotherapy can be stopped, but nimotuzumab / placebo should 
be continued; However, when intolerable toxicity of nimotuzumab 
occurs, the use of nimotuzumab can be stopped, but chemotherapy 
should be continued. Subjects without other specific anti-tumor 
treatment was allowed during the overall trial. 
Trial schedule 
It is expected to complete the enrollment within 24 months. 
Statistical 
methods 
SAS 9.2 software was used for statistical analysis.PPS was used to 
evaluate the efficacy of PPS. The safety index was analyzed by SS 
data. 


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
1. Research background 
According to the World Health Organization statistical bulletin published in 2014, 
the incidence and mortality of pancreatic cancer in 2012 ranked 12th and 7th 
respectively in malignant tumors; The standardized incidence of pancreatic cancer in 
the world population is 4.9/100000 in men and 3.6/100000 in women. Among them[1] 
which is higher in developed countries and regions than in developing countries and 
regions. In 2014, the American Cancer Association reported that the incidence and 
mortality of pancreatic cancer in the United States were increasing, and the 5-year 
relative survival rate of pancreatic cancer increased from 2% to 6% from 1975 to 2009, 
which was the cancer with the lowest improvement in survival[1-2].In China, the 
incidence of pancreatic cancer is also on the rise. The standardized incidence rates of 
pancreatic cancer in men and women are 4.5/100000 and 2.8/100000 respectively. It is 
estimated that 65700 new cases and 63700 deaths[1]will occur in 2014. According to 
the data of China Cancer annual report, the incidence and mortality of pancreatic 
cancer in China ranked seventh in 2010, reaching 40400 and 57700[[3-4], respectively. 
The early diagnosis of pancreatic cancer is very difficult, and the treatment effect 
is not ideal. The mortality rate is high, and the 5-year survival rate is only 
4.1%.Complete tumor resection is the only possible cure for pancreatic cancer, but 
only 5-15% of patients can perform radical surgery, and the median survival time is 
less than 12-18 months. The 2-year survival rate is 20-35%, and the 5-year survival 
rate is 5-10%.At the first visit to doctor, about 25% of patients with pancreatic cancer 
had locally advanced pancreatic cancer, and the median survival time was 6-9 months. 
About 60-70% of patients with metastatic pancreatic cancer had a median survival of 
3-5 months[5-12].At present, there is a lack of effective drugs and regimens for locally 
advanced or metastatic pancreatic cancer. Burris et al[13] found that survival time and 
clinical benefit rate of gemcitabine were better than that of 5-FU, which confirmed the 
therapeutic status of gemcitabine in advanced pancreatic cancer, but[13] survival time 
was less than 6 months. After that, a number of phase III trials compared gemcitabine 
with other cytotoxic drugs compared with gemcitabine monotherapy, and no evidence 
was found to be superior to gemcitabine monotherapy. Recently, a phase III clinical 
study showed that albumin paclitaxel combined with gemcitabine significantly 
prolonged the survival time and long-term survival rate[14-16], that is, the 1-year 
survival rate was increased by 59% (35% vs. 22%), the 2-year survival rate was 


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
doubled (9% vs. 4%), and the risk of death was reduced by 28%;PFS, ORR and other 
end points were significantly improved; Based on this result, which was approved by 
US FDA in September 2013 for albumin paclitaxel combined with gemcitabine for the 
first-line treatment of adult metastatic pancreatic cancer[17-19];However, according to 
the National Institute for Health and Clinical Excellence (NICE), the toxicity and side 
effects of albumin paclitaxel in the treatment of metastatic pancreatic cancer are 
obvious and can not be fully proved to be better than other treatment drugs. Therefore, 
it is not included in the national medical insurance reimbursement. 
Previous studies have shown that epidermal growth factor (EGF) and its receptor 
(EGFR) has been involved in the occurrence and development of malignant tumors. It 
plays an important role in the process. In recent years, substantial progress has been 
made in the research of EGFR targeted therapy. EGFR inhibitors combined with 
chemotherapy have the characteristics of high efficiency and low toxicity, which can 
be used to treat a variety of tumors, EGFR inhibitors can be divided into two 
categories: one is tyrosine kinase inhibitor (TKI) acting on the intracellular domain of 
EGFR receptor, including gefitinib (ireasa®), erlotinib (taceva®), etc. The other is 
monoclonal antibodies (mAbs) acting on the extracellular domain of EGFR receptor, 
including cetuximab (C225), panitumumab (vectibix®) and nimotuzumab (trade name: 
taixinsheng®) etc. 
It is known that EGFR expression is about 30% - 89% in pancreatic cancer, and it 
is associated with high invasiveness and poor prognosis of patients. In a double-blind, 
placebo-controlled phase III trial of patients with advanced or metastatic pancreatic 
cancer, 569 patients were randomly assigned to receive erlotinib (an EGFR-TKI) 
combined with gemcitabine or gemcitabine monotherapy[21]. Results: compared with 
gemcitabine monotherapy group, 569 patients with advanced or metastatic pancreatic 
cancer were randomly assigned to receive erlotinib (an EGFR-TKI) combined with 
gemcitabine or gemcitabine monotherapy[21],There were statistically significant 
improvements in OS (HR = 0.82; P = 0.038) and PFS (HR = 0.77; P = 0.004) in 
erlotinib group; The median survival time was 6.24 months in the combination group, 
and 23% in the 1-year survival rate, while 5.91 months and 17% in the single drug 
group. Adverse reactions such as rash and diarrhea increased in the combined group, 
but most of them were grade 1 or grade 2.Therefore, erlotinib combined with 
gemcitabine has been approved by FDA for the first-line treatment of locally advanced 


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
unresectable or metastatic pancreatic cancer. The NCCN guidelines also recommend 
gemcitabine combined with erlotinib as one of the treatment options for locally 
advanced or metastatic pancreatic cancer in good physical condition. 
Nimotuzumab is a new generation of recombinant humanized monoclonal antibody 
against EGFR with moderate affinity(10-9)。In 2008, it has been approved by the 
Ministry of foreign countries for the treatment of nasopharyngeal carcinoma, and has 
been approved by the Ministry of China and other countries for the treatment of 
esophageal cancer. In China, clinical trials of nimotuzumab combined with 
radiotherapy and chemotherapy are being carried out in China. The doses of 
nimotuzumab from 100mg to 800mg show good safety. In 2013, German scholars 
reported a randomized, double-blind, controlled phase II clinical trial[22]of gemcitabine 
combined with nimotuzumab in the treatment of advanced pancreatic cancer compared 
with gemcitabine combined with placebo[22]. A total of 192 patients were included in 
the study, with nimotuzumab 400mg /w, with good safety and no severe toxicity. Only 
13% of patients had skin toxicity of 1/2 grade. The median survival time (mOS): 8.7 
months in the experimental group vs. 6.0 months in the control group (P = 0.21), and 
the median progression free survival (MPFs): 5.4 months in the experimental group vs. 
3.7 months in the control group (P = 0.06), but the 1-year survival rate was 34.4% in 
the experimental group and 19.5% in the control group (P = 0.034).Further stratified 
analysis showed that MPFs: 5.5 months in the experimental group vs. 3.2 months in 
the control group (P = 0.0096) in the patients ≥ 62 years old; mOS: 8.8 months in the 
experimental group vs. 5.2 months in the control group (P = 0.034). 
A non-randomized, open, one arm clinical trial[23]of nimotuzumab combined with 
gemcitabine in the treatment of patients with unresectable locally advanced or 
metastatic pancreatic cancer[23]was reported by Chinese scholars. 18 subjects were 
enrolled in this study. They received nimotuzumab 200mg/w combined with 
gemcitabine 1000mg / m2.The results show that, The disease control rate (DCR) was 
55.6%, mOS was 9.29 months (3 months-20.43 months), mPFS was 3.71 months, and 
1-year survival rate was 38.9%.During the study period, 16 patients (88.8%) had at 
least one AE, of which 6 patients (33.3%) had grade 3 AE and no grade 4 AE. The 
most 
common 
AE 
was 
gastrointestinal 
reaction 
(77.8%), 
followed 
by 
myelosuppression (neutropenia 44.4%, thrombocytopenia 11.1%), and grade 1 rash in 
11.1% of patients. All toxic reactions were tolerable during the treatment, and no 


Protocol No. BPL-Nim-PC-1 
 Version date: June16, 2014 
 Version 1.1 
patient terminated the clinical trial because of AE. It is suggested that nimotuzumab 
combined with gemcitabine in the treatment of advanced pancreatic cancer is safe and 
may improve the curative effect. It is worth carrying out randomized large sample 
clinical trials. 
In order to verify whether nimotuzumab is effective in the treatment of advanced 
pancreatic cancer and expand its indications, with the approval of the national CFDA 
(approval No.: 2011l01239), Baitai biological Co., Ltd(Biotechplc.com). has entrusted 
the 81st Hospital of the Chinese people's Liberation Army and the Affiliated Cancer 
Hospital of Fudan University of Shanghai as the leading units of this clinical study. A 
double-blind, multicenter, registered clinical trial was conducted to determine the 
efficacy and safety of nimotuzumab combined with gemcitabine in the treatment of 
locally advanced or metastatic pancreatic cancer in Chinese with wild-type K-RAS. 
2. Research purpose
2.1 Primary purpose 
Objective to evaluate and compare the overall survival (OS) of nimotuzumab 
combined with gemcitabine versus placebo plus gemcitabine in the treatment of K-
RAS wild-type locally advanced or metastatic pancreatic cancer. 
2.2  Secondary purpose 
1) Time to disease progression (TTP), progression free survival (PFS).
2) Objective response rate (ORR), disease control rate (DCR).
3) Clinical benefit response (CBR).
4) Objective to evaluate the safety of nimotuzumab combined with gemcitabine
(according to NCI-CTCAE v4.03). 
3. Research overall design
In order to observe and evaluate the efficacy of nimotuzumab combined with
gemcitabine in the treatment of locally K-RAS wild type. In this study, prospective, 
randomized, parallel controlled, double-blind, multicenter clinical trial was used to 
evaluate the efficacy and safety of advanced or metastatic pancreatic cancer. 


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
3.1 Multicenter research 
At the same time, a number of national cancer centers were selected for  
competition. 
3.2 Central random 
Taking into account the following factors, DAS for IWRS was used to assign 
random numbers and dispense drugs. Four stratification factors and factor levels were 
set up. 
Tumor locations: 
○ Body and tail of pancreas 
○ Head of pancreas 
Have you had surgery 
 
○ yes 
 
○ no  
Have you had biliary obstruction been treated 
 
○ yes 
 
○ no 
Have you received adjuvant chemotherapy 
 
○ yes 
 
○ no 
3.3 Control drug selection 
In this trial, placebo combined with gemcitabine was used as a parallel control 
drug. 
3.4 Blinding method 
In this study, a double-blind and single simulation method was used. The package, 
shape and odor of nimotuzumab simulator were consistent with those of the trial drug 
(nimotuzumab) to ensure that the subjects and researchers were in a blind state during 
the trial. 


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
3.5 Sample size 
In this study, 276 subjects were enrolled, 138 in the experimental group and 138 
in the control group (see the sample size estimation for statistical analysis). 
4 Study population 
4.1  Inclusion criteria 
1. Age: 18-75 years old; 
2. Physical status:  KPS ≥ 60 score 
3. Locally advanced pancreatic adenocarcinoma diagnosed by histopathology or 
cytology that is not suitable for radical radiotherapy or surgery, or recurrent and 
metastatic pancreatic adenocarcinoma (it should be more than 6 months before the 
last adjuvant chemotherapy); 
4. According to recist1.1, there was at least one objective lesion that could be 
measured and evaluated (the longest diameter of the target lesion detected by 
spiral CT is more than or equal to 10 mm. If only lymph node metastasis occurs, 
the shortest diameter is required ≥15mm）； 
5. The expected survival time was more than 12 weeks; 
6. K-Ras in tumor tissue was wild type; 
7. Serum AST /ALT ≤ 2.5 times the upper limit of normal value (ULN), and AST / 
ALT ≤ 5 times ULN in patients with liver metastasis; Total bilirubin ≤ 2 times 
ULN, total bilirubin ≤ 3 times ULN in patients with liver metastasis; Absolute 
granulocyte count ≥1.5×109/L; Platelet≥100×109/L; Hemoglobin ≥ 90g / L; 
Creatinine  clearance rate ≥ 60ml / min; 
8. Patients voluntarily participated in the trial, signed informed consent forms and 
had good compliance; 
9. The patients of childbearing age and their spouses are willing to take 
contraceptive measures. 


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
4.2 Exclusion criteria 
1. Prior to this study, the following treatments were received: 
a) Anti-tumor chemotherapy and/or molecularly targeted therapy as a palliative 
means 
b) The target lesion had been previously treated with radiotherapy without 
progression 
c) Within 4 weeks or participating in other therapeutic / intervention clinical 
trials; 
2. Major surgery was performed within 4 weeks; 
3. There were brain metastasis or pia mater metastasis; 
4. Having a history of malignancy other than pancreatic cancer (except for cervical 
cancer or basal cell carcinoma that has been cured and other malignant tumors 
that have been cured for more than 5 years); 
5. Ascites with symptoms and requiring clinical treatment were complicated; 
6. Accompanied by other serious diseases, including but not limited to: 
a) Intractable congestive heart failure (NYHA grade III or IV, see APPENDIX  
5), unstable heart failure, angina pectoris, poorly controlled arrhythmia,  
uncontrolled moderate or above hypertension (SBP > 160mmHg or DBP >  
100mmHg),  
b) Active infection.  
c) Uncontrolled diabetes 
d) Mental illness affecting informed consent and / or protocol compliance 
e) HIV infection 
f) 
Other researchers think who is not suitable to participate in the experiment. 
7. Allergy to anti-EGFR antibody preparations is known.


Protocol No. BPL-Nim-PC-1 
 Version date: June16, 2014 
 Version 1.1 
4.3 Exit criteria 
4.3.1 Withdraw from research 
1)
Subjects can withdraw from the study at any time without any reason;
2)
If the subjects withdraw from the study ahead of time, the final visit should be
conducted according to the study schedule.
4.3.2 
Treatment of withdrawal from study medication 
In any of the following situations, the subject must withdraw from the study, but should 
continue to receive follow-up: 
1)
In case of clinically related events that seriously affect the safety of the subjects,
the researcher or the sponsor considers it necessary to terminate the treatment;
2)
Imaging examination was used to judge the disease progression;
3)
Pregnancy occurred during treatment;
4)
If it is necessary to use the drug without permission, the researchers of each
center shall discuss with the main researchers to decide whether the subjects need
to withdraw from the study;
5)
The subjects were lack of compliance and seriously violated the protocol.
4.4 Termination criteria 
In case of any of the following circumstances, the study may be terminated in advance 
after negotiation between the sponsor and the research center: 
1)
New information leads to adverse risk- benefit judgment of the study drug, such
as:
a)
Evidence of ineffective study treatment
b)
Obtain evidence of any significant but previously unknown adverse reactions or
unexpected increase in the degree or incidence of known adverse reactions, or
other adverse safety.


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
2) The sponsor and the research center believe that the study can not be continued 
regardless of medical or ethical factors; 
3) The subjects were slow to complete the study in an acceptable time; 
4) 
The trial drug was withdrawn from the marketing for safety reasons. 
 
5 Study drug and administration plan 
5.1 Research drug 
Nimotuzumab injection, produced by Biotech Pharmaceutical Co., Ltd., is a 
colorless and clear solution with the specification of 50mg / 10ml / piece (packed in 
vials).Each vial (capacity 13.5ml) contains 10ml of nimotuzumab solution, the 
concentration of mAb is 5 mg / ml, and the purity is not less than 95%.The 
composition of each component in the vial is shown in the table below. 
Table 1 The composition of nimotuzumab injection and its  components 
 
Components 
Content / ml 
Content / 10.0 ml 
h-R3 monoclonal antibody  
5 mg 
50 mg 
Sodium dihydrogen 
phosphate 
0.45 mg 
4.5 mg 
Sodium dihydrogen 
phosphate 
1.8 mg 
18.0 mg 
sodium chloride 
8.60 mg 
86.0 mg 
Polysorbate 80 
0.2 mg 
2.0 mg 
 
Note:h-R3 monoclonal antibody is not included in placebo, other ingredients, 
appearance and specifications are the same as those of nimotuzumab injection. 
The product should be stored at 2-8 ℃, and freezing is strictly prohibited; After 
diluted in normal saline, it can keep stable for 12h at 2-8 ℃ and 8h at room 
temperature. If the diluted solution is stored for more than the above time, it should 
not be used. The trial drugs nimotuzumab injection / placebo and gemcitabine were 
provided by Biotech Pharmaceutical Co., Ltd. for free, including labels and packages 
for clinical trials.


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
5.2 Grouping and administration scheme 
The trial was divided into two groups. 
The experimental group was treated with nimotuzumab and gemcitabine; 
The control group was treated with placebo (nimotuzumab simulant) and 
gemcitabine. 
1) Nimotuzumab injection / placebo: 400mg /w , intravenous drip, infusion time 
more than 60 minutes, once a week, until the disease progression or intolerable 
toxic reaction, or the subject asked to withdraw from the trial. 
Usage method: 400 mg (8 pieces) of nimotuzumab injection / placebo was added 
into 250 ml sterile normal saline for dilution, and the intravenous drip time was 
not less than 60 min. the patient's condition should be closely monitored during 
the course of administration and within 1 hour after the end of administration. In 
addition to sterile normal saline, nimotuzumab solution should not be mixed with 
any intravenous infusion drugs. 
2) Gemcitabine: 1000mg / m2, intravenous drip no less than 30 minutes, continuous 
use for 3 weeks, rest for 1 week (D1, 8, 15; Q28 d) every 4 weeks until the 
disease progressed or intolerable toxic reaction occurred, or the subject asked to 
withdraw from the trial. 
3) Usage method: each bottle (containing gemcitabine 200mg or 1000mg) should be 
injected with 5ml or 25ml sterile normal saline at least (containing gemcitabine 
concentration ≤ 40mg / ml), shaking to dissolve. The required dosage can be 
further diluted with sterile normal saline. The prepared gemcitabine solution 
should be stored at room temperature and used within 24 hours. Gemcitabine 
solution should not be refrigerated to prevent crystallization. According to the 
solubility of the drug, the concentration of the diluted drug should not exceed 
40mg / ml. if the concentration is greater than 40mg / ml, it may lead to 
incomplete dissolution of the drug, which should be avoided. 
At the first treatment, nimotuzumab / placebo should be given on the same day as 
gemcitabine, and then gemcitabine should be given 1 hour after the end of 
nimotuzumab / placebo infusion. Since then, nimotuzumab / placebo and gemcitabine 
were treated on the same day in the same order as before. 
 
 
 


Protocol No. BPL-Nim-PC-1 
 Version date: June16, 2014 
 Version 1.1 
5.3  Dose adjustment 
5.3.1 Adjustment of trial drug (nimotuzumab / placebo) 
During the study, the weekly dose of nimotuzumab / placebo should be given 
strictly according to the trial design, and should not be adjusted at will. 
The toxicity of either placebo or nimotuzumab can be adjusted according to the 
relevant study. In case of grade 3 or 4 adverse reactions (except allergy / 
hypersensitivity and blood pressure drop) during the trial, the researcher can adjust the 
dosage of nimotuzumab / placebo once according to the situation of the subjects 
to 200mg, if the toxicity can be recovered to grade 1 or below, the dose of 
nimotuzumab / placebo can be restored to 400mg, and the follow-up treatment can be 
continued at this dose. If grade 3 or 4 adverse reactions related to nimotuzumab / 
placebo occur again, they will not recover after the drug dose is reduced to 200mg, 
and follow-up treatment will be continued at this dose. 
Subjects must withdraw from nimotuzumab / placebo treatment but  remain in 
the study for chemotherapy if any of the following conditions occur: 
1)
Grade 3 or 4 allergy / hypersensitivity occurred;
2)
Subjects and / or researchers request or consider it necessary to terminate
nimotuzumab / placebo treatment in the event of AE; 
If possible, subjects who terminated treatment before disease progression would 
still be evaluated every 8 weeks until disease progression. 
In case of serious adverse events (SAE) related to the drug, such as anaphylactic 
shock, the drug should be stopped immediately and treated actively. The patient 
should be reported according to the prescribed procedures. At the same time, the 
patient should stop the treatment of nimotuzumab. If chemotherapy is delayed or 
terminated due to chemotherapy-related toxicity, the treatment with nimotuzumab can 
be continued.


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
 
Table 2  Treatment and dose adjustment of hypersensitivity 
 
Hypersensitivity 
(taixinsheng® related: 
respiratory spasm, dyspnea): 
CTC classification 
Treatment measures 
Grade 1 
Drop rate reduced to 50%, close monitoring to prevent 
deterioration. 
The duration of infusion was not more than 4 hours. 
Grade 2 
Stop the infusion. 
Give bronchodilator, oxygen and other medical 
measures. 
Once the allergy / hypersensitivity is recovered or 
reduced to grade 1, continue infusion at 50% of the 
original drip rate, and monitor closely to prevent 
deterioration. 
Grade 3 or 4 
Stop immediately and cut off the infusion pipeline of 
the subjects. 
Give adrenaline, bronchodilator, antihistamine drugs, 
intravenous infusion, vasopressor drugs, oxygen 
inhalation and other medical measures. 
The patient must withdraw from treatment immediately 
and no longer receive nimotuzumab. 


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
The common adverse reactions of nimotuzumab were fever, hypotension, nausea, 
dizziness and rash; Generally, it can be relieved by itself without affecting the 
continuous treatment. The lower incidence of adverse reactions included muscle pain, 
dyskinesia, dry mouth, flushing, weakness of lower limbs, drowsiness, loss of sense of 
direction, elevated creatinine level, leukopenia, hematuria, chest pain and cyanosis of 
the lips, which can be treated with conventional doses of analgesics and / or 
antihistamines. 
 
Table 3  treatment and dose adjustment of blood pressure drop 
 
NCI-CTCAE classification: 
decreased blood pressure 
Treatment measures 
Grade 1-2 
The drop rate of nimotuzumab was reduced by 50%. 
Grade 3 or 4 
Symptomatic treatment, rehydration; 
Monoguanidine was discontinued. 
 
Table 4  treatment and dose adjustment of skin rash 
 
NCI-CTCAE classification: 
rash 
Treatment measures 
Grade 1-2 
The drop rate of taixinsheng® was reduced by 
50%. 
Grade 3 or 4 
Hydrocortisone ointment or erythromycin ointment
was used locally and evaluated 2 weeks later; If no
remission, in addition to the above measures plus
oral kairuitan®, if necessary, the impact dose of
methylprednisolone can be given to reduce the dose
of taixinsheng® by 25%;If co-infection occurs, 
Using appropriate antibiotics. 
 
5.3.2 Gemcitabine dose adjustment 
In principle, all patients should be given the planned chemotherapy dose. If 
necessary, the dose can be adjusted according to the most serious hematology or other 
toxicity. Any patient who needs to reduce the dose will continue to receive the 
reduced dose treatment in the subsequent treatment cycle. If patients have multiple 


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
toxicities and the principle of dose adjustment is different, the minimum dose should 
be selected. If any patient has already reduced the dose twice, it is necessary to reduce 
the dose for the third time due to the toxic reaction, chemotherapy must be stopped. 
Chemotherapy can be delayed for up to 2 weeks, otherwise the chemotherapy needs to 
be terminated. The treatment of nimotuzumab was not delayed or terminated due to 
chemotherapy-related toxicity. If chemotherapy is terminated permanently, 
nimotuzumab monotherapy can be continued until the disease progresses.  
The dose adjustment of gemcitabine is shown in the following table: 
Table 5  Gemcitabine dose adjustment level 
 
Dose level 
0 
-1（80%） 
-2（50%） 
Gemcitabine (mg / m2) 
1000 
800 
500 
 
5.3.2.1 Hematological toxicity 
Patients receive the drug treatment in this study for the first time, they must have 
neutrophil ≥ 1.5×109/L, platelet ≥ 100×109/L, before starting chemotherapy, and the 
delay time of chemotherapy should not exceed 2 weeks. If hematologic toxicity 
occurs in the follow-up chemotherapy, and the patient does not recover to neutrophil ≥ 
1.5×10 9/ L within 2 weeks, platelet count will be increased no more than or equal to 
80×10 9/L, the chemotherapy should be terminated. If the patient is unable to receive  
chemotherapy due to toxicity, the administration can be delayed for 1 week, If the 
patients still can not receive chemotherapy after 1 week delay, they can continue to 
delay for 1 week. Once the delay exceeds 2 weeks, the patients will terminate the 
treatment; However, tumor evaluation should be carried out according to the original 
plan even if the treatment delay occurs. 
There is no need to reduce the dose of gemcitabine if grade 1 thrombocytopenia 
occurs; When grade 2 thrombocytopenia occurred, gemcitabine dose "reduced to 80% 
of the original plan"; When grade 3 thrombocytopenia occurs, gemcitabine dose is 
"reduced to 50% of the original plan". When grade 4 thrombocytopenia occurs, 
gemcitabine must be stopped. According to the minimum values of platelets and 
neutrophils in the previous cycle, the following dose adjustments were made to the 
following cycles of chemotherapy: 
 


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
Table 6  Hematologic toxicity and gemcitabine dose adjustment 
 
Platelet count（×10 9/L) 
Absolute neutrophil count（×10 9/L) 
Gemcitabine 
dose level 
< lower limit of normal value 
~ 75.0 and must 
>1 
0 
50~<75 
or 
0.5~<1 
-1 
25 ~ < 50 or 
< 0.5 (once) 
-2 
<25 
or 
< 0.5 (twice in a row) 
Drug 
withdrawal 
 
5.3.2.2 Non hematological toxicity 
 
Patients who use gemcitabine should have regular clinical examination of liver 
and kidney function to detect whether non hematologic toxicity occurs. According to 
the patient's tolerance to gemcitabine, the dose can be reduced in each treatment cycle 
or one treatment cycle. According to the clinician's opinion, the treatment can be 
stopped until the toxicity disappears. For non hematotoxicity, gemcitabine can be 
adjusted according to the highest level of toxicity. Patients with serum bilirubin 
≤Grade 2 and ALT/AST must be recovered The neurotoxicity recovered to ≤ NCI-
CTCAE 2 or baseline level. The dosage adjustment is shown in the table below 
Table 7 Nausea / vomiting and gemcitabine dose adjustment 
 
NCI-CTCAE classification v4.03 
Gemcitabine dose level 
Grade 0-2 (grade 3 nausea / vomiting) 
0 
Grade 3 (except grade 3 nausea / vomiting) 
-2 or stop taking medicine 
Grade 4 
Drug withdrawal 
If any of the following conditions occur, the subject must withdraw from 
chemotherapy, but can continue to receive nimotuzumab treatment in the study: 
1) Intolerable toxicity such as grade 3 nausea and / or grade 4 vomiting still 
occurred after prophylactic treatment; 
2) Any definite grade 4 drug-related toxicity; 
3) Delayed chemotherapy for more than 2 weeks. 
If possible, subjects who terminated treatment before disease progression would 
still be evaluated every 8 weeks until disease progression.


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
5.4 Combination therapy 
During the study period, the drugs that can be used together according to the 
needs are as follows: 
Adjuvant therapy, including prophylactic drugs, such as blood component 
transfusion, granulocyte colony-stimulating factor (G-CSF), antidiarrheal, antiemetic 
and analgesic drugs, are allowed and can be operated according to the clinical routine 
of each center; 
When the adverse events caused by the trial drug need to be treated, the drugs for 
symptomatic treatment can be given; Symptomatic treatment of skin toxicity, 
including softeners or other topical drugs, analgesics and vitamins B6, etc; 
When patients have symptoms due to other reasons, symptomatic drugs can be 
used. 
All drugs used at the same time should be recorded and explained on the CRF 
form. 
During the period of clinical research administration, other anti-tumor 
chemotherapy drugs and molecular targeted drugs, Chinese patent medicines with 
anti-pancreatic cancer indications and anti-tumor immune agents (thymosin and 
interferon, etc.) are not allowed to be used. 
6 Research steps and evaluation 
6.1 Research process 
All study reviews are summarized in the study flow chart in Appendix 1. 
6.1.1 Screening period check (I) 
The following will be carried out and recorded before screening period inspection (II) 
 
Assignment of subject number 
 
Signed written informed consent forms 
 
The time of diagnosis, the location of TNM and the date of diagnosis were        
analyzed 
 
10-20 tumor specimens were collected for K-RAS detection 
6.1.2 Screening period examination (II) 
Only the subjects whose tumor tissue test result is K-RAS wild type can carry out the 
following examination. The following items must be carried out and recorded: 
 
Verification of inclusion and exclusion criteria 
 
Collect demographic data (date of birth, gender and race) 


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
 
Medical history 
 
Physical examination (height, weight, within 7 days before screening) 
 
Vital signs (heart rate, blood pressure, respiration, body temperature, detected 
within 7 days before screening) 
 
Clinical benefit response (CBR) (detected 2-7 days before the first treatment 
of the study) 
 
ECG (within 2 weeks before screening) 
 
Blood biochemistry (ALT, AST, AKP, BIL, BUN, Cr, CRP) (detected within 
7 days before screening) 
 
Blood routine and electrolyte test (within 7 days before screening) 
 
Serum CA19-9 (detected within 7 days before screening) 
 
Routine urine test (within 7 days before screening) 
 
Pregnancy test (only for women of childbearing age, within 7 days before 
screening) 
 
Baseline assessment of tumor imaging (chest and abdominal spiral CT 
findings within 21 days before screening) 
 
The eligible subjects were assigned random number 
6.1.3 Baseline visit 
Only qualified subjects can enter the baseline visit. the following items must be 
carried out and recorded: 
 
Physical examination (within 7 days before the first treatment) 
 
Vital signs were detected within 7 days before treatment 
 
Body surface area (within 7 days before the first treatment) 
 
Clinical benefit response (CBR) (detected within 2-7 days before the first 
treatment) 
 
ECG (within 2 weeks before the first treatment) 
 
Blood routine and electrolyte examination (within 7 days before the first 
treatment) 
 
Blood biochemistry (ALT, AST, AKP, BIL, BUN, Cr, CRP) (detected within 
7 days before the first treatment) 
 
Serum CA19-9 (within 7 days before the first treatment) 
 
Routine urine test (within 7 days before the first treatment) 
 
Pregnancy test (only for women of childbearing age, within 7 days before the 


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
first treatment) 
Baseline assessment of tumor imaging (chest and abdominal spiral CT 
findings within 21 days before screening) 
 
If the screening results are within the time window, there is no need to repeat 
the detection in the baseline period. 
 
6.1.4 Treatment visit 
Gemcitabine was given on day 1, day 8 and day 8,15. Four doses of nimotuzumab / 
placebo were given on day 22.The following inspections and records are required: 
 
physical examination 
 
Body surface area 
 
Clinical benefit response (CBR) 
 
Blood routine and electrolyte examination 
 
Blood biochemistry (ALT, AST, AKP, BIL, BUN, Cr, CRP) 
 
Serum CA19-9 
 
Evaluation of drug combinations and current medical interventions 
 
Adverse events were observed and outcomes were recorded at any time (NCI-
CTCAE v4.03) 
 
Other examinations (if necessary) 
Hematological examination should be provided within 48 hours before each 
chemotherapy, and the times can be increased according to the situation. 


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
6.1.5 The efficacy evaluation visit was conducted every 8 weeks 
The following assessments will be conducted at the 8-week assessment visit: 
 
Physical examination 
 
Vital signs 
 
Clinical benefit response (CBR) 
 
CT or MRI scan for the evaluation of tumor efficacy 
 
Blood routine and electrolyte examination 
 
Blood biochemistry (ALT, AST, AKP, BIL, BUN, Cr, CRP) 
 
Serum CA19-9 
 
Combination and current medical interventions 
 
Evaluation of adverse events (NCI-CTCAE v4.03) 
Imaging examination in different periods should use the same detection technology as 
that in the baseline period. If the efficacy evaluation result is CR or PR, imaging 
examination should be carried out 4 weeks after the initial evaluation to confirm the 
curative effect. The time window of efficacy evaluation is ± 7 days.  
 
6.1.6 Final cancer assessment visit 
The following assessments will be performed at the final cancer assessment visit: 
 
Physical examination 
 
Vital signs 
 
Clinical benefit response (CBR) 
 
Blood routine and electrolyte examination 
 
Blood biochemistry (ALT, AST, AKP, BIL, BUN, Cr, CRP) 
 
Urine routine 
 
Serum CA19-9 
 
Imaging examination (chest and abdomen spiral CT) 
 
Evaluation of adverse events (follow up to 30 days after the last medication, 
NCI-CTCAE v4.03) 
 
6.1.7 Evaluation of early termination and withdrawal 
Patients must be terminated early during the trial. The reason and date of 
termination should be recorded in the patient's medical records and case report forms. 


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
When patients terminate the study, the investigator should complete all exit 
procedures as far as possible.  
Once the patients have disease progression, they should be followed up until 
death. 
If the patient stops treatment for any reason other than disease progression or 
death, follow-up should be conducted every 8 weeks (including tumor evaluation, 
toxicity, survival) until PD or receiving anti-tumor therapy outside the protocol. 
 
6.1.8 Follow-up 
Follow up will be conducted every 3 months. The following items need to be 
evaluated: 
 Survival state of subjects 
 Any new anti-tumor treatment 
 Any study drug-related AE was followed up until the AE was stable or the 
outcome was known 
  
6.2 Assessment 
6.2.1 Demographic and other baseline characteristics 
All baseline visit evaluations must be performed after confirmation of K-RAS 
status and within 14 days before randomization. Tumor evaluation earlier than 14 
days before randomization could not be used in this study. Complete the following 
checks: 
1) Demographic data: date of birth, gender and race need to be collected. 
2) K-ras evaluation: after the subjects sign the informed consent, the K-RAS 
status of tumor samples will be evaluated. K-ras status will be centrally 
assessed by a designated central pathology laboratory. Researchers must be 
clear about the results of K-RAS test before the next step of screening 
subjects. 
3) Diagnosis of primary tumor: the date of diagnosis, histology, location of the 
lesion and the diagnosis time must be recorded TNM staging. 
4) Medical history collection: to be recorded: 
Other than pancreatic cancer 
Treatment for diseases other than pancreatic cancer within 14 days before 


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
the start of the study (i.e. within 14 days before randomization) 
Previous treatment for pancreatic cancer, including chemotherapy, adjuvant 
chemotherapy, radiotherapy and surgery 
Concomitant treatment: the concomitant treatment and the medical measures 
received at baseline were recorded. 
5) Pregnancy test: the urine pregnancy test must be negative for all female 
subjects with fertility (within 7 days before the start of study treatment). 
6) Physical examination: height, weight and vital signs (heart rate, blood 
pressure, respiration, body temperature, etc.). 
7) Laboratory examination: mainly including blood routine (Hb, WBC, ANC, 
PLT), electrolyte (K+,Na+, Cl-, Ca2+, Mg2+), urine routine (pH, protein, 
RBC, WBC) and blood biochemistry (ALT, AST, AKP, BIL, BUN, Cr, 
CRP). 
8) Auxiliary imaging examination: CT or MRI scan will be performed within 
21 days of the first treatment to record the tumor status at baseline; At the 
same time, the number of organs with metastasis was confirmed, and target 
and non-target lesions were designated. 
9) Tumor evaluation: tumor specialist examination, including tumor related 
symptoms and physical examination of superficial lesions, combined with 
imaging examination to determine the detailed staging, measure the size of 
metastasis before treatment, and fill in the relevant forms. 
10) Behavior status score (KPS score standard, see APPENDIX 2). 
11) Pain assessment: including pain intensity and consumption of analgesics, see 
section 6.2.2.2 and APPENDIX 4. 
 
6.2.2 Efficacy evaluation 
The primary efficacy evaluation index was overall survival time (OS), and the 
secondary efficacy evaluation indexes were time to disease progression (TTP), 
progression free survival (PFS), objective remission rate (ORR), disease control rate 
(DCR), and clinical benefit response (CBR).


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
6.2.2.1 Efficacy evaluation criteria 
According to RECIST 1.1 (see APPENDIX 3 for details), the patients were 
divided into complete remission (CR) and partial remission(PR), stable (SD), 
progressive (PD).Response evaluation was performed every 8 weeks. if the patient 
achieved CR, or PR should be confirmed 4 weeks after the first evaluation. 
Partial or incomplete tumor evaluation will not be included in TTP, PFS, ORR, 
DCR unless the observable lesions have been evaluated as progression (according to 
recist1.1). 
 
6.2.2.2 Efficacy evaluation index 
Overall survival (OS) refers to the time from randomization to death due to any 
cause. Record the time of contact with the patient and the last visit before death. For 
patients who were still alive at the time point of the final analysis, the last contact time 
was taken as the survival time. In the analysis of survival and follow-up treatment, all 
patients were followed up until death, loss of follow-up or termination of the study. 
The log rank test will be used to analyze the overall survival. 
Time to disease progression (TTP): defined as from the date of randomization to 
the first observation of the disease. The time (days) between progression (imaging or 
clinical progress, whichever is earlier).The actual date of tumor evaluation will be 
used for calculation. The time to progression for patients who did not progress at the 
time of analysis or death will be calculated as the date of the last tumor evaluation. 
The time of disease progression was analyzed by the same method as OS. 
Progression free survival (PFS): the time a patient survives without significant 
tumor progression. If the appearance of new lesions is regarded as the standard of 
progression, the time point of progress is the date when the new lesions are observed 
for the first time. Progression free survival was defined as the time from 
randomization to death in patients who died of any other cause before disease 
progression was recorded. Patients without progression or death (i.e., progression free 
survival) at the time of the last tumor assessment will be used as the end point.


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
Objective response rate (ORR): refers to the proportion of patients whose tumor 
volume has reduced to a predetermined value and can maintain the minimum time 
limit, which is generally (CR + PR)%.Remission usually refers to the period from the 
beginning of curative effect to the confirmation of tumor progression. Both CR and PR 
subjects need to be confirmed and evaluated according to RECIST Standard Version 
1.1. 
Disease control rate (DCR): refers to the percentage of cases with remission and 
stable lesions after treatment in the total number of evaluable cases, that is, DCR = 
(CR + PR + SD)%. 
Clinical benefit response (CBR): only symptomatic patients were evaluated in the 
study, including pain (intensity of pain and consumption of analgesics), PS 
(performance status, evaluated according to KPS), and weight change. See 
APPENDIX 4 for evaluation criteria. 
Symptomatic pancreatic cancer was defined as having at least one of the 
following manifestations at baseline: 
1) KPS 60 or 70 score; 
2) They received morphine / opioid analgesia; 
3) The score of MPAC was more than or equal to 20; 
If the patients were asymptomatic at the time of admission, and the above 
symptoms appeared during the treatment, the evaluation was started when the 
symptoms appeared CBR. 


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
Table 8  Clinical benefit response assessment requirements 
 
Evaluation items 
Evaluation method 
Evaluation time point 
Pain intensity 
(pain log card) 
Vas100 (visual scale): on the 
horizontal line of 0-100 mm, 
the left "0" is painless, and the 
"100" at the right end is 
extremely painful. Patients are 
marked on the horizontal line 
to represent their own degree 
of pain. 
Patients were recorded daily to the pain log 
card. The researchers evaluated each week 
before treatment. 
● Observation phase: the pain intensity 
was recorded 2-7 days before the start of 
treatment, and the average vas100 score 
was used as the baseline pain intensity 
score. 
● Treatment stage: record daily 
Consumption of 
analgesics 
(pain log card) 
Total daily dose of analgesics 
Patients were recorded daily to the pain log 
card. The researchers evaluated each week 
before treatment. 
● Observation 
stage: 
the 
dosage 
of 
analgesic drugs was recorded 2-7 days 
before the start of study treatment; The 
average 
daily 
dose 
of 
analgesics 
received by the patients two days before 
the start of the study was used as their 
baseline analgesic consumption and will 
be used as a reference for CBR 
assessment. 
● Treatment stage: record daily 
PS 
KPS scoring standard 
They were evaluated by the researchers once 
a week before treatment 
weight 
They were evaluated by the researchers once 
a week before treatment 
 
The vas 100 score in the pain log card and the consumption of all analgesic 
treatment were transcribed on the CRF form by the researchers. The weekly analgesic 
treatment consumption will be calculated as the average daily analgesic treatment 
consumption. 
 


Protocol No. BPL-Nim-PC-1 
 Version date: June16, 2014 
 Version 1.1 
6.2.3 Safety assessment 
6.2.3.1 Definition 
Definition of adverse event (AE): it refers to the adverse medical events that 
occur after the subjects in clinical trials receiving a drug. No matter whether there was 
any adverse event within 30 days after the treatment, the adverse event was judged to 
be adverse from the beginning to the end of the study. 
Adverse drug reaction (ADR): refers to the normal usage and dosage of qualified 
drugs. Present adverse reactions not related to the purpose of medication or accidental. 
Adverse reactions in this study: adverse events determined to be related to the trial 
drug. 
Serious adverse event (SAE), including hospitalization, prolonged hospital stay, 
disability, life-threatening or death, and congenital malformation occurred during the 
clinical study. 
*Note: 1) adverse events should not be included in the disease progression (PD
according to the protocol) due to the development and deterioration of the tumor itself; 
However, PD related deaths during or within 30 days after the end of protocol 
treatment should be reported as SAE. 2) Obstructive jaundice or cholangitis caused by 
pancreatic cancer itself is not considered as a serious adverse event. 
6.2.3.2 Evaluation method 
1）During the protocol treatment, or within 30 days after the end of the protocol
treatment or before the start of other treatments other than the study protocol, the 
observed AE were evaluated according to the observation, examination items and the 
process specified in the process. All kinds of AE and their grades were recorded in 
CRF. 
The observed AE were evaluated according to NCI-CTCAE v4.0.3. 
2）Causal relationship with treatment plan
Any abnormal symptoms, signs, laboratory tests or other special examinations in 
the clinical study should be recorded in detail, and their correlation should be 


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
evaluated. According to the criteria of adverse reaction / event analysis, the association 
evaluation was divided into: 1- positive correlation;2 - probably related;3 - may be 
relevant;4 - may not be relevant;5 - definitely not be relevant. 
① There was a reasonable relationship between the time of starting medication 
and the occurrence of suspicious adverse reactions; 
② Whether the suspected adverse reactions conform to the known adverse 
reaction types of the drug; 
③ Whether the suspected adverse reactions can be explained by the effect of 
combined drugs, the patient's clinical condition or the influence of other treatments; 
④ Whether the suspected adverse reactions disappeared or alleviated after drug 
withdrawal or reduction; 
⑤ Whether the same reaction reappeared after repeated exposure to the suspected 
drug. Causal criteria: according to the above 1 ~ 5 indicators in order to determine. 
Table 9 Judgment of causality of adverse reactions 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: + "means affirmative;"-" means negative;"±" means that it is difficult to affirm or 
negate "?" The expression is not clear. 
The relationship between adverse events (including serious adverse events) and 
drugs should be determined as far as possible. If it is determined that it is definitely 
related, it is likely to be related and may be related, the three levels will be regarded as 
drug-induced adverse reactions, and whether they are serious adverse events will be 
considered according to the severity. 
Judge the result 
Judgment index 
 
① 
② 
③ 
④ 
⑤ 
Definitely 
+ 
+ 
－ 
         + 
+ 
It's probably related 
+ 
+ 
－ 
+ 
？ 
It may be relevant 
+ 
+ 
+ 
± 
？ 
Probably not 
+ 
－ 
± 
± 
？ 
Definitely not 
－ 
－
 
+ 
－ 
－ 


Protocol No. BPL-Nim-PC-1 
 Version date: June16, 2014 
 Version 1.1 
6.2.3.3 Emergency report and response of serious adverse events 
When serious adverse events occur during the treatment period or within 30 days 
after the end of the treatment, they should be treated according to the following 
provisions. However, severe obstructive jaundice or cholangitis caused by pancreatic 
cancer itself is not an urgent report. 
In case of serious adverse events in the process of clinical study, the researcher 
should immediately take appropriate treatment measures for the subjects, and report to 
the drug supervision and administration department, the health administration 
department and the sponsor within 24 hours, report to the ethics committee in time, 
and sign the report date. 
The sponsor and the researcher shall promptly study the serious adverse events 
occurred, take necessary measures to ensure the safety and interests of the subjects, 
report to the drug administration and health administration department in time, and 
inform other researchers of clinical research involving the same drug. 
SAE records should record the symptoms, severity, occurrence time, treatment 
time, measures taken, follow-up time and method, and outcome. 
Table 10  serious adverse event reports and contact numbers 
Reporting unit 
Telephone / fax 
contacts 
Responsible unit ethics 
committee 
Baitai biopharmaceutical Co., 
Ltd(Biotechplc.com) 
010-51571020-8834
Wang Yan 
CFDA drug registry 
CFDA Department of drug 
safety 


Protocol No. BPL-Nim-PC-1 
 Version date: June16, 2014 
 Version 1.1 
6.2.3.4 Pregnancy Report 
Pregnancy during the study period must be recorded and reported in the 
pregnancy report form. In order to ensure the safety of the subjects, the pregnancy 
must be reported within 2 weeks after learning of its occurrence. Follow up is 
necessary to determine the outcome (including early termination of pregnancy) and 
maternal and child status. Pregnancy complications and termination of pregnancy for 
medical reasons must be reported as AE or SAE. Spontaneous abortion must be 
reported as SAE. 
In addition, researchers must collect as much information as possible about the 
pregnancy of their female sexual partners after male subjects were enrolled in the 
study. Pregnancy information must be reported as described above. 
6.3 Biomarkers 
In addition to K-RAS status assessment (one of the inclusion criteria), this study 
will also carry out biomarker detection and exploratory analysis. During the study, 
formalin fixed and paraffin embedded tumor sections (10-20 pieces / patient) will be 
collected for candidate gene expression research and immune histo-chemical study. 
A central laboratory will be designated by the sponsor for K-RAS testing, and 
patients with wild-type K-RAS can enter the screening period (2). 
Other biomarkers except K-RAS were tested in the central laboratory designated 
by the sponsor after the sample collection


Protocol No. BPL-Nim-PC-1 
 Version date: June16, 2014 
 Version 1.1 
7 Blinding and randomization 
7.1 Blinding and blind base preservation 
In this study, a dynamic random variance minimization method was used. Das 
for IWRS automatically assigned random numbers according to the level of 
influencing factors. After the last subject assigned random numbers, the 
randomization project manager derived the first level blind seal from the random 
system and handed it over to the sponsor, including the second level blind background 
made during on-site blinding, Two copies of the blind base were sealed to the sponsor 
and the clinical research unit respectively. 
The drug distribution packaging was participated by blinders of the statistical 
unit and the personnel unrelated to the trial from the applicant. According to the 
treatment group corresponding to the drug package number generated by the software, 
the drug package number and drug verification code of the trial drug and control drug 
were filled in (or pasted) on the label. In this study, the central randomized system 
was used to distribute drugs according to the visit period, so the drugs were packaged 
according to the visit period, and the random number of each subject was unique. 
The package number is different, but the corresponding treatment plan is the same. 
The process of drug blinding is written into a document form by the blinder, that is, 
the blinding record. All the blinders sign on the blinding record and keep it as one of 
the documents of the clinical trial. 
The drug package number and verification code information were imported into Das 
for IWRS system after the completion of blinding for drug distribution. 
7.2 Emergency envelope 
An emergency letter (e-mail) will be set up for each random number, which will 
record the treatment group corresponding to the drug package number received by the 
subject. The emergency letter is used for emergency blind breaking, and the operation 
is strictly authorized. Only the research director of each center can open the electronic 
emergency letter. The operation track will retain the electronic signature, date and 
reading reason of the reader. 


Protocol No. BPL-Nim-PC-1 
 Version date: June16, 2014 
 Version 1.1 
7.3 Emergency unblinding 
When the subjects were aware of the adverse events, they were able to handle the 
adverse events. It should be operated by the researcher, and record the reason, time 
and place of breaking the blind in detail, and input the electronic signature. Within 24 
hours after breaking the blind, inform the clinical trial responsible (leading) unit, 
clinical inspectors and relevant statistical personnel, and explain the reasons for 
breaking the blind. The cases after breaking the blind should be regarded as falling off 
cases, and the case data should be kept intact. 
7.4 Unblinding requirements 
In this study, double blinding method is adopted. When all the data are entered 
into the database in duplicate, and the final statistical plan is confirmed through Q & 
A, verification, blinding review, the database will be locked. At this time, the first 
blinding is carried out by the main researchers of this study together with the 
statisticians, that is, the blind background of the corresponding groups (group A or 
group B) corresponding to the random number is revealed, so as to conduct statistical 
analysis of all the data after grouping. After the analysis was completed, the second 
blinding was performed by the main researchers at the clinical research summary 
meeting. All blinding procedures should be recorded. 


Protocol No. BPL-Nim-PC-1 
 Version date: June16, 2014 
 Version 1.1 
BPL-Nim-PC-1 
(for clinical study only) 
Drug package 
Verification 
Nimotuzumab injection /nimotuzumab injection simulator 
[CFDA approval No.] 2011L01239 
[indication] locally advanced or metastatic pancreatic cancer 
[usage and dosage] 400mg / week, once a week 
[specification and package] 50mg/10ml/piece, 8 pieces/box 
[storage] 2-8 ℃ 
[production batch No.] 
Biotechplc.com 
8 Drug management 
8.1 Drug specifications 
1)
Nimotuzumab injection, specification: 50mg / 10ml / Cilin bottle, production:
Biotech Pharmaceutical Co., Ltd.
2)
Gemcitabine, specifications: 200mg, 1000mg lyophilized powder injection,
sold in the market, purchased by Biotech Pharmaceutical Co., Ltd. and
provided free of charge.
3)
Placebo (nimotuzumab injection simulator): preparation buffer solution,
specification: 10ml / vial, production: Biotech Pharmaceutical Co., Ltd.
8.2 Drug packaging and labeling 
There were 8 drugs in each package, which was the dosage of one visit period. The 
contents of drug package labels include drug package number, drug verification code, 
indication, usage, expiration date, storage conditions and drug supplying unit, and the 
words "for clinical research use only" are marked (see the figure below). 
Figure 1    drug package label 


Protocol No. BPL-Nim-PC-1 
 Version date: June16, 2014 
 Version 1.1 
8.3 Drug delivery methods 
In this study, central randomization was used. First, appropriate drugs were 
delivered to each research center according to the expected progress of the trial, and 
then drugs were timely distributed according to the actual progress during the trial. 
They were distributed to the subjects by the trial medication management personnel of 
the research center. All drug distribution processes should be recorded accordingly. In 
order to ensure the timely supply of drugs, the central random system sets the drug 
storage alert quantity in advance. Once the stock is insufficient, the inspector can 
timely distribute the drugs according to the drug package number prompted by the 
system. After confirming that the drugs delivered to the research unit, the system will 
issue the drugs with corresponding package numbers to the applicants. The same 
procedure is used to adjust drugs between centers. 
After the subjects were screened and qualified, the researchers logged into the 
central random system, input the general information such as the subject's 
abbreviation, gender, age and other general information and dynamic random 
influencing factors information, applied for the random number, and recorded the 
random number of the subject in the course of the large medical record. Then, the 
drug issuer will apply for the drug number for the subject according to the random 
number, and the system will display the drug package number that the subject should 
apply for. When the drug number on the outer packaging system is consistent with 
that of the drug delivery system, the drug delivery system will display the drug 
number. 
8.4 Management 
Each research unit should establish strict storage and distribution system of 
clinical research drugs. The application unit shall send the research drug directly to 
each research center by special personnel, and establish a complete drug acceptance 
procedure. Each research unit establishes a pharmacy or designates a special research 
medication administrator for management. The drug should be stored and transported 
at 2-8 ℃ without freezing. A special "clinical research drug use record form" was 
established to register the date of drug release, drug number, subject serial number, 
recipient, drug administrator, etc. The researchers should distribute the drugs 
according to the order of each patient's visit, and should not choose the serial number. 


Protocol No. BPL-Nim-PC-1 
 Version date: June16, 2014 
 Version 1.1 
After the completion of the study, the unused drugs will be collected by the sponsor 
and destroyed after being checked and kept for a proper time. 
9 Research progress and completion time 
The enrollment of the patients is expected to be completed from December 2014 to 
December 2016. 
10 Data management and statistical analysis 
10.1 
Data management 
10.1.1 Electronic data management 
①DAS for EDC is used in the test data management.
②Construction of electronic case report form (eCRF): the data manager builds eCRF
according to the research protocol. 
③EDC system users use role and authority dual control. All users accessing EDC
need to fill in the user account application forms. After confirmation and approval of 
the sponsor, the system administrator creates the project administrator account and 
grants the project administrator permission. The project administrator user applies to 
create the account of researcher, research assistant (CRC), supervisor, inspector, data 
manager and grant different permissions to access EDC. such as the researchers of 
each center can only see the contents of the center and have the right to revise the data, 
the sponsor can only browse the EDC; The inspectors can read the EDC data of each 
center without the authority to revise the data, but can ask some questions. 
④Data entry: research assistants (CRC) are designated by the main researchers of
each institution, and CRC will input the original data into eCRF timely and accurately. 
eCRF is not the original record. 
⑤Data verification: at the same time of data entry, EDC conducts logic verification,
and sends out system questions in real time. In addition to system queries, data 
administrators conduct manual verification on text data, and issue manual queries if 
there are problems. 
⑥On site verification of source data (SDV): the inspectors log in DAS for EDC at
the research sites of each center, and 100% check the consistency of eCRF data with 
the original data. If problems are found, they can issue questions online at any time. 
⑦Question answer: the researcher can answer the question online in real time or


Protocol No. BPL-Nim-PC-1 
 Version date: June16, 2014 
 Version 1.1 
download the list of questions, and the researcher can answer the question offline, and 
then the CRC will input the question content into EDC. The data manager and the 
supervisor shall reply to the questions answered by the researcher, and issue the 
questions again if necessary until the data is "clean". 
⑧All the data were locked and analyzed by the participants and administrators, and
then all the data were confirmed and analyzed by the participants and administrators. 
After all the data are locked, the data administrator will import it into the designated 
database and submit it to the statisticians for statistical analysis. The locked data can 
not be edited again. The problems found after data locking can be corrected in the 
statistical analysis program after confirmation. After the data is locked, the researcher 
and the sponsor should sign the relevant documents if there is definite evidence to 
prove that it is necessary to unlock the data. 
⑨Unblinding: in this study, the second blinding method was used. After all the
research data were locked, the main researchers (PI) and The statisticians and the 
sponsor discuss the statistical plan together, and uncover the blind, that is, the group 
corresponding to the random number (After blinding, any modification to the database 
must be agreed in writing by the clinical research leader, biostatistician and data 
manager. After the statistical analysis, the second blinding was performed by the main 
researchers at the clinical research summary meeting. All blinding procedures should 
be recorded. 
⑩eCRF archiving: at the end of the trial, the eCRF and PDF electronic documents of
each subject were generated, and the CD was recorded in the research unit, and the 
retention period was 7 years after the completion of the experiment. 
EDC shutdown: after the trial, the data administrator will apply for EDC shutdown, 
cancel all account access rights after obtaining the permission of the sponsor, and 
close the EDC (i.e. offline) after the data is fully backed up. Within 7 years after the 
completion of the trial, the data management center can open the EDC system after 
making an appointment. 
10.1.2 Develop data management plan 
①The data management plan is written by the data administrator.
②The data management plan will serve as the guidance document for the whole data
management process, and then all processes shall operate according to the time and 


Protocol No. BPL-Nim-PC-1 
 Version date: June16, 2014 
 Version 1.1 
method defined therein. 
③The data management plan includes:
－ Management of data management plan, such as ownership, cover rules,
catalog, etc. 
－ The general situation of the study, such as the purpose of the study, the 
overall design of the study, etc. 
－ Schedule of data management work. In this schedule, the start and finish time 
of each link should be reflected. At the same time, the schedule should be 
coordinated with the overall schedule of the clinical trial. 
－ Allocation of users and permissions: including EDC system administrator 
(admin) and data administrator (DM), investigator, CRC, CRA, etc. 
－ Data management design, including database design and logical verification 
design. 
－ Data processing regulations 
－ Quality control data 
－ EDC off 
－ Data security measures  
－ EDC system emergency plan 


Protocol No. BPL-Nim-PC-1 
 Version date: June16, 2014 
 Version 1.1 
10.2 
Statistical analysis 
10.2.1 Sample size estimation 
In this study, overall survival (OS) was taken as the main efficacy index. 
According to the literature[13], OS of gemcitabine monotherapy group was 6 months.
In this study, it was predicted that the OS of the experimental group could be 
improved by adding nimotuzumab up to 8.7 months, according to the bilateral 
testα=0.05,1-β=0.80. Enrollment is completed within 24 months, and trials are 
expected to be completed 12 months after observation until the last case enrolled. The 
study group and the control group had a ratio of 1:1. Considering the deletion factor 
of 20%, the total number of cases was determined to be 276 cases, 138 cases in the 
experimental group and the control group. 
If the death event of the last case did not reach 80% after 12 months, the 
experiment continued to observe until the death event reached 80%. 
10.2.2 Analysis data set 
①Full analysis set (FAS): all the cases that were randomized into groups, used the
study drug at least once, and had the evaluation data of post medication efficacy
at least once. When the main efficacy indicators were missing, the previous
results were carried forward according to the intention to treat (ITT) analysis.
FAS is the main analysis set. Only FAS analysis without carrying forward was
used for secondary efficacy indicators.
②Per protocol set (PPS): refers to the set of cases that meet the inclusion criteria, do
not meet the exclusion criteria, and complete the treatment plan, i.e. analyze the
cases that meet the trial protocol, have good compliance, and complete the
contents specified in CRF (PP analysis).PP analysis was mainly used for the main
efficacy indicators.
③Safety data set (SS): the actual data that has been treated at least once and
recorded by safety indicators. The missing value of safety shall not be carried
forward; Some excluded cases that can be evaluated were included, such as the
cases whose age exceeded the inclusion criteria, but did not include the cases that
could not be judged for safety due to the use of prohibited drugs. The incidence of
adverse reactions was determined by the number of cases in the safety set as the
denominator.


Protocol No. BPL-Nim-PC-1 
 Version date: June16, 2014 
 Version 1.1 
10.2.3 Statistical method 
The endpoint analysis will be performed after 80% of deaths. 
(1) Case analysis
The total number of selected and completed cases in each center were listed, and
three analysis data sets (FAS, PPS, SS) were determined. 
The cases of shedding and rejection and their causes were listed. 
(2) Demographic data and baseline analysis
Baseline and other demographic characteristics were as follows:
The number of cases, mean value, standard deviation, median, minimum value 
and maximum value were calculated by continuous variable. 
Count and grade data were used to calculate frequency and composition ratio. 
Inferential statistical results (P values) are listed as descriptive results. 
(3) Compliance analysis
Analysis of medication compliance: compare whether the two groups of patients
used the study drug on time and in accordance with the amount, and did not use the 
drugs prohibited in the scheme. 
Analysis of combined drug use: the number of drug users in each combination 
should be counted and listed in detail. 
(4) Efficacy analysis
Analysis of main therapeutic indexes
Overall survival (OS), the median survival time, quartile time and 95% 
confidence interval of the two groups were listed respectively. Log rank test was used 
to compare the two groups, and Kaplan Meier curve of OS was drawn. Taking 
dynamic random influencing factors as covariates, the Cox proportional hazard model 
was used to calculate HR and its 95% confidence interval (CI). 
Analysis of secondary efficacy indicators 
Progression free survival (PFS), the median survival time, quartile time and 95% 
confidence interval of the two groups were listed respectively. Log rank test was used 
to compare the two groups, and Kaplan Meier curve of OS was drawn. Taking 
dynamic random influencing factors as covariates, the Cox proportional hazard model 


Protocol No. BPL-Nim-PC-1                        Version date: June16, 2014                                                 Version 1.1 
 
 
was used to calculate HR and its 95% confidence interval (CI). 
The median time to disease progression (TTP), the median survival time, quartile 
time and 95% confidence interval of the two groups were listed respectively. Log rank 
test was used to compare the two groups, and Kaplan Meier curve of OS was drawn. 
Taking dynamic random influencing factors as covariates, the Cox proportional 
hazard model was used to calculate HR and its 95% confidence interval (CI).  
Objective remission rate (ORR) was calculated and used χ2 test was used to 
compare the difference between groups. The logistic regression model was used to 
calculate the ratio and 95% of the ratio Confidence interval (CI). 
The disease control rate (DCR) was calculated at the end of the experiment, and 
CMH was used-χ2test. 
Clinical benefit response (CBR), the clinical benefit response efficiency of the two 
groups at the end of  the trial was calculated respectively CMH-χ2test. 
 
(5) Safety analysis 
• 
The incidence of adverse events and adverse reactions and their 95% 
confidence interval (CI) were calculated. 
• 
The frequency and frequency of adverse events and adverse reactions were 
listed by system, and the percentage was calculated 
• 
Detailed list of various adverse event cases 
• 
Detailed list of various adverse reactions 
• 
The abnormal rate of abnormal ECG and abnormal turn rate after physical 
examination were increased 
• 
The laboratory indexes, ECG, abnormal cases of physical examination and 
clinical explanation were listed. 
 
10.2.4 Statistical software and general requirements 
• 
SAS 9.2 software was used for analysis. 
• 
All statistical tests were performed with bilateral test. If p value is less than 
or equal to 0.05, the difference will be considered to be statistically 
significant. 
• 
Detailed statistical methods will be provided in the statistical analysis plan. 
 
 


Protocol No. BPL-Nim-PC-1 
 Version date: June16, 2014 
 Version 1.1 
11 Quality control of clinical research 
During the study, the clinical supervisors assigned by the sponsor regularly 
visited the research hospital according to the standard operating procedures, so as to 
ensure that all contents of the study protocol were strictly observed and the 
correctness and authenticity of the research data were filled in. 
•
The participants must be trained in a unified way, recording methods and
judgment criteria.
•
The whole clinical research process should be conducted in a strictly blind state.
•
In order to ensure the authenticity and reliability of eCRF, researchers should
record the contents of eCRF truthfully, carefully and carefully according to the
requirements of eCRF.
•
The criteria for abnormal laboratory examination were determined according to
the normal reference range of clinical research units and that of this study. The
judgment standard shall prevail.
•
All observation results and findings in clinical research should be verified to
ensure the reliability of the data and ensure that the conclusions in the clinical
study come from the original data.
•
In view of the possible shedding, active measures should be taken, and the case
shedding rate of each research unit should be controlled within 10%.
12 Ethical requirements and informed consent 
Before the start of this clinical study, the written consent forms of the ethics 
committee should be obtained. According to the guidelines of the GCP, any 
modification of the study protocol requires the approval of the ethics committee. If 
these modifications may cause harm to patients, the contents of informed consent 
should be updated and signed by the patients participating in the study. This clinical 
study must follow the Helsinki Declaration and the relevant Chinese clinical research 
norms and regulations. 
Before a subject is enrolled in this study, the research physician must fully 
introduce the purpose, procedure and possible risks of the clinical study to the subject 
or the subject's legal representative. Subjects should be informed that they have the 
right to withdraw from the study at any time and under any circumstances. Before 
enrollment, each subject or the legal representative of the subject must sign the 


Protocol No. BPL-Nim-PC-1 
 Version date: June16, 2014 
 Version 1.1 
informed consent form in duplicate (copy kept by the subject).It is the responsibility 
of the study physician to obtain informed consent forms before each subject enters the 
study and keeps it as a study file. 
13 Data preservation 
In order to ensure the evaluation and supervision of the State Food and Drug 
Administration and the sponsor on the clinical research, the clinical research unit 
should keep all the research data and original records of the whole process of the 
clinical research, including the confirmation of all subjects (which can effectively 
check different records, such as CRF and original hospital records), all signed 
informed consent forms, CRF, and Detailed records of drug distribution, etc. The 
research unit should keep these clinical data until 5 years after the clinical end. 
All the data of this clinical study belongs to the sponsor. Except as required by 
State Drug Administration (SDA), the researcher shall not provide it to any third party 
in any form without the written consent of the sponsor. 
14 Researchers 
 Omit


Protocol No. BPL-Nim-PC-1 
 Version date: June16, 2014 
 Version 1.1 
15 References 
1.
GLOBOCAN 2012. http://globocan.iarc.fr/Pages/fact_sheets_population.aspx.
2.
Siegel R1, Ma J, Zou Z, et al. Cancer statistics, 2014. CA Cancer J Clin.
2014;64(1):9-29.
3.
Ni QuanxingCurrent status of clinical epidemiology of pancreatic
cancerPancreatology2006; 2: 65-68.
4.
Chen W, Zheng R, Zhang S, et al. Annual report on status of cancer in China,
2010. Chin J Cancer Res. 2014;26(1):48-58.
5.
Xiong HQ, Carr K, Abbruzzese JL.Cytotoxic chemotherapy for pancreatic
cancer: Advances to date and future directions.Drugs. 2006;66(8):1059-72.
6.
Li D, Xie K, Wolff R, Abruzzese JL.Pancreatic Cancer.Lancet. 2004; 363 (9414):
1049-57.
7.
Van Cutsem E, Aerts R, Haustermans K, Systemic treatment of pancreatic
cancer.Eur J Gastroenterol Hepatol. 2004;16(3):265-74.
8.
Carmichael J.Clinical response benefit in patients with advanced pancreatic
cancer. Role of gemcitabine.Digestion. 1997;58(6):503-7.
9.
Eckel F, Schneider G, Schmid RM. Pancreatic cancer: a review of recent
advances.Expert Opin Investig Drugs. 2006; 15(11): 1395-410.
10. Oettle H, Arnold D, Hempel C, et al.The role of gemcitabine alone and in
combination in the treatment of pancreatic cancer.Anticancer Drugs. 2000;
11(10):771-86.
11. Rocha Lima CM, Flores AM. Gemcitabine doublets in advanced pancreatic
cancer: should we move on? J Clin Oncol. 2006;24(3):327-9.
12. Xiong HQ, Rosenberg A, LoBuglio A. Cetuximab, a monoclonal antibody
targeting the epidermal growth factor receptor, incombination with gemcitabine
for advanced pancreatic
cancer: a multicenter phase II Trial.J Clin Oncol. 2004;22(13):2610-6.
13. Burris HA 3rd, Moore MJ, Andersen J, et al. Improvements in survival and
clinical benefit with gemcitabine as first-line therapy for patients with advanced
pancreas cancer: a randomized trial.J Clin Oncol. 1997;15(6):2403-13.
14. Von Hoff DD,oRamanathan RK,aBorad MJ, et al. Gemcitabine plus nab-
paclitaxel is an active regimen in patients with advancedpancreatic cancer: a
phase I/II trial. J Clin Oncol. 2011;29(34):4548-54.


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15. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer
with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691-703.
16. Hoy SM. Albumin-bound Paclitaxel: a review of its use for the first-line
combination treatment of metastatic pancreatic cancer.Drugs. 2014;74(15):1757-
68.
17. Saif MW. U.S. Food and Drug Administration approves paclitaxel protein-bound
particles (Abraxane®) in combination with gemcitabine as first-line treatment of
patients with metastatic pancreatic cancer.JOP. 2013;14(6):686-8.
18. Cecco S, Aliberti M, Baldo P, et al. Safety and efficacy evaluation of albumin-
bound paclitaxel.Expert Opin Drug Saf. 2014;13(4):511-20.
19. Thota R,Pauff JM,Berlin JD.Treatment of metastatic pancreatic adenocarcinoma:
a review.Oncology (Williston Park). 2014;28(1):70-4.
20. Wang Liwei, Chen Donghui, Li Qi, etcConsensus of Chinese experts on
comprehensive diagnosis and treatment of pancreatic cancer (2014
Edition)Journal of clinical oncologyApril 2014, Volume 19, issue 4
21. Vickers MM, Powell ED, Asmis TR, et al.Comorbidity, age and overall survival
in patients with advanced pancreatic cancer - results from NCIC CTG PA.3: a
phase III trial of gemcitabine plus erlotinib or placebo. Eur J Cancer. 2012
Jul;48(10):1434-42.
22. Dirk Strumberg, Beate Schultheis, Matthias Philip Ebert, et al. Phase II,
randomized, double-blind placebo-controlled trial of nimotuzumab plus
gemcitabine compared with gemcitabine alone in patients (pts) with advanced
pancreatic cancer (PC).,2013 ASCO Annual Meeting. J Clin Oncol 31,2013
（suppl；abstr 4009）.
23. Dan Su, Shun-Chang Jiao, Li-JieWang, et al. Efficacy of nimotuzumab plus
gemcitabine usage as first-line treatment in patients with advanced pancreatic
cancer. Tumour Biol. 2014;35(3):2313-8.


Protocol No. BPL-Nim-PC-1 
Version date: June 16,2014 
Version 1.1 
 
 
APPENDIX 1: Schedule 
project 
Screening period 
(I) 
Screening period 
(II) 
Baseline 
period 
Treatment period 
Cycle1(W1-4)……. 
Every 8 weeks 
Final cancer visit assessment 
Every 3 
months 
Follow up 5) 
D1 
D8 
D15 
D22 
Informed consent forms 
╳ 
Assignment of subject screening 
number 
╳ 
Tumor diagnosis 
╳ 
Tissue specimen collection 
╳ 
K-RAS detection 
╳ 
Random number assignment of 
subjects 
╳ 
Check the inclusion and  exclusion  
criteria 
╳ 
Demographic data 
╳ 
Medical history 
╳ 
Physical examination 
╳ 
▲ 
╳ 
╳ 
╳ 
╳ 
╳ 
╳ 
CBR 
1） 
Pain intensity 
╳ 
▲ 
According to MPAC visual analog scale, the patients were evaluated once a 
day 
Analgesics consumption 
╳ 
▲ 
╳ 
╳ 
╳ 
╳ 
╳ 
╳ 
KPS score 
╳ 
▲ 
╳ 
╳ 
╳ 
╳ 
╳ 
╳ 
Weight 
╳ 
▲ 
╳ 
╳ 
╳ 
╳ 
╳ 
╳ 


Protocol No. BPL-Nim-PC-1 
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Vital signs 
╳ 
▲ 
╳ 
╳ 
╳ 
╳ 
╳ 
╳ 
Body surface area 
╳ 
╳ 
╳ 
╳ 
╳ 
╳ 
Electrocardiogram 
╳ 
★ 
╳ 
╳ 
Routine blood test 
╳ 
▲ 
╳ 
╳ 
╳ 
╳ 
╳ 
╳ 
Electrolyte 
╳ 
▲ 
╳ 
╳ 
╳ 
╳ 
╳ 
╳ 
Blood biochemistry 
╳ 
▲ 
╳ 
╳ 
╳ 
╳ 
╳ 
╳ 
Serum CA19-9 
╳ 
▲ 
╳ 
╳ 
╳ 
╳ 
╳ 
╳ 
Urine routine 
╳ 
▲ 
Pregnancy check 2) 
╳ 
▲ 
Imaging baseline assessment 3) 
╳ 
■ 
╳ 
╳ 
Nimotuzumab / placebo 
Administration 
╳ 
╳ 
╳ 
╳ 
╳ 
Gemcitabine administration 
╳ 
╳ 
╳ 
╳ 
Adverse event assessment 4) 
Keep a record 
Combination therapy 
Keep a record 
Follow up survival 
Keep a record 
Note: 
▲: the examination results within 1 week before administration can be directly included in the baseline results, and repeated measurement is not necessary. 
★:the examination results within 2 weeks before administration can be directly included in the baseline results without repeated measurement. 
■:  the examination results within 3 weeks before administration can be directly included in the baseline results without repeated measurement.
1） 
Clinical benefit rate evaluation: including pain (intensity of pain and consumption of analgesics), PS (performance status, evaluated according to KPS), and weight change. The pain intensity and the


Protocol No. BPL-Nim-PC-1 
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consumption of analgesics were recorded once a day and evaluated by CBR once a week. See APPENDIX 4 for details. 
2） 
It is only applicable to those with fertility.
3） 
Imaging examination in different periods should use the same detection technology as that in the baseline period. If the evaluation result is CR or 
PR was performed at 4 weeks after the initial evaluation, and the time window for efficacy evaluation was ± 7 days. 
4） 
Adverse events were followed up to 30 days after the last medication.
5） 
For patients who withdraw from the trial, the observation items in the following table should be followed up:
After withdrawal, the subjects could still come to the hospital for follow-up 
The subjects could not come to the hospital for follow-up after 
withdrawal 
Tumor evaluation of disease progression 
before withdrawal 
1)
Survival status was recorded (once every 3 months) 
2)
KPS score (once every 3 months) 
3)
New adverse events were recorded up to 1 month after the last 
administration of the trial drug 
4)
Record any anti-tumor treatment 
The following items were followed up by telephone: 
1)
Survival status (once every 3 months) 
2)
New adverse events were recorded up to 1 month after the last 
administration of the trial drug 
3)
Any anti-tumor treatment given by the hospital 
Evaluation of disease progression without 
withdrawal 
1)
Tumor imaging examination and evaluation were performed according 
to the experimental schedule
2)
Survival status was recorded( once  every 3 months) 
3)
KPS score (once every 3 months) 
4)
New adverse events were recorded up to 1 month after the last 
administration of the trial drug 
5)
Record any anti-tumor treatment 
The following items were followed up by telephone: 
1)
Survival status (once every 3 months) 
2)
New adverse events were recorded up to 1 month after the last 
administration of the trial drug 
3)
Any anti-tumor treatment given by other  hospital 
4)
The date and  basis of judging disease progression in other hospital 


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APPENDIX 2: KPS score 
Karnofsky functional status scoring criteria 
Physical condition 
score 
Normal, no symptoms and signs 
100 
Able to perform normal activities with minor symptoms and signs 
90 
Normal activity with reluctance, with some symptoms or signs 
80 
Cares for self but does not maintain normal life and work 
70 
Capable of most self-care, but occasionally requires assistance 
60 
Often require care 
50 
Cannot carry on any self-care and requires special care and assistance 40 
inability to take care of themselves severely 
30 
Very ill, requiring hospitalization and aggressive supportive care 
20 
Critically ill, near death 
10 
Death 
0 


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APPENDIX 3:Criteria for evaluating the efficacy of solid tumors (version 1.1) 
1 
Tumor measurability at baseline 
1.1 definition 
At baseline, tumor lesions / lymph nodes were classified as measurable and 
unmeasurable according to the following definitions: 
1.1.1 Measurable lesions 
Tumor focus: at least one diameter can be accurately measured (recorded as the 
maximum diameter), and its minimum length is as follows: 
•
CT scan 10 mm (no more than 5mm thick)
•
Clinical routine examination instrument 10 mm (tumor lesions that cannot be
accurately measured by diameter measuring instrument should be recorded as
non-measurable)
•
Chest X-ray 20 mm
•
Malignant lymph nodes: pathological enlargement and measurable, single
lymph node CT scan short diameter must be ≥ 15 mm. The thickness of CT
scan should not exceed 5 mm. During baseline and follow-up, only short
diameter was measured and followed up.
1.1.2 Unmeasurable lesions 
All other lesions, including small lesions (longest diameter < 10 mm or 
pathological lymph node short diameter ≥ 10 mm to < 15 mm) and unmeasurable 
lesions. Unmeasurable lesions include meningeal disease, ascites, pleural or 
pericardial effusion, inflammatory breast cancer, cutaneous / pulmonary 
carcinomatous lymphangitis, abdominal mass that cannot be diagnosed and followed 
up by imaging, and cystic lesions. 
1.1.3 Special considerations on lesion measurement 
Bone lesions, cystic lesions and lesions previously treated with local treatment 
need to be noted: 
Bone lesions: 
• Bone scan, PET scan or plain film are not suitable for measuring bone lesions, but
can be used to confirm the presence or disappearance of bone lesions;
• When osteolytic lesions or mixed osteolytic / osteogenic lesions have definite soft
tissue components and the soft tissue components meet the above measurable
definition, these lesions can be regarded as measurable lesions if they can be


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evaluated by tomographic imaging techniques such as CT or MRI; 
• Osteogenic lesions are  unmeasurable.
Cystic lesions: 
• The lesions that meet the definition criteria of simple cyst in radiology should not be
considered as malignant lesions because they are defined as simple cysts. They are
neither measurable nor unmeasurable lesions;
• If it is cystic metastasis and meets the above definition of measurability, it can be
regarded as measurable lesions. However, if there are non-cystic lesions in the same
patient, non-cystic lesions should be preferred as the target lesions.
Local treatment of lesions: 
• A lesion located at a site that has been treated with radiotherapy or other local
regional therapy is generally considered as a non-measurable lesion unless there is
definite progression of the lesion. The protocol should describe in detail the
conditions under which these lesions are measurable.
1.2 Description of measurement method 
1.2.1 Lesion measurement 
In clinical evaluation, all tumor measurements were recorded in metric system. 
All baseline assessments of tumor size should be completed as close as possible to the 
start of treatment and within 28 days (4 weeks) before treatment. 
1.2.2 Evaluation method 
The same techniques and methods should be used for baseline assessment and 
subsequent measurement of lesions. All lesions must be evaluated by imaging, except 
those that cannot be evaluated by imaging but only by clinical examination. 
Clinical lesions: only when the clinical lesions are located on the superficial 
surface and the diameter is greater than or equal to 10 mm, can they be considered as 
measurable lesions (such as skin nodules).For patients with skin lesions, it is 
recommended to measure the size of lesions with a ruler color photos as archive. 
When the lesions are evaluated by imaging and clinical examination at the same time, 
because imaging is more objective and can be reviewed repeatedly at the end of the 
study, imaging evaluation should be selected as far as possible. 
Chest X-ray: when tumor progression is an important end point, chest CT should 
be preferred because CT is more sensitive than X-ray, especially for new lesions. 


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Chest X-ray examination is only applicable when the boundary of the measured lesion 
is clear and the lung ventilation is good. 
CT, MRI: CT is currently the best and repeatable method for the evaluation of 
curative effect. The definition of measurability in this guideline is based on CT scan 
slice thickness ≤ 5 mm. If the CT slice thickness is greater than 5 mm, the minimum 
measurable lesion should be 2 times of the slice thickness. MRI is also acceptable in 
some cases (e.g. whole body scan). 
Ultrasound: ultrasound should not be used as a measurement method to measure 
the size of lesions. Because of its operation dependence, ultrasound examination does 
not have repeatability after measurement, and can not guarantee the consistency of 
different measurement techniques and measurements. If ultrasound is used to detect 
new lesions during the trial, CT or MRI should be used to confirm. If the radiation 
exposure of CT is considered, MRI can be used instead. 
Endoscopy, laparoscopy: these techniques are not recommended for objective 
tumor evaluation, but they can be used to confirm CR when biopsy specimens are 
obtained, or in trials with recurrence after CR or surgical resection as the study 
endpoint. 
Tumor markers: tumor markers cannot be used alone to evaluate the objective 
response of tumors. However, if the marker level exceeds the upper limit of normal at 
baseline, it must return to normal level when used to evaluate complete remission. 
When the tumor marker is included in the measurement, it is necessary to take into 
account the tumor markers. Specific criteria for remission of CA-125 (recurrent 
ovarian cancer) and PSA (recurrent prostate cancer) have been published. Moreover, 
the international gynecological cancer organization has formulated the CA-125 
progress standard, which will be added to the objective evaluation standard of ovarian 
cancer first-line treatment program. 
Cytology / histology techniques: these techniques can be used to identify PR and 
Cr (e.g., residual benign tumor tissue is often present in the lesions of germ cell 
tumors) under specific conditions specified in the protocol. When exudation may be a 
potential side effect of a treatment (such as treatment with paclitaxel compounds or 
angiogenesis inhibitors) and the measurable tumor meets the criteria of remission or 
disease stability, the occurrence or aggravation of tumor related exudation during 
treatment can be diagnosed by cytological techniques to distinguish remission (or 


Protocol No. BPL-Nim-PC-1 
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disease stability) from disease progression. 
2 
Evaluation of tumor remission 
2.1  Evaluation of all tumors and measurable lesions 
In order to evaluate objective remission or possible future progress, it is 
necessary to evaluate the total tumor load of all tumor lesions at baseline, which can 
be used as a reference for later measurement results. In clinical protocols with 
objective remission as the primary treatment endpoint, only patients with measurable 
lesions at baseline were included. Measurable lesions are defined as the presence of at 
least one measurable lesion. For those trials with disease progression (disease 
progression time or fixed date progression degree) as the primary treatment endpoint, 
the protocol inclusion criteria must specify whether it is limited to patients with 
measurable lesions or not. 
2.2 Baseline records of target and non target lesions 
When there is more than one measurable lesion at baseline, all lesions should be 
recorded and measured, with a total of no more than 5 lesions (no more than 2 lesions 
per organ). As the target lesions, all the involved organs should be represented (that is, 
patients with only one or two cumulative organs can select at most two or four target 
lesions as baseline measurement lesions). 
Target lesions must be selected based on size (longest diameter), be 
representative of all organs involved, and measurements must be reproducible. 
Sometimes, when the largest lesion can not be measured repeatedly, it can be re 
selected. 
Lymph nodes need special attention because they are normal tissues and can be 
detected by imaging even without tumor metastasis. Pathological lymph nodes 
defined as measurable nodules or even target lesions must meet the following criteria: 
CT measurement of short diameter ≥ 15 mm. The baseline only needs to detect the 
short diameter. Radiologists usually use the short diameter of the nodule to determine 
whether the nodule has metastasis. The sagittal plane or the sagittal plane of the MRI 
was used to detect the axial plane. The minimum value is the short diameter. For 
example, a 20 mm× A 30 mm abdominal nodule with a short diameter of 20 mm can 
be regarded as a malignant and measurable nodule. In this example, 20 mm is the 
measurement of the nodule. Nodules ≥ 10 mm but < 15 mm in diameter should not be 


Protocol No. BPL-Nim-PC-1 
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considered as target lesions. However, nodules less than 10 mm do not belong to the 
category of pathological nodules and need not be recorded and further observed. 
The sum of the calculated diameters of all target lesions (including the longest 
diameter of non nodular lesions and the short diameter of nodular lesions) will be 
reported as the sum of baseline diameters. If lymph node diameter is included, as 
mentioned above, only the short diameter is included. The sum of baseline diameters 
will be used as a reference value for the baseline level of the disease. 
All the other lesions, including pathological lymph nodes, can be regarded as non 
target lesions and need not be measured but be recorded during baseline evaluation. 
such as "existing", "missing" or in rare cases "clear progress". Extensive target lesions 
can be recorded with the target organs (e.g., massive enlargement of pelvic lymph 
nodes or large-scale liver metastasis). 
2.3  Mitigation criteria 
2.3.1 Target lesion assessment 
Complete response (CR): all target lesions disappeared, and the short diameter of 
all pathological lymph nodes (including target and non-target nodules) must be 
reduced to < 10 mm. 
Partial response (PR): the sum of the target lesion diameters was reduced by at 
least 30% from baseline. 
Disease progression (PD): Taking the minimum value of the sum of all measured 
target lesion diameters in the whole experimental study as reference, the relative 
increase of diameter sum is at least 20% (if the baseline measurement value is the 
minimum, the baseline value is used as reference); In addition, an increase of at least 
5 mm in the absolute value of diameter sum must be satisfied (the presence of one or 
more new lesions is also considered as disease progression). 
Disease stability (SD): the reduction of the target lesion did not reach PR, and the 
increase did not reach the PD level, which was between the two. The minimum value 
of the sum of diameters can be used as a reference. 
2.3.2 Considerations of target lesion evaluation 
Even if the diameter of the lymph node was within 10 mm, the value of the 
actual short diameter corresponding to the baseline is still recorded for each 
measurement, it was consistent with the actual measurement of the lymph node. This 


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means that if the lymph node is a target lesion, even if it reaches the criteria of 
complete remission, it cannot be said that all the lesions have disappeared, because the 
short diameter of normal lymph nodes is defined as < 10 mm. Target lymph node 
lesions need to be specifically recorded at specific locations in CRF tables or other 
recording modalities. For CR, the short diameter of all lymph nodes must be less than 
10 mm; For PR, SD and PD, the actual measurement of the short diameter of the 
target lymph node will be included in the sum of the target lesion diameters. 
Target lesions too small to be measured: in clinical studies, all lesions recorded 
at baseline (nodular or non-nodule) should be re-recorded in subsequent assessments, 
even if the lesion is very small (e.g. 2 mm).However, sometimes it may be too small 
to make CT images very blurred, and it is difficult for radiologists to define the exact 
value, which may be reported as "too small to measure". When this happens, it is 
important to record a value on the CRF table. If the radiologist thinks that the lesion 
may have disappeared, it should also be recorded as 0 mm. If the lesion does exist, but 
it is vague, and the accurate measurement value cannot be given, the default value is 
5 mm。(Note: this condition is unlikely to occur in lymph nodes, which normally 
have measurable size or are often surrounded by adipose tissue as in the 
retroperitoneal cavity; however, if the measurement value cannot be given, the default 
value is 5 mm).The default value of 5 mm is derived from the cutting thickness of CT 
scan (this value does not change with different cutting thickness values of CT).Since 
the probability of recurrence of the same measurement is small, providing this default 
value will reduce the risk of miscalculation. However, it should be reiterated that if 
the radiologist can give the exact value of the lesion size, even if the lesion diameter is 
less than 5 mm, the actual value must be recorded. 
Separated or combined lesions: when the non nodular lesions split into fragments, 
the longest diameters of the separated parts were added up to calculate the sum of the 
diameters of the lesions. Similarly, combined lesions can be distinguished by the 
plane between the junctional parts, and their maximum diameters are calculated. 
However, if the combination is inseparable, the longest diameter should be the longest 
of the whole body. 
2.3.3 Evaluation of non target lesions 
In this part, we define the remission criteria of non-target tumor. Although some non 
target lesions can be measured in practice, there is no need for measurement, and only 


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qualitative evaluation is needed at the time point specified in the protocol. 
Complete response (CR): all non-target lesions disappeared and tumor markers 
returned to normal level. All lymph nodes were of non-pathological size (short 
diameter < 10 mm). 
Non persistent or non-persistent or multiple tumor markers. 
Disease progression: clear progression of existing non-target lesions. Note: the 
presence of one or more new lesions is also considered as disease progression. 
2.3.4 Special considerations for evaluation of progression of non target lesions 
The definition of progression of non-target lesions is explained as follows: when 
patients have measurable non target lesions, even if the target lesions are assessed as 
stable or partial remission, to make a clear definition of progression on the basis of 
non-target lesions, the overall deterioration of non-target lesions must reach the extent 
that treatment must be terminated. However, the general increase in the size of one or 
more non target lesions is often insufficient to meet the progression criteria. Therefore, 
when the target lesions are stable or partially remitted, it is almost rare to define the 
overall tumor progression only by the changes of non-target lesions. 
When non target lesions are not measurable: in some phase III trials, this occurs 
when the inclusion criteria do not specify that measurable lesions must exist. The 
overall assessment was based on the above criteria, but there was no measurable data 
for the lesion in this case. It is not easy to evaluate the deterioration of non-target 
lesions (according to the definition: all non-target lesions must be truly unmeasurable). 
Therefore, when the overall disease load caused by the changes of non-target lesions 
is equivalent to the disease progression of the target lesions, it is necessary to establish 
an effective detection method to evaluate according to the definition of non-target 
lesions. If described as an increase in tumor load, it is equivalent to an additional 73% 
increase in volume (equivalent to a 20% increase in measurable lesion 
diameter).Another example is peritoneal effusion from "trace" to "large amount"; 
Lymphangiopathy changed from "local" to "widespread"; Or described as "enough to 
change the treatment" in the protocol. Examples include pleural effusion ranging from 
trace to large, lymphatic involvement spreading from the primary site to the distant, or 
may be described in the protocol as "therapeutic changes are necessary.". If a definite 
progression is found, the patient should be considered as disease progression in 
general at that point in time. It is better to have objective criteria for the evaluation of 


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unmeasurable lesions. Note that the increased criteria must be reliable. 
2.3.5 New lesions 
The appearance of new malignant lesions indicates the progress of the disease; 
Therefore, it is very important to evaluate the new lesions. At present, there is no 
specific standard for imaging detection of lesions, however, the discovery of a new 
lesion should be clear. For example, progress cannot be attributed to differences in 
imaging techniques, changes in imaging morphology, or other lesions other than 
tumors (e.g., some so-called new bone lesions are merely the cure of the original 
lesions or the recurrence of the original lesions).This is very important when a 
patient's baseline lesion shows partial or complete response. For example, a case of 
necrosis of a liver lesion may be identified as a new cystic lesion on CT, but it is not. 
New lesions detected in the follow-up and not detected in the baseline will be 
considered as new lesions. For example, if a patient with visceral lesions found at 
baseline has metastases when he has a CT or MRI cranial examination, the patient's 
intracranial metastases will be considered as the basis for disease progression, even if 
he does not have a cranial examination at baseline. 
If a new lesion is unclear, such as due to its small shape, further treatment and 
follow-up evaluation are needed to confirm whether it is a new lesion. If repeated 
examinations confirm that it is a new lesion, the time of disease progression should be 
counted from the time of its initial discovery. 
FDG-PET evaluation of lesions generally requires additional detection for 
supplementary confirmation. It is reasonable to combine FDG-PET and CT findings 
to evaluate the progress (especially for new suspicious diseases). FDG-PET can be 
used to confirm the new lesions, according to the following procedures: 
The baseline FDG-PET was negative, and the follow-up FDG-PET was positive, 
indicating the progression of the disease. 
No baseline FDG-PET was performed, and the subsequent FDG-PET results 
were positive 
If the follow-up FDG-PET positive results show that new lesions are consistent 
with CT findings, it is proved that the disease is progressing. 
If the follow-up FDG-PET positive results found new lesions can not be 
confirmed by CT examination results, it needs to be confirmed by CT (if confirmed, 
the time of disease progression starts from the abnormal findings of previous FDG-


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PET). 
If the positive results of FDG-PET follow-up are consistent with the existing 
lesions examined by CT, and the lesions have no progress in imaging detection, then 
the disease has no progress. 
2.4 Evaluation of the best overall efficacy 
The best overall efficacy evaluation is the best efficacy record from the 
beginning of the trial to the end of the trial, taking into account any necessary 
conditions for confirmation. Sometimes the curative effect reaction appears after the 
treatment, so the scheme should make clear whether the curative effect evaluation 
after the treatment is considered in the best overall curative effect evaluation. The 
protocol must define how the new treatment affects the best response before any 
progression. The best response depends on the results of target and non-target lesions 
and the performance of new lesions. In addition, it also depends on the nature of the 
trial, the requirements of the protocol and the criteria for measuring the results. 
Specifically, in non-randomized trials, efficacy response is the primary objective, and 
efficacy confirmation of PR or Cr is necessary to determine which is the best overall 
response. 
2.4.1 Point in time response 
It is assumed that there will be therapeutic response at specific time points of 
each protocol. Table 1 provides a summary of the overall response at each time point 
for a population of patients with measurable disease at baseline. 
If the patient has no measurable lesions (no target lesions), the assessment can be 
seen in Table 2. 
2.4.2 Missing lesions evaluations and non-evaluative explanations 
If there is no imaging or measurement of the lesion at a specific point in time, the 
patient cannot be evaluated at that point in time. If only part of the lesions can be 
evaluated in a single evaluation, this situation is usually regarded as no evaluation can 
be made at any time point, unless there is evidence that the missing lesion will not 
affect the evaluation of response at a given time point. This is likely to happen in the 
case of disease progression. For example, a patient has 3 total number of lesions 50 
mm, but only 2 lesions can be evaluated, the total is 80 mm, and the patient will be 
evaluated as disease progression, regardless of the impact of the missing lesions. 
2.4.3 Optimal total response: all time points 


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Once all the data of the patient are available, the optimal total response can be 
determined. 
Evaluation of the best overall response when the study does not need to confirm 
complete or partial response: the best response in the trial was the best response at all 
time points(for example, a patient is evaluated as SD in the first cycle, PR in the 
second cycle, and PD in the last cycle, but the best total response is PR. when the best 
overall response is SD, it must meet the minimum time from baseline specified in the 
protocol. If the criteria for the shortest time are not met, even the best overall response 
evaluation is SD, it is not recognized The best overall response of the patient will 
depend on subsequent evaluation. For example, a patient was evaluated as SD in the 
first cycle and PD in the second cycle, but it did not meet the minimum time 
requirement of SD, and the best overall response was PD. The loss of follow-up for 
the same patients who were evaluated as SD in the first cycle would be considered as 
non evaluable. 
When the study needs to confirm the complete or partial response, the 
assessment of the best total response: complete or partial remission can be declared 
only when each subject meets the criteria of partial or complete remission specified in 
the trial and is confirmed again at a subsequent time point (usually four weeks later) 
specifically mentioned in the protocol. In this case, see Table 3 for the best total 
response. 
2.4.4 Special tips for efficacy evaluation 
When nodular lesions are included in the total target lesion assessment and the 
nodule size is reduced to "normal" size (< 10 mm), they still have a lesion size scan 
report. In order to avoid overestimation of the situation reflected by the increase in 
nodule size, the measurement results will be recorded even if the nodule is normal. As 
mentioned earlier, this means that subjects with complete remission will not have a 
zero on the CRF table. 
Repeated "unmeasurable" time points will complicate the assessment of optimal 
efficacy if efficacy confirmation is required during the trial. The analysis plan of the 
trial must state that these missing data / assessments can be explained clearly in 
determining efficacy. For example, in most trials, the response of a subject's PR-NE-
PR can be regarded as the confirmation of curative effect. 
Symptomatic progression should be reported when the subject's overall health 


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deterioration requires discontinuation of treatment, but there is no objective evidence 
to prove it. Objective progress should be evaluated as far as possible even after the 
termination of treatment. Symptomatic deterioration is not an evaluative description 
of an objective response: it is the reason for discontinuation of treatment. The 
objective response of such subjects will be evaluated by the target and non-target 
lesions shown in Tables 1 to 3. 
Defined as early progression, early death and non-evaluable conditions are 
special cases of the study and should be clearly described in each protocol (depending 
on treatment interval and treatment cycle). 
In some cases, it is difficult to distinguish local lesions from normal tissues. 
When the assessment of complete response is based on such a definition, we 
recommend that biopsy be performed prior to the evaluation of the efficacy of 
complete remission of local lesions. FDG-PET was used to evaluate the efficacy of 
complete remission when abnormal imaging results of local lesions in some subjects 
were considered to represent focal fibrosis or scar formation. In this case, the 
application of FDG-PET should be prospectively described in the protocol, and 
supported by the reports of specialized medical literature on this situation. However, it 
must be realized that the limitations of FDG-PET and biopsy (including the resolving 
power and sensitivity of both) will lead to false positive results in complete remission 
assessment. 
Evaluation at each time point - subjects with target lesions (including or without non target lesions) 
Target lesion 
Non target lesions 
New lesions 
Total remission 
CR 
CR 
Non 
CR 
CR 
Non PD / non CR 
Non 
PR 
CR 
Cannot be evaluated 
Non 
PR 
PR 
Not progressing or fully evaluated 
Non 
PR 
SD 
Not progressing or fully evaluated 
Non 
SD 
Not fully evaluated 
Non progress 
Non 
NE 
PD 
Any situation 
Yes or non 
PD 
Any situation 
PD 
Yes or non 
PD 
Any situation 
Any situation 
Yes 
PD 


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CR = complete 
remission 
PR = partial remission 
SD = stable 
disease 
PD = disease progression 
NE = cannot be evaluated 
Evaluation at each time point - subjects with non-target lesions only 
Non target lesions 
New lesions 
Total remission 
CR 
Non 
CR 
Non CR or non PD 
Non 
Non CR or non PD 
Not fully evaluated 
Non 
Cannot be evaluated 
Indeterminate PD 
Yes or Non 
PD 
Any situation 
Yes 
PD 
Note: for non-target lesions, "non CR / non PD" refers to better efficacy than SD.As the SD is increasingly used as an end point 
for evaluating efficacy, non CR / non PD outcomes are developed  to address the absence of measurable lesions. 
For unclear progression findings (such as very small, uncertain new lesions; 
cystic or necrotic lesions of the original lesions), treatment can continue until the next 
evaluation. If disease progression is confirmed in the next assessment, the date of 
progression should be the date of previous suspected progression. 
The best overall efficacy of CR and PR needs to be confirmed 
The first time point with 
total remission 
The after  time point 
with total remission 
The best total remission 
CR  
CR  
CR 
CR  
PR 
SD，PD or PRa 
CR 
SD 
SD if it lasts long enough, PD otherwise 
CR 
PD 
SD if it lasts long enough, PD otherwise 
CR 
NE 
SD if it lasts long enough, NE otherwise 
PR 
CR 
PR 
PR 
PR 
PR 
PR 
SD 
SD 
PR 
PD 
SD if it lasts long enough, PD otherwise 
PR 
NE 
SD if it lasts long enough, NE otherwise 
NE 
NE 
NE 


Protocol No. BPL-Nim-PC-1 
Version date: June 16,2014 
 Version 1.1 
 
Note: CR is complete remission, PR is partial remission, SD is disease stability, PD is disease progression, NE is not evaluable. 
Superscript "a": if CR really occurs at the first time point and any disease occurs at a subsequent time point, even if the subject's 
efficacy meets the PR criteria relative to the baseline, the efficacy evaluation at the later time point is still PD (because the 
disease will recur after CR).The best response depends on the presence of SD within the shortest treatment interval. However, 
sometimes CR was evaluated for the first time, but subsequent time point scanning showed that small lesions still appeared. 
Therefore, in fact, the curative effect of subjects should be PR rather than CR at the first time point. In this case, the first CR 
judgment should be modified to PR, and the best response is PR. 
2.5 Frequency of tumor reassessment 
The frequency of tumor re-evaluation during treatment depends on the treatment 
plan and should be consistent with the type and schedule of treatment. However, in 
phase II trials where the benefit of treatment is not clear, it is reasonable to follow up 
every 6-8 weeks (the time design is at the end of a cycle), and the length of time 
interval can be adjusted under special programs or circumstances. The protocol should 
specify which tissue sites need to be evaluated at baseline (usually those that are most 
likely to be closely related to the metastatic lesions of the tumor type studied) and the 
frequency of evaluation repetition. Under normal circumstances, target lesions and 
non target lesions should be evaluated at each evaluation. In some optional cases, the 
evaluation frequency of some non target lesions can be smaller. For example, if the 
curative effect evaluation of the target disease is confirmed as CR or the progression 
of bone lesions is suspected, bone scan is required. 
At the end of treatment, re-evaluation of the tumor depends on whether the 
response rate or the time to an event (progression / death) is taken as the end point of 
the clinical trial. If it is the time of occurrence (e.g. TTP / DFs / PFS), it is necessary 
to conduct the routine repeated evaluation specified in the protocol. Especially in 
randomized controlled trials, the scheduled evaluation should be listed in the schedule 
(e.g. 6-8 weeks in the treatment or 3-4 months after the treatment), and should not be 
affected by other factors, such as treatment delay, administration interval and any 
other events that may lead to unbalanced treatment arm in the selection of disease 
evaluation time. 
2.6 Efficacy evaluation / confirmation of remission 
2.6.1 confirm 
For non-randomized clinical studies with efficacy as the main end point, the 
efficacy of PR and CR must be confirmed to ensure that the efficacy is not the result 
of evaluation error. This also allows for a reasonable interpretation of the results when 
historical data are available, but the efficacy in the historical data of these trials should 


Protocol No. BPL-Nim-PC-1 
Version date: June 16,2014 
 Version 1.1 
 
also be confirmed. But in other cases, such as randomized trials (phase II or phase III) 
or studies with disease stability or disease progression as the primary endpoint, 
efficacy confirmation is no longer required because it is not valuable for the 
interpretation of trial results. However, the elimination of the requirement of efficacy 
confirmation will make the central review of prevention of deviation more important, 
especially in non-blind experimental studies. 
In the case of SD, at least one measurement meets the SD standard specified in 
the protocol within the shortest time interval (generally no less than 6-8 weeks) after 
the start of the trial. 
2.6.2 The total remission period 
The total remission period is the time from the first measurement of CR or PR 
(whichever is measured first) to the time when the disease relapse or progression is 
first recorded (the minimum measurement recorded in the trial is used as a reference 
for disease progression).The total complete remission time was the time from the first 
time the CR criteria were measured to the time when the disease relapsed or 
progressed. 
2.6.3 Stable period of disease 
It is the time from the beginning of treatment to the progression of disease (in 
randomized trials, from the time of randomization), with the smallest sum in the trial 
as the reference (if the baseline sum is the smallest, it is used as the reference for PD 
calculation).The clinical relevance of stable disease varies with different studies and 
diseases. If, in a particular trial, the proportion of patients who maintain the shortest 
stable period is taken as the end point, the protocol should specify the shortest time 
interval between the two measurements in SD definition. 
Note: remission, stabilization and PFS are affected by the frequency of follow-up after baseline evaluation. The definition 
of standard follow-up frequency is not within the scope of this guideline. The frequency of follow-up should consider many 
factors, such as disease type and stage, treatment cycle and standard specification. However, if the comparison between tests is 
needed, the limit of accuracy of these measurement end points should be considered. 


Protocol No. BPL-Nim-PC-1 
Version date: June 16,2014 
 Version 1.1 
 
APPENDIX 4 Clinical benefit response (CBR) 
CBR included pain (intensity of pain and consumption of analgesics), PS 
(performance status, evaluated according to KPS) and weight changes. 
Clinical benefit assessment classification 
Main evaluation criteria: 
Pain 
①Pain intensity (assessed daily with MPAC 0-100 visual analogue scale)
Positive: improvement ≥ 50% compared with baseline and lasting for ≥ 4 weeks (assuming minimum 
pain score ≥ 20) 
Negative: any deterioration compared with baseline lasted for 4 weeks 
Stable: any other results 
②Consumption of analgesics (evaluated according to the consumption of equivalent dose of morphine, once a
week) 
Positive: compared with baseline, the consumption of analgesic drugs was more than or equal to 50%, 
and the minimum improvement was ≥ 10% 
Negative: any deterioration compared with baseline lasted for 4 weeks 
Stable: any other results 
KPS physical status score: once a week 
Positive: KPS 50, 60, 70 patients, compared with the baseline, the improvement was more than 20 KPS 
score, and lasted for more than 4 weeks 
Negative: any deterioration ≥ 20 KPS score compared with baseline and lasting for more than 4 weeks 
Stable: any other results 
Secondary evaluation criteria: Weekly evaluation 
Weight 
Positive: weight gain > 7% (non-fluid retention) compared with baseline and lasting for more than 4 
weeks 
Non positive: any other results 
According to the standard[13]developed by Burris et al., the classification of CBR was
evaluated. Effective: there is at least one positive improvement in the CBR index 
(pain, physical status or weight change) and no negative indicator is found, which can 
be rated as a clinical benefit case. Stable: pain, physical condition or weight change 
were rated as stable; Invalid: one of the three indicators was aggravated.


Protocol No. BPL-Nim-PC-1 
Version date: June 16,2014 
 Version 1.1 
 
APPENDIX 5: 
NYHA classification 
NYHA classification: the classification of heart failure, NYHA classification is 
based on the degree of activity of inducing heart failure symptoms, the damage of 
cardiac function is divided into four grades. This protocol was proposed by the New 
York Heart Association (NYHA) in 1928.In fact, NYHA classification is actually a 
classification of severity of symptoms in patients with stage C and stage D. 
Grade I: Patients with heart disease, but the amount of daily activities is not 
limited, general physical activities do not cause excessive fatigue, palpitations, asthma 
or angina pectoris. 
Grade II: the physical activity of patients with heart disease is slightly limited. 
There are no conscious symptoms at rest. General physical activity causes excessive 
fatigue, palpitation, asthma or angina pectoris. 
Grade III: Patients with heart disease, so that physical activity is significantly 
restricted. Rest without symptoms, but less than general physical activity can cause 
excessive fatigue, palpitations, asthma or angina pectoris. 
Grade IV: Patients with heart disease can not engage in any physical activity, and 
have symptoms of heart failure in resting state, which aggravates after physical 
activity. 
AHA supplement to the 1928 NYHA classification grade of cardiac function 
(1994) 
According to ECG, exercise load test, X-ray, echocardiography, radiology and 
other objective examination results, the second classification was made. 
Grade  A: objective evidence of no cardiovascular disease 
Grade  B: objective evidence of mild cardiovascular disease; 
Grade  C: objective evidence of moderate cardiovascular disease; 
Grade  D: objective evidence of severe cardiovascular disease 


Protocol No. BPL-Nim-PC-1 
Version date: June 16,2014 
 Version 1.1 
 
Signature page 
Scheme No.: BPL-Nim-PC-1 
Protocol Title: a prospective, randomized, double-blind, multicenter clinical trial of 
nimotuzumab combined with gemcitabine versus placebo plus gemcitabine in the 
treatment of locally advanced or metastatic pancreatic cancer of wild type K-RAS 
Trial drug: nimotuzumab injection 
All parties stated that the clinical trial protocol was jointly formulated by the sponsor, 
the researcher and the statistician. I agree to perform my duties in accordance with the 
provisions of the declaration of Helsinki and the code for quality management of 
clinical trials of drugs, and conduct this clinical trial in strict accordance with the 
requirements of the clinical trial protocol. 


60/ 61 


Protocol No. BPL-Nim-PC-1 
Version date: June 16,2014 
 Version 1.1 
 

SAP_001.pdf: 
NMPA clinical trial approval No. 2011L01239    
                                 Project No. EY140810       
Statistical Analysis Plan for Prospective, Randomized Controlled, Double-Blind, Multicenter Registered Clinical Studies of Nimotuzumab (Taxinsheng
®) Plus 
a
Gemcitabine versus Placebo Plus Gemcitabine in K-RAS Wild-Type Locally 
Advanced or Metastatic Pancreatic Cancer 
(TFLs Template)  
Sponsor: Baitai biopharmaceutical Co., Ltd                     
Beijing biovoice Technology Co., Ltd 
Tel: (86) 10-6758 7407, 6753 8432 
Address: room 2-2209, Shidai Fengfan building, No.15, Majiapu West Road, 
Fengtai District, Beijing 
Version: 2021-12-10 


MPA
 
 
clinical trial approval No. 
2011
L
01239                                     
Project No. EY140810 
 
  
 
 
 Statistical 
Analysis Plan for Prospective, Randomized Controlled, 
Double
-
Blind, Multicenter Registered Clinical Stu


Statistical Analysis Plan 
Beijing bozhiyin 
catalog 
List of abbreviations .......................................................................................................2 
1 
Study topics ................................................................................................................ 3 
2 
Purpose of the trial ..................................................................................................... 3 
2.1 Primary endpoint ................................................................................................ 3 
2.2 Secondary endpoint ............................................................................................ 3 
3 
Study design ............................................................................................................... 3 
3.1 Overall design ..................................................................................................... 3 
3.2 Multicenter .......................................................................................................... 3 
3.3 Central random ................................................................................................... 3 
3.4 Control drug selection ......................................................................................... 4 
3.5 Blind method ...................................................................................................... 4 
3.6 Sample size ......................................................................................................... 4 
4 
Study drug and administration method ...................................................................... 4 
4.1 Study drug ........................................................................................................... 4 
4.2 Grouping and administration method ................................................................. 5 
4.3 Combination therapy .......................................................................................... 5 
5 
Efficacy and safety evaluation ................................................................................... 5 
5.1 Evaluation of efficacy ......................................................................................... 5 
5.1.1 Primary endpoint .......................................................................................... 5 
5.1.2 Secondary endpoint ...................................................................................... 6 
5.2 Efficacy evaluation criteria ................................................................................. 6 
5.3 Definition of efficacy evaluation index .............................................................. 6 
5.4 Safety evaluation ................................................................................................ 7 
6 
Statistical analysis ...................................................................................................... 8 
6.1 Statistical content / method change of the scheme ............................................. 8 
6.2 Hypothesis test .................................................................................................... 8 
6.3 Sample size estimation ....................................................................................... 8 
6.4 Statistical analysis data set .................................................................................. 8 
6.5 Contents and methods of statistical analysis ...................................................... 8 
6.5.1 General considerations ................................................................................. 8 
6.5.2 Data definition and processing ..................................................................... 9 
6.5.3 Case distribution analysis ........................................................................... 12 
6.5.4 Demographic data and baseline analysis .................................................... 12 
6.5.5 Analysis of drug compliance and drug combination .................................. 13 
6.5.6 Efficacy analysis ........................................................................................ 13 
6.5.7 Safety analysis ............................................................................................ 15 
6.6 Interim analysis ................................................................................................. 17 
Appendix 1: EY140810_Clinical study of nimotuzumab combined with gemcitabine in 
the treatment of pancreatic cancer SAP_1.0_20211210 ............................................. 18 


Statistical Analysis Plan 
Beijing bozhiyin 
 
 
List of abbreviations 
abbreviation 
notes 
AE 
Adverse event 
ATC 
Systematic anatomy and chemotherapeutics 
CBR 
Clinical benefit rate 
CI 
Confidence interval 
CR 
Complete response 
CRF 
Case report form 
CS 
Clinical significance with abnormality 
CTCAE 
Terminology of adverse events 
DAS 
Data analysis system 
DCR 
Disease control rate 
eCRF 
Electronic case report form 
FAS 
Full analysis set 
G-CSF 
Granulocyte colony stimulating factor 
HR 
Hazard risk ratio 
IWRS 
Interactive network response system 
MedDRA 
Medical Dictionary of regulatory activities 
NCI 
National Cancer Research Center 
NCS 
No clinical significance with abnormality 
NMPA 
State Drug Administration 
ORR 
Objective response rate 
OS 
Overall survival 
PD 
Disease progression 
PFS 
Disease progression free survival 
PPS 
Compliance set 
PR 
Partial response 
PT 
Preferred term 
RECIST 
Criteria for evaluating the efficacy of solid tumors 
SD 
Stable disease 
SOC 
Systematic organ classification 
SS 
Security set 
TEAE 
Adverse events during treatment 
TTP 
Time of disease progression 
WHO 
World health organization 


Statistical Analysis Plan 
Beijing bozhiyin 
 
 
The combination therapy of nimotuzumab (taixinsheng®)and gemcitabine was compared with placebo 
and gemcitabine: A prospective, randomized, double-blind, multicenter registered clinical study of 
K-RAS wild-type locally advanced or metastatic pancreatic cancer 
 
Statistical Analysis Plan 
This statistical analysis plan is based on the prospective, randomized controlled, double-blind, 
multicenter registered clinical study of nimotuzumab (taixinsheng®)combined with gemcitabine versus 
placebo and gemcitabine in the treatment of K-ras wild-type locally advanced or metastatic pancreatic 
cancer (protocol No.: BPL-nim-pc-1, version date: June 16, 2014, protocol version number: 1.1)and 
electronic case report form (eCRF version date: 2019. eCRF version No.: 1.6) was formulated on July 25, 
2005.The statistical analysis plan will be finalized before the database is locked. 
 
1 Title 
A prospective, randomized, double-blind, multicenter, registered clinical trial of nimotuzumab 
(taixinsheng®)combined with gemcitabine versus placebo plus gemcitabine in the treatment of locally 
advanced or metastatic pancreatic cancer of K-ras wild type.  
 
2 Objective 
2.1 Primary endpoint 
Objective to evaluate and compare the overall survival (OS) of nimotuzumab combined with 
gemcitabine versus placebo plus gemcitabine in the treatment of K-ras wild-type locally advanced or 
metastatic pancreatic cancer. 
 
2.2 Secondary endpoint 
（1） Time to progression (TTP), progression free survival (PFS). 
（2） Objective response rate (ORR), disease control rate (DCR). 
（3） Clinical benefit rate (CBR). 
（4） Objective to evaluate the safety of nimotuzumab combined with gemcitabine (according to 
NCI-CTCAE v4.03). 
 
3 Study design 
3.1 Overall design 
In order to closely observe and scientifically evaluate the efficacy and safety of nimotuzumab 
combined with gemcitabine in the treatment of K-ras wild-type locally advanced or metastatic 
pancreatic cancer, a prospective, randomized, parallel controlled, double-blind, multicenter registered 
clinical trial will be initiated. 
 
3.2 Multicenter 
A number of qualified cancer centers in China will be selected at the same time. 
 
3.3 Central randomization 
Taking into account the following factors, DAS for IWRS will be used to assign random numbers 
and dispense drugs. 
Four stratification factors and factor levels will set up 
 
Tumor location 
 
Head of pancreas 


Statistical Analysis Plan 
Beijing bozhiyin 
 
 
 
Body and tail of pancreas 
 
Have you had surgery 
 
yes 
 
no 
 
Have biliary obstruction been treated 
 
yes 
 
no 
 
Have you received adjuvant chemotherapy 
 
yes 
 
no 
 
3.4 Control drug selection 
In this study, placebo combined with gemcitabine will be used as the parallel control group. 
 
3.5 Blind method 
In this study, a double-blind and single simulation method will be used. The package, shape and 
smell of nimotuzumab simulator will be consistent with those of the trial drug (nimotuzumab) to ensure 
that the subjects and researchers in a blind state during the trial. 
 
3.6 Sample size 
In this study, 276 subjects will be enrolled, 138 in the experimental group and 138 in the control 
group. After communication with CDE(Center for drug evaluation of China), CDE agreed to 
re-estimate the sample size based on the survival data of KRAS wild type pancreatic cancer in pcs07 
study in Germany. the median OS was assumed to be 5.67 months in gemcitabine group (control 
group), and the median OS will be extended to 11.62 months after treatment with nimotuzumab (trial or 
experimental group). The median OS will be up to 24 months and following up for 12 months, 
α=0.05,1-β=80%. Two groups at the ratio of 1:1, and the required sample size is 79 cases, there are 39 
cases in the control group and 40 cases in the trial group. The total number of events is 64, and the final 
analysis can be carried out. There were 36 events in the control group and 28 events in the 
experimental group). 
 
4 Investigational drug and administration method 
4.1 Investigational drug 
Nimotuzumab injection (taixinsheng®, produced by Baitai biopharmaceutical Co., Ltd., is a 
colorless and clear solution with the specification of 50mg/ 10ml / piece (packed in a Xilin bottle).Each 
vial (capacity 13.5ml) contains 10ml of nimotuzumab solution, the concentration of mAb is 5 mg/ ml, 
and the purity is not less than 95%.The composition of each component in the vial is shown in the table 
below. 
Table 4-1 composition and content of nimotuzumab injection 
 
Components 
Content / ml 
Content / 10.0 ml 
Monoclonal antibody against h-R3 
5 mg 
50 mg 
Sodium dihydrogen phosphate 
0.45 mg 
4.5 mg 
Sodium phosphate 
1.8 mg 
18.0 mg 
Sodium chloride 
8.69 mg 
86.9 mg 
Polysorbate 80 
0.2 mg 
2.0 mg 


Statistical Analysis Plan 
Beijing bozhiyin 
 
 
Note: except that h-R3 monoclonal antibody is not included in placebo, other ingredients, appearance and specifications are the same 
as those of nimotuzumab injection. 
 
The product should be stored at 2-8 ℃, and freezing is strictly prohibited. After dilution in 
normal saline, it can keep stable for 12h at 2-8 ℃ and 8h at room temperature. If the diluted solution is 
stored for more than the above time, it should not be used. 
The trial drugs nimotuzumab injection / placebo and gemcitabine are provided by Baitai 
biopharmaceutical Co., Ltd. for free, including labels and packages for clinical trials. 
 
4.2 Grouping and administration method 
The trial will be divided into two groups: the experimental group received nimotuzumab + 
gemcitabine treatment, while the control group received placebo (nimotuzumab simulator) + 
gemcitabine. 
 
（1） Nimotuzumab injection / placebo: 400mg / week, intravenous drip, infusion time 60 minutes 
or more, Once a week, to until the disease progressed or intolerable toxicity occurrs, or the 
subject asks to withdraw from the trial. 
Usage: 400 mg (8 pieces) of nimotuzumab injection / placebo will be added into 250 ml sterile 
normal saline for dilution, and the intravenous drip time is not less than 60 min. the patient's condition 
should be closely monitored during the course of administration and within 1 hour after the end of 
administration. In addition to sterile normal saline, nimotuzumab solution should not be mixed with 
any intravenous infusion drugs. 
（2） Gemcitabine: 1000mg / m2, intravenous drip for no less than 30 minutes, continuous use 
for 3 weeks, rest for 1 week (D1, 8, 15. Q28 days), every 4 weeks as a cycle, until the disease 
progression or intolerable toxic reaction, or the subject asks to withdraw from the trial. 
Usage: each bottle (containing gemcitabine 200mg or 1000mg) should be injected with 5ml or 
25ml sterile normal saline at least (containing gemcitabine concentration ≤ 40mg / ml), shaking to 
dissolve. The required dosage can be further diluted with sterile normal saline. The prepared gemcitabine 
solution should be stored at room temperature and used within 24 hours. Gemcitabine solution should 
not be refrigerated to prevent crystallization. According to the solubility of the drug, the concentration of 
the diluted drug should not exceed 40mg / ml. if the concentration is greater than 40mg / ml, it may lead 
to incomplete dissolution of the drug, which should be avoided. 
At the first treatment, nimotuzumab / placebo should be given on the same day as gemcitabine, 
and then gemcitabine should be given 1 hour after the end of nimotuzumab / placebo infusion. Since 
then, nimotuzumab / placebo and gemcitabine will be treated on the same day in the same order as 
before. 
 
4.3 Combination therapy 
During the study period, the drugs that can be used together according to the needs are as follows: 
Adjuvant therapy, including prophylactic drugs, such as blood component transfusion, 
granulocyte colony-stimulating factor (G-CSF), antidiarrheal, antiemetic and analgesic drugs, are 
allowed and can be operated according to the clinical routine of each center. 
When the adverse events caused by the trial drug need to be treated, the drugs for symptomatic 
treatment can be given. 
Symptomatic treatment of skin toxicity, including softeners or other topical drugs, analgesics and 
vitamins B6, etc. 
When the patient has other symptoms, it can be treated with drugs. 
 
5 Efficacy and safety evaluation 
5.1 Evaluation of efficacy 
5.1.1 Primary endpoint 
Overall survival time (OS). 


Statistical Analysis Plan 
Beijing bozhiyin 
 
 
5.1.2 Secondary endpoint 
1) Time to progression (TTP). 
2) Progression free survival (PFS). 
3) Objective response rate (ORR). 
4) Disease control rate (DCR). 
5) Clinical benefit rate (CBR). 
 
5.2 Efficacy evaluation criteria 
According to RECIST 1.1 standard, the patients will be divided into complete response (CR), 
partial response (PR), stable disease (SD) and progressive disease (PD).The response evaluation will be 
conducted every 8 weeks. If the patient achieved CR or PR, the efficacy should be confirmed 4 weeks 
after the first evaluation. 
Partial or incomplete tumor evaluation will not be included in TTP, PFS, ORR, DCR unless the 
observable lesions have been evaluated as progression (according to RECIST1.1). 
 
5.3 Definition of efficacy evaluation criteria 
 
Overall survival (OS) refers to the time from randomization to death due to any cause. 
For patients who are still alive as of the date of analysis or those who have lost follow-up for 
which there is no evidence to prove that they have died, the date of last contact with them 
(the last confirmed survival date) or the analysis cutoff date (whichever occurs first) shall be 
taken as the censor date. 
 
 
Time to disease progression (TTP): defined as the time (days) between the date of 
randomization and the first observation of disease progression (imaging or clinical progress, 
whichever is earlier).The actual date of tumor evaluation will be used for calculation. The 
time to progression for patients who will not progress at the time of analysis or death will be 
calculated as the date of the last tumor evaluation. 
 
 
Progression free survival (PFS): defined as the time from the beginning of randomization to 
progression or all-cause death. Progression free survival defined as the time from 
randomization to death in patients who will die of any other cause before disease progression. 
Patients without progression or death (i.e., progression free survival) at the time of the last 
tumor assessment will be used as the end point. 
 
 
Objective response rate (ORR): calculated from the day of the first administration, including the 
percentage of CR and PR subjects in all enrolled subjects (data will be calculated according to 
the best response in the whole study period).For patients with complete or partial response for 
the first time, the efficacy should be confirmed after 4 weeks. 
 
The imaging results will be evaluated according to RECIST Standard Version 1.1. 
Complete response (CR): all target lesions will be disappeared, and the short diameter of all 
pathological lymph nodes (including target and non-target nodules) must be reduced to < 10 
mm. 
Partial response (PR): the sum of the target lesion diameters will be reduced by at least 30% from 
baseline. 
Disease progression (PD): Taking the minimum value of the sum of all measured target 
lesion diameters during the whole study period as reference, the relative increase of diameter 
sum will be at least 20% (if the baseline measurement value is the minimum, the baseline 
value is used as reference).In addition, an increase of at least 5 mm in the absolute value of 
diameter sum must be satisfied (the presence of one or more new lesions is also considered 
as disease progression). 


Statistical Analysis Plan 
Beijing bozhiyin 
 
 
 
 
Disease control rate (DCR): the best overall assessment is the proportion of patients with 
confirmed complete and partial response and stable disease. For patients with stable disease, 
at least one lesion evaluation should meet the SD criteria at least 6 weeks after medication. 
 
 
Clinical benefit rate(CBR): Only symptomatic patients will be evaluated in the study, 
including pain (intensity of pain and consumption of analgesics), PS (performance status, 
evaluated according to KPS), and weight change.  
 
Symptomatic pancreatic cancer is defined as having at least one of the following 
manifestations at baseline: 
1) 
KPS 60 or 70. 
2) 
They shall receive morphine / opioid analgesia. 
3) 
The pain score is more than 20 points on MPAC pain visual analog scale. 
If the patients are in asymptomatic at the time of admission, and having the above 
symptoms during the treatment, the evaluation of CBR will be started when the symptoms occurs . 
 
Clinical benefit assessment classification 
Main evaluation criteria: 
Pain 
① Pain intensity (assessed daily with MPAC 0-100 visual analogue scale) 
Positive: improvement ≥ 50% compared with baseline and lasting for ≥ 4 weeks (assuming 
minimum pain score ≥ 20) 
Negative: any deterioration compared with baseline lasted for 4 weeks 
Stable: any other results 
② Consumption of analgesics (evaluated according to the consumption of equivalent dose of 
morphine, once a week) 
Positive: improvement ≥ 50% compared with baseline and lasting for ≥ 4 weeks (assuming 
minimum analgesic consumption ≥ 10) 
Negative: any deterioration compared with baseline lasted for 4 weeks 
Stable: any other results 
KPS physical status score: once a week 
Positive: KPS 50, 60, 70 patients, compared with the baseline, the improvement was more than 
20 points, and lasted for more than 4 weeks 
Negative: any deterioration ≥ 20 points compared with baseline and lasting for more than 4 
weeks 
Stable: any other results 
Secondary evaluation criteria: Weekly evaluation 
Weight 
Positive: weight gain > 7% (non-fluid retention) compared with baseline and lasting for more 
than 4 weeks 
Non positive: any other results 
 
According to the standards developed by Burris et al 
1) There is at least one positive index of body weight. 
2) Stable: pain, physical condition or weight change are rated as stable. 
3) Invalid: one of the three indicators is aggravated. 
 
5.4 Safety evaluation 
1) Adverse events (AE) include TEAE / ADR, SAE / SADR, TEAE / ADR leading to drug 
reduction, TEAE / ADR leading to drug withdrawal, TEAE / ADR leading to drug increment, 
TEAE / ADR leading to death and TEAE / ADR leading to withdrawal. 
 
2) Routine safety parameters (including vital signs, physical examination, laboratory examination 
(including blood routine examination, physical examination, laboratory examination, etc 


Statistical Analysis Plan 
Beijing bozhiyin 
 
 
Electrolytes, blood biochemistry, Serum CA19-9, urine routine test) and electrocardiogram 
(ECG). 
 
6 Statistical analysis 
6.1 Statistical content / method change of the protocol 
 
Sample size: after consulting CDE and obtaining approval, the sample size is adjusted according 
to external literature data. 
 
Handling of missing value: in the protocol, when the primary efficacy variables are missing, 
last observation carried forward (LOCF) cannot be implemented, and it is adjusted to section 
6.5.2.2 of SAP. 
 
6.2 Hypothesis test 
H0(invalid 
hypothesis):H1=H2, 
H1(alternative hypothesis): 
H1≠ H2, 
H1 is the hazard ratio of the experimental group, H2 is the hazard ratio of the control group. 
 
6.3 Sample size estimation 
After communication with CDE, CDE agreed to re-estimate the sample size based on the survival 
data of K-RAS wild type pancreatic cancer in pcs07 study in Germany: the median OS is assumed to be 
5.67 months in gemcitabine group (control group), and the median OS will be extended to 11.62 
months after treatment with nimotuzumab (trial Group). The median OS is 24 months and following up 
for 12 months, α=0.05,1-β=80%, trial group and control group are divided into two groups at the ratio 
of 1:1, and the required sample size is 79 cases, There are 39 cases in the control group and 40 cases in 
the study group. The total number of events is 64, and the final analysis can be carried out 
There are 36 events in the control group and 28 events in the experimental group). 
 
6.4 Statistical analysis data set 
 
Full analysis set (FAS): all the cases that are randomized into groups, using the study drug at 
least once, and having the efficacy evaluation data of post medication at least once. 
Those that do not meet the key inclusion criteria (items 3 and 6) will be excluded from FAS. 
 
 
Compliance protocol set (PPS): refers to the set of cases that meeting the inclusion criteria, 
do not meet the exclusion criteria, and complete the treatment, i.e. analyze the cases that 
meets the trial protocol, has good compliance, and completes the contents specified in CRF 
(PP analysis).PP analysis will be mainly used for the primary efficacy endpoint. 
 
 
Safety data set (SS): all patients who receive at least one dose of the study drug. This analysis set 
will be used for the safety analyses.. 
 
6.5 Contents and methods of statistical analysis 
6.5.1 General considerations 
 
All analyses will be conducted using SAS version 9.4 version. 
 
The default significance level will be two-sided 5%. Two-sided 95% confidence intervals 
will be presented and all tests will be two-sided, unless otherwise specified in the description 
of the analyses.. 
 
Since there are more than 20 centers involved in this study, it is anticipated that subject 
accrual will be sparse across centers and hence it is not necessary to include center effect in 
statistical modelling.  
 
The continuous variables will be described by number of subjects (n), means, standard 
deviation, median, 25th and 75th percentiles (Q1, Q3), minimum and maximum value, while 
the count data will be described by count(s) and percentages (%).. 
 
Unless otherwise specified, the decimal places of the minimum and maximum values shall 
be consistent with the original data recorded in the database, if the raw value has x decimal 
places, then the mean and the median and quartiles will have x+1 decimal places, the 
standard deviation will have x+2 decimal places. 


Statistical Analysis Plan 
Beijing bozhiyin 
 
 
The number of decimal places of all statistical data shall not exceed three. 
 
Percentage (%) : retain 1 decimal place, the second digit is rounded, for example, 52.34% is 
recorded as 52.3%, 0% is directly recorded as 0. 
 
6.5.2 Data definition and processing 
6.5.2.1 Date missing 
Missing date of first diagnosis of pancreatic cancer 
The imputation of partial dates will follow the following rules: 
 
If year, month and the data are all missing, do not impute.  
 
If only year of the date is known, month and day would be imputed as July 1st. 
 
If year and month of are known but the day of date is unknown, day will be imputed as 15. 
 
 
 
Previous / concomitant medication, concomitant treatment date missing, start date missing: 
 
If year, month and the data are all missing, do not impute.  
 
If only year of the date is known, month and day would be imputed as July 1st. 
 
If year and month of are known but the day of date is unknown, day will be imputed as 15. 
 
 
 
AE date missing 
AE start date missing: 
 
If the start date is completely missing, and the year (year only) or year / month (year / month 
only) is the same as the first treatment date, fill in with the minimum value of the first 
treatment date and AE end date. 
 
Otherwise, fill in the missing date and month with 1 day and 1 month. 
AE end date missing: 
 
If only the date is missing, if the patient's death and death month are the same as AE month 
and the date of death is missing, the last day of the month shall be filled in. otherwise, the 
date of death shall be used. 
 
If the date and month are missing, when the year and the last visit year are the same, the 
date of the last visit shall be used to fill in, and when the year is different, it shall be filled 
with December 31. 
 
Other cases are not filled in. 
 
Date of death missing 
If the subject is determined to have died, but the date of death is missing, it can be filled 
according to the following filling rules: 
 
If the date, year, and day are missing, they are filled with (last confirmed survival date + 1) 
 
If the day is missing, or the month and day are missing, fill in with the latest of the following 
dates 
（1） Last confirmed survival date + 1 
（2） If only the day is missing, the first day of the year is used. If both the month and day 
are missing or only the month is missing, the January 1 of the year in which the month 
is not missing is used 
 
New anti-tumor treatment date missing 


Statistical Analysis Plan 
Beijing bozhiyin 
 
 
Judgment criteria of anti-tumor treatment: the reasons of combined drug use are: anti-tumor 
treatment, anti-tumor, anti-tumor of traditional Chinese medicine, pancreatic cancer, tumor 
chemotherapy. 
Missing start date of new anti-tumor therapy 
For patients with progression, the relationship between the start date of new anti-tumor treatment 
and the date of progression should be collected as far as possible, and then filled in according to the 
following methods: 
 
If the start date of new anti-tumor treatment is after the progress, fill in with the latest of the 
following dates: 
（1） Progress date + 1 
（2） If only the day is missing, the first day of the year is used. If both the month and day 
are missing or only the month is missing, the January 1 of the year in which the month 
is not missing is used 
 
If the start date of the new anti-tumor treatment is before the progress, fill in with the earliest 
of the following dates: 
（1） Progress date-1 
（2） If only the day is missing, the first day of the year is used. If both the month and day 
are missing or only the month is missing, the January 1 of the year in which the month 
is not missing is used 
 
If the relationship between the start date of new anti-tumor treatment and the date of 
progression cannot be judged, the latest of the following dates shall be used for filling: 
（1） Progress date + 1 
（2） If only the day is missing, the first day of the year is used. If both the month and the 
day are missing or only the month is missing, the January 1 of the year without missing 
is used 
For subjects who will do not make progress, 
 
If the start date of the new anti-tumor treatment is after the date of the last imaging 
examination, fill in with the latest of the following dates: 
（3） Date of last imaging examination + 1 
（4） If only the day is missing, the first day of the year is used. If both the month and day 
are missing or only the month is missing, the January 1 of the year in which the month 
is not missing is used 
 
If the start date of the new anti-tumor treatment is before the date of the last imaging 
examination, fill in with the earliest of the following dates: 
（3） Date of last imaging examination - 1 
（4） If only the day is missing, the first day of the year is used. If both the month and day 
are missing or only the month is missing, the January 1 of the year in which the month 
is not missing is used 
 
If the relationship between the start date of the new anti-tumor treatment and the date of the 
last imaging examination cannot be judged, the earliest of the following dates should be 
filled in: 
（3） Date of last imaging examination + 1 
（4） If only the day is missing, the first day of the year is used. If both the month and the 
day are missing or only the month is missing, the January 1 of the year without missing 
is used 
For the cases of monthly and daily missing or only monthly missing, special care should be taken. 
Before filling with the 1st January of the year not missing, all relevant information (including remarks) 
that can be collected should be consulted to see if there are other more accurate dates that may be used 
for filling. 
 
New treatment end date missing 
The missing end date of new anti-tumor therapy will be not filled in. 
 
The dates in the data list are listed according to what is written on the CRF. 


Statistical Analysis Plan 
Beijing bozhiyin 
 
 
6.5.2.2 Missing value procession 
The missing data is not filled, and the actual data obtained is used for analysis. See 6.5.2.4 for 
censored rules. 
 
6.5.2.3 Baseline definition 
Unless otherwise specified, the baseline assessment refers to the last non- missing assessment before 
the first administration of the study drug. 
 
6.5.2.4 Data derivation and conversion 
 
The duration of pancreatic cancer (month) = (signing date of informed consent - date of first 
diagnosis of pancreatic cancer + 1) / 30.4375, rounding up or down to one decimal place. 
 
Age (yr) = int(date of signing informed consent - date of birth + 1) / 365.25, rounding down. 
 
The overall survival time (OS) (month) = (all cause death date /censor date - random date + 1) 
/ 30.4375, rounding up or down to one decimal place. For the lost subjects who will do not 
observe the death outcome, the date of the last recorded contact with the subjects will be taken 
as the censor date. For the subjects who will still survive at the time point of the final analysis, 
the last contact date will be used as the censor date. 
 
Progression free survival (PFS) (month) = (progression date / all cause death date / censor date - 
random date) 
+1) / 30.4375, rounding up or down to one decimal place. The censor rules are as follows: 
 
Table 6-1 PFS censored data rule list 
Data situation 
Censor date 
There is no baseline imaging assessment 
Randomization date 
There is no imaging assessment after baseline (the first planned 
imaging review. No death before assessment) 
Randomization date 
No disease progression or death occurs during the trial 
Date of last imaging assessment 
After two or more consecutive imaging evaluations, data are missing, 
disease progression or death 
Date of last imaging assessment (disease progression or 
Before death) 
New anti-tumor treatment is given before the disease progression 
Last image before new anti-tumor treatment 
Assessment date 
Note: 
1. The absence of two consecutive imaging assessments is defined as no imaging evaluation 
with an interval of more than 126 days (i.e. [2 * (8 weeks + 7 days time window)]). 
2. The progression / censored date of PFS is the date of imaging examination, not the date of 
tumor evaluation or visit. The overall efficacy evaluation of a visit may be based on the 
results of imaging examinations will be conducted on different dates. In this case, the 
progression / censor date of PFS is derived according to the following rules: first, determine 
the corresponding progress date of target lesion, non-target lesion and new lesion, and then 
select a date from the progress date of target, non-target and new lesion as the overall 
efficacy progress date of the visit. 
（1） Target lesion: if the target lesion is evaluated as progression and the imaging 
examination of different target lesions is not on the same day, the earliest date is selected as 
the target lesion progression date. 
（2） Non-target lesions: if the efficacy evaluation of non-target lesions is progressive, 
and the imaging examination of different non-target lesions is not on the same day, the 
earliest date is selected as the non-target disease progress date. 
（3） New lesions: if there are multiple new lesions and the imaging examination of 
different new lesions is not on the same day, the earliest date is selected as the date of new 
lesions. 
（4） If the overall efficacy evaluation is progression, if the target lesion progression date, 
non-target lesion progression date and new lesion occurrence date are not on the same day, 
the earliest date is selected as the overall efficacy progression date of the visit. 
（5） If the overall efficacy evaluation is not progressive, if the imaging examination date 
of target lesion and non-target lesion are not on the same day, the latest date is selected as the 
overall efficacy evaluation date of the visit. 


Statistical Analysis Plan 
Beijing bozhiyin 
 
 
 
 
Time to disease progression (TTP) (month) = (first observe disease progression (imaging or 
clinical progress, whichever is earlier) date / censor date - random date + 1) / 30.4375, 
rounding up or down to one decimal place. For all subjects, the date of tumor progression at or 
before the last assessment of the disease will be taken as the date of tumor progression. 
 
Objective response rate (ORR) = (CR + PR cases) / total cases×100%  
 
Disease control rate (DCR) = (CR + PR + SD cases) / total cases×100%  
 
Exposure time of test drug (d) = last application date of test drug - date of first application of test 
drug 
+1 
 
Test drug exposure (mg) = ∑ test drug dose 
 
Gemcitabine exposure time (d) = gemcitabine last medication date - gemcitabine first use date 
+1 
 
Gemcitabine exposure (mg) = ∑ gemcitabine dose 
 
6.5.3 Subject distribution analysis 
 
The number of subjects screening, randomly to enroll and complete the trial in the 
population and each center are listed, and three analysis data sets (FAS, PPS, SS) are 
determined. 
 
The number of screening cases, the number of screening failure subjects and the number and 
percentage of subjects with reasons are listed. 
 
The number and percentage of subjects who will be randomly enrolled, completed the trial, 
withdrawals and their reasons are calculated. 
 
The number and percentage of subjects with primary and secondary deviant protocol are 
summarized according to the type of deviation. 
 
The reasons for excluding PPS are classified and analyzed, and the number and percentage of 
subjects in different categories are calculated. 
 
A detailed list of subjects divided by population will be listed, including the reasons why they are 
not enrolled in PPS / FAS/ SS. 
 
The flow chart of subjects distribution will be drawn. 
 
6.5.4 Demographic data and baseline analysis 
Based on the actual data in FAS. 
Descriptive demographic data and other baseline eigenvalues: 
 
Continuous variables will be used to calculate the number of cases, mean, standard deviation, 
quartiles, minimum and maximum values: age, height, weight, body surface area, course of 
disease, vital signs (body temperature, pulse rate, respiration, systolic blood pressure, diastolic 
pressure), pain intensity, KPS score, number of target lesions, sum of target lesion diameters, 
and number of non-target lesions. 
 
 
Calculation count(s) and percentages (%) of qualitative variables: 
 
Age (< 65 years old, ≥ 65 years old) 
 
Gender (male, female) 
 
Ethnicity 
 
Occupation (manual, non-manual) 
 
History of surgery (with or without) 
 
Course of disease (< 1 year, ≥ 1 year) 
 
Diagnosis types of pancreatic cancer (locally advanced pancreatic adenocarcinoma, 
metastatic pancreatic adenocarcinoma, others) 
 
Tumor location (head, body and tail of pancreas) 
 
Have you received chemotherapy (yes, no) 
 
No, radiotherapy or not 


Statistical Analysis Plan 
Beijing bozhiyin 
 
 
 
Management of intestinal obstruction (yes, no) 
 
Drug allergy (with or without) 
 
Concomitant diseases (with or without) 
 
Concomitant treatment (with or without) 
 
Physical examination (normal, abnormal, not checked) 
 
K-RAS gene mutation detection (wild type, mutant type) 
 
Target lesion (with or without) 
 
Non-target lesions (with or without) 
 
KPS score (60-80, 90-100) 
 
 
Inferential statistical results (P values) are listed as descriptive results. 
 
6.5.5 Analysis of medication compliance and concomitant medications 
 
Based on the actual data of FAS and SS. 
 
6.5.5.1 Analysis of medication compliance 
 
Cumulative dose (mg) of nimotuzumab or simulant will be compared by t-test. 
 
Cumulative dose (mg) of gemcitabine will be compared by t-test. 
 
Total duration of exposure (days) of nimotuzumab or simulant will be compared by t-test.  
 
The time of gemcitabine exposure (d) will be compared by t-test. 
 
T test is used to compare the difference between the two groups. 
 
The medication situation of the subjects is described in the list. 
 
6.5.5.2 Analysis of concomitant medications 
 
Previous medication refers to the start date of the non-study drug used before the date of the first 
use of the study drug. 
 
Concomitant medication refers to the non-study drug that meets one of the following conditions: 
 
On or after the date of first use of study drugs. 
 
All non-study drug start dates are prior to the first study drug use date and continued on 
or after the first study drug administration date. 
 
If the end date of the non-study drug is missing or partially missing, if the content that is not 
missing (including the non-missing part of the start date and the end date of the study drug) 
can be used to judge whether it belongs to the medication before or during the treatment, it 
shall be judged. If it is impossible to judge, it is considered that the drug will be started 
before the date of the first use of the study drug and continued to be used during the 
treatment. 
 
WHO-ATC will be used to code the combined drugs. The number of cases and percentage 
will be calculated according to the first level classification and the second level classification 
of ATC. 
 
Make a list of concomitant medications. 
 
6.5.6 Efficacy analysis 
Primary efficacy variable:  
Primary analysis: 
 
The FAS data set is used, and all participants with K-ras wild-type locally advanced or 
metastatic pancreatic cancer are selected as the primary analysis population. 
 
Kaplan Meier method is used to analyze the overall survival time (OS). The number of 
events, censored number and percentage, median survival time, 25%, 75% survival time and 
95% confidence interval will be listed respectively (Brookmeyer-Crowley method). 


Statistical Analysis Plan 
Beijing bozhiyin 
 
 
 
 
The method of comparison between groups is as follows 
 
Primary analysis: The primary analysis of OS will be based on FAS set. The primary 
comparison of OS between the two groups is to be performed using log-rank test 
stratified by stratified factors collected by EDC. 
 
Sensitivity analysis 1: log rank test stratified by stratified factors collected by IWRS 
using to compare the differences between groups. 
 
Sensitivity analysis 2: using un-stratified log rank test to compare the differences between 
groups. 
 
 
The 6,12,18,24,36,48,60,72 and 84 months survival rates and 95% CI of the two groups will be 
calculated 
The confidence interval (log-log conversion) is used, and Kaplan Meier curve of survival rate is 
drawn. 
 
Taking stratified factors as covariates, Cox proportional hazard model (TIES = Efron) is 
used to calculate HR and its 95% confidence interval (Wald method). 
 
The OS and related variables are listed (random date, calculated OS date, censored status 
OS, date of death, last confirmed survival date, censored reason). 
 
At the same time, in order to evaluate the robustness of OS results, the above analysis will be 
repeated with PPS. 
 
Supporting analysis 
 
At the same time, subjects with K-ras wild-type locally advanced or metastatic pancreatic 
cancer who having not received biliary obstruction treatment are selected as the supporting 
analysis population. The same as the primary analysis method and population. 
 
Analysis of secondary efficacy indicators:  
 
The analysis will be based on FAS and supportive analysis will be conducted based on the 
population who having not received biliary obstruction treatment. 
 
Disease progression free survival (PFS) will be analyzed by Kaplan Meier method. The 
number of events, censored number and percentage, median progression free survival time, 
25%, 75% progression free survival time and 95% confidence interval are listed respectively 
(Brookmeyer-Crowley method). 
 
The method of comparison between groups is as follows 
 
Primary analysis: log rank test will be used to compare the differences between groups. 
 
Sensitivity analysis 1: log rank test will be used to compare the differences between 
groups. 
 
Sensitivity analysis 2: log rank test will be used to compare the differences between groups. 
 
The progression free survival (PFS) rate and 95% confidence interval (CI) at 3, 6, 9, 12, 18, 
24, 30 and 36 months are calculated and the Kaplan Meier curve of the two groups is drawn. 
 
Taking dynamic random influencing factors as covariates, Cox proportional hazard model 
(TIES = Efron) using to calculate HR and its 95% confidence interval (Wald method). 
 
PFS and related variables were listed (random date, PFS calculation date, censored status, 
PFS, progression date, death date, last effective imaging examination date, new anti-tumor 
treatment start date, censored reason). 
 
 
The time to disease progression (TTP) is analyzed by Kaplan Meier method. The number of 
events, censored number and percentage, median time to disease progression, 25%, 75% time 
to disease progression and their 95% confidence interval are listed respectively 
(Brookmeyer-Crowley method). 
 
The method of comparison between groups is as follows 


Statistical Analysis Plan 
Beijing bozhiyin 
 
 
 
Primary analysis: log rank test using to compare the differences between groups. 
 
Sensitivity analysis 1: log rank test using to compare the differences between group by 
the adjusted IWRS gathered data 
 
Sensitivity analysis 2: log rank test using to compare the differences between groups 
without the adjusted stratifications 
 
The disease progression rate and its 95% confidence interval at 3, 6, 9, 12, 18, 24, 30 and 36 
months in the two groups are calculated (using log-log conversion), and the Kaplan Meier 
curve of disease progression rate is drawn. 
 
Taking dynamic random influencing factors as covariates, Cox proportional hazard model 
(TIES = Efron) using to calculate HR and its 95% confidence interval (Wald method). 
 
TTP and related variables are listed (random date, TTP calculation date, censored status, 
TTP, progression date, disease progression date, last effective imaging examination date, 
start date of new anti-tumor treatment, and reasons for censored data). 
 
 
Subgroup analysis 
 
OS, PFS and TTP are analyzed according to the following factors and HR forest map was 
drawn. 
i. 
Location of tumor (head of pancreas vs. body and tail of pancreas) 
ii. Have you ever had surgery (yes vs. no) 
iii. Whether biliary obstruction has been treated (yes vs. no) 
iv. Have you received adjuvant chemotherapy (yes vs. no) 
v. Diagnosis types of pancreatic cancer (locally advanced pancreatic adenocarcinoma vs. 
metastatic pancreatic adenocarcinoma) 
vi. KPS score (60-80 vs. 90-100) 
vii. Gender (male vs. female) 
viii. Age (< 65 years vs. ≥ 65 years) 
ix. Duration of disease (< 1 year vs. ≥ 1 year) 
 
In each subgroup, HR and 95 %CI are calculated by non-stratified Cox regression and Wald 
method,, and median PFS is calculated by non-stratified log rank method. 
 
 
Objective response rate (ORR) is used χ2 test between the two groups are compared. Logistic 
regression model using to calculate ORs and 95% CI. 
 
Disease control rate (DCR) is used χ2 test between the two groups are compared. 
 
Clinical benefit rate (CBR) using to calculate the effective rate of the two groups. At the end, 
using the χ2 to test the differences between groups. 
 
6.5.7 Safety analysis 
 
Based on the actual data in SS. 
 
6.5.7.1 Adverse event 
 
Adverse events are coded according to the ICH Medical Dictionary of regulatory activities 
(MedDRA 24.0). 
 
Pre-treatment AE is defined as an adverse event occurring between the signing of informed 
consent form and the first dose of study drug. 
 
Treatment emergent adverse event (TEAE) is defined as an adverse event that occurs or 
aggravates after the first dose of the study drug. 
 
Adverse reactions: adverse events related to the study drug as "definitely related, likely to be 
related and possibly related". 


Statistical Analysis Plan 
Beijing bozhiyin 
 
 
 
TEAEs are summarized according to the following categories: 
 
TEAE/ADR 
 
SAE/SADR 
 
TEAE / ADR leading to drug interruption or dose reduction 
 
TEAE / ADR leading to permanent discontinuation of study medication 
 
TEAE / ADR causing death 
 
TEAE / ADR leading to withdrawal 
 
According to SOC and PT, all kinds of adverse events are summarized, and the number, 
number and incidence of adverse events are calculated. 
 
According to the different severity of SOC and PT (Grade 1, Grade 2, Grade 3, Grade 4, 
Grade 5), the number of cases, number of events and incidence rate are calculated. Each 
subject is counted at most once in the same severity level of the same term (SOC or PT). 
 
According to SOC and PT, the adverse events with incidence > 10% (PT incidence in either 
group of test group or control group) are summarized. 
 
A detailed list of various adverse events is listed. 
 
6.5.7.2 Laboratory examination 
 
The laboratory and blood biochemical indexes are summarized (Blood routine, electrolytes, 
blood biochemistry, serum CA19-9) measured value and change value are diachronic. 
 
Shift table of laboratory examination results (blood routine, electrolyte, blood biochemistry, 
Serum CA19-9, urine routine) from baseline to worst post-baseline value according to 
abnormality which will be assessed by investigator, including the unplanned visit after 
medication. 
 
List the subjects with normal baseline and abnormal after medication, including the results of 
examination value and clinical significance. 
 
A list of subjects whose baseline abnormality is not clinically significant and whose 
abnormality after medication has clinical significance is listed, including the results of 
examination value and clinical significance judgment. 
 
List the measured values of laboratory inspection. 
 
6.5.7.3 ECG examination 
 
Descriptive summary of ECG indicators (Heart rate, RR interval, PR interval, QRS duration 
QT interval and QTC) are measured and changed in a diachronic manner. 
 
The number and proportion of subjects with absolute prolongation of QTc after administration 
will be analyzed according to the following criteria: 
 
450ms< QTc≤480ms 
 
480ms< QTc≤500ms 
 
QTc>500ms 
 
The number and proportion of subjects with QTc prolongation relative to baseline will be 
analyzed according to the following criteria: 
 
30ms<ΔQTc≤60ms 
 
ΔQTc>60ms 
 
Shift table from baseline to worst post-baseline value according to abnormality assessed by 
investigator, including the unplanned visit after medication. 
 
The subjects with normal baseline and abnormal ECG after medication are listed, including 
the results of examination value and clinical significance. 
 
List the subjects whose ECG baseline abnormality has no clinical significance and whose 
abnormality after medication has clinical significance, including the results of examination 
value and clinical significance judgment. 
 
List the measured values of ECG. 


Statistical Analysis Plan 
Beijing bozhiyin 
 
 
 
6.5.7.4 Vital signs 
The changes and measured values of vital signs compared with baseline are analyzed by descriptive 
statistics. 
List the measured values of vital signs. 
 
6.5.7.5 Physical examination 
Shift table from baseline to worst post-baseline value according to abnormality that will be assessed 
by investigator, including the unplanned visit after medication. 
A list of subjects with normal baseline, abnormal after medication and subjects with clinically 
significant baseline abnormality and post medication abnormality are listed. 
List the measured values of physical examination. 
 
6.5.8 Supplementary analysis 
Subgroup analysis of OS is performed, the subgroup is the frequency of Drug Administration. 
The RMSTREG algorithm is used to analyze OS and PFS, and stratification factors are considered 
in the model. 
 
6.6 Interim analysis 
No formal interim analysis will be performed. 


Statistical Analysis Plan 
Beijing bozhiyin 
 
 
Appendix 1: EY140810_Clinical study of nimotuzumab combined with gemcitabine in the 
treatment of pancreatic cancer TFLS for SAP_1.0_20211210 
 


NMPA clinical trial approval No. 2011L01239    
                                 Project No. EY140810       
Statistical Analysis Plan for Prospective, Randomized Controlled, 
Double-Blind, Multicenter Registered Clinical Studies of Nimotuzumab (Taxinsheng
®) Plus 
Gemcitabine versus Placebo Plus Gemcitabine in K-RAS Wild-Type Locally 
Advanced or Metastatic Pancreatic Cancer 
(TFLs Template)  
Sponsor: Baitai
 biopharmaceutical Co., Ltd                   
 
 Beijing biovoice Technology Co., Ltd
 
-Tel: (86) 10-
6758 7407, 6753 8432
 
Address: room 2-
2209, Shidai Fengfan building, No.15, Majiapu West Road, Fengtai District, Beijing
 
Version: 2021-12- 10 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
Catalog 
1. 
Distribution of subjects ................................................... 13 
2. 
Baseline analysis ........................................................ 16 
3. 
Analysis of medication compliance and drug combination ...................... 23 
4. 
Efficacy analysis ........................................................ 24 
4.1 
Overall survival (OS) .................................................... 24 
4.2 
Overall survival (OS) (without treatment for biliary obstruction) ................. 34 
2.1 
Progression free survival (PFS) ............................................ 43 
4.3 
Time to progression (TTP) ................................................ 55 
2.2 
Objective remission rate analysis........................................... 64 
2.3 
Analysis of disease control rate ............................................ 65 
4.7 
Clinical benefit response analysis .......................................... 66 
5. 
Safety analysis .......................................................... 67 
5.1 
Analysis of adverse events ................................................ 67 
5.2 
Analysis of laboratory indexes ............................................. 70 
5.3 
Analysis of electrocardiogram ............................................. 72 
5.4 
Vital signs analysis ...................................................... 74 
5.5 
Analysis of physical examination .......................................... 75 
Table 1: completion of subjects ................................................. 76 
Table 2 demographic data ......................................................................................................... 77 
Table 3 medical history ............................................................................................................ 77 
Table 4 detailed list of medication compliance and combined drug use .................................. 79 
Table 5 list of relevant indicators for efficacy evaluation ........................................................ 80 
Table 6 list of detailed adverse events ...................................................................................... 82 
Table 7 abnormal value list of laboratory examination ............................................................ 84 
Table 8 abnormal value list of ECG examination ..................................................................... 86 
Table 9 list of vital signs ........................................................................................................... 86 
Table 10 physical examination list ........................................................................................... 86 
Table 11 list of pregnancy tests ................................................................................................ 87 
Annex 1 supplementary analysis ................................................................................................. 89 
Supplement 1, OS subgroup analysis (study drug use times) ....................................................... 89 
Supplement 2. RMSTREG ....................................................................................................... 89 
 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
Table contents 
Table 1-1 Screening failure (Screening subjects) ..................................................................................... 12 
Table 1-2 distribution of subjects in each center (enrolled subjects) ....................................................... 12 
Table 1-3 classification of subjects' completion (enrolled subjects) ........................................................ 13 
Table 1-4 classification of subjects' completion (without treatment of biliary obstruction) .................... 13 
Table 1-5 subjects who deviated from the protocol during the trial (enrolled subjects)........................... 13 
Table 1-6 classification analysis of reasons for non PPS subjects (enrolled subjects) ............................. 13 
Table 2-1 analysis of demographic data and baseline characteristics (FAS) ............................................ 15 
Table 2-2 surgery history (FAS)............................................................................................................... 16 
Table 2-3 current history of pancreatic cancer (FAS) .............................................................................. 16 
Table 2-4 target lesions (FAS) ................................................................................................................. 17 
Table 2-5 non target lesions (FAS) .......................................................................................................... 17 
Table 2-6 drug allergy (FAS) ................................................................................................................... 18 
Table 2-7 concomitant diseases (FAS) ..................................................................................................... 18 
Table 2-8 concomitant treatment (FAS) ................................................................................................... 18 
Table 2-9 vital signs (FAS) ...................................................................................................................... 18 
Table 2-10 physical examination (FAS) ................................................................................................... 19 
Table 2-11 clinical benefit response (FAS) .............................................................................................. 19 
Table 2-12 KRAS gene mutation detection (FAS) ................................................................................... 20 
Table 3-1 test drug exposure and time analysis (FAS) ............................................................................. 21 
SS-3 (drug exposure time scale) .............................................................................................................. 21 
Table 3-3 analysis of gemcitabine exposure and time (FAS) ................................................................... 21 
Table 3-4 gemcitabine exposure and time analysis (SS) .......................................................................... 21 
Table 3-5 treatment cycle (week) analysis (FAS) .................................................................................... 21 
Table 3-6 treatment cycle (week) analysis (SS) ....................................................................................... 21 
Table 3-7 ATC classification analysis of previous medication (FAS) ...................................................... 21 
Table 3-8 ATC classification analysis of previous medication (SS) ......................................................... 21 
Table 3-9 ATC classification analysis (FAS) ........................................................................................... 21 
Table 3-10 ATC classification analysis (SS) of combined drugs ............................................................. 21 
Table 4-1 overall survival (OS) (month) analysis (FAS) ......................................................................... 22 
Table 4-2 overall survival (OS) (month) inter group comparison results (FAS) ...................................... 22 
Table 4-3 overall survival rate (%) (FAS) at different time (month) ........................................................ 22 
Table 4-4 overall survival (OS) (month) subgroup analysis (FAS) .......................................................... 23 
Table 4-5 overall survival (OS) (month) analysis (PPS) .......................................................................... 27 
Table 4-6 overall survival (OS) (month) inter group comparison results (PPS) ...................................... 27 
Table 4-7 overall survival rate (%) (PPS) at different time (month) ........................................................ 27 
Table 4-8 overall survival (OS) (month) subgroup analysis (PPS) .......................................................... 28 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
Table 4-9 analysis of overall survival (OS) (month) (FAS) ..................................................................... 32 
Table 4-10 overall survival (OS) (month) between groups (without biliary obstruction treatment) (FAS)32 
Table 4-11 overall survival rate (%) (without biliary obstruction treatment) (FAS) ................................ 32 
Table 4-12 subgroup analysis of overall survival (OS) (month) (FAS).................................................... 33 
Table 4-13 analysis of overall survival (OS) (month) (PPS) .................................................................... 36 
Table 4-14 The Total survival time of patients with biliary obstruction (S-4) is compared ..................... 36 
Table 4-15 overall survival rate (%) at different time (month) (without biliary obstruction treatment) 
(PPS) ........................................................................................................................................................ 37 
Table 4-16 subgroup analysis of overall survival (OS) (month) (PPS) .................................................... 37 
Table 4-17 progression free survival (PFS) (month) analysis (FAS) ....................................................... 41 
Table 4-18 progression free survival (PFS) (month) inter group comparison results (FAS) .................... 41 
Table 4-19 progression free survival rate (%) (FAS) at different time (month) ....................................... 42 
Table 4-20 progression free survival (PFS) (month) subgroup analysis (FAS) ........................................ 42 
Table 4-21 analysis of progression free survival (PFS) (month) (FAS) ................................................... 47 
Table 4-22 comparison results of progression free survival (PFS) (month) (FAS) .................................. 47 
Table 4-23 progression free survival rate (%) at different time (month) (without treatment of biliary 
obstruction) (FAS) ................................................................................................................................... 48 
Table 4-24 subgroup analysis of progression free survival (PFS) (month) (FAS) ................................... 48 
Table 4-25 time to progression (TTP) (month) analysis (FAS) ................................................................ 53 
Table 4-26 time to progression (TTP) (month) inter group comparison results (FAS) ............................ 53 
Table 4-27 disease progression rate (%) (FAS) at different time (month)................................................ 53 
Table 4-28 time to progression (TTP) (month) subgroup analysis (FAS) ................................................ 54 
Table 4-29 analysis of time to progression (TTP) (month) (FAS) ........................................................... 58 
Table 4-30 time to progression (TTP) (month) results between groups (without treatment of biliary 
obstruction) (FAS) ................................................................................................................................... 58 
Table 4-31 disease progression rate (%) at different time (month) (without treatment of biliary 
obstruction) (FAS) ................................................................................................................................... 58 
Table 4-32 time to progression (TTP) (month) subgroup analysis (FAS) ................................................ 59 
Table 4-33 objective response rate (ORR) analysis (FAS) ....................................................................... 62 
Table 4-34 logistic regression (FAS) of related factors of objective response rate (ORR) ...................... 63 
Table 4-35 objective response rate (ORR) analysis (without treatment for biliary obstruction) (FAS) ... 63 
Table 4-36 logistic regression of objective response rate (ORR) (FAS) .................................................. 63 
Table 4-37 disease control rate (DCR) analysis (FAS) ............................................................................ 63 
Table 4-38 analysis of disease control rate (DCR) (FAS) ........................................................................ 63 
Table 4-39 clinical benefit response (CBR) analysis (FAS) ..................................................................... 64 
Table 4-40 analysis of clinical benefit response (CBR) (FAS) ................................................................ 64 
Table 5-1 incidence analysis of TEAE (SS) ............................................................................................. 65 
Table 5-2 TEAE systematic organ classification(SS) .............................................................................. 65 
Table 5-3 ADR systematic organ classification(SS) ................................................................................ 65 
Table 5-4 SAE systematic organ classification(SS) ................................................................................. 65 
Table 5-5 SADR systematic organ classification(SS) .............................................................................. 65 
Table 5-6 TEAE systematic organ classification(SS) leading to study drug reduction or suspension ..... 65 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
Table 5-7 ADR systematic organ classification(SS) leading to reduction or suspension of study drug ... 65 
AE-5: drug analysis caused by drug discontinuation ............................................................................... 65 
Table 5-9 ADR systematic organ classification(SS) leading to study drug withdrawal ........................... 65 
Table 5-10 TEAE systematic organ classification(SS) leading to death .................................................. 65 
Table 5-11 analysis of ADR subsystem leading to death (SS) ................................................................. 65 
Table 5-12 TEAE systematic organ classification(SS) leading to withdrawal test .................................. 65 
Table 5-13 analysis of ADR subsystem leading to withdrawal test (SS) ................................................. 65 
Table 5-14 systematic organ classificationof TEAE with different severity (SS) .................................... 66 
Table 5-15 systematic organ classificationof ADR with different severity (SS) ...................................... 66 
Table 5-16 SAE systematic organ classification(SS) with different severity ........................................... 66 
Table 5-17 SADR systematic organ classificationwith different severity (SS) ........................................ 66 
Table 5-18 TEAE systematic organ classification(SS) with different severity leading to reduction or 
suspension of study drug ......................................................................................................................... 66 
Table 5-19 ADR systematic organ classification(SS) with different severity leading to reduction or 
suspension of study drug ......................................................................................................................... 66 
Table 5-20 TEAE systematic organ classification(SS) of study drug withdrawal caused by different 
severity .................................................................................................................................................... 66 
Table 5-21 systematic organ classificationof ADR with different severity leading to withdrawal of study 
drug (SS) .................................................................................................................................................. 66 
Table 5-22 TEAE systematic organ classification(SS) of death caused by different severity .................. 66 
Table 5-23 analysis of ADR subsystem with different severity leading to death (SS) ............................. 66 
Table 5-24 TEAE systematic organ classification(SS) of withdrawal test caused by different severity .. 66 
Table 5-25 ADR systematic organ classification(SS) of withdrawal test caused by different severity .... 66 
Table 5-26 analysis of adverse events with incidence > 10% (SS) .......................................................... 67 
Table 5-27 white blood cell baseline and post medication outcome evaluation shift table (SS) .............. 69 
Table 5-28 shift table of neutrophil baseline and post drug outcome evaluation (SS) ............................. 69 
Table 5-29 shift table of hemoglobin baseline and post medication evaluation (SS) ............................... 69 
SS-5 and platelet shift table ..................................................................................................................... 69 
Table 5-31 shift table of C-reactive protein baseline and post medication results evaluation (SS) .......... 69 
Table 5-32 shift table of baseline and post medication evaluation of alanine aminotransferase (SS) ...... 69 
Table 5-33 shift table of baseline and post medication evaluation of glutamic oxaloacetic transaminase 
(SS) .......................................................................................................................................................... 69 
Table 5-34 shift table of baseline and post medication evaluation of alkaline phosphatase (SS) ............. 69 
Table 5-35 shift table of baseline and post medication evaluation of Total bilirubin (SS) ....................... 69 
Table 5-36 shift table of baseline and post medication evaluation of direct bilirubin (SS) ...................... 69 
Table 5-37 shift table of evaluation of urea nitrogen baseline and post medication results (SS) ............. 69 
Table 5-38 shift table of evaluation of baseline and post medication creatinine (SS) .............................. 69 
Table 5-39 shift table of potassium ion baseline and post medication results evaluation (SS) ................ 69 
Table 5-40 shift table of sodium ion baseline and post medication evaluation (SS) ................................ 69 
Table 5-41 shift table for evaluation of baseline and post medication results of chloride ion (SS).......... 69 
Table 5-42 shift table of evaluation of baseline and post medication calcium (SS) ................................. 69 
Table 5-43 shift table of baseline and post medication evaluation of magnesium ion (SS) ..................... 69 
Table 5-44 CA19-9 shift table of baseline and post medication outcome evaluation (SS) ...................... 69 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
Table 5-45 analysis of leukocyte changes (SS) ........................................................................................ 69 
Table 5-46 analysis of leukocyte measured changes (SS) ........................................................................ 70 
Table 5-47 analysis of neutrophil changes (SS) ....................................................................................... 70 
Table 5-48 analysis of neutrophil measured value (SS) ........................................................................... 70 
Table 5-49 analysis of hemoglobin change value (SS) ............................................................................ 70 
Table 5-50 analysis of measured hemoglobin values (SS) ....................................................................... 70 
Table 5-51 analysis of platelet changes (SS)............................................................................................ 70 
Statistical analysis of SS-5 ....................................................................................................................... 70 
Table 5-53 analysis of changes in C-reactive protein (SS) ...................................................................... 70 
Table 5-54 analysis of measured value of C-reactive protein (SS) .......................................................... 70 
Table 5-55 analysis of alanine aminotransferase (SS) ............................................................................. 70 
Table 5-56 analysis of glutamic pyruvic transaminase (SS) .................................................................... 70 
Table 5-57 analysis of changes in glutamic oxaloacetic transaminase (SS) ............................................. 70 
Table 5-58 analysis of measured values of glutamic oxaloacetic transaminase (SS) ............................... 70 
Table 5-59 analysis of changes in alkaline phosphatase (SS) .................................................................. 70 
Table 5-60 analysis of measured values of alkaline phosphatase (SS) ..................................................... 70 
Table 5-61 analysis of Total bilirubin (SS) .............................................................................................. 70 
Table 5-62 analysis of Total bilirubin measured value (SS) ..................................................................... 70 
Table 5-63 analysis of changes in direct bilirubin (SS) ........................................................................... 71 
Table 5-64 analysis of measured value of direct bilirubin (SS) ............................................................... 71 
Table 5-65 analysis of urea nitrogen change value (SS) .......................................................................... 71 
Table 5-66 analysis of measured urea nitrogen (SS) ................................................................................ 71 
Table 5-67 analysis of creatinine change (SS) ......................................................................................... 71 
Table 5-68 analysis of measured creatinine (SS) ..................................................................................... 71 
Table 5-69 analysis of potassium ion change value (SS) ......................................................................... 71 
Table 5-70 analysis of measured values of potassium ion (SS) ............................................................... 71 
Table 5-71 analysis of sodium ion change value (SS) ............................................................................. 71 
Table 5-72 analysis of measured values of sodium ion (SS) .................................................................... 71 
Table 5-73 analysis of chloride ion change value (SS) ............................................................................ 71 
SS-5 duration analysis ............................................................................................................................. 71 
Table 5-75 analysis of calcium ion change value (SS) ............................................................................. 71 
Table 5-76 analysis of measured values of calcium ion (SS) ................................................................... 71 
Table 5-77 analysis of magnesium ion change value (SS) ....................................................................... 71 
Table 5-78 analysis of measured values of magnesium ion (SS) ............................................................. 71 
Table 5-79 analysis of CA19-9 change value (SS) .................................................................................. 71 
Table 5-80 analysis of CA19-9 measured value (SS) .............................................................................. 71 
Table 5-81 analysis of HR (times / min) .................................................................................................. 71 
Table 5-82 analysis of measured HR (times / min) (SS) .......................................................................... 71 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
Table 5-83 analysis of RR interval (MS) (SS) ......................................................................................... 72 
Table 5-84 analysis of measured RR interval (MS) (SS) ......................................................................... 72 
Table 5-85 analysis of PR interval (MS) (SS) .......................................................................................... 72 
Table 5-86 analysis (SS) of PR interval (MS) .......................................................................................... 72 
Table 5-87 analysis of QRS interval (MS) (SS) ....................................................................................... 72 
Table 5-88 duration analysis (SS) of QRS interval (MS) ......................................................................... 72 
Table 5-89 analysis of QT interval (MS) (SS) ......................................................................................... 72 
Table 5-90 duration analysis (SS) of measured QT interval (MS) ........................................................... 72 
Table 5-91 analysis of QTc (MS) variation (SS) ...................................................................................... 72 
Table 5-92 analysis of QTc (MS) measured values (SS) .......................................................................... 72 
Table 5-93 analysis of QTc absolute prolongation after administration (SS) ........................................... 72 
Table 5-94 analysis of QTc relative prolongation after administration (SS) ............................................ 72 
Table 5-95 shift table of ECG baseline and post medication evaluation (SS) .......................................... 72 
Table 5-96 analysis of body temperature (℃) change (SS) ..................................................................... 73 
Table 5-97 analysis of measured body temperature (℃) ......................................................................... 73 
Table 5-98 analysis of pulse rate (times / min) ........................................................................................ 74 
Table 5-99 duration analysis (SS) of measured pulse rate (times / min) .................................................. 74 
Table 5-100 analysis (SS) of changes in respiration (times / min) ........................................................... 74 
Table 5-101 analysis (SS) of measured values of respiration (times / min) ............................................. 74 
Table 5-102 changes of systolic blood pressure (mmHg) analysis (SS) .................................................. 74 
Table 5-103 duration analysis of measured systolic blood pressure (mmHg) (SS) .................................. 74 
Table 5-104 analysis of changes in diastolic blood pressure (mmHg) (SS) ............................................. 74 
Table 5-105 duration diastolic blood pressure (mmHg) (SS) ................................................................... 74 
Table 5-106 analysis of height (CM) change (SS) ................................................................................... 74 
Table 5-107 analysis of measured height (CM) (SS) ............................................................................... 74 
Table 5-108 analysis of body weight (kg) change (SS) ........................................................................... 74 
Table 5-109 analysis of measured body weight (kg) (SS)........................................................................ 74 
Table 5-110 shift table of baseline and post medication evaluation of physical examination (SS) .......... 75 
Supplement Table 1-1 OS increase subgroup analysis (study drug administration times) (FAS) ............ 89 
Table 2-1 OS RMST analysis results (FAS) considering stratification factor .......................................... 89 
Supplement Table 2-2 RMST analysis results (PPS) of OS considering stratification factor .................. 90 
Table 2-3 PFS RMST analysis results considering stratification factor (FAS) ........................................ 90


TFLs for Statistical Analysis Plan                                                                                                                                    
 
List of figures 
Figure 1-1 flow chart of subjects distribution (enrolled subjects) ............................................................ 14 
Figure 4-1 Kaplan Meier curve (FAS) of survival rate at each time point ............................................... 23 
Fig.4-2 survival forest figure (FAS) (sample figure) ............................................................................... 26 
Figure 4-3 Kaplan Meier curve (PPS) of survival rate at each time point ............................................... 28 
Figure 4-4 survival forest figure (PPS) (sample) ..................................................................................... 31 
Figure 4-5 Kaplan Meier curve of survival rate at each time point (FAS) ............................................... 33 
Figure 4-6 survival forest figure (without biliary obstruction treatment) (FAS) (sample) ....................... 36 
Figure 4-7 Kaplan Meier curve of survival rate at each time point (PPS) ............................................... 37 
Figure 4-8 survival forest figure (without biliary obstruction treatment) (PPS) (sample) ....................... 41 
Figure 4-9 Kaplan Meier curve (FAS) of progression free survival at each time point ........................... 42 
Figure 4-10 forest figure of progression free survival (FAS) (sample) .................................................... 47 
Figure 4-11 The progression free survival rate of patients with biliary obstruction at each time point 
(meier-4) is not treated ............................................................................................................................. 48 
Figure 4-12 forest figure of progression free survival (FAS) (sample) .................................................... 52 
Figure 4-13 Kaplan Meier curve (FAS) of disease progression rate at each time point ........................... 54 
Figure 4-14 forest figure of disease progression time (FAS) (sample figure) .......................................... 57 
Figure 4-15 Kaplan Meier curve of disease progression rate at each time point (FAS) ........................... 59 
Fig. 4-16 forest chart of disease progression time (FAS) (sample figure without biliary obstruction 
treatment) ................................................................................................................................................. 62 
Figure 4-17 forest figure of objective response rate (ORR) logistic regression analysis (FAS) .............. 63 
Figure 4-18 forest figure of objective response rate (ORR) logistic regression analysis (FAS) .............. 63


TFLs for Statistical Analysis Plan                                                                                                                                    
 
List contents 
Table 1-1 list of subjects not enrolled (Screening subjects) ..................................................................... 76 
Table 1-2 list of test completion (randomized subjects) .......................................................................... 76 
Table 1-3 follow up summary list (randomized subjects) ........................................................................ 76 
Table 1-4 follow up list (randomized subjects) ........................................................................................ 76 
Table 1-5 subjects with protocol deviation (randomized subjects) .......................................................... 76 
Table 1-6 detailed list of subject population division (randomized subjects) .......................................... 77 
Table 2-1 subject data list (FAS) .............................................................................................................. 77 
Table 3-1 surgical history (FAS) .............................................................................................................. 77 
Table 2-2 current history of cancer (FAS) ................................................................................................ 77 
Table 3-2 allergy history (FAS) ............................................................................................................... 78 
Table 3-3 concomitant diseases (FAS) ..................................................................................................... 78 
Table 3-4 concomitant treatment (FAS) ................................................................................................... 78 
Table 3-5 KRAS gene mutation detection (FAS) ..................................................................................... 79 
Table 4-1 detailed list of drug administration compliance (SS) ............................................................... 79 
Table 4-2 list of compliance with SS ....................................................................................................... 79 
Table 4-3 detailed list of previous medication (SS) ................................................................................. 80 
Table 4-4 detailed list of drug combinations (SS) .................................................................................... 80 
Table 5-1 clinical benefit response (FAS) ................................................................................................ 80 
Table 5-2 tumor imaging assessment-1 (FAS) ......................................................................................... 81 
Table 5-3 tumor imaging assessment-2 (FAS) ......................................................................................... 81 
Table 5-4 efficacy evaluation (FAS) ........................................................................................................ 81 
Table 5-5 overall survival (OS) and related lists (FAS) ........................................................................... 81 
Table 5-6 progression free survival (PFS) and related lists (FAS) ........................................................... 82 
Table 5-7 TTP and Fas ............................................................................................................................. 82 
Table 6-1 detailed TEAE list (SS)............................................................................................................ 82 
Table 6-2 ADR detailed list (SS) ............................................................................................................. 82 
Table 6-3 SAE detailed list (SS) .............................................................................................................. 82 
Table 6-4 SADR detailed list (SS) ........................................................................................................... 82 
Table 6-5 detailed list of TEAEs (SS) leading to reduction or suspension of study drug ........................ 82 
Table 6-6 detailed list of ADRs (SS) leading to reduction or suspension of study drug .......................... 82 
Table 6-7 detailed list of TEAEs leading to study drug withdrawal (SS) ................................................ 82 
Table 6-8 detailed list of ADRs leading to study drug withdrawal (SS) .................................................. 82 
Table 6-9 detailed list of death causing TEAEs (SS) ............................................................................... 82 
Table 6-10 detailed list of ADRs causing death (SS) ............................................................................... 82 
Table 6-11 detailed list of TEAEs leading to withdrawal from the test (SS) ........................................... 82 
Table 6-12 detailed list of ADRs leading to withdrawal from the test (SS) ............................................. 82 
Detailed list of sae-1 ................................................................................................................................ 83 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
Table 6-14 SAE detailed list-2 (SS) ......................................................................................................... 84 
Table 7-1 list of abnormal blood routine values (normal baseline → abnormal after treatment) (SS) ..... 84 
Table 7-2 list of abnormal blood routine values (baseline NCS → CS after treatment) (SS) .................. 84 
Table 7-3 list of measured blood routine values (SS) .............................................................................. 84 
Table 7-4 list of abnormal urine routine values (normal baseline → abnormal after treatment) (SS) ...... 84 
Table 7-5 list of abnormal urine routine values (baseline NCS → CS after treatment) (SS) ................... 85 
Table 7-6 list of measured urine routine values (SS) ............................................................................... 85 
Table 7-7 list of abnormal blood biochemical values (normal baseline → abnormal after treatment) (SS)85 
Table 7-8 list of abnormal blood biochemical values (baseline NCS → CS after treatment) (SS) .......... 85 
Table 7-9 list of blood biochemical measured values (SS) ...................................................................... 85 
Table 7-10 list of abnormal electrolyte values (baseline normal → abnormal after treatment) (SS) ....... 85 
Table 7-11 list of abnormal electrolyte values (baseline NCS → post-treatment CS) (SS) ..................... 85 
Table 7-12 list of measured values of electrolyte (SS) ............................................................................. 85 
Table 7-13 abnormal value list of tumor indicators (normal baseline → abnormal after treatment) (SS) 85 
Table 7-14 abnormal value list of tumor indicators (baseline NCS → CS after treatment) (SS) ............. 85 
Table 7-15 list of measured values of tumor index examination (SS) ...................................................... 85 
Table 8-1 list of abnormal ECG values (baseline normal → abnormal after treatment) (SS) .................. 86 
Table 8-2 list of abnormal ECG values (baseline NCS → CS after treatment) (SS) ................................ 86 
ECG 3-8 list of measured values ............................................................................................................. 86 
Table 9-1 list of measured values of vital signs (SS) ............................................................................... 86 
Table 10-1 list of abnormal values of physical examination (baseline normal → abnormal after 
treatment) (SS) ......................................................................................................................................... 86 
Table 10-2 list of measured values of physical examination (SS) ............................................................ 86 
Table 11-1 list of pregnancy tests (SS) .................................................................................................... 87 
Table 11-2 pregnancy report form (SS) ................................................................................................... 87 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
List of abbreviations 
abbreviation 
notes 
ADR 
Adverse reactions 
AE 
Adverse event 
ATC 
Anatomical therapeutics and chemical classification system 
CBR 
Clinical benefit rate 
CI 
Confidence interval 
CIL 
Lower limit of confidence interval 
CIU 
Upper limit of confidence interval 
CR 
Complete response 
CS 
Clinically Significant 
CTCAE 
Common Terminology Criteria for Adverse Events 
DAS 
Data analysis system 
DCR 
Disease control rate 
DF 
Degree of freedom 
eCRF 
Electronic case report form 
FAS 
Full analysis set 
HR 
Hazard ratio 
HR 
Heart rate 
IWRS 
Interactive Web Response System 
Max 
Maximum 
MedDRA 
Medical Dictionary of regulatory activities 
Min 
Minimum 
NCI 
National Cancer Research Center 
NCS 
Not Clinically Significant 
ND 
Not Detected 
NE 
Not evaluable 
NMPA 
National Medical Products Administration 
OR 
Odds ratio 
ORR 
Objective response rate 
OS 
Overall survival 
PD 
Disease progression 
PFS 
Disease progression free survival 
PPS 
Per protocol set 
PR 
Partialresponse 
PT 
Preferred term 
Q1 
Lower quartile 
Q3 
Upper quartile 
RECIST 
Criteria for evaluating the efficacy of solid tumors 
SADR 
Serious adverse reactions 
SAE 
Serious adverse events 
SD 
Standard deviation 
SD 
Stable disease 
SE 
Standard error 
SOC 
Systematic organ classification 
SS 
Safety set 
TEAE 
Treatment-Emergent Adverse Event 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
TTP 
Time to disease progression 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


TFLs for Statistical Analysis Plan 
 
Statistical Analysis Plan for Prospective, Randomized Controlled, Double-Blind, Multicenter 
Registered Clinical Studies of Nimotuzumab (Taixinsheng®) Plus Gemcitabine versus Placebo Plus 
Gemcitabine in K-RAS Wild-Type Locally Advanced or Metastatic Pancreatic Cancer  
(TFLs Template)  
1. Distribution of subjects 
Table 1-1 Screening failure (Screening subjects) 
index 
Statistical 
results 
Summary 
Screen 
XXX 
Screen failure n% 
XX(XX.X) 
Screen failure reason 
Not meeting the inclusion criteria n% 
XX(XX.X) 
Meeting the exclusion criteria n% 
XX(XX.X) 
Subjects withdraw n% 
XX(XX.X) 
Other n% 
XX(XX.X) 
Center 1 
Screen 
XXX 
Screen failure n% 
XX(XX.X) 
Screen failure reason 
Not meeting the inclusion criteria n% 
XX(XX.X) 
Meeting the exclusion criteria n% 
XX(XX.X) 
Subjects asked to withdraw n% 
XX(XX.X) 
Other n% 
XX(XX.X) 
…. 
Center XX 
Screen 
XXX 
Screen failure n% 
XX(XX.X) 
Screen failure reason 
Not meeting the inclusion criteria n% 
XX(XX.X) 
Meeting the exclusion criteria n% 
XX(XX.X) 
Subjects asked to withdraw n% 
XX(XX.X) 
Other n% 
XX(XX.X) 
%Subjects were screened based on summary / center. 
Table 1-2 distribution of subjects in each center (enrolled subjects) 
index 
Experimental 
group 
Control 
group 
Total 
Summary 
Screen 
 XXX 
Randomly enrolled 
XX 
XX 
XX 
Complete 
XX 
XX 
XX 
FAS 
XX 
XX 
XX 
PPS 
XX 
XX 
XX 
SS 
XX 
XX 
XX 
Center 1 
Screen 
XX 
Randomly enrolled 
XX 
XX 
XX 
Complete 
XX 
XX 
XX 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
FAS 
XX 
XX 
XX 
 
 
PPS 
 
XX 
 
XX 
 
XX 
SS 
XX 
XX 
XX 
… 
 
 
 
Screen 
 
 
XX 
Randomly enrolled 
XX 
XX 
XX 
Complete 
XX 
XX 
XX 
FAS 
XX 
XX 
XX 
PPS 
XX 
XX 
XX 
SS 
XX 
XX 
XX 
Center XX 
 
 
 
Screen 
 
 
XX 
Randomly enrolled 
XX 
XX 
XX 
Complete 
XX 
XX 
XX 
FAS 
XX 
XX 
XX 
PPS 
XX 
XX 
XX 
SS 
XX 
XX 
XX 
 
Table 1-3 classification of subjects' completion (enrolled subjects) 
Table 1-4 classification of subjects' completion (without treatment of biliary obstruction)  
index 
Experimental 
group 
Control group 
Total 
Randomization (n) 
XX 
XX 
XX 
Completed n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Withdrawn n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Reasons for withdrawn 
Subjects ask to withdraw from the trial actively (%) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Loss of follow-up n (%) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
In the course of treatment, the disease progressed or 
deteriorated, and the researchers considered that who is not 
suitable to continue trial n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
The patient is pregnant or not using enough contraceptive 
measures 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
The researchers believe that the compliance is poor and the 
medication can not be carried out on time 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Use of drugs or foods prohibited in the protocol n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Occurrence of adverse events n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Other reasons n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
%Based on randomized subjects. 
 
Table 1-5 subjects who deviated from the protocol during the trial (enrolled subjects) 
index 
Experimental 
group 
Control 
group 
Total 
Randomization (n) 
XX 
XX 
XX 
At least 1 PD n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Primary PD n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Primary PD 1 N% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Primary PD 2 n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
…… n(%)* 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Secondary PD n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Secondary PD 1 N% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
Secondary PD 2 N% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
…… n(%) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
PD: Protocol deviation.% Based on randomized subjects. 
 
Table 1-6 classification analysis of reasons for non PPS subjects (enrolled subjects) 
 
index 
Experimental group 
Control group 
Total 
Randomization (n) 
XXX 
XXX 
XXX 
Never received study drug n% 
XX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
Combined forbidden drugs n% 
XX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
…… n(%) 
XX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
%Based on randomized subjects. 
 
Figure 1-1 Flow chart of subjects distribution (enrolled subjects) 
 
Screen (N= ) 
Screening failure reasons (N=) 
reason1(N=) 
reason2(N=) 
Randomization(N=) 
Un-treatment reasons (N=) 
reason1(N=) 
reason2(N=) 
Double blind treatment(N=)  
Exprimental 
group(N=)  
Control group(N=)  
Withdrawal reasons (N=)  
reason1(N=) 
reason2(N=) 
Withdrawal reasons(N=)  
reason1(N=) 
reason2(N=) 
PPS(N=)  
FAS(N=) 
SS(N=) 
PPS(N=)  
FAS(N=) 
SS(N=) 
Complete(N=)  
Complete(N=)  


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
2. Baseline analysis 
Table 2-1 analysis of demographic data and baseline characteristics (FAS) 
Experimental group 
Control group 
Total 
 
Statistics 
P 
value 
method 
Age (yr)* 
 
N 
XX 
XX 
XX 
X.XX 
X 
X.XX 
X 
T-test 
Mean±SD  
XX.X±XX.  
XX 
XX.X±XX.X  
X 
XX.X±XX.  
XX 
Median 
XX.X 
XX.X 
XX.X 
Q1~Q3 
XX.X~XX. 
X 
XX.X~XX.X 
XX.X~XX.X 
Min~Max 
XX ~XX 
XX ~XX 
XX ~XX 
Age 
N 
XX 
XX 
XX 
X.XX 
X 
X.XX 
X 
Chisq/Fisher 
< 65 years old, n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
≥65 years old, n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Height (cm) 
N 
XX 
XX 
XX 
X.XX 
X 
X.XX 
X 
T-test 
Mean±SD  
XX.XX±XX  
.XXX 
XX.XX±XX.  
XXX 
XX.XX±XX  
.XXX 
Median 
XX.XX 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX 
.XX 
XX.XX~XX. 
XX 
XX.XX~XX. 
XX 
Min~Max 
XX.X~XX. 
X 
XX.X~XX.X 
XX.X~XX.X 
Weight (kg) 
N 
XX 
XX 
XX 
X.XX 
X 
X.XX 
X 
T-test 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
Mean±SD  
XX.XX±XX  
.XXX 
XX.XX±XX.  
XXX 
XX.XX±XX  
.XXX 
Median 
XX.XX 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX 
.XX 
XX.XX~XX. 
XX 
XX.XX~XX. 
XX 
Min~Max 
XX.X~XX. 
X 
XX.X~XX.X 
XX.X~XX.X 
Body surface area (m2) 
N 
XX 
XX 
XX 
X.XX 
X 
X.XX 
X 
T-test 
Mean±SD  
XX.XX±XX  
.XXX 
XX.XX±XX.  
XXX 
XX.XX±XX  
.XXX 
Median 
XX.XX 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX 
.XX 
XX.XX~XX. 
XX 
XX.XX~XX. 
XX 
Min~Max 
XX.X~XX. 
X 
XX.X~XX.X 
XX.X~XX.X 
Gender 
N 
XX 
XX 
XX 
X.XX 
X 
X.XX 
X 
Chisq/Fisher 
Male, n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Female, n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Nation 
N 
XX 
XX 
XX 
X.XX 
X 
X.XX 
X 
Chisq/Fisher 
Han 
nationality,
n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Other, n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Occupation 
N 
XXX 
XXX 
XXX 
X.XX 
X 
X.XX 
X 
Chisq/Fisher 
Physical 
labor,
n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Non 
manual
labor, n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
*: age = (date of signing informed consent - date of birth +1) / 365.25, rounded down. 
 
 
 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
Table 2-2 surgery history (FAS) 
 
Experimental 
group 
Control 
group 
Total 
statistic 
P value 
method 
N 
XX 
XX 
XX 
X.XXX 
X.XXX 
Chisq/Fisher 
N/A 
    XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
YES  n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
 
Table 2-3 current history of pancreatic cancer (FAS) 
index 
Experimental 
group 
Control group 
Total 
Statistics 
 
P value 
method 
Course 
of 
disease 
(month)* 
N 
XX 
XX 
XX 
X.XX X 
X.XX X 
Wilcoxon 
Mean±SD  
XX.XX±XX  
.XXX 
XX.XX±XX.X  
XX 
XX.XX±XX.X  
XX 
Median 
XX.XX 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX 
.XX 
XX.XX~XX.X X 
XX.XX~XX.X X 
Min~Max 
XX.X~XX. 
X 
XX.X~XX.X 
XX.X~XX.X 
Course of disease 
N 
XX 
XX 
XX 
X.XX X 
X.XX X 
Chisq/Fisher 
< 1 year, n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
≥ 1 year, n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Diagnosis type 
N 
XX 
XX 
XX 
X.XX X 
X.XX X 
R*C 
Locally 
advanced 
pancreas 
Adenocarcino
ma, n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Metastatic 
pancreas 
Adenocarcino
ma, n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Other, n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Tumor site 
N 
XX 
XX 
XX 
X.XX X 
X.XX X 
R*C 
Pancreatic 
head, n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Pancreatic body, 
n (%) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Tail of pancreas, 
n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
 
index 
Experimental 
group 
Control 
group 
Total 
Statisti
cs  
P value 
method 
Have you received 
chemotherapy 
N 
XX 
XX 
XX 
X.XX 
X 
X.XX 
X 
Chisq/Fisher
Yes, n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
No, n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Have you received 
radiotherapy 
N 
XX 
XX 
XX 
X.XX 
X 
X.XX 
X 
Chisq/Fisher
Yes, n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
No, n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Have 
biliary 
tract 
occurred 
management 
of 
obstruction 
N 
XX 
XX 
XX 
X.XX 
X 
X.XX 
X 
Chisq/Fisher
Yes, n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
No, n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
*: course of disease (month) = (date of informed consent signing - date of first diagnosis of pancreatic cancer + 1) / 30.4375, 
rounded to one decimal place. 
 
Table 2-4 target lesions (FAS) 
index 
Experimental 
group 
Control group 
Total 
Statistics 
 
P value 
method 
Target lesion 
N 
XX 
XX 
XX 
X.XX X 
X.XX 
X 
Chisq/Fisher 
YES n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
N / A 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Number 
of 
target
lesions 
N 
XX 
XX 
XX 
X.XX X 
X.XX 
X 
T-test 
Mean±SD  
XX.XX±XX  
.XXX 
XX.XX±XX.X  
XX 
XX.XX±XX.X  
XX 
Median 
XX.XX 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX 
.XX 
XX.XX~XX.X 
X 
XX.XX~XX.X 
X 
Min~Max 
XX.X~XX. 
X 
XX.X~XX.X 
XX.X~XX.X 
Sum of target lesion
diameters 
(mm) 
N 
XX 
XX 
XX 
X.XX 
X 
X.XX 
X 
T-test 
Mean±SD  
XX.XX±XX  
.XXX 
XX.XX±XX.X  
XX 
XX.XX±XX.X  
XX 
Median 
XX.XX 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX 
.XX 
XX.XX~XX.X 
X 
XX.XX~XX.X 
X 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
Min~Max 
XX.X~XX. 
X 
XX.X~XX.X 
XX.X~XX.X 
 
 
Table 2-5 non target lesions (FAS) 
index 
Experimental 
group 
Control group 
Total 
 
Statistics 
 
P 
value 
method 
Non-target lesions 
N 
XX 
XX 
XX 
X.XX X 
X.XX 
X 
Chisq/Fisher 
YES n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
N / A 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Number 
of 
non-target
lesions 
N 
XX 
XX 
XX 
X.XX X 
X.XX 
X 
T-test 
Mean±SD  
XX.XX±XX  
.XXX 
XX.XX±XX.X  
XX 
XX.XX±XX.X  
XX 
Median 
XX.XX 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX 
.XX 
XX.XX~XX.X 
X 
XX.XX~XX.X 
X 
Min~Max 
XX.X~XX. 
X 
XX.X~XX.X 
XX.X~XX.X 
 
Table 2-6 drug allergy (FAS) 
 
Experimental group 
Control group 
Total 
statistic 
P value 
 method 
N 
XX 
XX 
XX 
X.XXX 
X.XX
X 
 Chisq/Fisher 
N / A 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
YES n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
 
Table 2-7 Medical history (FAS) 
Experimental 
group 
Control group 
Total 
statistic 
P value 
method 
N 
XX 
XX 
XX 
X.XXX 
X.XXX 
Chisq/Fisher 
N / A 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
YES n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
 
Table 2-8 Previous treatment (FAS) 
Experimental 
group 
Control 
group 
Total 
statistic 
P value 
method 
N 
XX 
XX 
XX 
X.XXX 
X.XXX 
Chisq/Fisher 
N / A 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
YES n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
 
 
Table 2-9 vital signs (FAS) 
index 
Experimental 
group 
Control group 
Total 
Statistics 
 
P value 
method 
Body 
temperature 
(℃) 
N 
XX 
XX 
XX 
X.XX X 
X.XX X 
T-test 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
Mean±SD  
XX.XX±XX.  
XXX 
XX.XX±XX.  
XXX 
XX.XX±XX  
.XXX 
Median 
XX.XX 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX
. XX 
XX.XX~XX. 
XX 
XX.XX~XX. XX 
Min~Max 
XX.X~XX.X 
XX.X~XX.X 
XX.X~XX.X 
Pulse rate (times / 
min) 
N 
XX 
XX 
XX 
X.XX X 
X.XX X 
T-test 
Mean±SD  
XX.X±XX.X X 
XX.X±XX.X X 
XX.X±XX. X 
Median 
XX.X 
XX.X 
XX.X 
Q1~Q3 
XX.X~XX.X 
XX.X~XX.X 
XX.X~XX.X 
Min~Max 
XX ~XX 
XX ~XX 
XX ~XX 
Breathing (times / min) 
N 
XX 
XX 
XX 
X.XX X 
X.XX 
T-test 
Mean±SD  
XX.X±XX.X X 
XX.X±XX.X X 
XX.X±XX.XX  
Median 
XX.X 
XX.X 
XX.X 
Q1~Q3 
XX.X~XX.X 
XX.X~XX.X 
XX.X~XX.X 
Min~Max 
XX ~XX 
XX ~XX 
XX ~XX 
Systolic blood pressure 
(mmHg) 
N 
XX 
XX 
XX 
X.XX X 
X.XX 
T-test 
Mean±SD  
XX.X±XX.X  
X 
XX.X±XX.X  
X 
XX.X±XX.  
XX 
Median 
XX.X 
XX.X 
XX.X 
Q1~Q3 
XX.X~XX.X 
XX.X~XX.X 
XX.X~XX.X 
Min~Max 
XX ~XX 
XX ~XX 
XX ~XX 
Diastolic 
blood 
pressure (mmHg) 
N 
XX 
XX 
XX 
X.XX X 
X.XX 
T-test 
Mean±SD  
XX.X±XX.X X 
XX.X±XX.X X 
XX.X±XX.XX  
Median 
XX.X 
XX.X 
XX.X 
Q1~Q3 
XX.X~XX.X 
XX.X~XX.X 
XX.X~XX.X 
Min~Max 
XX ~XX 
XX ~XX 
XX ~XX 
 
Table 2-10 physical examination (FAS) 
Experimenta
l group 
Control 
group 
Total 
Statistic 
P value 
method 
N 
XX 
XX 
XX 
X.XXX 
X.XXX 
Chisq/Fisher 
Normal, n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Abnormal, n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Not checked, n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
 
Table 2-11 clinical benefit rate (FAS) 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
index 
Experimenta
group 
Control group 
Total 
Statistics 
P value 
method 
Pain intensity (mm) 
N 
XX 
XX 
XX 
X.XX X X 
T-test 
Mean±SD  
XX.XX±XX  
.XXX 
XX.XX±XX.X  
XX 
XX.XX±XX.X  
XX 
Median 
XX.XX 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX.XX 
         XX.X X 
          XX.X X 
Min~Max 
XX.X~XX. 
X 
XX.X~XX.X 
XX.X~XX.X 
KPS score 
N 
XX 
XX 
XX 
X.XX 
X.XX 
T-test 
Mean±SD  
XX.X±XX. XX  
XX.X±XX .XX 
XX.X±XX.XX  
Median 
XX.X 
XX.X 
XX.X 
Q1~Q3 
XX.X~XX. X 
XX.X~XX.X 
XX.X~XX.X 
Min~Max 
XX ~XX 
XX ~XX 
XX ~XX 
KPS score 
N 
XX 
XX 
XX 
X.XX X 
XX X 
Chisq/Fisher 
60-80 n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
90-100  
n(%) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
 
Table 2-12 KRAS gene mutation detection (FAS) 
Experimental 
group 
Control group 
Total 
statistic 
P value 
method 
N 
XX 
XX 
XX 
X.XXX 
X.XXX 
Chisq/Fisher 
Wild type, n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Mutant, n% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
3. Analysis of medication compliance and concomitant medications 
Table 3-1 analysis of exposure and time of trial drug (FAS)  
Table 3-2 exposure and time analysis (SS)  
Table 3-3 exposure and time analysis (FAS)  
Table 3-4 exposure and time analysis of gemcitabine(SS) 
index 
Experimental group 
Control group 
statistic 
P value 
method 
Drug exposure (mg) 
N 
XXX 
XXX 
X.XXX 
X.XXX 
T-test 
Mean±SD  
XX.XX±XX.XX  
XX.XX±XX.XX  
Median 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX.XX 
XX.XX~XX.XX 
Min~Max 
XX.XX~XX.XX 
XX.XX~XX.XX 
Drug exposure time (d) 
N 
XXX 
XXX 
X.XXX 
X.XXX 
T-test 
Mean±SD  
XX.XX±XX.XX  
XX.XX±XX.XX  
Median 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX.XX 
XX.XX~XX.XX 
Min~Max 
XX.XX~XX.XX 
XX.XX~XX.XX 
 
Table 3-5 treatment cycle (week) analysis (FAS)  
Table 3-6 treatment cycle (week) analysis (SS) 
Experimental 
group 
Control group 
statistic 
P value 
method 
N 
XXX 
XXX 
X.XXX 
X.XXX 
T-test 
Mean±SD  
XX.XX±XX.XX  
XX.XX±XX.XX  
Median 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX.XX 
XX.XX~XX.XX 
Min~Max 
XX.XX~XX.XX 
XX.XX~XX.XX 
 
Table 3-7 ATC classification analysis of prior concomitant medications (FAS)  
Table 3-8 ATC classification analysis of prior concomitant medications (SS)  
Table 3-9 ATC classification analysis of concomitant medications (FAS)  
Table 3-10 ATC classification analysis  of concomitant medications(SS) 
ATC level 1 Classification 
Experimental 
group 
Control 
group 
ATC secondary classification 
Preferred term 
N 
XXX 
XXX 
Total N% 
XX(XX.X) 
XX(XX.X) 
ATC1 n(%) 
XX(XX.X) 
XX(XX.X) 
ATC2 n(%) 
XX(XX.X) 
XX(XX.X) 
PT n(%) 
XX(XX.X) 
XX(XX.X) 
… 
XX(XX.X) 
XX(XX.X) 
… 
XX(XX.X) 
XX(XX.X) 


TFLs for Statistical Analysis Plan 
 
4.
Efficacy analysis
4.1 Overall survival (OS) 
Table 4-1 overall survival (OS) (month) analysis (FAS) 
index 
Experimental 
group 
Control group 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X)
XX.X (XX.X~XX.X)
50%(95%CI) 
XX.X (XX.X~XX.X)
XX.X (XX.X~XX.X)
75%(95%CI) 
XX.X (XX.X~XX.X)
XX.X (XX.X~XX.X)
Table 4-2 overall survival (OS) (month) between group comparison results (FAS) 
method 
Statistical results 
Primary analysis 
Statistics (P value) 
X.XXX(X.XXX)
Sensitivity analysis 1 
Statistics (P value) 
X.XXX(X.XXX)
Sensitivity analysis 2 
Statistics (P value) 
X.XXX(X.XXX)
Note: 
Primary analysis: log rank test using to correct the stratified factors collected by EDC. 
Sensitivity analysis 1: log rank test using to correct stratification factors collected by IWRS. 
Sensitivity analysis 2: log rank test without correction of stratification factors is used. 
Table 4-3 overall survival rate (%)at different time (month) (FAS) 
time 
(month
) 
Experimental 
group 
Control group 
Number 
of deaths 
(n) 
censore
d 
Number 
(n) 
Exposure 
to 
Risk (n) 
survival 
rate 
(%) 
The 
survival 
rate 95% CI 
Number 
of deaths 
(n) 
censored 
number 
(n) 
Exposure 
to 
Risk (n) 
survival rate 
(%) 
The 
survival 
rate 95% CI 
3 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
6 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
9 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
12 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
18 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
 
 
 
 
Figure 4-1 Kaplan Meier curve of survival rate at each time point (FAS) 
 
Table 4-4 overall survival (OS) (month) subgroup analysis (FAS) 
index 
Experi
mental 
group 
Control group 
Tumor location 
Head of pancreas 
N 
XX 
XX 
Censored(%) 
XX(X
X.X) 
XX(XX.X) 
Number of deaths 
XX(X
X.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Body and tail of pancreas 
N 
XX 
XX 
Censored(%) 
XX(X
X.X) 
XX(XX.X) 
Number of deaths 
XX(X
X.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Have you had surgery 
yes 
N 
XX 
XX 
Censored(%) 
XX(X
X.X) 
XX(XX.X) 
Number of deaths 
XX(X
X.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Group 1
Group 2 
Group 1 
Group 2 
Xlab 
Ylab


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
no 
N 
XX 
XX 
Censored(%) 
XX(X
X.X) 
XX(XX.X) 
Number of deaths 
XX(X
X.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X 
(XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X 
(XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X 
(XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Have you biliary obstruction been  treated 
 
 
yes 
 
 
N 
XX 
XX 
Censored(%) 
XX(X
X.X) 
XX(XX.X) 
Number of deaths 
XX(X
X.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X
XX.X (XX.X~XX.X) 
no 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Have you received adjuvant chemotherapy 
 
 
yes 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
no 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Diagnostic types of pancreatic cancer 
 
 
Locally 
advanced 
pancreatic 
adenocarcinoma 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Metastatic adenocarcinoma of pancreas 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
KPS score 
 
 
60-80  
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
90-100  
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Gender 
male 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
female 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Age 
< 65 years old 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
≥ 65 years old 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Course of disease 
< 1 year 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
X.X (XX.X~XX.X) 
X.X (XX.X~XX.X) 
50%(95%CI) 
X.X (XX.X~XX.X) 
X.X (XX.X~XX.X) 
75%(95%CI) 
X.X (XX.X~XX.X) 
X.X (XX.X~XX.X) 
≥ 1 year 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
         Kaplan Meier estimation 
(month) 
25%(95%CI) 
X.X (XX.X~XX.X) 
X.X (XX.X~XX.X) 
50%(95%CI) 
X.X (XX.X~XX.X) 
X.X (XX.X~XX.X) 
75%(95%CI) 
X.X (XX.X~XX.X) 
X.X(XX.X~XX.X) 
 
Fig. 4-2 survival forest figure (sample figure) (FAS) 


TFLs for Statistical Analysis Plan 
 
Note: All subjects are stratified by Cox regression to calculate Hazard ratio. Stratified factors are randomized factors from 
EDC, and Wald method using to calculate HR 95% CI. 
In the other subgroups, HR is calculated by non-stratified Cox regression, HR 95% CI is calculated by Wald method, and median 
OS is calculated by non-stratified log rank method.  
Table 4-5 overall survival (OS) (month) analysis (PPS) 
index 
Experimental 
group 
Control 
group 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X)
XX.X (XX.X~XX.X)
50%(95%CI) 
XX.X (XX.X~XX.X)
XX.X (XX.X~XX.X)
75%(95%CI) 
XX.X (XX.X~XX.X)
XX.X (XX.X~XX.X)
Table 4-6 overall survival (OS) (month) inter-group comparison results (PPS) 
method 
Statistical results 
Principal analysis 
Statistics (P value) 
X.XXX(X.XXX)
Sensitivity analysis 1 
Statistics (P value) 
X.XXX(X.XXX)
Sensitivity analysis 2 
Statistics (P value) 
X.XXX(X.XXX)
Note: 
Main analysis: log rank test using to correct the stratified factors collected by EDC. 
Sensitivity analysis 1: log rank test using to correct stratification factors collected by IWRS. 
Sensitivity analysis 2: log rank test without correction of stratification factors. 
Table 4-7 overall survival rate (%) (PPS) at different time (month) 
time 
(month
) 
Experimental 
group 
Control group 
Number of 
deaths 
(n) 
censored 
Number 
(n) 
Exposure 
to 
Risk (n) 
survival 
rate 
(%) 
The 
survival 
rate is 95% CI 
Number 
of deaths 
(n) 
Number 
of 
omission
s 
(n) 
Exposure 
to 
Risk (n) 
survival 
rate 
(%) 
The survival rate 
is 95% CI 
3 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
6 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
9 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
12 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
18 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
 
 
 
Figure 4-3 Kaplan Meier curve of survival rate at each time point  (PPS) 
 
Table 4-8 overall survival (OS) (month) subgroup analysis (PPS) 
index 
Experimental group 
Control group 
Tumor location 
Head of pancreas 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Body and tail of pancreas 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Have you had surgery 
yes 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
no 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier 
estimation 
 
Group 1
Group 2 
Group 1 
Group 2 
Xlab 
Ylab


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
(month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Have biliary obstruction been treated 
yes 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation
(month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
no 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier 
estimation 
(month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Have 
you 
received 
adjuvant 
chemotherapy 
yes 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier 
estimation 
(month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
no 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier 
estimation 
(month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Diagnostic types of pancreatic cancer 
Locally advanced pancreatic 
adenocarcinoma 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier 
estimation 
(month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Metastatic adenocarcinoma of 
pancreas 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation 
(month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
KPS score 
60-80 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
90-100 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Gender 
male 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
female 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Age 
< 65 years old 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
≥  65 years old 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Course of disease 
 
 
< 1 year 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
≥ 1 year 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Figure 4-4 survival forest figure (PPS) (sample) 
Note: 


TFLs for Statistical Analysis Plan 
 
All subjects are stratified by Cox regression to calculate hazard ratio. Stratified factors are randomized factors from EDC, 
and Wald method using to calculate HR 95% CI； 
In the other subgroups, HR is calculated by non-stratified Cox regression, HR 95% CI is calculated by 
Wald method, and median OS is calculated by non-stratified log rank method. 
4.2 Overall survival (OS) (without treatment for biliary obstruction) 
Table 4-9 analysis of overall survival (OS) (month) (FAS) 
index 
Experimental 
group 
Control 
group 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X)
XX.X (XX.X~XX.X)
50%(95%CI) 
XX.X (XX.X~XX.X)
XX.X (XX.X~XX.X)
75%(95%CI) 
XX.X (XX.X~XX.X)
XX.X (XX.X~XX.X)
Table 4-10 overall survival (OS) (month) between groups (without biliary obstruction treatment) (FAS) 
Method 
Statistical results 
Principal analysis 
Statistics (P value) 
X.XXX(X.XXX)
Sensitivity analysis 1 
Statistics (P value) 
X.XXX(X.XXX)
Sensitivity analysis 2 
Statistics (P value) 
X.XXX(X.XXX)
Note: 
Main analysis: the patients are divided into three groups: tumor location, whether received surgery, whether received adjuvant 
chemotherapy or not Log rank test. 
Sensitivity analysis 1: log rank test using to adjust the stratification factors (tumor location, whether received surgery, whether 
received adjuvant chemotherapy) collected by IWRS. 
Sensitivity analysis 2: log rank test without correction of stratification factors. 
Table 4-11 overall survival rate (%) (without biliary obstruction treatment) (FAS) 
time 
(month) 
Experimental 
group 
Control group 
Number 
of deaths 
(n) 
censored 
Number 
(n) 
Exposure to 
Risk (n) 
survival 
rate 
(%) 
The 
survival 
rate is 95% CI 
Number 
of deaths 
(n) 
Number of 
omissions 
(n) 
Exposure to 
Risk (n) 
survival 
rate 
(%) 
The 
survival 
rate is 95% CI 
3 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
6 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
9 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
12 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
18 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
 
 
 
Figure 4-5 Kaplan Meier curve of survival rate at each time point (FAS)  
 
Table 4-12 subgroup analysis of overall survival (OS) (month) (FAS) 
index 
Experimental group 
Control group 
Tumor location 
Head of pancreas 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation 
(month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Body and tail of pancreas 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation 
(month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Have you had surgery 
yes 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation 
(month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
no 
N 
XX 
XX 
Group 1
Group 2
Group 1
Group 2
Xlab
Ylab


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Have you received adjuvant chemotherapy 
 
 
yes 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
no 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Diagnostic types of pancreatic cancer 
 
 
Locally advanced pancreatic adenocarcinoma 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Metastatic adenocarcinoma of pancreas 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
KPS score 
 
 
60-80  
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
90-100  
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Gender 
 
 
male 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
female 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Age 
 
 
< 65 years old 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
≥ 65 years old 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Course of disease 
 
 
< 1 year 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
≥ 1 year 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
 
Image of untreated biliary tract obstruction (FAS-6) 
Note: 
Stratified Cox regression using to calculate HR. Random factors are tumor location, surgery, adjuvant chemotherapy. Wald 
method is used to calculate HR 95% CI. 
In the other subgroups, HR is calculated by non-stratified Cox regression, HR 95% CI is calculated by Wald method, and 
median OS is calculated by non-stratified log rank method. 
 
Table 4-13 analysis of overall survival (OS) (month) (PPS) 
index 
Experimental 
group 
Control 
group 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
 
 
 
 
 
 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
Table 4-14 comparison results of overall survival (OS) (month) between groups (without biliary 
obstruction treatment) (PPS) 
 
method 
Statistical results 
Principal analysis 
Statistics (P value) 
X.XXX(X.XXX) 
Sensitivity analysis 1 
Statistics (P value) 
X.XXX(X.XXX) 
Sensitivity analysis 2 
Statistics (P value) 
X.XXX(X.XXX) 
Note: 
Main analysis: the patients are divided into groups on randomized stratification factor (tumor location, whether received surgery, 
whether received adjuvant chemotherapy or not ) to do log rank test. 
Sensitivity analysis 1: log rank test is used to adjust the stratification factors (tumor location, whether 
received surgery, whether received adjuvant chemotherapy) collected by IWRS. 
Sensitivity analysis 2: log -rank test without correction of stratification factors is used. 
 
Table 4-15 overall survival rate (%) at different time (month) (without biliary obstruction treatment) 
(PPS) 
time 
(month
) 
Experimental 
group 
Control group 
Number 
of deaths 
(n) 
censor
ed 
Numbe
r (n) 
Exposure 
to 
Risk (n) 
survival 
rate 
(%) 
The 
survival 
rate is 95% CI 
Number 
of deaths 
(n) 
Number 
of 
omissions 
(n) 
Exposure 
to 
Risk (n) 
survival 
rate 
(%) 
The 
survival 
rate is 95% CI 
3 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
6 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
9 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
12 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
18 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
 
 
Figure 4-7 Kaplan Meier curve of survival rate at each time point (PPS) 
 
 
 
 
 
 
 
 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
 
Table 4-16 subgroup analysis of overall survival (OS) (month) (PPS) 
index 
Experimental group 
Control group 
Tumor location 
Head of pancreas 
N 
 XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan 
Meier 
estimation 
(month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Body and tail of pancreas 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Have you had  surgery 
 
 
yes 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
no 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Have you received adjuvant chemotherapy 
 
 
yes 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
no 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Diagnostic types of pancreatic cancer 
Locally 
advanced 
pancreatic 
adenocarcinoma 
N 
  XX 
XX 
Censored(%) 
             XX(XX.X) 
          XX(XX.X) 
Number of deaths 
             XX(XX.X) 
         XX(XX.X) 
Kaplan 
Meier 
estimation 
(month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X)  
XX.X (XX.X~XX.X) 
Metastatic adenocarcinoma of pancreas 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
KPS score 
 
 
60-80  
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
90-100  
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Gender 
 
 
male 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
female 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
Age 
 
 
< 65 years old 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
≥ 65 years old 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Course of disease 
 
 
< 1 year 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
≥ 1 year 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
 
 
Figure 4-8 survival forest figure (without biliary obstruction treatment) (PPS) (sample) 
Note: 
Stratified Cox regression is used to calculate HR. Random factors are tumor location, surgery, adjuvant 
chemotherapy. Wald method using to calculate HR 95% CI. 
In the other subgroups, HR is calculated by non-stratified Cox regression, HR 95% CI is calculated by Wald 
method, and median OS is calculated by non-stratified log rank method. 
 
4.3 Progression free survival (PFS) 
 
Table 4-17 progression free survival (PFS) (month) analysis (FAS) 
index 
Experimental 
group 
Control group 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
 
 
 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
Table 4-18 progression free survival (PFS) (month) results are compared 
Method 
Statistical results 
Principal analysis 
Statistics (P value) 
X.XXX(X.XXX) 
Sensitivity analysis 1 
Statistics (P value) 
X.XXX(X.XXX) 
Sensitivity analysis 2 
Statistics (P value) 
X.XXX(X.XXX) 
Note: 
Main analysis: log rank test is used to correct the stratified factors collected by EDC. 
Sensitivity analysis 1: log rank test is used to correct stratification factors collected by IWRS. 
Sensitivity analysis 2: log rank test without correction of stratification factors is used. 
 
Table 4-19 progression free survival rate (%) (FAS) at different time (month) 
Experimental group 
Control group 
time 
(month
) 
Numb
er of 
new 
lesion
s 
(n) 
Numb
er 
of 
deaths 
(n) 
Censo
red(n) 
Expos
ure to 
risk 
(n) 
Disease 
progres
sion 
free rate 
(%) 
Progression 
free survival 
95%CI 
Nu
mbe
r of 
new 
lesi
ons 
(n) 
Numbe
r of 
deaths 
(n) 
Censo
red (n) 
Expos
ure to 
risk 
(n) 
Diseas
e 
progre
ssion 
free 
rate 
(%) 
Progression 
free survival 
95% CI 
3 
XX 
XX 
XX 
XX 
XX.X XX.X～XX.X 
XX 
XX 
XX 
XX 
XX.X 
XX.X～XX.X
6 
XX 
XX 
XX 
XX 
XX.X XX.X～XX.X 
XX 
XX 
XX 
XX 
XX.X 
XX.X～XX.X
9 
XX 
XX 
XX 
XX 
XX.X XX.X～XX.X 
XX 
XX 
XX 
XX 
XX.X 
XX.X～XX.X
12 
XX 
XX 
XX 
XX 
XX.X XX.X～XX.X 
XX 
XX 
XX 
XX 
XX.X 
XX.X～XX.X
18 
XX 
XX 
XX 
XX 
XX.X XX.X～XX.X 
XX 
XX 
XX 
XX 
XX.X 
XX.X～XX.X
 
 
Figure 4-9 Kaplan Meier curve of progression free survival at each time point (FAS) 
 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
Table 4-20 progression free survival (PFS) (month) subgroup analysis (FAS) 
index 
Experimental group 
Control group 
Tumor location 
 
 
Head of pancreas 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Body and tail of pancreas 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Have you had  surgery 
 
 
yes 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
no 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Have biliary obstruction been treated 
 
 
yes 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
no 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Have you received adjuvant chemotherapy 
 
 
yes 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
no 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Diagnostic types of pancreatic cancer 
 
 
Locally advanced pancreatic adenocarcinoma 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Metastatic adenocarcinoma of pancreas 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
KPS score 
 
 
60-80  
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
90-100  
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Gender 
 
 
male 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
female 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Age 
 
 
< 65 years old 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
≥ 65 years old 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Course of disease 
 
 
< 1 year 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
≥ 1 year 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
 
 
Figure 4-10 forest figure of progression free survival (FAS) (sample) 
Note: 
All subjects use stratified Cox regression to calculate HR. Stratified factors are random factors from EDC, and Wald method is 
used to calculate HR 95% CI. 
In the other subgroups, HR is calculated by non-stratified Cox regression, HR 95% CI is calculated by Wald method, and median 
PFS is calculated by non-stratified log rank method.  
 
Table 4-21 analysis of progression free survival (PFS) (Not treated for biliary obstruction)(month) 
(FAS) 
index 
Experimental group 
Control group 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
 
 
 
 
 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
Table 4-22 comparison results of progression free survival (PFS)(Not treated for biliary obstruction) 
(month) (FAS) 
method 
Statistical 
results 
Principal analysis 
Statistics (P value) 
X.XXX(X.XXX) 
Sensitivity analysis 1 
Statistics (P value) 
X.XXX(X.XXX) 
Sensitivity analysis 2 
Statistics (P value) 
X.XXX(X.XXX) 
Note: 
Main analysis: the patients are divided into three groups: tumor location, whether received surgery, whether received adjuvant 
chemotherapy or not (log rank test). 
Sensitivity analysis 1: log rank test is used to adjust the stratification factors (tumor location, whether received surgery, whether 
received adjuvant chemotherapy) collected by IWRS. 
Sensitivity analysis 2: log rank test without correction of stratification factors is used. 
 
Table 4-23 progression free survival rate (%) at different time (month) (without treatment of biliary 
obstruction) (FAS) 
Experimental group 
Control group 
time 
(month
) 
Numb
er of 
new 
lesion
s 
(n) 
Numb
er 
of 
deaths 
(n) 
Censo
red (n) 
Expo
sure 
to 
risk 
(n) 
Disea
se 
progr
essio
n free 
rate 
(%) 
Progression free 
survival 
95%CI 
Numb
er of 
new 
lesions 
(n) 
Numbe
r of 
deaths 
(n) 
Censo
red (n) 
Expos
ure to 
risk 
(n) 
Disea
se 
progr
essio
n free 
rate 
(%) 
Progression free 
survival 95% 
CI 
3 
XX 
XX 
XX 
XX 
XX.X XX.X～XX.X 
XX 
XX 
XX 
XX 
XX.X 
XX.X～XX.X
6 
XX 
XX 
XX 
XX 
XX.X XX.X～XX.X 
XX 
XX 
XX 
XX 
XX.X 
XX.X～XX.X
9 
XX 
XX 
XX 
XX 
XX.X XX.X～XX.X 
XX 
XX 
XX 
XX 
XX.X 
XX.X～XX.X
12 
XX 
XX 
XX 
XX 
XX.X XX.X～XX.X 
XX 
XX 
XX 
XX 
XX.X 
XX.X～XX.X
18 
XX 
XX 
XX 
XX 
XX.X XX.X～XX.X 
XX 
XX 
XX 
XX 
XX.X 
XX.X～XX.X
 
 
 
Figure 4-11 Kaplan Meier curve of progression free survival at each time point (FAS) 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
Table 4-24 subgroup analysis of progression free survival (PFS) (Not treated for biliary 
obstruction)(month) (FAS) 
index 
Experimental group 
Control group 
Tumor location 
Head of pancreas 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Body and tail of pancreas 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Have you had surgery 
yes 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
no 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Have you received adjuvant chemotherapy 
yes 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
no 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Diagnostic types of pancreatic cancer 
Locally 
advanced 
pancreatic 
adenocarcinoma 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Metastatic 
adenocarcinoma 
of 
pancreas 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
KPS score 
60-80  
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
90-100 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
 Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Gender 
male 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
 Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
female 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
  Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Age 
< 65 years old 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
 Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
≥ 65 years old 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
 Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Course of disease 
< 1 year 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
≥ 1 year 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Total events 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
 
Figure 4-12 Forest figure of progression free survival (Not treated for biliary obstruction) (sample) 
(FAS) 
Note: 
Stratified Cox regression is used to calculate HR. Random factors (tumor location, surgery, adjuvant chemotherapy) are used 
to calculate HR. Wald method is used to calculate HR 95% CI. 
In the other subgroups, HR is calculated by non -stratified Cox regression, HR 95% CI is calculated by Wald method, and 
median PFS is calculated by non -stratified log rank method. 
 
 
 
 
 
 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
4.4 Time to progression (TTP)  
Table 4-25 time to progression (TTP) (month) analysis (FAS) 
index 
Experimental 
group 
Control 
group 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of disease progression 
events (%) 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
 
Table 4-26 time to progression (TTP) (month) inter group comparison results (FAS) 
method 
Statistical results 
Principal analysis 
Statistics (P value) 
X.XXX(X.XXX) 
Sensitivity analysis 1 
Statistics (P value) 
X.XXX(X.XXX) 
Sensitivity analysis 2 
Statistics (P value) 
X.XXX(X.XXX) 
Note: 
Main analysis: log rank test is used to correct the stratified factors collected by EDC. 
Sensitivity analysis 1: log rank test is used to correct stratification factors collected by IWRS. 
Sensitivity analysis 2: log rank test without correction of stratification factors is used. 
 
Table 4-27 time to disease progression rate (%) (FAS) 
Experimental group 
Control group 
time 
(month
) 
Disease 
progress
ion 
(n) 
Censored 
(n) 
Exposur
e to risk 
(n) 
Disease 
progress
ion rate 
(%) 
Disease 
progression 
rate 
95%CI 
Disease 
progression 
(n) 
Number 
of 
omission
s 
(n) 
Exposur
e to risk 
(n) 
Disease 
progress
ion rate 
(%) 
Disease 
progression 
rate 
95%CI 
3 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
6 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
9 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
12 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
18 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
 
 
 
Figure 4-13 Kaplan Meier curve of disease progression rate at each time point (FAS) 
 
Table 4-28 time to progression (TTP) (month) subgroup analysis (FAS) 
index 
Experimental 
group 
Control group 
Tumor location 
Head of pancreas 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Body and tail of pancreas 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Have you had surgery 
yes 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
no 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Have biliary obstruction been treated 
yes 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
no 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Have you received adjuvant chemotherapy 
yes 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
no 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Diagnostic types of pancreatic cancer 
Locally 
advanced 
pancreatic 
adenocarcinoma 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Metastatic adenocarcinoma of pancreas 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
KPS score 
 
 
60-80  
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
90-100  
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Gender 
 
 
male 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
female 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Age 
 
 
< 65 years old 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
≥ 65 years old 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Course of disease 
< 1 year 


TFLs for Statistical Analysis Plan 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X)
XX.X (XX.X~XX.X)
50%(95%CI) 
XX.X (XX.X~XX.X)
XX.X (XX.X~XX.X)
75%(95%CI) 
XX.X (XX.X~XX.X)
XX.X (XX.X~XX.X)
≥ 1 year 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X)
XX.X (XX.X~XX.X)
50%(95%CI) 
XX.X (XX.X~XX.X)
XX.X (XX.X~XX.X)
75%(95%CI) 
XX.X (XX.X~XX.X)
XX.X (XX.X~XX.X)
Figure 4-14 forest figure of disease progression time (sample figure) (FAS) 
Note: 
All subjects  are stratified Cox regression to calculate HR. Stratified factors are random factors from EDC, and Wald method 
is used to calculate HR 95% CI； 
In the other subgroups, HR is calculated by non-stratified Cox regression, HR 95% CI is calculated by Wald method, and median 
TTP is calculated by non -stratified log rank method. 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
Table 4-29 analysis of time to progression (TTP) (month) (FAS) 
index 
Experimental 
group 
Control group 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of disease progression 
events (%) 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
 
Table 4-30 time to progression (TTP) (month) results between groups (without treatment of biliary 
obstruction)(FAS) 
method 
Statistical results 
Principal analysis 
Statistics (P value) 
X.XXX(X.
XXX) 
Sensitivity analysis 1 
Statistics (P value) 
X.XXX(X.
XXX) 
Sensitivity analysis 2 
Statistics (P value) 
X.XXX(X.
XXX) 
Note: 
Main analysis: the patients are divided into three groups: tumor location, whether received surgery, whether 
received adjuvant chemotherapy or not to do log rank test. 
Sensitivity analysis 1: log rank test is used to adjust the stratification factors (tumor location, whether received 
surgery, whether received adjuvant chemotherapy) collected by IWRS. 
Sensitivity analysis 2: log rank test without correction of stratification factors is used. 
 
Table 4-31 disease progression rate (%) at different time (month) (without treatment of biliary 
obstruction) (FAS) 
Experimental group 
Control group 
time 
(month) 
Disease 
progressi
on 
(n) 
Cens
ored 
(n) 
Exposure 
to risk (n) 
Disease 
progressi
on rate 
(%) 
Disease 
progression rate 
95%CI 
Disease 
progress
ion (n) 
Number 
of 
omissions 
(n) 
Exposure 
to risk (n) 
Disease 
progressi
on rate 
(%) 
Disease 
progression 
rate 
95%CI 
3 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
6 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
9 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
12 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
18 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 
XX 
XX 
XX 
XX.X 
XX.X～XX.X 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
 
 
Figure 4-15 Kaplan Meier curve of disease progression rate at each time point 
(Not treated for biliary obstruction) (FAS) 
 
Table 4-32 time to progression (TTP) (month) subgroup analysis (Not treated for biliary obstruction) 
(FAS) 
index 
Experimental group 
Control group 
Tumor location 
Head of pancreas 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Body and tail of pancreas 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Have you had  surgery 
yes 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
no 
N 
XX 
XX 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Have you received adjuvant chemotherapy 
 
 
yes 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
no 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Diagnostic types of pancreatic cancer 
 
 
Locally 
advanced 
pancreatic 
adenocarcinoma 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Metastatic adenocarcinoma of pancreas 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
KPS score 
 
 
60-80  
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
90-100  
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Gender 
male 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
female 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Age 
 
 
< 65 years old 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
≥65 years old 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
Course of disease 
 
 
< 1 year 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
≥ 1 year 
 
 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Progressive events 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
 
 
25%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
50%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
 
index 
Experimental group 
Control group 
75%(95%CI) 
XX.X (XX.X~XX.X) 
XX.X (XX.X~XX.X) 
 
Fig. 4-16 forest chart of disease progression time  
(sample figure without biliary obstruction treatment) (FAS) 
Note: 
Stratified Cox regression is used to calculate HR. Random factors (tumor location, surgery, adjuvant chemotherapy) 
are used to calculate hr. Wald method is used to calculate HR 95% CI. 
In the other subgroups, HR is calculated by non-stratified Cox regression, HR 95% CI is calculated by Wald 
method, and median TTP is calculated by non-stratified log rank method. 
 
4.5 Objective remission rate analysis 
Table 4-33 objective response rate (ORR) analysis (FAS) 
Experimental 
group 
Control group 
statistic 
P value 
method 
N 
XX 
XX 
CR n(%) 
XX(XX.X) 
XX(XX.X) 
PR n(%) 
XX(XX.X) 
XX(XX.X) 
SD n(%) 
XX(XX.X) 
XX(XX.X) 
PD n(%) 
XX(XX.X) 
XX(XX.X) 
NE n(%) 
XX(XX.X) 
XX(XX.X) 
ORR 
XX(XX.X) 
XX(XX.X) 
X.XXX 
X.XXX 
Chisq/Fi
sher 
ORR 95%CI 
XX.X～XX.X 
XX.X～XX.X 
 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
 
Table 4-34 logistic regression (FAS) of related factors of objective response rate (ORR) 
variable 
parameter 
estimation 
Standard 
error 
Wald χ2 
P value 
OR 
value 
ORvalue 95% CI 
Intercept term 
X.XXX 
X.XXX 
X.XXX 
group 
Experimental group vs 
Control group 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX~X.XXX 
Tumor location 
Head of pancreas vs 
body and tail of pancreas 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX~X.XXX 
… 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX~X.XXX 
The correction factors in logistic model are the same as subgroup factors. 
 
 
Figure 4-17 forest figure of objective response rate (ORR) logistic regression analysis (FAS) 
 
Table 4-35 objective response rate (ORR) analysis (without treatment for biliary obstruction) (FAS) 
Experimental 
group 
Control group 
statistic 
P value 
method 
N 
XX 
XX 
CR n(%) 
XX(XX.X) 
XX(XX.X) 
PR n(%) 
XX(XX.X) 
XX(XX.X) 
SD n(%) 
XX(XX.X) 
XX(XX.X) 
PD n(%) 
XX(XX.X) 
XX(XX.X) 
NE n(%) 
XX(XX.X) 
XX(XX.X) 
ORR 
XX(XX.X) 
XX(XX.X) 
X.XXX 
X.XXX 
Chisq/Fisher 
ORR 95%CI 
XX.X～XX.X 
XX.X～XX.X 
 
Table 4-36 logistic regression of objective response rate (ORR) (FAS) 
variable 
parameter 
estimation 
Standard 
error 
Wald χ2 
P value 
OR value 
OR value 95% CI 
Intercept term 
X.XXX 
X.XXX 
X.XXX 
group 
Experimental 
group 
vs Control group 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX~X.XXX 
Tumor location Head of pancreas vs 
body 
and 
tail 
of 
pancreas 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX~X.XXX 
… 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX~X.XXX 
The correction factors in logistic model are the same as subgroup factors. 
 
Figure 4-18 forest figure of objective response rate (ORR) logistic regression analysis (FAS) 
 
4.6 Analysis of disease control rate 
 
Table 4-37 disease control rate (DCR) analysis (FAS) 
Experimental 
group 
Control group 
statistic 
P value 
method 
N 
XX 
XX 
CR n(%) 
XX(XX.X) 
XX(XX.X) 
PR n(%) 
XX(XX.X) 
XX(XX.X) 
SD n(%) 
XX(XX.X) 
XX(XX.X) 
PD n(%) 
XX(XX.X) 
XX(XX.X) 
NE n(%) 
XX(XX.X) 
XX(XX.X) 
DCR 
XX(XX.X) 
XX(XX.X) 
X.XXX 
X.XXX 
Chisq/Fisher 
DCR 95%CI 
XX.X～XX.X 
XX.X～XX.X 
DCR: the best overall assessment is the proportion of patients with confirmed complete and partial remission and stable disease. 
For patients with stable disease, at least one lesion evaluation should meet the SD criteria at least 6 weeks after medication. 
 
 
 
 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
Table 4-38 analysis of disease control rate (DCR) (without treatment for biliary obstruction) (FAS) 
Experimenta
l group 
Control 
group 
statistic 
P 
value 
method 
N 
XX 
XX 
CR n(%) 
XX(XX.X) 
XX(XX.X) 
PR n(%) 
XX(XX.X) 
XX(XX.X) 
SD n(%) 
XX(XX.X) 
XX(XX.X) 
PD n(%) 
XX(XX.X) 
XX(XX.X) 
NE n(%) 
XX(XX.X) 
XX(XX.X) 
DCR 
XX(XX.X) 
XX(XX.X) 
X.XXX 
X.XXX 
Chisq/Fisher 
DCR 95%CI 
XX.X～XX.X 
XX.X～XX.X 
DCR: the best overall assessment is the proportion of patients with confirmed complete and partial 
remission and stable disease. For patients with stable disease, at least one lesion evaluation should 
meet the SD criteria at least 6 weeks after medication. 
 
4.7 Clinical benefit response analysis 
 
Table 4-39 clinical benefit rate (CBR) analysis (FAS) 
Experimental group 
Control group 
statistic 
P value 
method 
N 
XX 
XX 
  X.XXX 
X.XXX 
Chisq/Fisher 
Effective n% 
XX(XX.X) 
XX(XX.X) 
Stable / ineffective n% 
XX(XX.X) 
XX(XX.X) 
 
Table 4-40 analysis of clinical benefit rate (CBR) (without treatment for biliary obstruction)  (FAS) 
Experimental group 
Control group 
statistic 
P value 
method 
N 
XX 
XX 
X.XXX 
X.XXX 
Chisq/Fisher 
Effective n% 
XX(XX.X) 
XX(XX.X) 
Stable / ineffective n% 
XX(XX.X) 
XX(XX.X) 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
 
5. Safety analysis 
5.1 Analysis of adverse events 
Table 5-1 incidence analysis of TEAE (SS) 
index 
Experimental 
group 
Control group 
statistic 
P value 
method 
N 
XXX 
XXX 
TEAE n(%) 
XX(XX.X) 
XX(XX.X) 
X.XXX 
X.XXX 
Chisq/Fisher 
ADR n(%) 
XX(XX.X) 
XX(XX.X) 
X.XXX 
X.XXX 
Chisq/Fisher 
SAE n(%) 
XX(XX.X) 
XX(XX.X) 
X.XXX 
X.XXX 
Chisq/Fisher 
SADR n(%) 
XX(XX.X) 
XX(XX.X) 
X.XXX 
X.XXX 
Chisq/Fisher 
Leading to drug reduction or suspension 
TEAE n% 
XX(XX.X) 
XX(XX.X) 
X.XXX 
X.XXX 
Chisq/Fisher 
Leading to drug reduction or suspension 
ADR n% 
XX(XX.X) 
XX(XX.X) 
X.XXX 
X.XXX 
Chisq/Fisher 
Lead to drug withdrawal TEAE n% 
XX(XX.X) 
XX(XX.X) 
X.XXX 
X.XXX 
Chisq/Fisher 
Leading to drug withdrawal ADR n% 
XX(XX.X) 
XX(XX.X) 
X.XXX 
X.XXX 
Chisq/Fisher 
Cause death TEAE n% 
XX(XX.X) 
XX(XX.X) 
X.XXX 
X.XXX 
Chisq/Fisher 
Cause death ADR n% 
XX(XX.X) 
XX(XX.X) 
X.XXX 
X.XXX 
Chisq/Fisher 
TEAE leading  to withdraw n% 
XX(XX.X) 
XX(XX.X) 
X.XXX 
X.XXX 
Chisq/Fisher 
ADR leading  to withdraw n% 
XX(XX.X) 
XX(XX.X) 
X.XXX 
X.XXX 
Chisq/Fisher 
Note: the relationship with the study drug is definitely related, likely to be related, and may be related, which are all regarded as 
drug-related TEAEs. 
 
Table 5-2 TEAE systematic organ classification(SS) 
Table 5-3 ADR systematic organ classification(SS)  
Table 5-4 SAE systematic organ classification(SS)  
Table 5-5 SADR systematic organ classification(SS) 
Table 5-6 TEAE subsystem analysis leading to study drug reduction or suspension  (SS) 
Table 5-7 ADR systematic organ classification leading to study drug reduction or suspension  (SS) 
Table 5-8 TEAE systematic organ classification leading to study drug withdrawal (SS) 
Table 5-9 ADR systematic organ classification leading to study drug discontinuation  (SS) 
Table 5-10 TEAE systematic organ classification leading to death  (SS) 
Table 5-11 Analysis of death caused by ADR  
Table 5-12 TEAE systematic organ classification leading to withdrawal trial (SS) 
Table 5-13 ADR systematic organ classification leading to withdrawal trial (SS) 
SOC 
Experimental group
Control group 
PT 
Number of 
cases 
Frequency 
Number of 
cases 
Frequency 
N 
XX
X 
XXX 
Total N% 
XXX(XX.X) 
XXX 
XXX(XX.X) 
XXX 
SOC1 n(%) 
XXX(XX.X) 
XXX 
XXX(XX.X) 
XXX 
PT1 n(%) 
XXX(XX.X) 
XXX 
XXX(XX.X) 
XXX 
PT2 n(%) 
XXX(XX.X) 
XXX 
XXX(XX.X) 
XXX 
… 
SOC2 
XXX(XX.X) 
XXX 
XXX(XX.X) 
XXX 
PT1 n(%) 
XXX(XX.X) 
XXX 
XXX(XX.X) 
XXX 
PT2 n(%) 
XXX(XX.X) 
XXX 
XXX(XX.X) 
XXX 
… 
SOC3 
XXX(XX.X) 
XXX 
XXX(XX.X) 
XXX 
PT1 n(%) 
XXX(XX.X) 
XXX 
XXX(XX.X) 
XXX 
PT2 n(%) 
XXX(XX.X) 
XXX 
XXX(XX.X) 
XXX 
… 
Note:  
MedDRA 24.0 is used for coding. SOC and PT were arranged in descending order according to the Total number of AE cases. 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
n: patients are counted once within each System Organ Class (SOC) and Preferred Term (PT).. 
.Percentages are based on the number of patients in safety population. 
N: The Total number of subjects in each group in the safety analysis set.. 
%The percentage of adverse events in the Total number of subjects in each group.. 
 
Table 5-14 TEAE systematic organ classification (SS)  
Table 5-15 ADR systematic organ classification (SS)  
Table 5-16 SAE systematic organ classification (SS)  
Table 5-17 SADR systematic organ classification with different severity (SS) 
Table 5-18 TEAE systematic organ classification with different severity leading to study drug 
reduction or suspension (SS) 
Table 5-19 ADR systematic organ classification with different severity leading to study drug reduction 
or suspension (SS) 
Table 5-20 TEAE systematic organ classification with different severity leading to study drug 
withdrawal (SS) 
Table 5-21 ADR systematic organ classification of ADR with different severity leading to study drug 
withdrawal (SS) 
Table 5-22  TEAE systematic organ classification with different severity leading to death (SS) 
Table 5-23  ADR systematic organ classification with different severity leading to death (SS) 
Table 5-24 TEAE systematic organ classification with different severity leading to withdrawal (SS) 
Table 5-25 ADR systematic organ classification leading to withdrawal test with different severity (SS) 
Systematic organ  classification 
Experimental 
group 
Control 
group 
Preferred term 
Severity 
n(%) 
events 
n(%) 
events 
N 
XXX 
XXX 
Total  N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 1 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 2 n% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 3 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 4 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 5 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
SOC1 n(%) 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 1 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 2 n% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 3 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 4 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 5 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
PT1 n(%) 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 1 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 2 n% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 3 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 4 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 5 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
PT2 n(%) 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 1 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 2 n% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 3 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 4 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 5 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
… 
SOC2 n(%) 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 1 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 2 n% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 3 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
Grade 4 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 5 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
PT1 n(%) 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 1 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 2 n% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 3 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 4 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 5 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
PT2 n(%) 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 1 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 2 n% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 3 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 4 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 5 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
… 
SOC3 n(%) 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 1 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 2 n% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 3 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 4 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 5 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
PT1 n(%) 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 1 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 2 n% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 3 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 4 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 5 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
PT2 n(%) 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 1 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 2 n% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 3 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 4 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
Grade 5 N% 
XX(XX.X) 
XX 
XX(XX.X) 
XX 
… 
Note:  
MedDRA 24.0 is used for coding. The number of PT and SOC is in descending order. 
n: If a patient experienced more than one adverse event, the patient is counted only once within a SOC or PT with the maximum 
severity. . 
Percentages are based on the number of patients in safety population.. 
N: The Total number of subjects in each group in the safety analysis set. 
%The percentage of adverse events in the Total number of subjects in each group.   
 
Table 5-26 analysis of adverse events with incidence > 10% (SS) 
SOC 
Experimental group 
Control group 
PT 
Number of  
cases 
Frequency 
Number of 
cases 
Frequency 
N 
XXX 
 
XXX 
 
SOC1 n(%) 
XXX(XX.X) 
XXX 
XXX(XX.X) 
XXX 
PT1 n(%) 
XXX(XX.X) 
XXX 
XXX(XX.X) 
XXX 
PT2 n(%) 
XXX(XX.X) 
XXX 
XXX(XX.X) 
XXX 
… 
 
 
 
 
SOC2 n(%) 
XXX(XX.X) 
XXX 
XXX(XX.X) 
XXX 
PT1 n(%) 
XXX(XX.X) 
XXX 
XXX(XX.X) 
XXX 
PT2 n(%) 
XXX(XX.X) 
XXX 
XXX(XX.X) 
XXX 
… 
 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
SOC3 n(%) 
XXX(XX.X) 
XXX 
XXX(XX.X) 
XXX 
PT1 n(%) 
XXX(XX.X) 
XXX 
XXX(XX.X) 
XXX 
PT2 n(%) 
XXX(XX.X) 
XXX 
XXX(XX.X) 
XXX 
… 
Note:  
adverse events with PT incidence > 10% in the trial group or Control group will be included. 
PT is arranged in descending order according to the number of AE cases. 
 
5.2 Analysis of laboratory criteria 
Table 5-27 white blood cell baseline and post medication outcome evaluation shift table (SS) 
Table 5-28 neutrophil baseline and post medication outcome evaluation shift table (SS)  
Table 5-29 hemoglobin baseline and post medication result evaluation shift table (SS)  
Table 5-30 platelet baseline and post medication result evaluation shift table (SS) 
Table 5-31 shift table of evaluation of C-reactive protein baseline and post medication results (SS)  
Table 5-32 shift table of glutamic pyruvic transaminase baseline and post medication result evaluation 
(SS)  
Table 5-33 shift table of baseline and post-administration evaluation of aspartate aminotransferase 
Table 5-34 shift table of alkaline phosphatase baseline and post medication result evaluation (SS)  
Table 5-35 shift table of Total bilirubin baseline and post medication result evaluation (SS) 
Table 5-36 shift table of direct bilirubin baseline and post medication outcome evaluation (SS)  
Table 5-37 shift table of urea nitrogen baseline and post medication result evaluation (SS) 
Table 5-38 shift table of creatinine baseline and post medication outcome evaluation (SS)  
Table 5-39 potassium baseline and post medication result evaluation cross  
Table 5-40 sodium baseline and post medication result evaluation shift table (SS)  
Table 5-41 chloride baseline and post medication result evaluation shift table (SS)  
Table 5-42 calcium baseline and post medication result evaluation shift table (SS) 
Table 5-43 shift table of baseline and post medication evaluation of magnesium (SS) 
Table 5-44 CA19-9 shift table of baseline and post medication outcome evaluation (SS) 
group 
baseline 
Most 
extreme 
post-
baseline visit value 
N 
normal 
NCS 
CS 
ND 
n(%) 
n(%) 
n(%) 
n(%) 
n(%) 
Experimental group 
N n(%) 
XX 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
Normal n% 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
NCS n(%) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
CS n(%) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
ND n(%) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
Control group 
N n(%) 
XX 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
Normal n% 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
NCS n(%) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
CS n(%) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
ND n(%) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
Note: the judgment of clinical significance after medication is recorded by the most serious judgment. 
Table 5-45 analysis of leukocyte changes (SS) 
Visit 
Experimental group 
Control group 
C1D8 
N 
XXX 
XXX 
Mean±SD  
XX.XX±XX.XX  
XX.XX±XX.XX  
Median 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX.XX 
XX.XX~XX.XX 
Min~Max 
XX.XX~XX.XX 
XX.XX~XX.XX 
… 
N 
XXX 
XXX 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
Mean±SD  
XX.XX±XX.XX  
XX.XX±XX.XX  
Median 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX.XX 
XX.XX~XX.XX 
Min~Max 
XX.XX~XX.XX 
XX.XX~XX.XX 
CxDx 
N 
XXX 
XXX 
Mean±SD  
XX.XX±XX.XX  
XX.XX±XX.XX  
Median 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX.XX 
XX.XX~XX.XX 
Min~Max 
XX.XX~XX.XX 
XX.XX~XX.XX 
 
Table 5-46 analysis of leukocyte changes (SS) 
Visit 
Experimental group 
Control group 
baseline 
N 
XXX 
XXX 
Mean±SD  
XX.XX±X.XX  
XX.XX±X.XX  
Median 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX.XX 
XX.XX~XX.XX 
Min~Max 
XX.XX~XX.XX 
XX.XX~XX.XX 
C1D8 
 
N 
XXX 
XXX 
Mean±SD  
XX.XX±XX.XX  
XX.XX±XX.XX  
Median 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX.XX 
XX.XX~XX.XX 
Min~Max 
XX.XX~XX.XX 
XX.XX~XX.XX 
… 
 
 
N 
XXX 
XXX 
Mean±SD  
XX.XX±XX.XX  
XX.XX±XX.XX  
Median 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX.XX 
XX.XX~XX.XX 
Min~Max 
XX.XX~XX.XX 
XX.XX~XX.XX 
CxDx 
 
 
N 
XXX 
XXX 
Mean±SD  
XX.XX±XX.XX  
XX.XX±XX.XX  
Median 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX.XX 
XX.XX~XX.XX 
Min~Max 
XX.XX~XX.XX 
XX.XX~XX.XX 
 
Repeat the following Table: 
Table 5-47 analysis of neutrophil changes (SS)  
Table 5-48 analysis of measured neutrophil changes (SS)  
Table 5-49 analysis of hemoglobin changes (SS)  
Table 5-50 analysis of measured hemoglobin changes (SS)  
Table 5-51 analysis of platelet changes (SS)  
Table 5-52 analysis of measured platelet changes (SS)  
Table 5-53 analysis of C reaction protein changes (SS)  
Table 5-54 analysis of measured C reaction protein changes (SS)  
Table 5-55 analysis of ALT changes (SS)  
Table 5-56 analysis of measured ALT changes (SS)  
Table 5-57 analysis of AST changes (SS)  
Table 5-58 analysis of measured AST changes (SS)  
Table 5-59 analysis of ALP changes (SS)  
Table 5-60 analysis of measured ALP changes (SS)  
Table 5-61 analysis of total bilirubin changes (SS)  
Table 5-62 analysis of measured total bilirubin changes (SS) 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
Table 5-63 analysis of direct bilirubin change (SS)  
Table 5-64 analysis of measured direct bilirubin changes (SS)  
Table 5-65 analysis of urea nitrogen changes (SS) 
Table 5-66 analysis of measured urea nitrogen changes (SS)  
Table 5-67 analysis of creatinine changes (SS)  
Table 5-68 analysis of measured creatinine changes (SS)  
Table 5-69 analysis of potassium changes (SS)  
Table 5-70 analysis of measured potassium changes (SS)  
Table 5-71 analysis of sodium changes (SS)  
Table 5-72 analysis of measured sodium changes (SS)  
Table 5-73 analysis of chloridion changes (SS)  
Table 5-74 analysis of measured chloridion changes (SS)  
Table 5-75 analysis of calcium changes (SS)  
Table 5-76 analysis of measured calcium changes (SS)  
Table 5-77 analysis of magnesium changes (SS)  
Table 5-78 analysis of measured magnesium changes (SS)  
Table 5-79 analysis of CA19-9 changes (SS)  
Table 5-80 analysis of measured CA19-9 changes (SS) 
 
5.3 Analysis of electrocardiogram 
Table 5-81 analysis of HR by visit(times / min) 
Visit 
Experimental group 
  Control group 
C1D8 
N 
XXX 
XXX 
Mean±SD  
XX.XX±XX.XX  
XX.XX±XX.XX  
Median 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX.XX 
XX.XX~XX.XX 
Min~Max 
XX.XX~XX.XX 
XX.XX~XX.XX 
… 
 
 
N 
XXX 
XXX 
Mean±SD  
XX.XX±XX.XX  
XX.XX±XX.XX  
Median 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX.XX 
XX.XX~XX.XX 
Min~Max 
XX.XX~XX.XX 
XX.XX~XX.XX 
CxDx 
 
 
N 
XXX 
XXX 
Mean±SD  
XX.XX±XX.XX  
XX.XX±XX.XX  
Median 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX.XX 
XX.XX~XX.XX 
Min~Max 
XX.XX~XX.XX 
XX.XX~XX.XX 
Note: visits include: 8 ~ 144wk, once every 8 weeks. 
 
Table 5-82 analysis of measured HR (times / min) (SS) 
Visit 
Experimental group 
Control group 
baseline 
N 
XXX 
XXX 
Mean±SD  
XX.XX±X.XX  
XX.XX±X.XX  
Median 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX.XX 
XX.XX~XX.XX 
Min~Max 
XX.XX~XX.XX 
XX.XX~XX.XX 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
 
Visit 
Experimental group 
Control group 
C1D8 
N 
XXX 
XXX 
Mean±SD  
XX.XX±XX.XX  
XX.XX±XX.XX  
Median 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX.XX 
XX.XX~XX.XX 
Min~Max 
XX.XX~XX.XX 
XX.XX~XX.XX 
… 
N 
XXX 
XXX 
Mean±SD  
XX.XX±XX.XX  
XX.XX±XX.XX  
Median 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX.XX 
XX.XX~XX.XX 
Min~Max 
XX.XX~XX.XX 
XX.XX~XX.XX 
CxDx 
N 
XXX 
XXX 
Mean±SD  
XX.XX±XX.XX  
XX.XX±XX.XX  
Median 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX.XX 
XX.XX~XX.XX 
Min~Max 
XX.XX~XX.XX 
XX.XX~XX.XX 
Note: visit includes: baseline, 8 ~ 144wk, once every 8 weeks. 
 
Repeat the following Table: 
Table 5-83 analysis of RR interval (ms) (SS) 
Table 5-84 analysis  of measured RR interval (ms) (SS) 
Table 5-85 analysis of PR interval (ms)  
Table 5-86 analysis of measured PR interval (ms)  
Table 5-87 analysis of QRS interval (ms)  
Table 5-88 analysis of measured QRS interval (ms)   
Table 5-89 analysis of QT interval (ms) (SS)  
Table 5-90 analysis of measured QT interval (ms) (SS)   
Table 5-91 analysis of QTc (ms) (SS) 
Table 5-92 analysis of measured QTc (ms) changes (SS) 
Table 5-93 analysis of QTc absolute prolongation after administration (SS) 
Experimental 
group 
Control group 
Total 
N 
XX 
XX 
XX 
450ms<QTc≤480ms 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
480ms<QTc≤500ms 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
QTc>500ms 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Note: the QTc maximum after baseline is recorded. 
 
Table 5-94 analysis of QTc relative prolongation after administration (SS) 
Experimental 
group 
Control group 
Total 
N 
XX 
XX 
XX 
30ms<ΔQTc≤60ms 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
ΔQTc>60ms 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
 
Table 5-95 shift table of ECG baseline and post medication evaluation (SS) 
group 
baseline 
After medication 
N 
normal 
NCS 
CS 
ND 
n(%) 
n(%) 
n(%) 
n(%) 
n(%) 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
 
group 
baseline 
Most extreme post-baseline 
visit value 
N 
normal 
NCS 
CS 
ND 
n(%) 
n(%) 
n(%) 
n(%) 
n(%) 
Experimental group 
N n(%) 
XX 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
Normal n% 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
NCS n(%) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
CS n(%) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
ND n(%) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
Control group 
N n(%) 
XX 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
Normal n% 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
NCS n(%) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
CS n(%) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
ND n(%) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
Note: the judgment of clinical significance after medication is recorded by the most serious judgment. 
 
5.4 Vital signs analysis 
Table 5-96 analysis of body temperature (℃) change (SS) 
Visit 
Experimental group 
Control group 
C1D1 
N 
XXX 
XXX 
Mean±SD  
XX.XX±XX.XX  
XX.XX±XX.XX  
Median 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX.XX 
XX.XX~XX.XX 
Min~Max 
XX.XX~XX.XX 
XX.XX~XX.XX 
… 
N 
XXX 
XXX 
Mean±SD  
XX.XX±XX.XX  
XX.XX±XX.XX  
Median 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX.XX 
XX.XX~XX.XX 
Min~Max 
XX.XX~XX.XX 
XX.XX~XX.XX 
CxDx 
N 
XXX 
XXX 
Mean±SD  
XX.XX±XX.XX  
XX.XX±XX.XX  
Median 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX.XX 
XX.XX~XX.XX 
Min~Max 
XX.XX~XX.XX 
XX.XX~XX.XX 
Note: the visit includes: 1 ~ 144wk, once a week. 
 
Table 5-97 analysis of measured body temperature (℃) 
Visit 
Experimental group 
Control group 
baseline 
N 
XXX 
XXX 
Mean±SD  
XX.XX±X.XX  
XX.XX±X.XX  
Median 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX.XX 
XX.XX~XX.XX 
Min~Max 
XX.XX~XX.XX 
XX.XX~XX.XX 
C1D1 
N 
XXX 
XXX 
Mean±SD  
XX.XX±XX.XX  
XX.XX±XX.XX  
Median 
XX.XX 
XX.XX 


TFLs for Statistical Analysis Plan                                                                                                                                    
 
 
Q1~Q3 
XX.XX~XX.XX 
XX.XX~XX.XX 
Min~Max 
XX.XX~XX.XX 
XX.XX~XX.XX 
… 
N 
XXX 
XXX 
Mean±SD  
XX.XX±XX.XX  
XX.XX±XX.XX  
Median 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX.XX 
XX.XX~XX.XX 
Min~Max 
XX.XX~XX.XX 
XX.XX~XX.XX 
CxDx 
N 
XXX 
XXX 
Mean±SD  
XX.XX±XX.XX  
XX.XX±XX.XX  
Median 
XX.XX 
XX.XX 
Q1~Q3 
XX.XX~XX.XX 
XX.XX~XX.XX 
Min~Max 
XX.XX~XX.XX 
XX.XX~XX.XX 
Note: the visit includes: 1 ~ 144wk, once a week. 
 
Repeat the following Table: 
Table 5-98 analysis  of pulse rate (beats / min) (SS) 
Table 5-99 analysis of measured pulse rate (SS)  
Table 5-100 analysis of change value of respiration (time / min)  
Table 5-101 analysis of measured value of respiration (time / min) 
Table 5-102 analysis of systolic blood pressure (mmHg)  
Table 5-103 analysis of measured systolic blood pressure (SS)   
Table 5-104 analysis of diastolic blood pressure (SS)  
Table 5-105 analysis of measured diastolic blood pressure (SS)  
Table 5-106 analysis of changes in height (cm) 
Table 5-107 analysis of measured height (cm)  
Table 5-108 analysis of weight (kg)  
Table 5-109 analysis of measured weight (kg) (SS) 
 
5.5 Analysis of physical examination 
Table 5-110 shift table of baseline and post medication evaluation of physical examination (SS) 
index 
baseline 
group 
N 
normal 
abnormal 
ND 
Most extreme 
post-baseline visit 
value 
n(%) 
n(%) 
n(%) 
n(%) 
N n(%) 
XX 
XX(X.X) 
XX(X.X) 
XX(X.X) 
Normal n% 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
Abnormal n% 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
ND n(%) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
XX(X.X) 
Note: the judgment of clinical significance after medication is recorded by the most serious judgment. 


TFLs for Statistical Analysis Plan 
 
 
 
List 1: completion of subjects 
List 1-1 subjects not enrolled (Screening subjects) 
Screening 
number 
Screening failure 
reason 
Screening failure reason 
classification 
 
List 1-2 trial completion (randomized subjects) 
group 
center 
Random 
number 
Gender 
Age 
(yr) 
Complete the 
test 
Last 
treatment
period 
Completion 
date 
Exit date 
Reasons for exit 
Other reasons 
Details 
of 
adverse 
events 
Yes / no 
 
List1-3 follow up summary list (randomized subjects) 
group 
center 
Random 
number 
Gender 
Age (yr) 
Follow up end date 
Reasons for the end of 
follow-up 
Other reasons 
Date of death 
Lost date 
 
List1-4 follow up (randomized subjects) 
group 
center 
Random 
number 
Ge
nd
er 
Age 
(yr) 
follow-
up 
Follow  
up method 
Follow  
up date 
Survival  
state 
KPS  
score 
Whether adverse 
events occurred 
within 1 month after 
the last use of the trial 
drug 
Any anti-tumor 
treatment 
Anti 
tumor 
treatment 
details 
To 
judge 
whether the 
disease 
progression 
Progres
s day 
stage 
Judgi
ng by 
evidenc
e 
Yes / no 
Yes / no 
 
List 1-5 subjects with protocol deviation (randomized subjects) 
group 
center 
Random 
number 
Gende
r 
Age (yr) 
Protocol 
deviation 
classification 
Specific 
description 
of 
protocol
deviation 
Severity 


TFLs for Statistical Analysis Plan 
 
 
 
… 
… 
… 
… 
… 
… 
 
List 1-6 details of subject population division (randomized subjects) 
group 
center 
Random number 
Gender 
Age (yr) 
PPS 
FAS 
SS 
Cause classification 
Detailed description of the 
cause 
 
List 2 demographic data 
List 2-1 subject data (FAS) 
group 
center 
Random 
number 
sign 
Infor
med 
date 
Date 
of 
visit 
date of birth 
Age (yr) 
Gender 
Height (cm) 
Weight (kg) 
Body surface area 
(m2) 
nation 
occupatio
n 
Native 
place 
 
List medical history   
List 3-1 surgical history (FAS) 
group 
center 
Random 
number 
gende
r 
Age 
(yr) 
History of 
surgery 
Surgery 
type 
Surgery time 
Reasons 
for 
implementation 
Selective 
surgery meter 
Draw 
Elective surgery 
type 
Elective 
surgery 
time 
Implementation of 
elective surgery 
reason 
Yes / no 
 
 
 
 
 
 
 
 
 


TFLs for Statistical Analysis Plan 
 
 
List 2-2 current history of cancer (FAS) 
group 
cen
ter 
Rando
m 
num
ber 
Gen
der 
Yr  
(ag
e) 
Date  
of  
first  
diagnosi
s 
Course 
of 
disease 
(mon
th) 
Pathological  
type 
Diagnos
is  
type 
Other  
types 
Tumor  
site 
TNM  
score 
stage 
chemot
herapy 
Chemothe
rapy 
regimen 
start 
time 
End 
time 
radiot
herap
y 
Radi
othe
rapy 
plan 
sta
rt 
ti
me 
En
d 
ti
me 
Bil
iar
y 
ob
str
uct
ion 
 
yes 
/ 
no 
yes 
/ 
no 
yes 
/ 
no 
 
List 3-2 allergy history (FAS) 
group 
center 
Random 
number 
Drug allergy 
Drug description 
Yes / no 
 
List 3-3 concomitant diseases (FAS) 
group 
center 
Random 
number 
Gender 
Age (yr) 
Concomitant 
diseases 
Name of disease 
start time 
End time 
At present, it 
continues 
Yes / no 
Yes / no 
 
List 3-4 concomitant treatment (FAS) 
group 
center 
Random 
number 
Ge
nd
er 
Ag
e 
(yr) 
Conco
mitant 
therap
y 
Generic 
name of 
drug 
ATC1 
ATC2 
ATC5 
Total 
daily 
dose 
Reaso
ns for 
use 
start time 
End time 
Continue to 
use 
Yes/ 
nothin
g 
Yes / no 


TFLs for Statistical Analysis Plan 
 
 
 
List 3-5 KRAS gene mutation detection (FAS) 
group 
center 
Random 
number 
Gende
r 
Age (yr) 
Name of visit 
Inspection date 
Inspection 
results 
 
List 4 details of medication compliance and combined drug use  
List 4-1 details of test drug medication compliance (SS)   
yearbody AdministrationDrug 
number Dosage
Reasons 
for 
downward 
adjustment
Is 
it 
suspended 
during 
administration 
drug 
Start time 
of 
drug 
suspension
End time 
of 
drug 
suspension
Reasons 
for 
drug 
suspension
groupcenter randomgenderage heavy
Recovery 
medicine 
At the time of 
administration 
Administration 
dosage 
Is 
the 
medication 
administered down regulation 
during administration dosage 
Down 
regulation 
time 
The dosage 
of 
down 
regulating 
agent 
number
(yr 
) 
(kg 
) 
Yes/ 
no 
 
 
 
 
 
 
 
 
 


TFLs for Statistical Analysis Plan 
 
 
List 4-2 details of gemcitabine medication compliance (SS) 
year 
body 
 
 
Reason
s 
for 
down 
dosage 
 
 
 
 
 
 
Is 
the 
Administratio
n suspended 
Medication 
 
 
 
 
 
Start time 
of 
drug 
suspensio
n 
 
 
 
 
 
End time 
of 
drug 
suspensio
n 
 
 
 
 
Reasons 
for drug 
suspensio
n 
grou
p 
cente
r 
rando
m 
number 
gende
r 
age 
(yr 
) 
heavy 
(kg 
) 
Administ
ration 
At the time 
of 
administrati
on 
Dosage 
Administrati
on 
 
During the 
administratio
n, whether 
the dosage is 
down 
 
Dosag
e 
down 
time 
Dosage after 
down the 
administrati
on  
Yes/ 
no 
 
List 4-3 details of previous medication (SS)  
List 4-4 details of combined medication (SS)   
 
 
 
grou
p 
 
 
 
cent
er 
 
 
 
Random 
numbe
r 
 
 
 
Gen
der 
 
 
Yr  
(age
) 
 
 
Body 
weight 
(kg 
) 
 
 
 
eneric name 
of drug 
 
 
 
ATC 1 
 
 
 
ATC 2 
 
 
 
ATC 
5 
 
 
 
Dosag
e per 
time 
 
 
 
Specific
ations 
 
 
 
Frequency 
of 
administratio
n 
 
 
     
Route 
of 
administrat
ion 
 
 
 
Reasons for 
medication 
 
 
 
t 
Date 
of 
medicatio
n 
 
 
End date 
of 
medicati
on 
 
The 
last 
visit 
is 
still 
takin
g 
Note: it is arranged by group, center, random number, start date, end date and drug name. 
 
List 5 relevant indicators for efficacy evaluation 
List 5-1 clinical benefit response (FAS)  


TFLs for Statistical Analysis Plan 
 
 
group 
center 
Random 
number 
gende
r 
Age 
(yr) 
weight 
(kg) 
Name of 
visit 
Whether to carry out 
clinical benefit 
Reaction evaluation 
Pain intensity 
(mm) 
Analgesics 
name 
Analgesics 
consume 
KPS score 
 
Clinical benefit 
assessment 
classification 
 
List 5-2 tumor imaging assessment-1 (FAS) 
group 
center 
Random 
number 
Ge
nd
er 
Age 
(yr) 
weight 
(kg) 
Name 
of 
visit 
Target 
lesio
n 
Target 
lesion 
site 
Date 
of 
deter
minati
on 
measu
ring 
metho
d 
Other 
metho
ds 
Meas
ureme
nt 
type 
measurement 
result 
(mm) 
The 
lesions 
had 
special 
changes 
Detail
s 
of 
chang
es 
Sum 
of 
measurement 
results (mm) 
Yes/ 
no 
Yes / no 
 
List5-3 tumor imaging assessment-2 (FAS) 
group 
center 
Random 
number 
Ge
nd
er 
Age 
(yr) 
weight 
(kg) 
Name 
of 
visit 
Non-
target 
lesion
s 
Non 
target 
lesion 
site 
Date 
of 
deter
minati
on 
measu
ring 
metho
d 
Other 
metho
ds 
Meas
ureme
nt 
type 
measurement 
result 
(mm) 
Lesio
n 
chang
es 
New 
lesio
ns 
Date 
of 
discov
ery 
New 
diseases 
Detail
s  
Yes / no 
Yes/ 
nothin
g 
 
List 5-4 efficacy evaluation (FAS) 
group 
center 
Random 
number 
nature
other 
Age 
(yr) 
weight 
(kg) 
Name of 
visit 
call 
Daily 
assessment 
stage 
Target lesion 
assessment 
Target lesion 
He assessed 
Non-target 
lesions 
assessment 
Non target 
lesions 
He assessed 
Overall 
efficacy 
assessment 
The other-side 
overall effect  
 


TFLs for Statistical Analysis Plan 
 
 
 
List5-5 overall survival (OS) and related lists (FAS) 
group 
center 
Random 
number 
Gender 
Age (yr) 
Weight (kg) 
Random date 
Calculate OS date 
Censored 
status 
OS(month) 
Date of death 
Final 
confirmation 
of 
survival date 
Reasons 
for 
censoring 
 
List5-6 progression free survival (PFS) and related lists (FAS) 
group 
center 
Random 
number 
gender
Age 
(yr) 
weight 
(kg) 
random 
date 
Calculate PFS 
date 
censored 
state 
PFS(month) 
progress 
date 
death 
date 
Last valid 
Imaging examination date 
New 
anti-tumor
therapy 
Treatment 
start 
date 
censored 
reason 
 
List 5-7 TTP and FAS 
group 
center 
Random 
number 
natur
e 
other 
Age 
(yr) 
weight 
(kg) 
random 
date 
Calculate TTP 
date 
censored 
state 
TTP(month) 
progress 
date 
Last valid shadow 
Date of imaging 
examination 
New antitumor 
therapy 
Start date 
censored 
reason 
 
List 6 detailed adverse events 
list 6-1 TEAE details (SS)  
list 6-2 ADR details (SS)  
list 6-3 SAE details (SS)   
list 6-4 SADR details (SS)  
list 6-5   TEAEs leading to reduction or suspension of study drug  


TFLs for Statistical Analysis Plan 
 
 
list 6-6 ADRs causing reduction or suspension of study drug  (SS) 
list 6-7 TEAEs leading to withdrawal of study drug (SS) 
list 6-8 ADRs leading to study drug withdrawal (SS)  
list 6-9 TEAEs leading to death (SS) 
list 6-10 ADRs causing death (SS) 
list 6-11 TEAEs leading to withdrawal of trial (SS)  
list 6-12 ADRs leading to withdrawal of trial  (SS) 
grou
p 
cente
r 
Rando
m 
numbe
r 
Gende
r 
Ag
e 
(Y 
r) 
Body 
weigh
t (k 
g) 
AE 
nam
e 
P 
T 
S 
O 
C 
Star
t 
dat
e 
NCI-CTCA 
E4.0 
classificatio
n 
Measures 
taken 
for the 
study 
medic
ation 
Other 
drugs 
Treatme
nt 
Correlatio
n 
with 
study 
drug 
SA 
E 
Advers
e event 
outcom
e 
Date of 
recover
y 
Recover
y date 
Sequel
a 
Remissio
n date 
Date
of 
deat
h 
AE 
sig
n 
out 
 
Ye
s / 
no 
yes 
/ 
no 
Note: it is arranged by group, center, random number, AE start date and AE name. 
MedDRA 23.0 or above is used for coding. 
 
List 6-13 SAE detailed -1 (SS) 
group 
center 
Random number 
Report type 
Reporting time 
Name of medical institution and 
specialty 
Telephone 
Name of sponsor 


TFLs for Statistical Analysis Plan 
Telephone number of sponsor 
unit 
Chinese name of trial drug 
English name of trial drug 
Drug category 
What kind of drugs 
Clinical study staging 
Drug dosage form 
Subject abbreviation 
Gender 
date of birth 
national 
Subject disease diagnosis 
SAE situation 
Time of SAE occurrence 
SAE response severity 
Measures for the trial drug 
SAE outcome 
sequela 
Time of death 
Relationship between SAE and 
trial drug 
Breaking blindness 
Domestic reports of SAE 
Foreign reports of SAE 
List 6-14 SAE detailed-2 (SS) 
group 
center 
Random 
number 
Report type 
Detailed description of 
SAE 
List 7 abnormal value list of laboratory examination 


TFLs for Statistical Analysis Plan 
list 7-1 abnormal blood routine values (normal baseline → abnormal after treatment) (SS) 
list 7-2 abnormal value list of blood routine (baseline NCS → CS after treatment) (SS) 
list 7-3 measured blood routine values (SS) 
group 
center 
Random 
number 
Gender 
Age (yr) 
Weight (kg) 
Name of visit 
Sampling date 
Inspection index 
Detection 
value 
Compan
y 
Determination 
of 
clinical significance 
Note: examination index: white blood cell, neutrophil, hemoglobin, platelet, C-reactive protein. 
NCS: abnormal without clinical significance, CS: abnormal with clinical significance. 
List 7-4 abnormal urine routine values (normal baseline → abnormal after treatment) (SS) 
List 7-5 abnormal urine routine values (baseline NCS → CS after treatment) (SS)  
List 7-6 measured urine routine values (SS) 
group 
center 
Random 
number 
Gender 
Age (yr) 
Weight (kg) 
Name of visit 
Sampling date 
Inspection index 
Check value 
Compan
y 
Determination 
of 
clinical significance 
Note: examination indexes:Urine, white blood cell test. 
NCS: abnormal without clinical significance, CS: abnormal with clinical significance. 
List 7-7 blood biochemical abnormal values (normal baseline → abnormal after treatment) (SS) 
List 7-8 abnormal blood biochemical values (baseline NCS → CS after treatment) (SS)   
List 7-9 blood biochemical measured values (SS) 
group 
center 
Random 
number 
Gender 
Age (yr) 
Weight (kg) 
Name of visit 
Sampling date 
Inspection index 
Check value 
Compan
y 
Determination 
of 
clinical significance 
Note: examination indexes: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, Total bilirubin, direct bilirubin, urea nitrogen, creatinine. 
NCS: abnormal without clinical significance, CS: abnormal with clinical significance. 
List 7-10 electrolyte abnormal value (baseline normal → abnormal after treatment) (SS) 
List 7-11 electrolyte abnormal value (baseline NCS → CS after treatment) (SS)   
List 7-12 electrolyte measured value (SS)  
group 
center 
Random 
number 
Gender 
Age (yr) 
Weight (kg) 
Name of visit 
Inspection date 
Inspection index 
Check value 
Compan
y 
Determination 
of 
clinical significance 


TFLs for Statistical Analysis Plan 
Note: examination index: potassium, sodium, chlorine, calcium and magnesium. 
NCS: abnormal without clinical significance, CS: abnormal with clinical significance. 
List 7-13 abnormal value of tumor index examination (normal baseline → abnormal after treatment) (SS) 
List 7-14 abnormal value of tumor index examination (baseline NCS → CS after treatment) (SS)  
List 7-15 measured value of tumor index examination (SS)   
group 
center 
Random 
number 
Gender 
Age (yr) 
Weight (kg) 
Name of visit 
Sampling date 
CA19-9 
(carbohydrate 
antigen) 
detection value 
Compan
y 
Other units 
Determination 
of 
clinical significance 
Note: NCS: abnormal has no clinical significance, CS: abnormal has clinical significance. 
List 8 abnormal value list of ECG examination 
List 8-1 ECG abnormal value  (baseline normal → abnormal after treatment) (SS) 
List 8-2 ECG abnormal value  (baseline NCS → CS after treatment) (SS)  
List 8-3 ECG measured value  (SS)   
group 
center 
Random 
number 
Gender 
Ag
e 
(yr) 
Weight 
(kg) 
Name 
of 
visit 
Inspection 
date 
HR (times / 
min) 
R-R(ms)
P-R(ms)
QRS(ms) 
QT(ms) 
QTc(ms) Results 
description 
Determination of 
clinical 
significance 
Note: NCS: abnormal has no clinical significance, CS: abnormal has clinical significance. 
List 9 vital signs 
List 9-1 measured values of vital signs (SS) 
group 
other 
cente
r 
random 
numb
er 
gender 
Age 
(yr) 
Visit 
name 
Date of visit 
Body 
temperature 
(℃) 
Pulse rate (times / 
min) 
breathing 
(minutes) 
systolic 
pressure 
(mmHg) 
diastolic 
pressure 
(mmHg) 
height 
(cm) 
Weight (kg) 
Body 
surface 
area (m2) 
List 10 physical examination list 
List 10-1 abnormal values of physical examination (baseline normal → abnormal after treatment) (SS) 
List10-2 measured values of physical examination (SS)   
group 
center 
Random 
Gender 
Age (yr) 
Weight (kg) 
Name of visit 
Physical 
examination 
Description of abnormal physical 


TFLs for Statistical Analysis Plan 
number 
results 
examination 
List 11 pregnancy tests 
List 11-1 pregnancy tests (SS) 
group 
center 
Random 
number 
Age (yr) 
Weight (kg) 
Name of visit 
Inspection date 
Inspection results 
List 11-2 pregnancy report form (SS) 
Group 
Center
Random number 
Pregnancy during the trial 
Report type 
Follow up times 
Researcher 
Contact number 
Subject abbreviation 
Gender 
Date of birth 
Random number 
Date of diagnosis of pregnancy 
Date of last menstruation 
Pregnancy outcome 
Date 
of 
termination 
of 
pregnancy 
Date of birth 
Sex of fetus 
Other supplements 


TFLs for Statistical Analysis Plan 
Is the outcome of the fetus or 
infant for SAE 
SAE reasons 
Contraceptive 
methods 
of 
subjects 
Previous pregnancies (beyond 
this time) 
abortion 
Other risk factors 
Did SAE happen before the trial 
of subjects 
SAE descriptions 
Drugs taken by subjects during 
the first 6 months of pregnancy 
(including research use) 
Drug 
package 
number) 
information 
Other 
supplementary 
information 
Note: only pregnant women during the trial were listed. 


TFLs for Statistical Analysis Plan   
Supplement 1, OS subgroup analysis (study drug use times) 
Supplement table 1-1 OS increases by the subgroup analysis (study drug administration times) (FAS) 
index 
Experimental group 
Control group 
Number of study drug administration 
< 6 times 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X)
XX.X (XX.X~XX.X)
50%(95%CI) 
XX.X (XX.X~XX.X)
XX.X (XX.X~XX.X)
75%(95%CI) 
XX.X (XX.X~XX.X)
XX.X (XX.X~XX.X)
HR(95%CI) 
X.X(X.X~X.X)
>= 6 times 
N 
XX 
XX 
Censored(%) 
XX(XX.X) 
XX(XX.X) 
Number of deaths 
XX(XX.X) 
XX(XX.X) 
Kaplan Meier estimation (month) 
25%(95%CI) 
XX.X (XX.X~XX.X)
XX.X (XX.X~XX.X)
50%(95%CI) 
XX.X (XX.X~XX.X)
XX.X (XX.X~XX.X)
75%(95%CI) 
XX.X (XX.X~XX.X)
XX.X (XX.X~XX.X)
HR(95%CI) 
X.X(X.X~X.X)
Supplement 2. RMSTREG 
In this model, the stratification factor is also considered. 
Table 2-1 OS RMST analysis results considering stratification factor (FAS) 
Analysis of Parameter Estimates 
Parameter 
DF 
Estimate 
SE 
95% Confidence Limits 
Chi-Square 
Pr > ChiSq 


Intercept 
X 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
Tumor location 
X 
X.XXX 
X.XXX 
X.XXX
X.XXX 
X.XXX 
X.XXX 
Surgery history 
X 
X.XXX 
X.XXX 
X.XXX
X.XXX 
X.XXX 
X.XXX 
Management for biliary obstruction 
X 
X.XXX 
X.XXX 
X.XXX
X.XXX 
X.XXX 
X.XXX 
Adjuvant chemotherapy 
X 
X.XXX 
X.XXX 
X.XXX
X.XXX 
X.XXX 
X.XXX 
Group (trial group) 
X 
X.XXX 
X.XXX 
X.XXX
X.XXX 
X.XXX 
X.XXX 
Note: link = log, estimation method = PV, tau = 75. 
Supplement Table 2-2 RMST analysis results  of OS considering stratification factor (PPS) 
Analysis of Parameter Estimates 
Parameter 
DF 
Estimate 
SE 
95% Confidence Limits 
Chi-Square 
Pr > ChiSq 
Intercept 
X 
X.XXX 
X.XXX 
X.XXX
X.XXX 
X.XXX 
X.XXX 
Tumor location 
X 
X.XXX 
X.XXX 
X.XXX
X.XXX 
X.XXX 
X.XXX 
Surgery history 
X 
X.XXX 
X.XXX 
X.XXX
X.XXX 
X.XXX 
X.XXX 
Management for biliary obstruction 
X 
X.XXX 
X.XXX 
X.XXX
X.XXX 
X.XXX 
X.XXX 
Adjuvant chemotherapy 
X 
X.XXX 
X.XXX 
X.XXX
X.XXX 
X.XXX 
X.XXX 
Group (trial group) 
X 
X.XXX 
X.XXX 
X.XXX
X.XXX 
X.XXX 
X.XXX 
Note: link = log, estimation method = PV, tau = 75. 
Table 2-3 PFS RMST analysis results considering stratification factor (FAS) 
Analysis of Parameter Estimates 
Parameter 
DF 
Estimate 
SE 
95% Confidence Limits 
Chi-Square 
Pr > ChiSq 
Intercept 
X 
X.XXX 
X.XXX 
X.XXX
X.XXX 
X.XXX
X.XXX 
Tumor location 
X 
X.XXX 
X.XXX 
X.XXX
X.XXX 
X.XXX 
X.XXX 
Surgery history 
X 
X.XXX 
X.XXX 
X.XXX
X.XXX 
X.XXX
X.XXX 


Management for biliary obstruction 
X 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
X.XXX
X.XXX 
Adjuvant chemotherapy 
X 
X.XXX 
X.XXX 
X.XXX
X.XXX 
X.XXX
X.XXX 
Group (trial group) 
X 
X.XXX 
X.XXX 
X.XXX
X.XXX 
X.XXX
X.XXX 
Link = log, estimation method = PV, tau = 31.