A Randomized Controlled Study Comparing the Efficacy of QL1706 Combined With Chemotherapy in the Treatment of Immune-mediated Non-small Cell Lung Cancer
Phase: PHASE2
Conditions: NSCLC (Advanced Non-small Cell Lung Cancer)
Sponsor: Anhui Provincial Cancer Hospital

 
 
 
 
 
Randomized controlled study of QL1706 
combined chemotherapy versus 
chemotherapy for immune-treated non-
small cell lung cancer 
 
Trial cases 
 
 
 
 
 
 
 
 
Program 
version 
number 
V2.0 
Version date 
April 21,2025 
Lead researcher 
Professor Yuan Shuanghu 
Lead research unit 
West District, First Affiliated Hospital of 
China 
University 
of 
Science 
and 
Technology 
 
 
 declaration of secrecy  
This document is provided solely for review by investigators, ethics committees, and relevant 
regulatory authorities. All rights to pharmaceutical-related information herein belong to the collaborating 
pharmaceutical partners. Without obtaining written consent from the partners, except for necessary 

 
Randomized controlled study of the comparison of chemotherapy with chemotherapy for immune treated patients with QL1706 
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Program version number/date: v2.0/2025.04.21 
Programme signature page 
I have read and understood this trial protocol (Version: v2.0; Version Date: April 
21,2025), and hereby consent to conduct this trial in accordance with its provisions and 
related supporting documents. I will provide the protocol to my research team and 
engage in discussions to ensure their full comprehension. I acknowledge that the 
collaborating organization may request termination of the trial or cessation of 
participant enrollment at any time for specified reasons, and I may terminate the trial 
to protect participants' rights. I hereby commit to strictly complying with all applicable 
regulations and Good Clinical Practice (GCP) standards throughout the trial. 
At the same time, as the principal investigator of this trial, I coordinated the overall 
process of the trial. 
 
 
 
 
 
 surname 
and
personal
 
 sign 
one's 
name ：
 
 date ： 
 

 
Randomized controlled study of the comparison of chemotherapy with chemotherapy for immune treated patients with QL1706 
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Program version number/date: v2.0/2025.04.21 
 catalogue  
Programme summary 6 ........................................................................................................... 7 
1. Background information 21 .............................................................................................. 22 
1.1 Epidemiology and Current Status of Treatment for Driver Gene Negative Non-small 
Cell Lung Cancer 21 ............................................................................................................ 22 
1.2 Current status of immunotherapy after driving gene-negative non-small cell lung 
cancer developed drug resistance 22 ................................................................................... 23 
1.3 Mechanism of action of QL170625 ............................................................................... 26 
2. Objective and endpoints of the study 26 .......................................................................... 27 
2.1 Research purpose 26 ...................................................................................................... 27 
2.2 Primary study endpoints 27 ........................................................................................... 27 
2.3 Secondary endpoints 27 ................................................................................................. 27 
3. Design of the test 28 ............................................................................................................ 28 
3.1 Overall design 28 ........................................................................................................... 28 
3.2 Duration of the study 27 ................................................................................................ 28 
4. Trial population 28 ............................................................................................................. 29 
4.1 Sample size 29 ............................................................................................................... 29 
4.2 Selection criteria 30 ....................................................................................................... 29 
4.3 Exclusion criteria 30 ...................................................................................................... 30 
4.4 Termination criteria 32 .................................................................................................. 32 
4.5 Removal/removal criteria 33 ......................................................................................... 33 
5. Data collection management and research steps 33 ........................................................ 33 
5.1 Data collection plan 33 .................................................................................................. 33 
5.2 Filling in and transfer of case report form 34 ................................................................ 34 
5.3 Database locking 34 ....................................................................................................... 34 
5.4 Screening period visits 34 .............................................................................................. 34 
5.5 Trial period 36 ............................................................................................................... 36 
5.6 End of trial treatment/withdrawal from study 37........................................................... 37 
5.7 Follow-up period 38....................................................................................................... 38 
6. Test drugs 48 ....................................................................................................................... 48 
6.1 Drug name and specification 48 .................................................................................... 48 
6.2 Drug management 48 ..................................................................................................... 48 
6.4 Combination of drugs 49 ............................................................................................... 49 
7 Efficacy evaluation 50 ......................................................................................................... 50 
7.1 Efficacy evaluation criteria 50 ....................................................................................... 50 
7.2 Efficacy evaluation methods 51 ..................................................................................... 51 
7.3 Intervals for evaluation of efficacy 51 ........................................................................... 51 
8 Detection of adverse events 51 ........................................................................................... 51 
8.1 Adverse events 51 .......................................................................................................... 51 

 
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8.2 Classification of adverse events 52 ................................................................................ 52 
8.3 Judgment of the relationship between adverse events and treatment 52 ....................... 52 
8.4 Serious Adverse Events (SAE) 53 ................................................................................. 53 
8.5 Recording of adverse events 56 ..................................................................................... 56 
9. Statistics 57 ......................................................................................................................... 57 
9.1 Statistical analysis data set 57 ........................................................................................ 57 
9.2 Statistical analysis methods 57 ...................................................................................... 57 
9.3 Analysis of efficacy endpoints 58 .................................................................................. 58 
9.4 Adverse event analysis 58.............................................................................................. 58 
10 Quality control and test records 59 ................................................................................. 59 
10.1 Data quality assurance 59 ............................................................................................ 59 
10.2 Test records 59 ............................................................................................................. 59 
10.3 List reporting and rapid reporting of adverse events 60 .............................................. 60 
10.4 Test plan violations 60 ................................................................................................. 59 
11 Ethics Information and Confidentiality Agreement 61 ................................................. 60 
11.1 Ethics approval and informed consent 61 .................................................................... 60 
11.2 Confidentiality Agreement 62 ..................................................................................... 61 
12 Programme revisions 58 ................................................................................................... 61 
13 Results published 62 .......................................................................................................... 61 
13.1 Ownership and use of research data and findings 59 ................................................... 61 
13.2 Data dissemination 62 .................................................................................................. 61 
14 References 63 ..................................................................................................................... 62 
Appendix 1. NCI CTCAE v5.0 66 ......................................................................................... 65 
Appendix 2. Criteria for the evaluation of therapeutic effects in solid tumors 1.1 Edition 
67 .............................................................................................................................................. 66 
Appendix 3. Relationship between adverse events and investigational drug 78 .............. 77 
Appendix 4. ECOG Physical Status Score Criteria 79 ....................................................... 78 
 

 
Randomized controlled study of the comparison of chemotherapy with chemotherapy for immune treated patients with QL1706 
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 scenario summary  
 
 research topic  
Randomized controlled study of QL1706 combined 
chemotherapy versus chemotherapy for immune-treated non-
small cell lung cancer 
 project number  
QL1706-NSCLC-A001 
 version number  
V2.0 
Lead researcher 
Professor Yuan Shuanghu 
Sponsor 
West District, First Affiliated Hospital of China University of 
Science and Technology 
Cooperative units 
Qilu Pharmaceutical Co., LTD 
Nature of study 
Prospective, multicenter, open-label, randomized, controlled study 
Type of study 
Clinical trial initiated by the investigator (IIT) 
 subject investigated  Immune-treated locally advanced or recurrent/metastatic non-
small cell lung cancer 
 purpose of research  
To explore the efficacy and safety of combined chemotherapy 
with QU1706 compared with chemotherapy for immunotherapy 
in locally advanced or recurrent/metastatic non-small cell lung 
cancer 
Number of patients 
planned for 
enrollment 
96 cases 
 research on drug  
QL1706：5mg/kg，iv，d1； 
Gisicitabine: 1000mg/m2, iv, d1, d8; 
Doxorubicin: 60mg/m2, iv, d1; 
Three weeks is a cycle 
 research design  
This prospective, multicenter, open-label randomized controlled 
study enrolled 96 patients with immune-treated locally advanced 
or recurrent/metastatic non-small cell lung cancer. Participants 
were randomly assigned in a 1:1 ratio to either the experimental 
group receiving the combination of QL1706 and docetaxel or 
gemcitabine, or the control group receiving docetaxel or 
gemcitabine alone.  

 
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Point of research 
Main destinations: 
➢ Progression-Free Survival (PFS) 
Secondary endpoints: 
➢ Objective Response Rate (ORR) 
➢ Disease Control Rate (DCR) 
➢ Relief duration (DOR, Duration of Response) 
➢ Overall Survival (OS) 
➢ Safety evaluation (AE, Adverse Events). 
Sample size 
determination 
This prospective, open-label, randomized controlled trial was 
designed based on literature data. The control group received 
standard chemotherapy with a median progression-free survival 
(mPFS) of 3 months, while the experimental group receiving the 
Aeto combination therapy (antibody plus chemotherapy and 
radiotherapy) had a projected mPFS of 6 months. With a total 
study duration of 24 months (including enrollment and follow-up), 
the mid-term enrollment time (assuming uniform enrollment rate) 
was set at 12 months. Using a significance level of α=0.05 and 
beta=0.2, the calculated sample size was 38 patients per group. 
Considering a 20% dropout rate, each group required 48 additional 
participants, resulting in a total enrollment of 96 patients. 
 
Entry criteria 
 
 
 
 
 
Patients must meet all of the following criteria to be enrolled: 
1. Voluntary participation in the study and signing of informed 
consent; 
2. Age ≥ 18 years old, ≤75 years old; 
3. Diagnosed as NSCLC by histology or cytology; 
4. No EGFR sensitive mutation or ALK gene translocation; 
5. 
Patients who previously received PD-1/PD-L1 inhibitors and platinum-
containing double-drug chemotherapy as first-line treatment for 

 
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Entry criteria 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Entry criteria 
 
 
 
advanced metastatic or relapsed NSCLC and developed disease 
progression during or after treatment; 
6. At least one measurable lesion as the target lesion (RECIST 
v1.1 criteria); 
7. ECOG score: 0-2 points; 
8. The survival period is expected to be no less than 12 weeks; 
9. Women of childbearing age must have a negative pregnancy 
test (serum or urine) within 28 days prior to enrollment and 
voluntarily use appropriate methods of contraception during 
the observation period and for 8 weeks after the last dose; for 
men, surgical sterilization or consent to use appropriate 
methods of contraception during the observation period and 
for 8 weeks after the last dose; 
10. Laboratory findings during the screening period indicate 
normal organ function: a) Hematology (no blood transfusion 
or hematopoietic cell/granulocyte colony factor therapy 
within 14 days): Neutrophil count (NEU) ≥1.5×10^9/L 
(1,500/mm³); 
Platelet 
count 
(PLT) 
≥100×10^9/L 
(100,000/mm³); Hemoglobin ≥90 g/L; b) Liver: Total 
bilirubin (TBil) ≤ULN; Alanine aminotransferase (AST) and 
Aspartate aminotransferase (ALT) ≤1.5×ULN; AST or ALT 
1.5-3.5×ULN; Alkaline phosphatase (ALP) ≤2.5×ULN; c) 
Kidneys: Calculated creatinine clearance (CrCl) ≥30 mL/min; 
d) Coagulation: International Normalized Ratio (INR) ≤1.5, 
with 
Prothrombin 
Time 
(PT) 
or Activated 
Partial 
Thromboplastin Time (APTT) ≤1.5×ULN; j) INR ≤1.5 and 
APTT ≤1.5×ULN. 
11. Patients who the researchers think could benefit. 

 
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Exclusion criteria 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Exclusion criteria 
 
 
 
 
 
 
 
 
 
Patients will not be eligible if they meet any of the following 
criteria: 
1. There are EGFR sensitive mutations or ALK gene 
translocation changes. 
2. Had previously received PD1/CTLA4 bispecific antibody 
therapy; 
3. The adverse reactions caused by previous treatment have not 
recovered to CTCAE (version 5.0) level 1 or below (except 
for the toxicity of level 2 or less that is judged by the 
investigator to be long-term, cannot be restored and does not 
increase safety risk); 
4. Symptomatic central nervous system metastases. Patients 
who have received treatment for brain metastases and are 
considered stable by the investigator may be considered for 
participation in this study; 
5. Patients with poorly controlled tumor-related pain who 
require analgesic treatment must receive a stable dose of 
treatment prior to participation in the study; 
6. Patients with clinical symptoms or unstable chest water or 
ascites or pericardial effusion after symptomatic treatment; 
7. Known to be susceptible to epalopritovorirelium and its 
components, planned chemotherapy drugs and those with a 
history of severe allergic reactions; 
8. Patients with or suspected of having active autoimmune 
diseases, including but not limited to systemic lupus 
erythematosus, rheumatoid arthritis, inflammatory bowel 
disease, etc., excluding: type 1 diabetes and hypothyroidism 
that can be controlled by stable dose replacement therapy, 
and skin diseases (such as psoriasis, vitiligo) that do not 
require systemic treatment; 
9. History of interstitial lung disease or drug-induced interstitial 
lung disease or pneumonia; 

 
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Exclusion criteria 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
10. Patients who received systemic corticosteroid drugs 
(Prednisone> 10mg/day or equivalent dose) or other 
immunosuppressive drugs within 14 days prior to study 
medication; 
11. History of immune deficiency, including other acquired or 
congenital immune deficiency diseases, or history of organ 
transplantation, or allogeneic hematopoietic stem cell 
transplantation or solid organ transplantation; live vaccine 
vaccination within 4 weeks prior to the first study 
medication; 
12. Patients with severe cardiovascular and cerebrovascular 
diseases: a) Uncontrolled hypertension or pulmonary 
hypertension; b) Unstable angina or history of myocardial 
infarction, coronary artery bypass grafting (CABG), or stent 
implantation within 6 months prior to study medication; c) 
Chronic heart failure with cardiac function grade ≥2 (New 
York Heart Association NYHA classification); d) Left 
ventricular ejection fraction (LVEF) <50%; e) Severe 
arrhythmias requiring pharmacotherapy (excluding atrial 
fibrillation or paroxysmal supraventricular tachycardia). 
Examples include: males with QTcF>450 msec or females 
with QTcF>470 msec, complete left bundle branch block 
(LBBB), or third-degree block; f) Cerebrovascular accidents 
(CVA) or transient ischemic attacks (TIA) within 6 months 
prior to study medication. 
13. Positive human immunodeficiency virus (HIV) antibody test 
results with active hepatitis B or C. Participants may enroll 
in this study under the following conditions: a) Positive 
hepatitis B core antibody (HBcAb) or hepatitis B surface 
antigen (HBsAg), but HBV DNA levels below the research 
center's lower limit (negative) or <500 IU/mL, with clinical 
treatment and symptoms that researchers determine exclude 
active infection; b) Positive hepatitis C antibody with HCV 

 
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Exclusion criteria 
RNA levels below the research center's lower limit 
(negative). 
14. Having had any active malignancy other than the study 
disease within the last 5 years, except for malignancies that 
are expected to be cured by treatment (including but not 
limited to well-treated thyroid carcinoma, cervical carcinoma 
in situ, basal or squamous cell skin cancer, or breast ductal 
carcinoma in situ treated with radical surgery); 
15. Those with a history of psychotropic drug abuse and unable 
to quit or those with a history of mental disorder; 
16. Pregnant or lactating women; 
17. The study authors believe the patient was not fit for any of 
the other conditions in this study. 
Termination 
standards 
The subject must withdraw/stop treatment if one or more of the 
following occurs: 
1. Patients who showed disease progression on 
medical imaging and were judged by the 
investigator to have no benefit from continued 
medication; 
2. The subject is still unable to tolerate the toxicity 
after dose adjustment; 
3. The subject withdraws informed consent and 
requests to withdraw; 
4. Pregnancy events occurred in subjects during the 
study; 
5. The investigator identifies other circumstances 
that necessitate withdrawal from the study. 
Criteria for 
removal/removal 
1. Failure to complete at least one cycle of clinical trial study 
according to this protocol due to non-test drug factors, and 
inability to evaluate safety and effectiveness; 
2. Serious breach of protocol. 

 
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3. 
Patients were not correctly enrolled in the study for treatment with the 
drug. 
Duration of study 
This study is expected to last 36 months, including a 24-month 
participant enrollment period, a 9-month follow-up period, and a 
3-month data consolidation and report preparation period. 
(Additionally, the study timeline is a projected period. Any 
changes in enrollment or follow-up timing during actual 
implementation do not constitute protocol violations, until the 
completion of participant enrollment and the final participant's 
follow-up). 
 statistical treatment  
The Kaplan-Meier method was used to plot the progression-free 
survival (PFS) curve with 95% confidence interval. The overall 
survival (OS) curve was constructed using the same method to 
estimate mean progression-free survival (mPFS), mean overall 
survival (mOS), and their corresponding 95% confidence 
intervals. ORR and DCR were calculated along with their 95% 
confidence intervals. Safety analysis primarily employed 
descriptive statistics, including tabular descriptions of adverse 
events (AEs) in this trial, covering incidence rates, severity 
levels, causality relationships, contributing factors, implemented 
interventions, and clinical outcomes. 

 
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Program version number/date: v2.0/2025.04.21 
Research flow chart 
 
 time  
 project  
Screening period* 
 experimental stage  
 follow-up period  
D-28~D-7 
(±7 days) 
D-6~D1 (±7 
days) 
Period X 
Treatm
ent 
compl
etion/w
ithdra
wal 
Safety 25 
Efficacy 26 
Survival 27 
Day 1 of Week 2 
(C2D1±7) 
Day 1 of cycle 3 
(C3D1±7) 
Day 1 of Week 4 
(C4D1±7) 
Day 1 of X weeks 
(CxD1±7) 
 basic data  
Sign informed consent 
× 
 
 
 
 
 
 
 
Demographic data 1 
× 
 
 
 
 
 
 
 
Medical history 2 
× 
 
 
 
 
 
 
 
Combined medication 3 
× 
 
 
 
 
 
 
 
Laboratory/auxiliary examinations 
Blood routine 4 
 
× 
× 
× 
× 
× 
× 
 
 
Routine urine 5 
 
× 
× 
× 
× 
× 
× 
 
 
Blood Biochemistry 6 
 
× 
× 
× 
× 
× 
× 
 
 

 
Randomized controlled study of the comparison of chemotherapy with chemotherapy for immune treated patients with QL1706 
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Program version number/date: v2.0/2025.04.21 
 
 time  
 project  
Screening period* 
 experimental stage  
 follow-up period  
D-28~D-7 
(±7 days) 
D-6~D1 (±7 
days) 
Period X 
Treatm
ent 
compl
etion/w
ithdra
wal 
Safety 25 
Efficacy 26 
Survival 27 
Day 1 of Week 2 
(C2D1±7) 
Day 1 of cycle 3 
(C3D1±7) 
Day 1 of Week 4 
(C4D1±7) 
Day 1 of X weeks 
(CxD1±7) 
Coagulation 7 
 
× 
× 
× 
× 
× 
× 
 
 
Thyroid function test 8 
 
× 
× 
× 
× 
× 
× 
 
 
Pregnancy test 9 
× 
 
 
 
 
× 
 
 
Virological tests 10 
× 
 
 
 
 
× 
 
 
Electrocardiogram 11 
× 
 
 
 
 
× 
 
 
Ultrasound 12 
× 
 
 
 
 
× 
 
 
 clinical assessment  
Life signs 13 
 
× 
 
 
 
 
× 
 
 
Physical 14 
 
× 
 
 
 
 
× 
 
 
ECOG score 15 
 
× 
× 
× 
× 
× 
× 
 
 

 
Randomized controlled study of the comparison of chemotherapy with chemotherapy for immune treated patients with QL1706 
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Program version number/date: v2.0/2025.04.21 
 
 time  
 project  
Screening period* 
 experimental stage  
 follow-up period  
D-28~D-7 
(±7 days) 
D-6~D1 (±7 
days) 
Period X 
Treatm
ent 
compl
etion/w
ithdra
wal 
Safety 25 
Efficacy 26 
Survival 27 
Day 1 of Week 2 
(C2D1±7) 
Day 1 of cycle 3 
(C3D1±7) 
Day 1 of Week 4 
(C4D1±7) 
Day 1 of X weeks 
(CxD1±7) 
NYHA classify  
× 
 
 
 
 
× 
 
 
Adverse event 16 
From the date of informed consent to 28 days after the last medication 
 
End point indicators of efficacy and related evaluation 
Imaging studies 17 
× 
Check at the end of each two weeks, and the allowable time window is ±7 
days 
× 
 
 
Progress of disease 18 
 
 
 
 
 
 
 
 
× 
Death 19 
 
 
 
 
 
 
 
 
 
× 
 research on drug  
QL170620 
 
5mg/kg，iv，d1 
 
 
 
Gisicabine 21 
 
1000mg/m2，iv，d1、d8 
 
 
 

 
Randomized controlled study of the comparison of chemotherapy with chemotherapy for immune treated patients with QL1706 
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Program version number/date: v2.0/2025.04.21 
 
 time  
 project  
Screening period* 
 experimental stage  
 follow-up period  
D-28~D-7 
(±7 days) 
D-6~D1 (±7 
days) 
Period X 
Treatm
ent 
compl
etion/w
ithdra
wal 
Safety 25 
Efficacy 26 
Survival 27 
Day 1 of Week 2 
(C2D1±7) 
Day 1 of cycle 3 
(C3D1±7) 
Day 1 of Week 4 
(C4D1±7) 
Day 1 of X weeks 
(CxD1±7) 
Doxorubicin 22 
 
60mg/m2，iv，d1 
 
 
 
Other records 
Distribution of drugs 23 
 
× 
 
 
Pharmaceutical recovery 23 
 
× 
 
 
Follow-up treatment of tumor 24 
 
 
 
 
 
 
 
 
 
 pour ： 
1. Demographic data (abbreviated name, gender, ethnicity, marital status, date of birth, height, weight); 
2. Medical history: This includes the patient's prior history and treatment of driver gene-negative non-small cell lung cancer (NSCLC), 
covering clinical/pathological diagnosis, timing of diagnosis, clinical/pathological staging, EGFR status, microsatellite status; surgical 
intervention, neoadjuvant therapy, adjuvant therapy, radiotherapy, immunotherapy; other tumor history (excluding driver gene-negative 
NSCLC), smoking/alcohol consumption history (current or former use), medication allergies (drug names, allergic reactions), as well as 
comorbid conditions/symptoms (names, duration, treatment received, prognosis). 

 
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3. Compliance Monitoring: Document all concomitant medications from the screening period through study completion. These records must 
include: drug name, dosage, route of administration, frequency, therapeutic purpose, and start/end dates. If a participant initiates new 
systemic anti-tumor therapy during safety monitoring, only adverse events related to the investigational medication should be recorded as 
concomitant treatments. 
4. Complete blood count (CBC) results obtained within 7 days prior to the first medication administration. This includes: red blood cell count 
(RBC), hemoglobin (Hb), white blood cell count (WBC), platelet count (PLT), and white blood cell differential [lymphocyte count (LYM) 
and neutrophil count (ANC)]. CBC tests are performed on the 21st±7th day of each treatment cycle and once at the time of treatment 
completion/withdrawal (if not conducted within 7 days). 
5. Routine urinalysis results within 7 days prior to the first medication administration. This includes: Urinary white blood cells (UWBC), 
urinary protein (UPRO), urinary red blood cells (URBC), and urinary glucose (UGLU). Testing is conducted once per treatment cycle and 
once upon treatment completion/exit (if not performed within 7 days). 
6. Blood biochemical tests shall be based on the results obtained within 7 days prior to the first medication administration. These include: liver 
function [total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin 
(ALB), total protein (TP)] and renal function [urea (UREA), serum creatinine (Cr)]. Fasting blood glucose (FBG) and lipid profile 
(triglycerides, cholesterol) are also required. When necessary, additional cardiac enzyme spectrum tests may be performed, including but not 
limited to creatine kinase (CK), creatine kinase-microsomal (CK-MB), α-hydroxybutyrate dehydrogenase (HBDH), and troponin T (cTnT), 
as determined by the investigator based on the subject's condition. Testing is conducted once per treatment cycle and once upon treatment 
completion/withdrawal (if not performed within 7 days). 
7. The coagulation function was examined within 7 days before the first medication, once per cycle during the treatment period, and once at 
the end of treatment withdrawal (if not done within 7 days); 
8. Examination results within 7 days before the first medication of thyroid function acceptance, once per cycle during treatment, and once at 
the end/withdrawal of treatment (if not performed within 7 days); 
9. Pregnancy tests, women of childbearing age will have a urine or serum pregnancy test within 28 days prior to the first dose and at the time 
of the study treatment termination visit. If the urine pregnancy test result cannot be confirmed as negative, a serum pregnancy test will be 
performed with the serum pregnancy results being used as the criterion; 

 
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10. Viral testing requires test results from this center within 28 days prior to initial treatment initiation. During the screening phase, hepatitis B 
serology panel (HBsAg, HBsAb, HBcAb, HBeAg, HBeAb), along with HCV antibody and HIV antibody tests will be conducted. HBsAg-
positive cases will undergo HBV DNA testing, while HCV antibody-positive patients will receive HCV RNA testing. Additional tests may 
be performed when necessary. For hepatitis B virus carriers, regular viral activity monitoring is recommended throughout the study period, 
with one final test required upon treatment completion (if not conducted within 7 days). 
11. Electrocardiogram: 12 lead electrocardiogram was used to detect the results within 28 days before the first medication in the screening 
period, and one test was performed at the end/treatment withdrawal (if not performed within 7 days prior); 
12. Cardiac color Doppler ultrasound: Screening results must be obtained within 28 days prior to the first medication administration, with one 
final examination conducted at treatment completion or withdrawal (if not performed within the preceding 7 days). The primary monitoring 
focus is on changes in LVEF levels. If LVEF decreases to below 50% with a baseline decline of ≥10%, or if participants experience 
symptoms such as chest pain or palpitations, investigators may conduct additional examinations based on clinical circumstances. 
13. Life signs: including body temperature, blood pressure, respiratory rate and heart rate; screening period (examination results within 7 days 
before the first medication), when the investigator deems it necessary during the trial, additional examinations may be added as appropriate; 
1 examination at the end of treatment/withdrawal (if not performed within 7 days prior); 
14. Physical Examination: This includes the head and face, skin system, lymph nodes, eyes, ears, nose, and throat, mouth, respiratory system, 
cardiovascular system, abdomen, genitourinary system, musculoskeletal system, nervous system, and mental status. Comprehensive 
physical examination results are recorded during the screening period (within 7 days prior to initial medication administration) and at study 
completion. Investigators may add additional examinations as needed during the trial period. One check-up is required upon treatment 
completion/withdrawal (if not conducted within the previous 7 days). 
15. ECOG score, screening period (test results within 7 days prior to first medication), treatment period once per cycle, and treatment 
completion/withdrawal assessment; 
16. Adverse Events: Monitoring will commence on the day participants sign the informed consent form and continue until at least 28 days after 
the final study medication administration. Detailed documentation shall be maintained of adverse events, concomitant 
medications/treatment, and scheduled examinations throughout this period. Follow-up will continue until the adverse event resolves, the 

 
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Program version number/date: v2.0/2025.04.21 
participant initiates new anti-tumor therapy, or the investigator determines that the condition has reached a stable state that is no longer 
considered relapsed. Adverse Event (AE) and laboratory test safety evaluations will be conducted according to the NCI CTCAE 5.0 version. 
17. Imaging examinations: The screening period includes pulmonary imaging, with additional chest-abdominal, cranial, neck, and pelvic scans 
as clinically indicated. Contrast-enhanced CT, MRI, or PET-CT may be used. Baseline tumor assessment can be relaxed to within 28 days 
prior to initial dosing. CT/MRI results obtained before informed consent signing that meet criteria may be used for screening evaluation. 
Routine bone scans are generally unnecessary unless bone metastasis is suspected, with whole-body bone scans permitted using results from 
within 2 months prior to initial dosing. Investigators may add scan sites during baseline or subsequent tumor evaluations as clinically 
indicated (for areas without baseline screening findings, investigators may adjust based on clinical practice). During the trial period, imaging 
examinations should be conducted every 2 cycles±7 under identical conditions (including contrast agent use) as baseline findings (bone 
scans are performed when bone progression is suspected or CR confirmation is required). New lesions should be examined promptly if 
suspected. The imaging window for tumors is ±7 days, with additional imaging allowed if disease progression (e.g., symptom worsening) is 
suspected. Treatment period imaging timing is determined at initiation of study therapy, excluding drug suspension due to toxic reactions. 
Non-screening period imaging allows ±7 days; participants withdrawing early for non-progression reasons (e.g., adverse events, 
management issues) will undergo a treatment completion evaluation upon withdrawal. 
18. Disease Progression: For participants who discontinued trial treatment for reasons other than imaging-confirmed disease progression, if no 
imaging evaluation was performed within 28 days prior to trial termination, an imaging evaluation must be conducted at the time of 
treatment cessation. Additionally, tumor response should continue to be monitored according to the protocol-specified follow-up schedule 
until documented disease progression or initiation of new cancer therapy is confirmed. 
19. Death: During the first year after treatment, survival status and subsequent anti-tumor treatment were collected every 3 months (±7 days) 
through clinical or telephone follow-up. From the second year after treatment, follow-up was conducted every 6 months (±15 days) until 
death; 
20. QL1706:5mg/kg, iv, d1, record the time and dose of each injection; 
21. Gisicabine: 1000mg/m2, iv, d1, d8, record the time and dose of each injection; 

 
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22. Doxorubicin: 60mg/m2, iv, d1, record the time and dose of each drug; 
23. Drug recovery/distribution: Except for the drug distribution in the first cycle and the drug recovery after the end of treatment, the drug will 
be collected and distributed at the end of each cycle, and corresponding records will be made; 
24. Follow-up of subsequent cancer treatment: it is necessary to record whether the subject has received other cancer treatment from the time of 
withdrawal or end of treatment until the death of the patient; it is not necessary to record the combined use of other diseases; 
25. Safety Follow-up: From the date of informed consent to at least 28 days after the final study medication administration, investigators may 
select clinical evaluation measures such as complete blood count, biochemical tests, electrocardiogram (ECG), echocardiography, physical 
examination, vital signs, or ECOG score based on individual patient conditions for non-scheduled examinations. Adverse drug-related 
events shall be followed up until they disappear, reach baseline levels ≤1 grade, achieve stabilization, or are reasonably explained (e.g., loss 
to follow-up, death). 
26. Efficacy Follow-up: Participants who are not PD or did not die were required to undergo efficacy follow-up. Starting from the end of the last 
tumor imaging assessment during the study period, participants received tumor imaging evaluations at least once every 12 weeks (±7 days) 
until either PD, initiation of other anti-tumor medications, or death (whichever occurred first). Detailed records were maintained for each 
follow-up time and tumor imaging evaluation results. 
27. Survival Follow-up: All non-deceased subjects who complete safety and efficacy follow-up (with subsequent completion as the benchmark) 
must undergo survival follow-up. Starting from the date of completing safety and efficacy follow-up (with subsequent completion as the 
benchmark), telephone inquiries or clinical visits shall be conducted at least once every 3 months (±7 days) during the first year, and every 
6 months (±14 days) thereafter. These visits shall involve the subject, their family members, or a local physician to collect survival 
information (death date and cause of death). The follow-up will continue until the subject's death, loss to follow-up, or completion of OS 
data collection (whichever occurs first). Each survival follow-up session must be meticulously documented. 
28. All the examination items and frequencies in the flow chart are recommended. When necessary, the investigator can increase or decrease the 
frequency and examination items according to the actual clinical diagnosis and treatment of the subject and the status of the subject; 

 
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29. The laboratory and ancillary examination results involved in this study can be examined by an external hospital, and the results of the 
external hospital examination should be provided to the research center. The investigator will judge whether the results can be used for 
efficacy evaluation. 
 

 
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1.  background information  
1.1 Epidemiology and treatment status of driving gene 
negative non-small cell lung cancer 
Lung cancer is the leading cause of cancer-related deaths globally. According to 
the 2023 Global Cancer Statistics, there were approximately 2.47 million new cases 
and 1.76 million deaths from lung cancer annually, accounting for 18.4% of all cancer-
related deaths [1], with driver gene-negative NSCLC constituting about 30%-40% of 
all NSCLC cases. In China, lung cancer ranks first in both incidence and mortality rates, 
with approximately 870,000 new cases and 760,000 deaths reported in 2022 [2]. Among 
Chinese NSCLC patients, EGFR mutation rates are about 50%, ALK fusions about 5%, 
other mutations (ROS1, RET, etc.) about 5%-10%, and driver gene-negative 
proportions about 30%-40% [3]. Traditional therapies for driver gene-negative 
advanced non-small cell lung cancer have shown limited clinical efficacy. In recent 
years, the emergence of immune checkpoint inhibitors (ICI) has significantly 
transformed the treatment landscape for advanced non-small cell lung cancer patients, 
markedly extending overall survival in late-stage tumor patients. 
Programmed Cell Death Receptor 1 (PD-1) and programmed cell death ligand 1 
(PD-L1), among other immunotherapy drugs, have been among the most significant 
research advancements in oncology in recent years [4]. In advanced non-small cell lung 
cancer (NSCLC) patients, with the publication of Keynote and Checkmate series 
studies, pembrolizumab and nivolumab monotherapy have surpassed chemotherapy as 
single-line treatment regimens for advanced NSCLC [5]. In China, first-line indications 
for advanced NSCLC have been successively approved for pembrolizumab, sintilimab, 
carfilizumab, tislelizumab, and toripalimab [6]. For advanced driver gene-negative 
NSCLC, immunotherapy, especially PD-1 and PD-L1 inhibitors, has significantly 
improved patient prognosis, with a 5-year overall survival rate reaching 20%, and even 
up to 40% in patients with high PD-L1 expression [7]. Therefore, immunotherapy has 
become one of the standard treatment regimens recommended by the guidelines of the 
National Comprehensive Cancer Network (NCCN) and the Chinese Society of Clinical 
Oncology (CSCO) for first-line treatment of driver gene-negative advanced NSCLC, 

 
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and has become a mainstream therapeutic option in clinical practice. Nevertheless, a 
significant proportion of patients still show no response to treatment or only respond 
for a limited period. The median progression-free survival (mPFS) summarized from 
some clinical trials ranges from 4 to 10 months [8]. Research data shows that among 
208 patients who developed acquired resistance after ICI use, 55.3% showed 
oligoprogression and 44.7% showed systemic progression. Oligoprogression is the 
primary progression pattern following immune therapy resistance [9]. For subsequent 
treatment of previously immunotherapy-treated patients, the current standard regimen 
remains chemotherapy-based. However, the efficacy of these programs is generally 
large and the side effects are large, which can not meet the current clinical treatment 
needs [10]. 
1.2 Current status of immunotherapy after treatment in 
driving gene negative non-small cell lung cancer 
At present, there is no clinical treatment for patients with driving gene-negative 
advanced NSCLC who develop resistance to first-line immunotherapy or combination 
of immunotherapy and chemotherapy. Second-line chemotherapy such as docetaxel is 
the standard treatment recommended by NCCN guidelines and CSCO guidelines. A 
2018 retrospective study by Park et al. [11] in South Korea enrolled 73 patients with 
NSCLC experiencing progression after immunotherapy (including nivolumab, 
pembrolizumab, or dutasterib), with 13.7% as second-line patients and 86.3% as 
subsequent-line patients. The treatment group received platinum-containing double-
agent chemotherapy or monotherapy, achieving an objective response rate (ORR) of 
53.4%, with progression-free survival (mPFS) of 4.2 months and overall survival (mOS) 
of 8.1 months. At the 2022 World Conference on Lung Cancer (WCLC), Auclin et al. 
[12] presented a multicenter retrospective analysis of 143 patients with advanced 
NSCLC who developed progression after first-line immunotherapy combined with 
chemotherapy. These patients received second-line treatments including platinum-
based double-agent re-challenge regimens, paclitaxel ± anti-angiogenic therapy, or 
other chemotherapeutic agents (such as gemcitabine, vinorelbine, or pemetrexed). The 
results showed a disease control rate (DCR) of 38% and mOS of 8.1 months for second-
line treatment. Notably, patients with first-line treatment responses lasting over 6 
months demonstrated more significant benefits from second-line therapy, achieving an 

 
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mOS of 12.7 months. Another retrospective study conducted by Liu et al. [13], 
presented at the 2022 World Congress of Lung Cancer (WCLC), enrolled 467 patients 
with advanced NSCLC who had previously received either concurrent or sequential 
treatment with PD-1/PD-L1 inhibitors and platinum-based double-drug chemotherapy. 
These patients subsequently underwent subsequent treatment with paclitaxel 
monotherapy or paclitaxel combined with chemotherapy. The results indicated a 
median overall survival (mOS) of 8.9 months for those receiving paclitaxel as a second-
line treatment. Therefore, this study suggests that for patients experiencing resistance 
to first-line immunotherapy or combination chemotherapy, second-line chemotherapy 
can still provide some survival benefit, though the gains are limited. This highlights the 
need to explore new therapeutic approaches. 
The question of whether continuing immunotherapy after progression in patients 
with secondary resistance to immunotherapy has been a widely discussed issue, and 
some studies have explored the efficacy of continued immunotherapy following 
secondary resistance. A retrospective study published in 2021 by Xu et al. [9] included 
208 stage IV NSCLC patients who developed progression after immunotherapy that 
had stabilized their disease for at least three months (at least two cycles). These patients 
received various treatment regimens post-progression, including continued 
immunotherapy, localized therapy, anti-angiogenic therapy, and combinations thereof. 
The results showed that patients who continued immunotherapy had significantly 
longer median overall survival (mOS) compared to those who discontinued 
immunotherapy (26.3 vs. 18.5 months). The BTCRC-LUN15-029 study, presented at 
the 2021 American Society of Clinical Oncology (ASCO) meeting, enrolled 35 patients 
with PD-1/PD-L1 inhibitors showing progression-free survival (PFS>3 months). 
Following PD treatment, these patients received pembrolizumab combined with 
adjuvant chemotherapy (gemcitabine, docetaxel, pemetrexed). The primary endpoints 
were progression-free survival (mPFS) of 5.2 months (RECIST 1.1 criteria) and overall 
survival (mOS) of 26.8 months. Among the participants, 23.5% achieved partial 
response (PR), while 53% showed stable disease (SD). Compared with historical 
controls receiving monotherapy, the combination of pembrolizumab and adjuvant 
chemotherapy demonstrated prolonged progression-free survival in advanced non-
small cell lung cancer (NSCLC) patients with immune checkpoint inhibitors-induced 
disease progression [14]. The LUNG-MAP S1800A study was a randomized Phase II 
trial targeting stage IV or relapsed/refractory non-small cell lung cancer (NSCLC) 

 
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patients who had previously received immunotherapy. Participants were enrolled after 
84 days of platinum-containing dual-drug combination/sequnized PD-1/PD-L1 therapy, 
with progression. They were randomly assigned in a 1:1 ratio to either pembrolizumab 
plus ramusosinib or investigator-selected standard chemotherapy regimens (docetaxel 
plus ramusosinib, docetaxel, gemcitabine, pemetrexed [for non-squamous cell 
carcinoma]). The median overall survival (mOS) was 14.5 months in the 
pembrolizumab group versus 11.6 months in the ramusosinib group. Compared with 
standard treatment regimens, the combination of pembrolizumab plus ramusosinib 
significantly improved survival in patients with prior chemotherapy and 
immunotherapy [15]. These findings suggest that for patients with first-line 
immunotherapy resistance or combination chemotherapy resistance, second-line 
immunotherapy re-challenge may still offer limited survival benefits, necessitating 
exploration of new treatment strategies. 
Currently, numerous novel approaches targeting immune resistance in non-small 
cell lung cancer (NSCLC) patients are undergoing clinical trials. These include 
combinations of various immune checkpoint inhibitors, antibody-drug conjugates 
(ADCs), tumor vaccines, histone deacetylase inhibitors (HDACi), autologous tumor-
infiltrating lymphocyte (TIL) therapy, and microbiota transplantation therapy. The 
combination of PD-1/PD-L1 inhibitors with novel immune checkpoint modulators such 
as CTLA-4, T-cell immunoglobulins, TIGIT (T cell immunoglobulin and ITIM domain 
protein), lymphocyte activation gene-3 (LAG-3), and T-cell immunoglobulin mucins-
3 (TIM-3) may serve as a potential strategy to overcome immune resistance. The 
RECLAIM study [16], a prospective Phase II trial, enrolled 30 patients with PD-L1-
low (1%-49%) or PD-L1-negative (<1%) advanced NSCLC who had previously 
received chemotherapy or anti-PD-1 therapy. These patients were treated with a 
combination of PD-1 inhibitors (nivolumab) + CTLA-4 inhibitors (ipilimumab) + 
radiotherapy. The results showed 33% objective response rate (ORR) in patients with 
radiologically evaluable disease, demonstrating that the combination of PD-1 inhibitors, 
CTLA-4 inhibitors, and radiotherapy exhibits potent antitumor activity in 
immunorefractory patients with PD-L1-low or PD-L1-negative tumors. 

 
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1.3 The mechanism of action of QL1706 
The injection formulation of Iparomlimab-Tuvonralimab (Drug Designator: QL-
1706) is a novel combination antibody developed by Qilu Pharmaceutical Co., Ltd. This 
innovative therapeutic combines two engineered monoclonal antibodies in a fixed 2:1 
ratio: Iparomlimab (PD-1-targeting IgG4 antibody) and Tuvonralimab (CTLA-4-
targeting IgG1 antibody). The dual-action mechanism blocks both PD-1 and CTLA-4 
simultaneously. The anti-PD-1 component utilizes a conventional IgG4 framework, 
preventing adhesion-dependent cell-mediated cytotoxicity (ADCC) and complement-
dependent cell-mediated cytotoxicity (CDC) effects that could eliminate activated 
CD4+ and CD8+ T cells. This design preserves T-cell viability while enhancing 
interferon-γ (IFNγ) production within tumor microenvironments, thereby boosting 
immune efficacy. The anti-CTLA-4 component targets CTLA-4, an immune 
checkpoint molecule that inhibits T-cell activation. When binding to CTLA-4 on 
regulatory T cells (Tregs), the IgG1-based Tuvonralimab triggers ADCC-mediated 
cytotoxicity, eliminating tumor-suppressing Tregs and ultimately improving antitumor 
outcomes. Furthermore, to enhance therapeutic efficacy and safety, the Fc region of 
tovoririzumab was meticulously engineered to reduce its binding affinity with FcRs. 
This modification shortened the drug's half-life to one week while maintaining 
therapeutic effectiveness, effectively mitigating potential adverse reactions caused by 
prolonged CTLA-4 suppression. The combination of these two monoclonal antibodies 
(QL1706) creates a potent synergistic effect. While effectively reversing T-cell 
activation suppression and preserving effector T cell activity, it simultaneously targets 
Treg cells to improve the tumor microenvironment. This mechanism establishes a 
positive feedback loop within the tumor immune circuitry. 
Preclinical studies demonstrated that in PD-1-resistant mouse models, the 
combination of QL1706 and chemotherapy significantly reduced tumor volume 
(p<0.001) without increasing immunotoxicity [17]. Furthermore, in the Phase I study 
of QL1706 [18],20 patients with immune-resistant non-small cell lung cancer achieved 
partial response (PR) in 3 cases, yielding an objective response rate (ORR) of 15% (95% 
CI: 3.2%-37.9%). The incidence of grade 3-4 treatment-related adverse events (TRAEs) 
was 12% across all dose groups, significantly lower than the 33% observed in 

 
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traditional dual-immunotherapy regimens like O+Y [19]. No treatment-related deaths 
occurred during the study. 
In summary, immunotherapies remain a cornerstone treatment for advanced non-
small cell lung cancer (NSCLC). However, the emergence of drug resistance after 
immunotherapy has significantly impacted patient survival and prognosis. While initial 
studies have explored resistance mechanisms, more research is needed to clarify key 
contributing factors and develop effective prevention strategies. Preclinical and Phase 
I clinical trials of QL1706 have demonstrated promising preliminary efficacy and good 
tolerability in PD-1-resistant NSCLC. Building on these findings, this study proposes 
an exploratory trial comparing QL1706 combined chemotherapy with monotherapy in 
treating immune-treated drive-negative NSCLC patients. 
 
 
2. Research objectives and endpoints 
2.1 Research purpose 
To evaluate the efficacy and safety of combined chemotherapy with QU1706 in 
treating immune-mediated, driver gene-negative, non-small cell lung cancer. 
2.2 Primary study endpoints 
Progression-free survival (PFS): time from initiation of treatment to first disease 
progression or death from any cause; 
2.3 Secondary study endpoints 
Objective response rate (ORR): refers to the proportion of patients whose tumor 
volume is reduced by 30% and can be maintained for more than 4 weeks, that is, the 
sum of complete response and partial response (CR+PR). 
Disease control rate (DCR): refers to the number of patients with tumors that 
have shrunk or remained stable and have remained stable for a certain period of time 
after receiving treatment with QL1706 combined chemotherapy or chemotherapy 
regimen; 

 
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Response duration (DOR): The time from the first assessment of complete or 
partial tumor response to the first assessment of tumor progression or death. 
Overall survival (OS): time from initiation of medication to death due to any 
cause; 
Adverse Events (AE): Collect all adverse events that occurred in subjects from 
the date of signing an informed consent to 28 days after discontinuation of 
medication. This includes clinical symptoms and abnormal vital signs, as well as 
abnormalities in laboratory tests. The clinical manifestations, severity, timing, 
duration, management methods, and prognosis of these events are recorded, along 
with their correlation to the investigational drug. 
3.  experiment design  
3.1 system design  
This prospective, multicenter, open-label randomized controlled study enrolled 
96 patients with immune-treated driver gene-negative locally advanced or 
recurrent/metastatic non-small cell lung cancer. The patients were randomly assigned 
in a 1:1 ratio to receive the experimental group QL1706 combined with docetaxel or 
gemcitabine regimen, and the control group received docetaxel or gemcitabine 
regimen. 
3.2 Duration of the study 
This study is expected to last 36 months, including a 24-month enrollment period. 
⚫ Date of enrollment/entry of the first patient into the study: March 2025; 
⚫ Last patient enrollment date: February 2027; 
⚫ Date of study completion: November 2027 (9 months after the last eligible 
patient was enrolled); 
⚫ Database lock date: December 2027; 
⚫ 
Report date: February 2028. 
Note: If the actual duration of the study changes, it is not a protocol violation. 

 
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4. Trial population 
4.1 Sample size 
This prospective, open-label, randomized controlled trial was designed based on 
literature data. The control group received standard chemotherapy with a median 
progression-free survival (mPFS) of 3 months, while the experimental group 
receiving the Aito combination therapy (antibody plus chemotherapy and 
radiotherapy) was projected to achieve a mPFS of 6 months. The total study duration 
(enrollment + follow-up) was 24 months, with a mid-term enrollment period of 12 
months (assuming uniform enrollment rate). Using a significance level of α=0.05 and 
beta=0.2, the calculated sample size was 38 patients per group. Considering a 20% 
dropout rate, each group required 48 additional patients, resulting in a total enrollment 
of 96 patients. 
4.2 Selection criteria 
Participants must meet all of the following criteria to be enrolled: 
1. Voluntary participation in the study and signing an informed consent form; 
2. Age ≥ 18 years old, ≤75 years old; 
3. Diagnosed as NSCLC by histology or cytology; 
4. No EGFR sensitive mutation or ALK gene translocation; 
5. Patients who previously received PD-1/PD-L1 inhibitors in combination with or 
sequential platinum-containing double drug chemotherapy as first-line treatment 
for advanced metastatic or relapsed NSCLC and who developed disease 
progression during or after treatment; 
6. At least one measurable lesion as the target lesion (RECIST v1.1 criteria); 
7. ECOG score: 0-2 points; 
8. The survival period is expected to be no less than 12 weeks; 
9. Women of childbearing age must have a negative pregnancy test (serum or urine) 
within 28 days prior to enrollment and voluntarily use appropriate methods of 
contraception during the observation period and for 8 weeks after the last dose; for 

 
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men, surgical sterilization or consent to use appropriate methods of contraception 
during the observation period and for 8 weeks after the last dose; 
10. Laboratory findings during the screening period indicate normal organ function: a) 
Hematology (no blood transfusion or hematopoietic cell/granulocyte colony factor 
therapy within 14 days): Neutrophil count (NEU) ≥1.5×10^9/L (1,500/mm³); 
Platelet count (PLT) ≥100×10^9/L (100,000/mm³); Hemoglobin ≥90 g/L; b) 
Liver: Total bilirubin (TBil) ≤ULN; Alanine aminotransferase (AST) and 
Aspartate aminotransferase (ALT) ≤1.5×ULN; AST or ALT 1.5-3.5×ULN; 
Alkaline phosphatase (ALP) ≤2.5×ULN; c) Kidney: Calculated creatinine 
clearance (CrCl) ≥30 mL/min; d) Coagulation: International Normalized Ratio 
(INR) ≤1.5, with Prothrombin Time (PT) or Activated Partial Thromboplastin 
Time (APTT) ≤1.5×ULN; j) International Normalized Ratio (INR) ≤1.5; 
Activated Partial Thromboplastin Time (APTT) ≤1.5×ULN; 
11. Patients who the researchers think could benefit. 
4.3 Exclusion criteria 
Participants will not be eligible for inclusion if they meet any of the following 
criteria: 
1. The presence of EGFR sensitive mutation or ALK gene translocation; 
2. Had previously received PD1/CTLA4 bispecific antibody therapy; 
3. The adverse reactions caused by previous treatment have not recovered to 
CTCAE (version 5.0) level 1 or below (except for the toxicity of level 2 or less 
that is judged by the investigator to be long-term, cannot be restored, and does 
not increase safety risk); 
4. Symptomatic central nervous system metastases. Patients who have received 
treatment for brain metastases and are considered stable by the investigator may 
be considered for participation in this study; 

 
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5. Patients with poorly controlled tumor-related pain who require analgesic 
treatment must receive a stable dose of treatment prior to participation in the 
study; 
6. Patients with clinical symptoms or unstable chest, abdominal or pericardial fluid 
after symptomatic treatment; 
7. Known to be susceptible to epalopritovorirelium and its components, planned 
chemotherapy drugs and those with a history of severe allergic reactions; 
8. Patients with or suspected of having active autoimmune diseases, including but 
not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory 
bowel disease, etc., excluding: type 1 diabetes and hypothyroidism that can be 
controlled by stable dose replacement therapy, and skin diseases (such as 
psoriasis, vitiligo) that do not require systemic treatment; 
9. History of interstitial lung disease or drug-induced interstitial lung disease or 
pneumonia; 
10. Patients who received systemic corticosteroid drugs (Prednisone> 10mg/day or 
equivalent dose) or other immunosuppressive drugs within 14 days prior to study 
medication; 
11. History of immune deficiency, including other acquired or congenital immune 
deficiency diseases, or history of organ transplantation, or allogeneic 
hematopoietic stem cell transplantation or solid organ transplantation; live 
vaccine vaccination within 4 weeks prior to the first study medication; 
12. Patients with severe cardiovascular and cerebrovascular diseases: a) Uncontrolled 
hypertension or pulmonary hypertension; b) Unstable angina or history of 
myocardial infarction, coronary artery bypass grafting (CABG), or stent 
implantation within 6 months prior to study medication; c) Chronic heart failure 
with cardiac function grade ≥2 (New York Heart Association NYHA 
classification); d) Left ventricular ejection fraction (LVEF) <50%; e) Severe 
arrhythmias requiring pharmacotherapy (excluding atrial fibrillation or 
paroxysmal supraventricular tachycardia). Examples include: males with 
QTcF>450 msec or females with QTcF>470 msec, complete left bundle branch 
block (LBBB), or third-degree block; f) Cerebrovascular accidents (CVA) or 
transient ischemic attacks (TIA) occurring within 6 months prior to study 
medication. 

 
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13. Positive human immunodeficiency virus (HIV) antibody test results with active 
hepatitis B or C. Participants may enroll in this study under the following 
conditions: a) Positive hepatitis B core antibody (HBcAb) or hepatitis B surface 
antigen (HBsAg), but HBV DNA levels below the research center's lower limit 
(negative) or <500 IU/mL, with clinical treatment and symptoms that researchers 
determine exclude active infection; b) Positive hepatitis C antibody with HCV 
RNA levels below the research center's lower limit (negative). 
14. Having had any active malignancy other than the study disease within 5 years, 
except for those that are expected to be cured by treatment (including but not 
limited to well-treated thyroid carcinoma, cervical carcinoma in situ, basal or 
squamous cell skin cancer, or breast ductal carcinoma in situ treated with radical 
surgery); 
15. Those with a history of psychotropic drug abuse and unable to quit or those with 
a history of mental disorder; 
16. Pregnant or lactating women; 
17. The study authors believe that the patient was not fit for any of the other 
conditions in this study. 
4.4 Termination criteria 
The subject must discontinue/treat if one or more of the following occurs: 
1) Patients who show disease progression on medical imaging examination and are 
judged by the investigator to have no benefit from continued medication; 
2) The subject is still unable to tolerate the toxicity after dose adjustment; 
3) The subject withdraws the informed consent and requests to quit; 
4) Pregnancy events occurred during the study; 
5) Other circumstances in which the investigator considers it necessary to withdraw 
from the study. 
4.5 Removal/removal criteria 
The subject is excluded if one or more of the following conditions occurs: 
1) Failure to complete at least one cycle of clinical trial study according to this 
protocol due to non-trial drug factors, and safety and effectiveness evaluation 

 
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cannot be performed; 
2) Serious breach of the plan. 
3) Patients were not correctly enrolled in the study for drug treatment. 
5. Data collection management and research 
steps 
5.1 Data collection plan 
This study is divided into four phases: screening, trial, treatment completion/exit, 
and follow-up. Prior to enrollment, patients must read and sign the current ethics 
committee (EC)-approved informed consent form. All study procedures must be 
conducted within the timeframes specified in the study schedule. The duration for safety 
data collection runs from the date of informed consent (ICF) until 28 days after the last 
medication administration. Adverse events will be assessed according to the NCI 
CTCAE 5.0 criteria. All adverse events will be recorded in the Case Report Form (CRF) 
from ICF signing until study completion. Each participant will undergo scheduled visits, 
with specific data being documented at different time points during these visits. 
The laboratory and ancillary test results involved in this study can be examined by 
an external hospital, and the results of the external hospital examination should be 
provided to the research center. The investigator will decide whether to accept the test 
results or re-examine them. 
All examinations/inspections are recommended, and specific examinations/inspections 
are subject to clinical practice. 
5.2 Filling in and transfer of case report form 
The case report form is completed by the investigator, and each selected case must 
complete the case report form. After the completed case report form is reviewed by the 
clinical monitor, the first copy is transferred to the data administrator for data entry and 
management. 

 
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5.3 Database locking  
After the data is reviewed and confirmed that the database is correct, the principal 
investigator, sponsor, and statistical analyst will lock the data. The locked data file will 
not be modified. 
5.4 Screening period visits 
After signing the informed consent form, the subject enters the screening period. 
Physical examinations, vital signs, and laboratory tests (including complete 
blood count, urinalysis, biochemical blood tests, coagulation function, etc.) must be 
conducted within 7 days prior to initiating study treatment. Blood HCG levels, tumor 
imaging studies (head plain scan with contrast-enhanced MRI, chest-abdominal 
contrast-enhanced CT or MRI), 12-lead ECG, and echocardiography must be 
performed within 28 days prior to treatment initiation. For laboratory test results, 
imaging findings (bone scans permitted for results from two months prior to informed 
consent), 12-lead ECG, and cardiac color Doppler ultrasound obtained within 7 days 
before signing the informed consent form: If these tests sufficiently support the 
investigator's assessment of the subject's eligibility for enrollment criteria during the 
screening period, they need not be repeated; otherwise, retesting is required during the 
screening phase. 
⚫ 
Demographic data collection: demographic data (abbreviated name, gender, ethnicity, 
marital status, date of birth, height, weight); 
⚫ 
Medical history inquiry: This includes the patient's prior history and treatment of non-
small cell lung cancer (clinical/pathological diagnosis, timing of diagnosis, 
clinical/pathological staging, EGFR status, microsatellite status; surgical intervention, 
neoadjuvant therapy, adjuvant therapy, radiotherapy, immunotherapy; other tumor 
conditions besides small cell lung cancer; smoking/alcohol consumption history (current 
status and cessation), drug allergies (medication names, allergic reactions), pre-existing 
or comorbid conditions/symptoms (disease/symptom names, duration, treatment 
received, prognosis); 
⚫ 
ECOG grade ； 
⚫ 
Life signs: including body temperature, blood pressure, respiratory rate and heart rate; 
⚫ 
Physical examination: including head and face, skin system, lymph nodes, eyes, ears, 
nose and throat, oral cavity, respiratory system, cardiovascular system, abdomen, 

 
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reproductive and urinary system, musculoskeletal, nervous system and mental state; 
⚫ 
Blood routine: including white blood cells, red blood cells, hemoglobin, platelets, 
neutrophils, lymphocytes absolute count; 
⚫ 
Urinary routine: including protein, sugar, red blood cells and white blood cells in urine; 
⚫ 
Blood Biochemistry: Includes total bilirubin, direct bilirubin, indirect bilirubin, ALT, 
AST, AKP, γ-GT, LDH, total protein, albumin, urea or blood urea nitrogen, creatinine, 
uric acid, fasting blood glucose, triglycerides, and cholesterol. When necessary, add 
cardiac enzyme spectrum tests including but not limited to creatine kinase (CK), creatine 
kinase isoenzyme (CK-MB), α-hydroxybutyrate dehydrogenase (BHD), and troponin T 
(cTnT), as determined by the investigator based on the subject's condition. 
⚫ 
Coagulation: including clotting time, thrombin time, prothrombin time, partial activated 
prothrombin time, etc.; 
⚫ 
Thyroid function test: including total triiodothyronine (TT3), total thyroxine (TT4), free 
triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH); 
⚫ 
Pregnancy test: Women of childbearing age will have a urine or serum pregnancy test 
within 28 days prior to the first dose and at the time of the study treatment termination 
visit. If the urine pregnancy test result cannot be confirmed as negative, a serum 
pregnancy test will be performed with the serum pregnancy results being used as the 
criterion; 
⚫ 
Viral detection: including hepatitis B five (HBsAg, HBsAb, HBcAb, HBeAg, HBeAb) 
test, HCV antibody and HIV antibody test. If HBsAg is positive, further HBV DNA test 
will be conducted; if HCV antibody is positive, further HCV RNA test will be conducted; 
⚫ 
Electrocardiogram: 12 lead electrocardiogram was used for detection; 
⚫ 
Echocardiography: mainly followed up the changes of LVEF, such as when LVEF 
decreased to <50% and decreased by more than 10% compared with the baseline, or when 
subjects had chest pain, palpitations and other symptoms; 
⚫ 
Tumor imaging evaluation: The screening phase includes non-small cell lung cancer 
examinations. Additional scans such as abdominal, cranial, neck, pelvic, and bone scans 
may be added based on clinical indications when necessary, using enhanced CT, PET-CT, 
or MRI modalities. Baseline tumor assessment can be relaxed to include CT/MRI results 
obtained within 28 days prior to initial administration and within 7 days before signing 
informed consent, provided they meet eligibility criteria for screening. Routine bone 
scans are generally unnecessary unless bone metastasis is suspected. Whole-body bone 
scans should be performed using results from within two months prior to the first 
medication administration. 
⚫ 
Concomitant medication: The record of combined medication should include drug name, 
dosage, route of administration, frequency of administration, purpose of administration 

 
Randomized controlled study of the comparison of chemotherapy with chemotherapy for immune treated patients with QL1706 
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Program version number/date: v2.0/2025.04.21 
and start and end date from the day of signing the informed consent; 
⚫ 
Adverse events: monitoring begins on the day of signing the informed consent form; 
⚫ 
After completing all the above screening assessments, qualified candidates are assigned 
a subject number. 
5.5 Trial period 
The treatment period begins with the first dose to the subject. The initial study 
medication should be administered as close as possible to the completion of screening 
tests and confirmation of eligibility criteria. Each treatment cycle is 3 weeks. 
The following examinations must be completed within the timeframe specified in 
the trial protocol (±7 days). In case of statutory holidays, these may be advanced 
accordingly, with the reason for exceeding the deadline recorded in the Case Report 
Form (CRF). For participants residing outside the study region, the required 
examinations may be conducted at their local hospital starting from the second cycle 
(preferably performed at the participating center). The results should be 
communicated to the investigator, who will determine whether further testing at the 
research facility is necessary. 
According to the clinical condition of the subjects, the researchers can increase 
the examination items or improve the frequency of visits to ensure the safety of the 
subjects to the greatest extent. 
⚫ 
ECOG score, vital signs, blood routine, blood biochemical, urine routine, coagulation, thyroid 
function: once per cycle, the investigator may increase the frequency of examination according 
to the clinical condition of the subject when necessary; 
⚫ 
Tumor imaging examinations: The timing for tumor imaging examinations during the 
treatment period is determined after the initiation of study treatment, excluding any drug 
suspension due to toxic reactions during this period. The allowable time window for tumor 
imaging examinations is ±7 days, with specific assessment time points as follows: 
✓ 
This will be assessed at the end of every 2 cycles until the subject progresses, becomes 
intolerant to toxicity, or begins new cancer treatment; 
✓ 
At the end of treatment or at the time of subject withdrawal (if no tumor assessment has 
been performed within the previous 4 weeks). 
Note: During the treatment phase, imaging examinations should be conducted under the same 
conditions as baseline evaluations. Chest lesions identified at baseline should be re-evaluated 
every two treatment cycles. Baseline examinations for head and abdominal areas should also be 

 
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Program version number/date: v2.0/2025.04.21 
performed. Any new lesions detected beyond these criteria during the baseline period or suspected 
new lesions in later stages require timely follow-up. Additional imaging may be arranged when 
disease progression is suspected (e.g., symptom worsening). Patients with pre-existing bone 
metastases should undergo bone scans at least every 8 cycles (approximately 6 months), while 
routine bone scans are generally unnecessary unless bone metastasis is suspected. 
⚫ 
Concomitant medication/treatment: Record concomitant medication/treatment information 
during the study at any time; 
⚫ 
Adverse events: observe and record adverse events during the study at any time; 
⚫ 
Medication recovery/distribution: Keep records of medication recovery and distribution. 
5.6 End of trial treatment/withdrawal from study 
Participants continue treatment until disease progression, toxicity intolerance, 
withdrawal of informed consent, or the investigator determines that discontinuation is 
necessary. When study treatment is discontinued or participants withdraw from the 
study, if the patient has not undergone testing within 7 days prior to study completion 
(excluding tumor imaging evaluations), the following tests should be performed: 
⚫ 
ECOG grade ； 
⚫ 
 vital sign ； 
⚫ 
 check-up ； 
⚫ 
 routine blood test ； 
⚫ 
 routine urine test ； 
⚫ 
Blood biochemistry; 
⚫ 
 thyroid function ； 
⚫ 
 pregnancy tests ； 
⚫ 
12 leads electrocardiogram; 
⚫ 
Cardiac color ultrasound; 
⚫ 
Tumor imaging: if not performed within the last 4 weeks; 
⚫ 
Combined medication/therapy: real-time recording; 
⚫ 
Adverse events: real-time recording; 

 
Randomized controlled study of the comparison of chemotherapy with chemotherapy for immune treated patients with QL1706 
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Program version number/date: v2.0/2025.04.21 
5.7 Follow-up period 
The follow-up period begins the day after the last medication of the subject is 
determined to be in the group and will continue until the completion of survival 
follow-up (those who did not receive medication at enrollment do not need to be 
followed up), or 9 months after the last subject is enrolled, or the study is considered 
to be terminated early by the investigator. 
⚫ 
Safety Follow-up: At least 28 days after the last study medication administration, 
investigators may select clinical evaluation measures such as complete blood count, 
biochemical tests, coagulation profiles, thyroid function tests, electrocardiograms, 
echocardiograms, physical examinations, vital signs, or ECOG scores based on the subject's 
specific condition. These will be recorded as scheduled follow-up evaluations. The follow-
up must continue until all severe or drug-related toxicities have resolved to NCI-CTC-AE 
5.0 Grade I or lower, the subject initiates new anti-tumor therapy, or the investigator 
determines that the condition has stabilized at an unrelieved level (whichever occurs first). 
⚫ 
Efficacy Follow-up: For participants withdrawn due to non-disease progression or non-fatal 
reasons, tumor imaging assessments shall be conducted every 12 weeks (±7 days) starting 
from the end of the last tumor imaging evaluation during the study period. These assessments 
will continue until either PD, initiation of other anti-tumor medications, or death (whichever 
occurs first). Detailed records shall be maintained for each follow-up time and tumor 
imaging evaluation results. 
⚫ 
Survival Follow-up (OS Data Collection): All non-murdered subjects who completed safety 
and efficacy follow-up (with subsequent completion as the benchmark) are required to 
undergo survival follow-up. Starting from the completion of these follow-up procedures 
(with subsequent completion as the benchmark), follow-ups will be conducted every 3 
months (±7 days) during the first year after treatment termination. From the second year 
onward, follow-ups will be performed every 6 months (±14 days) via telephone interviews 
or clinical visits with the subjects, their family members, or local physicians to collect 
survival information (death date and cause of death). This process will continue until the 
subject's death, loss of contact, or completion of OS data collection (whichever occurs first). 
Each survival follow-up must be meticulously documented and entered into the 
corresponding CRF form. 
The following table lists the follow-up and evaluation items, and all data from 
these evaluations must be recorded in the subject's original file.

 
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Program version number/date: v2.0/2025.04.21 
 
 time  
 project  
Screening period* 
 experimental stage  
 follow-up period  
D-28~D-7 
(±7 days) 
D-6~D1 (±7 
days) 
Period X 
Treatm
ent 
compl
etion/w
ithdra
wal 
Safety 25 
Efficacy 26 
Survival 27 
Day 1 of Week 2 
(C2D1±7) 
Day 1 of cycle 3 
(C3D1±7) 
Day 1 of Week 4 
(C4D1±7) 
Day 1 of X weeks 
(CxD1±7) 
 basic data  
Sign informed consent 
× 
 
 
 
 
 
 
 
Demographic data 1 
× 
 
 
 
 
 
 
 
History 2 
× 
 
 
 
 
 
 
 
Combined medication 3 
× 
 
 
 
 
 
 
 
Laboratory/auxiliary examinations 
Blood routine 4 
 
× 
× 
× 
× 
× 
× 
 
 
Routine urine 5 
 
× 
× 
× 
× 
× 
× 
 
 
Blood Biochemistry 6 
 
× 
× 
× 
× 
× 
× 
 
 
Coagulation 7 
 
× 
× 
× 
× 
× 
× 
 
 

 
Randomized controlled study of the comparison of chemotherapy with chemotherapy for immune treated patients with QL1706 
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Program version number/date: v2.0/2025.04.21 
 
 time  
 project  
Screening period* 
 experimental stage  
 follow-up period  
D-28~D-7 
(±7 days) 
D-6~D1 (±7 
days) 
Period X 
Treatm
ent 
compl
etion/w
ithdra
wal 
Safety 25 
Efficacy 26 
Survival 27 
Day 1 of Week 2 
(C2D1±7) 
Day 1 of cycle 3 
(C3D1±7) 
Day 1 of Week 4 
(C4D1±7) 
Day 1 of X weeks 
(CxD1±7) 
Thyroid function test 8 
 
× 
× 
× 
× 
× 
× 
 
 
Pregnancy test 9 
× 
 
 
 
 
× 
 
 
Virological tests 10 
× 
 
 
 
 
× 
 
 
Electrocardiogram 11 
× 
 
 
 
 
× 
 
 
Ultrasound心动图12 
× 
 
 
 
 
× 
 
 
 clinical assessment  
Life signs 13 
 
× 
 
 
 
 
× 
 
 
Physical 14 
 
× 
 
 
 
 
× 
 
 
ECOG score 15 
 
× 
× 
× 
× 
× 
× 
 
 
NYHA classify  
× 
 
 
 
 
× 
 
 

 
Randomized controlled study of the comparison of chemotherapy with chemotherapy for immune treated patients with QL1706 
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Program version number/date: v2.0/2025.04.21 
 
 time  
 project  
Screening period* 
 experimental stage  
 follow-up period  
D-28~D-7 
(±7 days) 
D-6~D1 (±7 
days) 
Period X 
Treatm
ent 
compl
etion/w
ithdra
wal 
Safety 25 
Efficacy 26 
Survival 27 
Day 1 of Week 2 
(C2D1±7) 
Day 1 of cycle 3 
(C3D1±7) 
Day 1 of Week 4 
(C4D1±7) 
Day 1 of X weeks 
(CxD1±7) 
Adverse event 16 
From the date of informed consent to 28 days after the last medication 
 
End point indicators of efficacy and related evaluation 
Imaging studies 17 
× 
Check at the end of each two weeks, and the allowable time window is ±7 
days 
× 
 
 
Progress of disease 18 
 
 
 
 
 
 
 
 
× 
Death 19 
 
 
 
 
 
 
 
 
 
× 
 research on drug  
QL170620 
 
5mg/kg，iv，d1 
 
 
 
Gisicabine 21 
 
1000mg/m2，iv，d1、d8 
 
 
 
Doxorubicin 22 
 
60mg/m2，iv，d1 
 
 
 

 
Randomized controlled study of the comparison of chemotherapy with chemotherapy for immune treated patients with QL1706 
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Program version number/date: v2.0/2025.04.21 
 
 time  
 project  
Screening period* 
 experimental stage  
 follow-up period  
D-28~D-7 
(±7 days) 
D-6~D1 (±7 
days) 
Period X 
Treatm
ent 
compl
etion/w
ithdra
wal 
Safety 25 
Efficacy 26 
Survival 27 
Day 1 of Week 2 
(C2D1±7) 
Day 1 of cycle 3 
(C3D1±7) 
Day 1 of Week 4 
(C4D1±7) 
Day 1 of X weeks 
(CxD1±7) 
Other records 
Distribution of drugs 23 
 
× 
 
 
Pharmaceutical recovery 23 
 
× 
 
 
Follow-up treatment of tumor 24 
 
 
 
 
 
 
 
 
 
 pour ： 
1. Demographic data (abbreviated name, gender, ethnicity, marital status, date of birth, height, weight); 
2. Medical history: This includes the patient's prior history and treatment of driver gene-negative non-small cell lung cancer (NSCLC), 
covering clinical/pathological diagnosis, timing of diagnosis, clinical/pathological staging, EGFR status, microsatellite status; surgical 
intervention, neoadjuvant therapy, adjuvant therapy, radiotherapy, immunotherapy; other tumor-related medical history (excluding driver 
gene-negative NSCLC), smoking/alcohol consumption history (current or former use), drug allergy history (medication names, allergic 
reactions), as well as comorbid conditions/symptoms (disease/symptom names, duration, treatment received, and outcomes). 
3. Compliance Monitoring: Document all concomitant medications from the screening period through study completion. The documentation 
should include drug names, dosages, administration routes, frequencies, therapeutic purposes, and dates of start and end. If a participant 

 
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Program version number/date: v2.0/2025.04.21 
initiates new systemic anti-tumor therapy during safety monitoring, only records adverse events related to the study medication's 
concomitant treatments shall be included. 
4. Complete blood count (CBC) results obtained within 7 days prior to the first medication administration. This includes: red blood cell count 
(RBC), hemoglobin (Hb), white blood cell count (WBC), platelet count (PLT), and differential leukocyte count [lymphocyte count (LYM), 
neutrophil count (ANC)]. CBC tests are performed on the 21st±7th day of each treatment cycle, with one additional test required upon 
treatment completion or discontinuation (if not conducted within 7 days). 
5. Routine urinalysis results within 7 days prior to the first medication administration. This includes: Urinary white blood cells (UWBC), 
urinary protein (UPRO), urinary red blood cells (URBC), and urinary glucose (UGLU). Testing is conducted once per treatment cycle and 
once upon treatment completion/withdrawal (if not performed within 7 days). 
6. Blood biochemical tests shall be based on the results obtained within 7 days prior to the first medication administration. These include: liver 
function [total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin 
(ALB), total protein (TP)] and renal function [urea (UREA), serum creatinine (Cr)]. Fasting blood glucose (FBG) and lipid profile 
(triglycerides, cholesterol) are also required. When necessary, additional cardiac enzyme spectrum tests may be performed, including but not 
limited to creatine kinase (CK), creatine kinase-microsomal (CK-MB), α-hydroxybutyrate dehydrogenase (HBDH), and troponin T (cTnT), 
as determined by the investigator based on the subject's condition. Testing is conducted once per treatment cycle and once upon treatment 
completion/exit (if not performed within 7 days). 
7. The coagulation function was examined within 7 days before the first medication, once per cycle during the treatment period, and once at 
the end of treatment withdrawal (if not done within 7 days); 
8. Examination results within 7 days before the first medication of thyroid function acceptance, once per cycle during the treatment period, and 
once at the end/withdrawal of treatment (if not performed within 7 days); 
9. Pregnancy tests, women of childbearing age will have a urine or serum pregnancy test within 28 days prior to the first dose and at the time 
of the study treatment termination visit. If the urine pregnancy test result cannot be confirmed as negative, a serum pregnancy test will be 
performed and the serum pregnancy result will prevail; 
10. Viral testing requires test results from this center within 28 days prior to initial treatment initiation. During the screening phase, hepatitis B 
serology panel (HBsAg, HBsAb, HBcAb, HBeAg, HBeAb), along with HCV antibody and HIV antibody tests will be conducted. HBsAg-

 
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Program version number/date: v2.0/2025.04.21 
positive cases will undergo HBV DNA testing, while HCV antibody-positive patients will receive HCV RNA testing. Additional tests may 
be administered when necessary. For hepatitis B virus carriers, regular viral activity monitoring is recommended throughout the study 
period, with one final test required upon treatment completion/withdrawal (if not performed within 7 days). 
11. Electrocardiogram: 12 lead electrocardiogram was used to detect the results within 28 days before the first medication in the screening 
period, and one test was performed at the end/treatment withdrawal (if not performed within 7 days prior); 
12. Cardiac color Doppler ultrasound: Screening results must be obtained within 28 days prior to the first medication administration, with one 
final examination conducted at treatment completion/withdrawal (if not performed within the preceding 7 days). The primary monitoring 
focus is on changes in LVEF levels. If LVEF decreases to below 50% with a baseline decline of ≥10%, or if participants experience 
symptoms such as chest pain or palpitations, investigators may conduct additional examinations based on clinical circumstances. 
13. Life signs: including body temperature, blood pressure, respiratory rate and heart rate; screening period (examination results within 7 days 
before the first medication), when the investigator deems it necessary during the trial, additional examinations may be added as appropriate; 
one examination at the end of treatment/withdrawal (if not performed within 7 days prior); 
14. Physical Examination: This includes the head and face, skin system, lymph nodes, eyes, ears, nose, and throat, mouth, respiratory system, 
cardiovascular system, abdomen, genitourinary system, musculoskeletal system, nervous system, and mental status. Comprehensive 
physical examination results are recorded during the screening period (within 7 days prior to initial medication administration) and at study 
completion. Investigators may add additional examinations as needed during the trial period. One check-up is required upon treatment 
completion/withdrawal (if not conducted within the previous 7 days). 
15. ECOG score, screening period (test results within 7 days prior to first medication), treatment period once per cycle, and treatment 
completion/withdrawal assessment; 
16. Adverse Events: Monitoring will commence on the day participants sign the informed consent form and continue until at least 28 days after 
the final study medication administration. Detailed documentation will include adverse events, concomitant medications/therapies, and 
scheduled unannounced examinations throughout this period. Follow-up will continue until the adverse event resolves, the participant 
initiates new anti-tumor therapy, or the investigator determines that the condition has reached a stable, non-resolvable state. Adverse Event 
(AE) and laboratory test safety evaluations will be conducted according to the NCI CTCAE 5.0 version. 

 
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Program version number/date: v2.0/2025.04.21 
17. Imaging examinations: The screening period includes pulmonary imaging, with additional chest-abdominal, cranial, neck, and pelvic 
examinations as clinically indicated. Contrast-enhanced CT, MRI, or PET-CT may be used. Baseline tumor assessment can be relaxed to 
within 28 days prior to initial dosing, provided CT/MRI results obtained before informed consent meet eligibility criteria for screening 
evaluation. Routine bone scans are generally unnecessary unless bone metastasis is suspected, with whole-body bone scans permitted using 
results from within two months prior to initial administration. Investigators may add scan sites during baseline or subsequent tumor 
evaluations as clinically indicated (for non-metastatic areas identified during screening, investigators may adjust based on clinical practice). 
During the trial period, imaging examinations should be conducted every 2 cycles±7 under identical conditions to baseline scans (including 
contrast agent use), with bone scans performed when bone progression is suspected or for CR confirmation. New lesions should be 
examined promptly if identified. The allowable time window for tumor imaging is ±7 days, with additional imaging permitted if disease 
progression is suspected (e.g., symptom worsening). Treatment duration-based imaging timing starts from the initiation of study therapy, 
excluding periods when dosing is paused due to toxic reactions. For non-commissioned participants, the allowable time window for post-
screening imaging is ±7 days. If participants withdraw early due to non-disease progression reasons (e.g., adverse events, management 
issues), a final treatment completion evaluation should be conducted upon withdrawal. 
18. Progression of Disease: For participants who discontinued trial treatment for reasons other than imaging-confirmed disease progression, if 
no imaging evaluation was performed within 28 days prior to trial termination, an imaging evaluation must be conducted at the time of 
treatment termination. Additionally, tumor response should continue to be monitored at the prescribed follow-up frequency specified in the 
protocol until documented disease progression or initiation of new cancer therapy. 
19. Death: During the first year after treatment, survival status and subsequent anti-tumor treatment were collected every 3 months (±7 days) 
through clinical or telephone follow-up. From the second year after treatment, follow-up was conducted every 6 months (±15 days) until 
death; 
20. QL1706:5mg/kg, iv, d1, record the time and dose of each injection; 
21. Gisicabine: 1000mg/m2, iv, d1, d8, record the time and dose of each injection; 
22. Doxorubicin: 60mg/m2, iv, d1, record the time and dose of each drug; 

 
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Program version number/date: v2.0/2025.04.21 
23. Drug recovery/distribution: Except for the drug distribution in the first cycle and the drug recovery after the end of treatment, the drug will 
be collected and distributed at the end of each cycle, and corresponding records will be made; 
24. Follow-up of subsequent cancer treatment: it is necessary to record whether the subject has received other cancer treatment from the time of 
withdrawal or end of treatment until the death of the patient; it is not necessary to record the combined use of other diseases; 
25. Safety Follow-up: From the date of informed consent to at least 28 days after the final study medication administration, investigators may 
select clinical evaluation measures such as complete blood count, biochemical tests, electrocardiogram (ECG), echocardiography, physical 
examination, vital signs, or ECOG score as scheduled follow-up records based on individual patient conditions. Adverse drug-related events 
shall be followed up until they disappear, reach baseline levels ≤1 grade, achieve stabilization, or are reasonably explained (e.g., loss to 
follow-up, death). 
26. Efficacy Follow-up: Participants who are not PD or did not die were required to undergo efficacy follow-up. Starting from the end of the last 
tumor imaging assessment during the study period, participants received tumor imaging evaluations at least once every 12 weeks (±7 days) 
until either PD, initiation of other anti-tumor medications, or death (whichever occurred first). Detailed records were maintained for each 
follow-up time and tumor imaging evaluation results. 
27. Survival Follow-up: All non-murdered subjects who complete safety and efficacy follow-up (with subsequent completion as the benchmark) 
must undergo survival follow-up. Starting from the date of completing these follow-up procedures (with subsequent completion as the 
benchmark), telephone inquiries or clinical visits shall be conducted at least once every 3 months (±7 days) during the first year, and every 
6 months (±14 days) thereafter. These visits shall involve the subject, their family members, or a local physician to collect survival 
information (death date and cause of death). The follow-up will continue until the subject's death, loss to follow-up, or completion of OS 
data collection (whichever occurs first). Detailed records shall be maintained for each survival follow-up session. 
28. All the examination items and frequencies in the flow chart are recommended. When necessary, the investigator can increase or decrease the 
frequency and examination items according to the actual clinical diagnosis and treatment of the subject and the status of the subject; 
29. The laboratory and ancillary examination results involved in this study can be examined by an external hospital, and the results of the 
external hospital examination should be provided to the research center. The investigator will judge whether the results can be used for 
efficacy evaluation. 

 
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6. Trial drug 
6.1 Drug Name and Specifications 
0. 
QL1706:50mg (2ml)/bottle. Developed by Qilu Pharmaceutical Co., LTD. Store at 2-8 
degrees Celsius, light and sealed. 
1. 
Gisicabine: 0.2g per vial. Developed by Qilu Pharmaceutical Co., Ltd. Store at room 
temperature (15℃ to 30℃) in a sealed container. 
2. 
Doxorubicin: 20mg (1ml)/piece, developed by Qilu Pharmaceutical Co., LTD. 2-8 
degrees, lightproof, sealed storage. 
6.2 Drug management 
3. 
QL1706 Injection The investigational drug was administered on the first day of each 
visit and administered in accordance with the requirements and specifications at the 
hospital. 
4. 
Gisicitabine The investigational drug was administered on the first day of each visit 
and injected at the hospital as required and in accordance with specifications. 
5. 
Doxorubicin The investigational drug was administered on the first day of each visit 
and administered in accordance with the required specifications at the hospital. 
6. 
The test center shall keep all the test drugs in a safe and compliant place, and be 
managed by a special person (drug receiving, storage, distribution, recovery, etc.). 
7. 
Researchers in charge of drug management need to record the number of drugs 
distributed and returned per subject at each follow-up visit, as well as the 
corresponding date of follow-up. 
8. 
All investigational drugs entering or leaving the clinical trial facility shall be 

 
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Program version number/date: v2.0/2025.04.21 
documented (including unused drugs and packaging). Participants must return all 
unused drugs and empty packaging to the investigator during each follow-up visit. At 
the end of the trial, the investigator will return them to the sponsor for inventory and 
destruction. 
6.4 Combination therapy 
During the trial, the subjects may receive appropriate supportive treatment for 
adverse events in addition to the trial drug. Other anti-tumor treatments shall not be 
taken during the study to avoid affecting the evaluation of the efficacy of the trial drug. 
The specific regulations are as follows: 
⚫ Throughout the study, subjects were not allowed to use any systemic anti-
tumor measures other than the investigational drug, which could be combined 
with local treatment. 
⚫ After evaluating the relationship between adverse events and trial medications, 
researchers may implement appropriate supportive therapies. These 
treatments, including antiemetics, antidiarrheals, antipyretics, antihistamines, 
anti-rash medications, antihypertensive drugs, analgesics, antibiotics, and 
other interventions such as blood products, should be documented in the Case 
Report Form (CRF) with their start and duration. 
⚫ Non-hematological toxicity can be treated with appropriate medication at 
grade 2 and recorded in the combined medication. 
⚫ Blood toxicity can be treated with appropriate medication at level 3 and 
recorded in the combined medication. 
⚫ When the subject's hemoglobin is 5.0g/L-8.0g/L, it is up to the investigator to 
decide whether erythropoietin (EPO) therapy should be given; when 
hemoglobin is <5.0g/L, component transfusion should be given. 
⚫ When the subject's platelet count was <50.0×109/L, interleukin-11 or 
thrombopoietin (TPO) was administered; if the platelet count was <25.0×
109/L or bleeding tendency occurred, component transfusion was 
administered. 

 
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Program version number/date: v2.0/2025.04.21 
⚫ When the neutrophil count of the subject is <1.0~0.5 × 109 /L but without 
fever, the investigator decides whether to give cytokine therapy such as G-
CSF; if grade 3 neutropenia with temperature above 38.5℃ or grade 4 
neutropenia occurs, cytokine therapy should be given. 
⚫ For subjects who were already using bone regulators (e.g., bisphosphonates, 
RANK ligands, etc.) prior to the screening period, the original drug and dose 
should be maintained during the trial; for subjects who did not use bone 
regulators prior to the screening period, it is not recommended to add bone 
regulators during the trial. 
⚫ 
All information about concomitant drugs received by the subject (generic 
name of the drug, purpose of administration, dosage, time of administration, 
etc.) should be fully recorded in the original data. 
7. Efficacy evaluation 
7.1 Efficacy evaluation criteria 
⚫ The efficacy was evaluated according to the RECIST v1.1 version (2009) 
criteria for solid tumors (see appendix). The efficacy was divided into four 
grades: complete response, partial response, disease progression and stability. 
⚫ Complete remission (CR): All lesions are gone. The short diameter of all 
pathological lymph nodes (including target and non-target nodes) must be 
reduced to <10mm, and tumor markers return to normal levels. 
⚫ Partial response (PR): The total length of the target lesion LD decreased by at 
least 30% compared with the total length of the baseline lesion LD. 
⚫ Progression (PD): The total number of lesions with LD at the target site is 
increased by at least 20% compared to the minimum number of lesions with 
LD recorded since the start of treatment, and the absolute number of lesions 
with LD is increased by at least 5mm. Progression is also considered when 
one or more new lesions are present. 
⚫ Stable disease (SD): the degree of reduction of the target lesion is not up to 
PR, and the degree of increase is not up to PD level, between the two. During 

 
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the study, the minimum value of the sum of diameters can be used as a 
reference. 
7.2 Efficacy evaluation methods 
The size of the subject's lesion is assessed by imaging (including CT, MRI, bone 
scan, or other imaging data that the investigator considers to be of therapeutic value). 
The imaging method used for all follow-up times in the subject must be consistent with 
the baseline. 
7.3 Intervals for Efficacy Evaluation 
During the study treatment, an assessment was performed every 2 treatment cycles 
(±7 days) until disease progression or initiation of new anti-tumor therapy (whichever 
occurred first). 
If a subject withdraws from the study for reasons other than disease progression 
(such as adverse events, management reasons, etc.), an end-of-treatment assessment 
will be performed at the time of withdrawal. 
8 Detection of adverse events 
 
8.1 Adverse events 
Adverse Event (AE) is defined as any adverse medical event that occurs in a 
subject following administration of the investigational drug. These events may manifest 
as symptoms, signs, disease manifestations, or abnormal laboratory findings, though 
not necessarily causally related to the investigational drug. This includes recurrence of 
pre-existing conditions during clinical trials, regardless of whether treatment-related. 
Clinical invasive procedures themselves are not considered adverse events, but the 
underlying causes of these procedures should be classified as adverse events. 
Events occurring at the pre-and post-treatment stages are also considered AE 
according to regulations. Therefore, safety monitoring of AE or SAE reporting should 

 
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begin when the subject enters the study (signs an informed consent) and end at the study 
completion visit. 
8.2 Classification of adverse events 
Refer to the NCI-CTCAE 5.0 version for the classification of adverse drug events. 
If an adverse event is not listed in the NCI-CTCAE 5.0 version, refer to the following 
criteria: 
 grade  Clinical description of severity 
1 
Mild; no clinical symptoms or with mild clinical symptoms; only clinical 
or laboratory abnormalities; no treatment required 
2 
Moderate; requires small, local or non-invasive treatment; age-appropriate 
limitations in the use of tools for daily living activities (ADLs), use of tools 
for daily living refers to cooking, shopping, phone calls, counting money, 
etc 
3 
The condition is severe or presents with serious medical symptoms that are 
not immediately life-threatening; requires hospitalization or prolonged 
hospital stays; leads to disability; or impairs the ability to perform self-care 
activities (ADLs). Self-care activities include: bathing, dressing and 
undressing, eating, using the bathroom, taking medication, etc. This does 
not mean being bedridden. 
4 
Life-threatening; requires urgent treatment 
5 
Causes death 
8.3 Judgment of the relationship between adverse events and 
treatment 
The potential association between adverse events (AEs) and treatment modalities 
was evaluated using a five-level classification system (definite, probable, possible, 
possible, and none) (see Table 1). The first three levels indicate treatment-related 
associations. When calculating the incidence of adverse reactions, the three categories 
are combined as the numerator, with the total number of participants evaluated for 
safety as the denominator. 
Table 1 Criteria for AE and treatment 
 standard  
Must be 
related 
Probably 
related 
Probably 
relevant 
It may not 
matter 
 have 
nothin
g to 

 
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do 
with  
Reasonable 
chronological order 
 yes  
 yes  
 yes  
 yes  
 deny  
Known types of drug 
reactions 
 yes  
 yes  
 yes  
 deny  
 deny  
The cause can be 
improved by removal 
 yes  
 yes  
Yes or no 
Yes or no 
 deny  
Re-dosing can repeat 
 yes  
？ 
？ 
？ 
 deny  
There may be another 
explanation for the 
reaction 
 deny  
 deny  
 deny  
 yes  
 yes  
8.4 Serious Adverse Events (SAE) 
(1) Definition of serious adverse events 
Serious adverse events (SAE) refer to medical events that occur during clinical 
study and require hospitalization or prolonged hospital stay, disability, impairment of 
work capacity, life-threatening or fatal, or leading to congenital malformations. They 
include the following medical events: 
⚫ -Mortal incidents; 
⚫ Life-threatening events (defined as a risk of immediate death to the subject at 
the time of the event); 
⚫ Events requiring hospitalization or prolonged hospital stay; 
⚫ Events that may lead to permanent or severe disability/function 
impairment/impact on work capacity; 
⚫ Congenital abnormalities or birth defects; ` 
⚫ Other significant medical events (defined as events that endanger the subject 
or require intervention to prevent the occurrence of any of these conditions). 
(2)  encyesis  
If a subject becomes pregnant during the clinical trial, the subject is withdrawn 
from the group. The investigator shall report to the sponsor within 24 hours of learning 
of the pregnancy and report to the ethics in a timely manner. 

 
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(3) Disease progression and death 
Disease progression is defined as a subject's condition worsening caused by the 
trial medication's intended indication, including imaging findings and clinical symptom 
or sign progression. The emergence of new metastatic lesions relative to the primary 
tumor or progression of existing metastases is considered disease progression. Life-
threatening events requiring hospitalization or prolonged hospital stays, or those 
resulting in permanent disability/function impairment/work capacity loss, congenital 
abnormalities, or birth defects caused by symptoms/signs of disease progression are not 
accelerated reporting as SAEs. Deaths caused by symptoms/signs of disease 
progression are reported as accelerated SAEs. If there is any uncertainty regarding 
whether an SAE was caused by disease progression, it should be reported as an SAE. 
In this study population, disease progression is an expected occurrence. The term 
"disease progression" should not be reported as an adverse event (AE). When a 
participant experiences a confirmed progression event, it must be documented as an AE. 
For example, if a participant develops epilepsy that is determined to be associated with 
brain metastasis, the AE should be recorded as "epilepsy" rather than "disease 
progression" or "brain metastasis". 
The term "death" should not be used as an AE or SAE term, but as the outcome of 
the event. Events that cause or lead to death should be recorded as AE or SAE. If the 
cause of death is unknown and cannot be determined at the time of reporting, the AE or 
SAE term should be recorded as "cause of death unknown". 
(4) Other antitumor treatments are being administered 
If a participant initiates other anti-tumor therapy within 30 days after the last use 
of the study drug, only those serious adverse events related to the study drug will be 
collected following the start of new anti-tumor treatment. If death occurs within 30 days 
after the last use of the study drug, it must be promptly reported as a serious adverse 
event regardless of whether the participant is receiving other treatments. 
(5)  hospitalization  
Adverse events in clinical studies that lead to hospitalization or prolonged length 
of stay should be considered serious adverse events. Any initial admission to a 
medical institution (even less than 24 hours) meets this criterion. 
Hospitalization does not include the following: 
⚫ 
 rehabilitation agency  
⚫ 
 sanatorium  

 
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⚫ 
Admission to the general emergency room 
⚫ 
Same-day surgery (e.g. outpatient/day/non-bed surgery) 
Hospitalization or prolonged hospital stay unrelated to the worsening of adverse 
events is not a serious adverse event in itself, such as: 
⚫ 
Admission due to pre-existing disease without new adverse events or 
worsening of pre-existing disease (e.g., laboratory abnormalities that persist 
since the time of study initiation); 
⚫ 
Managed reasons for hospitalization (e.g., annual routine physical 
examinations); 
⚫ 
Hospitalization during clinical study as specified in the study protocol (e.g., 
as required by the study protocol); 
⚫ 
Adolescent hospitalization unrelated to the deterioration of adverse events 
(e.g., elective cosmetic surgery); 
⚫ 
Pre-arranged treatments or surgical procedures should be recorded in the 
baseline data of the entire study protocol and/or the individual subject; 
⚫ 
Admission was due to the use of blood products. 
Diagnostic or therapeutic invasive procedures (such as surgery) and non-invasive 
operations should not be reported as adverse events. However, when the underlying 
medical condition necessitating such procedures meets the definition of an adverse 
event, they must be reported. For example, acute appendicitis occurring during the 
adverse event reporting period should be classified as an adverse event, while the 
subsequent appendectomy performed for this condition should be recorded as the 
treatment method for that adverse event. 
(6) Reporting procedures for SAE 
The reporting period for serious adverse events (SAEs) should commence from 
the date of subject's informed consent and continue until 30 days after the final 
medication administration, inclusive of the 30th day. During the trial, if an SAE occurs 
– whether in initial reports or follow-up communications – investigators must 
immediately complete the Serious Adverse Event Report Form, sign it with the date, 
notify the sponsor within 24 hours of receiving the SAE, and report to relevant 
authorities as required by regulations. 
Severe adverse events should be thoroughly documented with detailed records of 
symptoms, severity levels, occurrence time, intervention timing, implemented 

 
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measures, follow-up schedules and methods, clinical outcomes, and their relationship 
to treatment. If the intensity of an ongoing severe adverse event or its connection to 
treatment changes, the sponsor must be immediately notified through follow-up 
reporting. All severe adverse events should be monitored until full recovery or 
stabilization is achieved. 
8.5 Recording of adverse events 
Document all adverse events (AEs) during the study period in detail, including 
their names, severity levels, occurrence timing, duration, management measures, 
clinical outcomes, and relationship to treatment. These records must be accurately 
documented in the Case Report Form (CRF). Abnormal laboratory test results should 
be recorded on the CRF and followed up with at least one repeat test per week until 
normalization or study completion. All adverse events occurring within 28 days after 
the final medication administration must be reported and documented. 
 
9. Statistics 
9.1 Statistical analysis data set 
Full Analysis Set (FAS): Following the intention-to-treat (ITT) principle, this 
analysis evaluates treatment efficacy for all randomized participants who received at 
least one medication dose. For cases with incomplete treatment data, the last observed 
data (LOCF) is applied to the final trial outcomes. 
Protocol-compliant cases: All cases that comply with the trial protocol, 
demonstrate good adherence, do not use prohibited medications during the trial 
period, and complete the required content in the Case Report Form. No data 
imputation is performed for missing information. Both FAS and PPS are statistically 
analyzed to evaluate drug efficacy. 
Safety Analysis Set (SAS): All enrolled cases, all patients who have used the trial 
drug at least once and have a post-treatment safety record, are included in the safety 
analysis set. This data set is used for safety analysis. 

 
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9.2 Statistical analysis methods 
Unless otherwise specified, all data will be summarized by treatment group using 
appropriate statistical measures for each data type: Numerical data will be described 
using mean (Mean), standard deviation (STD), median (Median), minimum (Minimum), 
and maximum (Maximum); Categorical data will be presented as frequency (Frequency) 
and percentage (Percentage). For time-to-event data, the Kaplan-Meier (KM) survival 
analysis will estimate median survival time. When necessary, survival curves will be 
plotted with 95% confidence intervals for median time to events. 
9.3 Analysis of efficacy endpoints 
Primary endpoint of efficacy: 
Progression-free survival (PFS): Kaplan-Meier method was used to analyze PFS, 
estimate median PFS and 95%CI, and draw survival curve 
Secondary endpoints were: 
Objective response rate (ORR, based on RECIST v1.1 criteria): percentage of 
subjects with complete response (CR) and partial response (PR) in the total analysis set 
and its 95% CI. 
Disease Control Rate (DCR): percentage of subjects with complete response (CR), 
partial response (PR), and disease stabilization (SD) in the total analysis set and its 95% 
CI; 
Relief duration (DOR): Statistical analysis of DOR using Kaplan-Meier method 
to estimate median DOR and 95%CI; 
Overall survival (OS): Statistical analysis of OS using Kaplan-Meier method to 
estimate median OS and 95%CI; 
9.4 Adverse event analysis 
This study primarily employs descriptive statistical analysis to systematically 
document adverse events and reactions (defined as "adverse events with a 'definitely 
related, likely related, or possibly related' association to the investigational drug") 
observed during the trial. Laboratory test results are described to examine pre-trial 
normality that became abnormal post-treatment, along with the correlation between 

 
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these abnormalities and the investigational drug. Chi-square tests were conducted to 
evaluate the incidence rates of adverse reactions across different stratified groups. 
10 Quality control and test records 
10.1 Data quality assurance 
The testing center shall establish an internal quality assurance system to strictly 
monitor and control the quality of its laboratory tests. The center must ensure the 
accuracy and reliability of test results, with standardized criteria for interpreting 
abnormal values. All relevant laboratory data should be promptly and accurately 
recorded in CRFs, and original reports or copies must be attached to medical records. 
Abnormal data must be verified, with relevant researchers providing explanations when 
necessary. Follow-up tracking should continue until the data normalize or stabilize. 
10.2 Test records 
All trial data are documented in the Case Report Form (CRF). Investigators are 
responsible for recording trial data on CRF in a timely, accurate, complete, authentic, 
and legally compliant manner, ensuring consistency with original records. All errors or 
omissions have been corrected or marked, and are signed by the investigator with a date. 
11.2.1 Original records 
Original records serve to verify the authentic existence of subjects and ensure data 
integrity and authenticity. All data recorded on CRFs originate from original 
documentation and must remain consistent with these records. Where discrepancies 
exist between CRF entries and original records, corrections should be made according 
to the original documentation or reasonable explanations provided. Original records are 
stored at each clinical trial center. The following documents are included in the original 
records: 
⚫ 
Laboratory test report of this center; 
⚫ 
Other medical examination data of the subject; 
⚫ 
The discharge summary of the subject. 
10.2.2 Access to raw data and files 

 
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In addition to the investigator, personnel related to the trial, members of the ethics 
committee and personnel of the pharmaceutical administration agency have the right to 
access the original data and documents related to the trial. When the above personnel 
request to access the trial documents, the investigator shall provide complete 
information. 
10.2.3 Preservation of test records 
To ensure proper evaluation and supervision by the ethics committee and sponsor, 
the trial center must maintain all relevant clinical trial documentation in compliance 
with Good Clinical Practice (GCP) requirements. This includes identity-verification 
documents (such as original signed informed consent forms, Case Report Forms [CRFs], 
and original medical records), along with distribution/recovery records for 
investigational drugs. All trial-related materials shall be retained for five years 
following the completion of the clinical trial. 
 
10.3 List reporting and rapid reporting of adverse events 
Reports of adverse events can be classified as list reports and rapid reports 
according to severity. 
The adverse events reported in the list are common general adverse events and do 
not require urgent treatment. 
The investigator shall immediately report to the sponsor and the drug manufacturer 
(within 24 hours of SAE awareness) any serious adverse events that occur during the 
trial, and recommend reporting to the GCP Center safety officer (as required by the 
center), followed by timely follow-up and summary reports. 
10.4 Breach of test protocol 
The investigator/assistant investigator shall keep a detailed record of any protocol 
violations that occur during the trial and submit it to the principal investigator at the 
center and the sponsor, stating whether the behavior was caused by the elimination of 
potential harm to the subject or other unavoidable medical reasons. 

 
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11 Ethics Information and Confidentiality 
Agreement 
This trial is conducted in compliance with the Chinese Good Clinical Practice 
(2020 Edition) and the Helsinki Declaration (2013 Edition). In accordance with 
standard medical practice, investigators are responsible for diagnosing and treating 
participants. Should any urgent safety issues arise during the trial, or if serious 
violations of the protocol, Good Clinical Practice (GCP), or the Helsinki Declaration 
occur, investigators must immediately notify their collaborating partners to ensure 
participant safety. 
11.1 Ethics approval and informed consent 
Prior to initiating a clinical trial, all documents including the study protocol and 
informed consent forms must be reviewed and approved by the ethics committee of the 
responsible institution. Investigators are required to report any progress of the trial and 
serious adverse events occurring during the trial to the ethics committee. Any 
modifications to the study protocol or informed consent forms must be submitted to the 
ethics committee for review and approval. Before enrolling participants, investigators 
must fully explain the purpose, procedures, and potential risks/benefits of the trial to 
the participants (or their guardians in special circumstances). Participants must be 
informed of their right to withdraw at any time. Each participant (or guardian in special 
circumstances) must sign an informed consent form before enrollment. Investigating 
physicians must obtain signed, dated, and contact information-based informed consent 
forms from all participants prior to study entry. The original copy shall be archived at 
the institution as trial documentation, while copies are provided to participants for 
retention. Any modifications to the informed consent form must be documented and 
submitted to the ethics committee for review and approval. Approved revised versions 
of the informed consent form must also be archived at the institution. All patients or 
independent witnesses affected by changes to the informed consent form, as well as 
individuals involved in discussions about the form, must sign and date the updated 
version. The original copy remains archived at the institution, while copies are provided 
to participants for retention. 

 
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11.2 Confidentiality Agreement 
All materials, information (oral or written), and unpublished documents provided 
by the investigator—including the study protocol and CRF—shall remain the 
investigator's exclusive property. Without the investigator's prior written consent, no 
individual may disclose such materials to unauthorized personnel. Except for 
information permitted by regulations, the investigator must maintain confidentiality 
regarding all information received, obtained, or derived during this research process, 
taking all necessary steps to ensure confidentiality is maintained. 
12 Programme revisions 
Any revisions to the protocol will be documented in a written version signed by 
the investigator. The signed version will be attached to this protocol. Any revisions to 
this protocol may require submission in accordance with local regulations. 
13. Results published 
13.1 Ownership and use of research data and findings 
The data shall not be used without the permission of the partner. The Scientific 
Committee has full access to the final data to enable proper academic analysis and 
reporting of the results. 
13.2 Data dissemination 
The publication or release of the results of the trial in a paper or conference shall 
be negotiated between the researcher and the partner. The researcher shall not disclose 
the results of the trial in any form without the written consent of the partner. 
All participating researchers and committee members have granted full 
authorization to the Scientific Committee for the initial publication of research 
findings. No other publications are permitted prior to the initial release. Any 
subsequent publications by study participants (including sub-studies) must be 

 
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approved by the Scientific Committee and must reference both this study and its 
initial publication. 
The parties may delay the publication or communication for a limited period of 
time, in order to protect the confidentiality or ownership of any information contained 
therein. 
14 References 
1. Sung H, Sung H,  et al. Global Cancer Statistics 2020: GLOBOCAN Estimates. CA 
Cancer J Clin. 2021. 
2. Zheng RS, Zheng RS,  et al. Cancer Incidence and Mortality in China, 2022. JNCC. 
2023. 
3. Wu YL, Wu YL,  et al. Genomic Landscape of Chinese Lung Cancer Patients. J 
Thorac Oncol. 2020. 
4. Huang MY, Jiang XM, Wang BL, Huang MY, Jiang XM, Wang BL,  et al. 
Combination therapy with PD-1/PD-L1 blockade in non-small cell lung cancer: 
strategies and mechanisms. Pharmacol Ther. 2021 Mar;219:107694. 
5. Franchi M, Pellegrini G, Corrao G. Effectiveness and Cost-Effectiveness Profile of 
Second-Line Treatments with Nivolumab, Pembrolizumab and Atezolizumab in 
Patients with Advanced Non-Small Cell Lung Cancer. Pharmaceuticals (Basel). 2022 
Apr 18;15(4):489. 
6. Dafni U, Tsourti Z, Vervita K, Dafni U, Tsourti Z, Vervita K,  et al. Immune 
checkpoint inhibitors, alone or in combination with chemotherapy, as first-line 
treatment for advanced non-small cell lung cancer. A systematic review and network 
meta-analysis. Lung Cancer. 2019 Aug;134:127-140. 
7. Garon EB, Hellmann MD, Rizvi NA, Garon EB, Hellmann MD, Rizvi NA,  et al. 
Five‑year overall survival for patients with advanced non-small-cell lung cancer 
treated with pembrolizumab: results from the phase Ⅰ KEYNOTE-001 study[J]. J 
Clin Oncol, 2019,37(28):2518-2527. DOI: 10.1200/JCO.19.00934. 
8. Muto S, Inomata S, Yamaguchi H, et al. [Resistance Mechanisms to Immune 
Checkpoint Inhibitor and Its Overcome with Focus on β-Catenin in Lung 
Cancer]. Gan To Kagaku Ryoho. 2022. 49(9): 928-931. 

 
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9. Xu Y, Li H, Fan Y. Progression Patterns, Treatment, and Prognosis Beyond 
Resistance of Responders to Immunotherapy in Advanced Non-Small Cell Lung 
Cancer [J]. Front Oncol, 2021, 11: 642883. DOI: 10.3389/ fonc.2021.642883. 
10. Diker O, Olgun P. Salvage chemotherapy in patients with nonsmall cell lung 
cancer after prior immunotherapy: a retrospective, real-life experience study. 
Anticancer Drugs. 2022 Sep 1;33(8):752-757. 
11. Park SE, Lee SH, Ahn JS, Park SE, Lee SH, Ahn JS,  et al. Increased response 
rates to salvage chemotherapy administered after PD-1/PD-L1 inhibitors in patients 
with non‑small cell lung cancer[J]. J Thorac Oncol, 2018, 13(1): 106‑111. DOI: 
10.1016/j.jtho.2017.10.011. 
12. Auclin E, Benitez‑Montanez J, Gorria T, et al. OA07.06 second line treatment 
outcomes after progression on immunotherapy plus chemotherapy (IO-CT) in 
advanced non-small cell lung cancer (aNSCLC) [J]. J Thorac Oncol, 2022, 17(9 
Supplement): S22. DOI: https://doi.org/10.1016/j.jtho.2022.07.043. 
13. Liu S, Hu X, Chirovsky D, Liu S, Hu X, Chirovsky D,  et al. OA07.04 overall 
survival in patients with advanced NSCLC receiving taxane-containing regimen after 
exposure to immunotherapy and platinum‑doublet[J]. J Thorac Oncol, 2022, 17(9 
Supplement): S21. DOI: https://doi. org/10.1016/j.jtho.2022.07.041. 
14. Shukla N, Althouse SK, Perkins S, Shukla N, Althouse SK, Perkins S,  et al. A 
phase Ⅱ trial of chemotherapy plus pembrolizumab in patients with advanced 
NSCLC previously treated with a PD-1 or PD-L1 inhibitor: big ten cancer research 
consortium BTCRC-LUN15-029[J]. J Thorac Oncol, 2021, 39(15 Suppl): 9073. DOI: 
10.1200/JCO.2021.39.15_suppl.9073. 
15. Reckamp KL, Redman MW, Dragnev KH, Reckamp KL, Redman MW, Dragnev 
KH,  et al. Phase Ⅱrandomized study of ramucirumab and pembrolizumab versus 
standard of care in advanced non-small-cell lung cancer previously treated with 
immunotherapy-lung-map S1800A[J]. J Clin Oncol, 2022, 40(21): 2295‑2306. DOI: 
10.1200/JCO.22.00912. 
16. Bahce I, Schneiders F, Hashemi S, et al. 1020P Rescue by radiotherapy and anti-
CTLA4/PD-1 after failure of anti-PD-1 therapy in metastatic NSCLC patients: the 
RECLAIM study[J]. Ann Oncol, 2022, 33: S1021. 
DOI:https://doi.org/10.1016/j.annonc.2022.07.1146. 

 
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17. Wang J, Wang J,  et al. QL1706 + Chemotherapy in PD-1 Resistant NSCLC 
Models. AACR Annual Meeting. 2023 (Abstract LB002). 
18. Wang J, Wang J,  et al. Phase I Trial of QL1706 in Solid Tumors. ASCO. 2023 
(Abstract 2505). 
19. Hellmann MD, Hellmann MD,  et al. Nivolumab plus Ipilimumab in 
NSCLC. NEJM. 2019. 
 
 
 

 
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Appendix 1. NCI CTCAE v5.0 
Partial Common Toxicity Criteria (CTC) classification (5.0) from the National Cancer 
Institute (NCI) 
For the full criteria, please refer to NCI CTCAE v5.0 or the following online 
information from the NCI website: 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. 
 
 

 
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Appendix 2. Criteria for the evaluation of 
efficacy in solid tumors 1.1 Edition 
1 Measurability of the tumor at baseline level 
1.1 Definitions 
At baseline, tumor lesions/lymph nodes will be classified as measurable or non-
measurable according to the following definitions: 
1.1.1 Measurable lesions 
Tumors: At least one measurable diameter (recorded as the maximum diameter) 
with a minimum length of: 
⚫ CT scan 10 mm (CT scan layer thickness not greater than 5mm) 
⚫ Clinical routine examination instrument 10 mm (if the tumor lesion can not be 
accurately measured by the measuring instrument, it should be recorded as 
unmeasurable) 
⚫ Chest X-ray 20 mm 
⚫ Malignant lymph node: Pathologically enlarged and measurable, the short diameter 
of a single lymph node on CT scan must be ≥15 mm (the recommended thickness 
of CT scan layer is not more than 5 mm). In baseline and follow-up, only the short 
diameter is measured and followed up. 
1.1.2 Non-measurable lesions 
All other lesions, including small ones (maximum diameter <10 mm or pathological 
lymph nodes with short diameters ≥ 10 mm to <15 mm) and those that cannot be 
measured. Unmeasurable lesions include: meningeal diseases, ascites, pleural or 
pericardial effusions, inflammatory breast cancer, cutaneous/pulmonary carcinomatous 
lymphangitis, imaging-uncertain abdominal masses requiring follow-up, and cystic 
lesions. 
1.2 Description of measurement method 
1.2.1 Focal measurements 
During clinical evaluation, all tumor measurements should be recorded in metric 
meters. All baseline assessments of tumor lesion size should be performed as close as 

 
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possible to the start of treatment and must be completed within 28 days (4 weeks) prior 
to the start of treatment. 
1.2.2 Evaluation method 
Baseline assessment and follow-up measurements of lesions should be performed 
using the same techniques and methods. All lesions must be evaluated by imaging 
except those that cannot be evaluated by imaging and only by clinical examination. 
Clinical Lesions: A lesion is considered measurable only when superficial and 
measuring ≥10 mm in diameter (e.g., skin nodules). For patients with skin lesions, it is 
recommended to archive color photographs containing a ruler for measuring lesion size. 
When both imaging and clinical evaluations are used, imaging should be preferred as it 
provides greater objectivity and allows for repeated review at the conclusion of research. 
Chest X-ray: When tumor progression is an important research endpoint, chest CT 
should be prioritized because CT is more sensitive than X-ray, especially for new 
lesions. Chest X-ray is only applicable when the lesion boundary is clear and the lung 
ventilation is good. 
CT and MRI: CT remains the gold standard for efficacy evaluation due to its 
superior repeatability. This guideline defines measurability based on CT scans with a 
thickness ≤5 mm. For areas thicker than 5 mm, lesions should be at least twice as thick 
to achieve measurable results. MRI may also be acceptable in specific scenarios, such 
as whole-body scans. 
Ultrasound: Ultrasound should not be used as a measurement method for assessing 
lesion size. Due to its operational dependency, ultrasound examinations lack 
repeatability after measurement, and cannot ensure technical consistency or 
measurement uniformity across different measurements. If new lesions are detected 
during testing using ultrasound, CT or MRI should be employed for confirmation. 
When considering radiation exposure risks associated with CT scans, MRI may serve 
as an alternative. 
Endoscopy, laparoscopy: These techniques are not recommended for objective 
evaluation of tumors, but they can be used to confirm CR in biopsy specimens obtained 
and to confirm recurrence in trials where the study endpoint is CR followed by 
recurrence or surgical resection. 
Tumor markers: While tumor markers cannot be used alone to assess objective 
tumor response, baseline levels exceeding normal ranges must return to normal 

 
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thresholds for complete response evaluation. Given that marker levels vary by disease 
type, these factors should be considered when establishing measurement criteria in 
clinical protocols. Specific criteria for CA-125 response (in recurrent ovarian cancer) 
and PSA response (in recurrent prostate cancer) have been published. Furthermore, the 
International Gynecologic Cancer Organization has developed CA-125 progression 
criteria that will soon be incorporated into the objective evaluation standards for first-
line ovarian cancer treatment regimens. 
Cytological/Histological Techniques: In specific scenarios outlined in the 
protocol, these techniques can be employed to differentiate between Progressed 
Relapse (PR) and Cured Relapse (CR) (for example, residual benign tumor tissue is 
frequently observed in germ cell tumors). When exudates may indicate potential side 
effects of therapy (such as treatment with taxane compounds or angiogenesis inhibitors), 
and when measurable tumor response meets remission or disease stabilization criteria, 
the presence or exacerbation of tumor-associated exudates during treatment can be 
confirmed through cytological analysis. This approach helps distinguish between 
clinical responses (or stable disease status) and disease progression. 
2. Tumor response assessment 
2.1 Assessment of all tumors and measurable lesions 
To evaluate objective response or potential future progression, it is essential to conduct 
baseline assessment of tumor burden in all lesions as a reference for subsequent 
measurements. In clinical trials with objective response as the primary endpoint, only 
patients with measurable lesions at baseline are eligible for enrollment. Measurable 
lesions are defined as those containing at least one detectable lesion. For studies 
targeting disease progression (measured over time or at fixed intervals), the eligibility 
criteria must explicitly specify whether participants with measurable lesions or those 
without measurable lesions are eligible. 
2.2 Baseline records of target and non-target lesions 
When there are more than one measurable lesions during baseline evaluation, all 
lesions should be recorded and measured, with a total of no more than 5 lesions (no 
more than 2 per organ), as the target lesions represent all involved organs (that is, a 
patient with one or two cumulative organs can choose a maximum of two or four target 
lesions as baseline measured lesions). 
Target lesions must be selected based on size (longest diameter), represent all 
involved organs, and measurements must be well reproducible. Sometimes a new, 

 
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repeatable maximum lesion may be selected when the largest lesion cannot be measured 
repeatedly. 
Lymph nodes require special attention as normal tissues that can be detected on 
imaging even without tumor metastasis. Pathological lymph nodes defined as 
measurable nodules or target lesions must meet the following criteria: CT-measured 
short diameter ≥15 mm. Baseline measurements only require short diameter 
assessment. Radiologists typically use the short diameter to determine whether a nodule 
has undergone tumor metastasis. Nodule size is generally represented by two-
dimensional imaging data (CT uses axial planes, while MRI selects one plane from 
axial, sagittal, or coronal views). The minimum value is taken as the short diameter. 
For example, a 20 mm× 30 mm abdominal nodule with a short diameter of 20 mm can 
be considered malignant and measurable. In this case, 20 mm represents the measured 
value. Nodules measuring ≥10 mm but <15 mm should not be regarded as target lesions. 
Nodules smaller than <10 mm do not fall under the category of pathological nodes and 
need neither documentation nor further observation. 
The total baseline diameter is calculated as the sum of all target lesion diameters 
(including the maximum diameter of non-nodular lesions and the minimum diameter 
of nodular lesions). If lymph node diameter is included, only the minimum diameter 
will be counted, as mentioned above. This baseline diameter total serves as a reference 
value for assessing disease baseline levels. 
All other lesions, including pathological lymph nodes, are considered non-target 
lesions and do not require measurement. However, they should be documented during 
baseline evaluation, such as when recorded as "present,"  "absent," or in rare cases 
"confirmed progression." Extensive target lesions may be combined with target organ 
records (e.g., multiple enlarged pelvic lymph nodes or extensive liver metastases). 
2.3 Mitigation criteria 
2.3.1 Target lesion assessment 
Complete remission (CR): all target lesions are absent and the short diameter of 
all pathological lymph nodes (including target and non-target nodules) must be reduced 
to <10 mm. 
Partial response (PR): a reduction of at least 30% in the sum of the diameter of 
the target lesions compared to baseline levels. 

 
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Progression (PD): The minimum value of the sum of all measured lesion 
diameters throughout the study is used as the reference. Disease progression is 
confirmed when the diameter and relative increase reach at least 20% (using baseline 
measurements as reference if baseline values are available). Additionally, an absolute 
increase of at least 5 mm in the total diameter (including the presence of new lesions) 
must be met. 
Stable disease (SD): the degree of reduction of the target lesion is not up to PR, and the 
degree of increase is not up to PD level, between the two. During the study, the 
minimum value of the sum of diameters can be used as a reference. 
2.3.2 Evaluation of non-target lesions 
This section defines the criteria for response to non-target lesions. Although some non-
target lesions are actually measurable, they do not need to be measured and only 
qualitative assessment is required at the time points specified in the protocol. 
Complete response (CR): All non-target lesions are eliminated and tumor markers 
return to normal levels. All lymph nodes are non-pathological in size (shorter than 10 
mm). 
Non-completion/non-progression: presence of one or more non-target lesions and/or 
sustained tumor marker levels beyond normal levels. 
Disease progression: There is clear progression of existing non-target lesions. Note: 
The presence of one or more new lesions is also considered disease progression. 
2.3.3 New lesions 
The emergence of new malignant lesions signals disease progression, making their 
evaluation crucial. While no specific imaging criteria exist for detecting new lesions, 
their identification should be clearly established. For instance, disease progression 
cannot be attributed to variations in imaging techniques, morphological changes in 
imaging, or other pathological conditions (such as so-called new bone lesions being 
merely cured or recurrent cases of the original lesion). This is particularly important 
when partial or complete response is observed in baseline lesions. A case in point: 
necrosis of a liver lesion might be reported as a new cystic lesion on CT scans, but it 
may not actually represent a new occurrence. 
Lesions detected during follow-up but not identified in baseline evaluations are 
considered new lesions and indicate disease progression. For example, if a patient with 
visceral lesions detected at baseline develops metastatic lesions on subsequent cranial 
CT or MRI scans, these intracranial metastases would be recognized as evidence of 

 
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disease progression, even if the patient had not undergone cranial imaging during their 
initial evaluation. 
If a new lesion is not clearly identified, such as due to its small size, further 
treatment and follow-up evaluation are required 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 calculated from the time of initial detection. 
2.4 Best overall efficacy evaluation 
The best overall response is defined as the optimal therapeutic outcome recorded 
from the start to the conclusion of a clinical trial, with all necessary conditions being 
considered for confirmation. Since responses may persist beyond treatment completion, 
protocols must specify whether post-treatment evaluations are included in this 
assessment. The protocol should clearly define how new therapies administered prior 
to disease progression affect the overall response. A patient's best response depends on 
outcomes from both target and non-target lesions, along with manifestations of new 
lesions. Additionally, it relies on the study design, protocol requirements, and outcome 
metrics. Specifically, in non-randomized trials, response status becomes the primary 
objective, with confirmation of partial response (PR) or complete response (CR) being 
mandatory to establish the best overall response. 
2.4.1 Point-in-time response 
Assuming that therapeutic responses occur at specific time points in each protocol, 
Table 1 will provide a summary of the overall therapeutic response at each time point 
in a patient population with measurable disease at baseline levels. 
If the patient has no measurable lesion (no target lesion), the evaluation can be 
seen in Table 2. 
2.4.2 Best overall relief: all time points 
Once all the patient's data is available, the best overall response can be determined. 
Evaluation of Best Overall Response (BOR) in Studies Not Requiring 
Confirmation of Complete or Partial Efficacy: The best response in a trial is determined 
by the highest response observed across all time points. For example, a patient may 
achieve SD in the first cycle, PR in the second cycle, and PD in the final cycle, yet still 
be evaluated as having PR for BOR. When BOR is assessed as SD, the patient must 
meet the protocol-specified minimum duration from baseline. Failure to meet this 
minimum duration renders any BOR evaluation of SD invalid, with subsequent 
assessments determining the BOR status. For instance, a patient who achieves SD in 

 
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the first cycle and PD in the second cycle but fails to meet the SD minimum duration 
requirement would be evaluated as PD for BOR. Similarly, a patient who achieves SD 
in the first cycle but becomes untraceable will be considered non-evaluable. 
Evaluation of Best Overall Response (BOR) in Studies Requiring Confirmation of 
Complete or Partial Efficacy: A complete or partial response can only be declared when 
all participants meet the trial's partial or complete remission criteria, and subsequent 
efficacy confirmation is specifically requested at a later time point (typically four weeks 
post-treatment). The definition of BOR in this context is detailed in Table 3. 
Table 1 Response at time points: subjects with target lesions (including or excluding 
non-target lesions) 
Target lesion 
Non-target lesions 
New lesions 
Overall relief 
CR 
CR 
 mistake  
CR 
CR 
Non-CR/non-PD 
 mistake  
PR 
CR 
Can not evaluate 
 mistake  
PR 
PR 
Non-progression or 
incomplete 
assessment 
 mistake  
PR 
SD 
Non-progression or 
incomplete 
assessment 
 mistake  
SD 
Can not be fully 
assessed 
Non-progress 
 mistake  
NE 
PD 
Any circumstances 
Yes or no 
PD 
Any circumstances 
PD 
Yes or no 
PD 
Any circumstances 
Any circumstances 
 yes  
PD 
CR= 
complete 
remission  
PR= 
partial 
remission  
SD= disease stable PD= PD  
NE= 
Not 
assessable 
Table 2 Response at time points-subjects with only non-target lesions 
Non-target lesions 
New lesions 
Overall relief 
CR 
 mistake  
CR 
Not CR or PD 
 mistake  
Not CR or PD 
Can not be fully assessed 
 mistake  
Can not evaluate 

 
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PD that can not be clearly 
identified 
Yes or no 
PD 
Any circumstances 
 yes  
PD 
Note: For non-target lesions, "non-CR/non-PD" refers to response better than SD. 
Since SD is increasingly being used as an endpoint for evaluating treatment efficacy, 
the definition of non-CR/non-PD was established to address the unmet need for 
measurable lesion-free status. 
For unclear progression findings (e.g., very small new lesions of uncertain nature; 
cystic changes or necrotic lesions in existing lesions), treatment may continue until the 
next evaluation. If disease progression is confirmed during the next evaluation, the date 
of progression should be recorded as the date when the suspected progression was first 
observed. 
 
Table 3 Best overall response required to confirm CR and PR efficacy 
The first 
time 
point 
showed total 
remission 
Then the 
total time to 
remission 
Best overall relief 
CR 
CR 
CR 
CR 
PR 
SD, PD or PRa 
CR 
SD 
If the SD lasts long enough, it is SD; otherwise, it 
should be PD 
CR 
PD 
If the SD lasts long enough, it is SD; otherwise, it 
should be PD 
CR 
NE 
If the SD lasts long enough, it is SD; otherwise, it 
should be NE 
PR 
CR 
PR 
PR 
PR 
PR 
PR 
SD 
SD 
PR 
PD 
If the SD lasts long enough, it is SD; otherwise, it 
should be PD 
PR 
NE 
If the SD lasts long enough, it is SD; otherwise, it 
should be NE 

 
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NE 
NE 
NE 
Note: CR denotes complete response, PR indicates partial response, SD signifies 
disease stabilization, PD represents disease progression, and NE stands for non-
evaluable. Superscript "a" applies when true CR is achieved at the first time point. If 
any disease reappears at subsequent time points, even if meeting PR criteria relative to 
baseline, the efficacy evaluation will remain PD in later stages (as disease reemerges 
after CR). The best response is determined by whether SD occurs within the shortest 
possible treatment interval. However, cases where initial CR is followed by subsequent 
scans showing residual lesions may require revision. In such instances, the initial CR 
should be revised to PR, while the best response should be classified as PR. 
2.6. Efficacy evaluation/Confirmation of remission 
2.6.1. Confirmation 
For non-randomized clinical studies with primary endpoints focused on therapeutic 
efficacy, it is essential to confirm the effectiveness of Partial Response (PR) and 
Complete Response (CR) to ensure these outcomes are not due to evaluation errors. 
This requirement also allows reasonable interpretation of results when historical data 
are available, though such data must have undergone prior validation. However, in all 
other scenarios—such as randomized trials (Phase II or III) or studies with primary 
endpoints targeting disease stabilization or progression—therapeutic confirmation 
becomes unnecessary as it holds no value for interpreting trial outcomes. The removal 
of this requirement, however, makes central review to prevent bias particularly crucial, 
especially in non-blind experimental studies. 
In the case of SD, at least one measurement in line with the SD criteria specified in the 
protocol shall be made within the shortest possible interval after the start of the test 
(generally not less than 6 to 8 weeks). 
2.6.2 Total remission period 
The total remission period is defined as the time from the first measurement meeting 
the criteria for CR or PR (whichever was achieved first) to the first documented 
recurrence or disease progression (with the minimum measurable value recorded during 
the trial serving as the reference for disease progression). The total complete response 
period refers to the duration between the initial measurement meeting CR criteria and 
the first confirmed recurrence or disease progression. 
2.6.3. Disease stable phase 

 
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The disease progression time is defined as the duration from treatment initiation to 
disease progression (in randomized trials, starting from randomization). The minimum 
total sum observed in the trial serves as a reference point (if baseline totals are minimal, 
this serves as the basis for PD calculation). The clinical significance of disease 
stabilization periods varies across studies and diseases. When a specific trial uses the 
proportion of patients maintaining the shortest stabilization period as its primary 
endpoint, the protocol must explicitly specify the minimum interval between 
measurements in the stabilization period definition. 
Note: The impact of follow-up frequency during remission, stable disease, and 
progression-free survival (PFS) after baseline evaluation should be considered. The 
definition criteria for follow-up frequency are not within the scope of this guideline. 
Follow-up frequency should take into account multiple factors such as disease type and 
stage, treatment duration, and standard protocols. However, when conducting inter-
experiment comparisons, limitations in the accuracy of these endpoints must be 
addressed. 
 
 
 
 

 
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Appendix 3. Relationship between adverse 
events and investigational drug 
The relationship between adverse events and the test drug was evaluated according 
to the 5-level classification standard of "definitely related, probably related, 
undetermined, probably unrelated, definitely unrelated", and the three items of 
"definitely related, probably related and undetermined" were combined to be 
considered as adverse reactions. The incidence of adverse reactions was calculated 
accordingly (see the table below for details). 
Criteria for judging the causal relationship between adverse events and drugs 
 metric  
Must be 
related 
Probably 
relevant 
Can not 
decide 
It 
may 
not 
matter 
It 
certainly 
doesn't 
matter 
The 
time 
of 
AE 
occurrence 
coincides 
with 
the 
time 
of 
medication 
+ 
+ 
+ 
+ 
- 
AE and drug are known to 
have adverse reactions 
+ 
+ 
+ 
- 
- 
AE 
improved 
or 
disappeared 
after 
discontinuation of the 
drug 
+ 
+ 
± 
± 
- 
AE occurred again after 
re-administration 
+ 
？ 
？ 
？ 
- 
The AE can not be 
explained by other causes 
+ 
+ 
± 
± 
- 

 
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Appendix 4. ECOG Physical Status Rating 
Criteria 
 
 scoring  
 activity level  
0 
It's perfectly normal to be able to do all the normal things without any 
restrictions 
1 
No strenuous physical activity, but can walk and engage in light physical 
activity or office work 
2 
Can walk around and live on their own, but can not do any work, spend 
no more than 50% of the day in bed 
3 
Living a barely self-sufficient life, requiring bed rest or sitting in a chair 
for more than 50% of the day 
4 
Complete loss of mobility and severe inability to care for themselves, 
requiring bed or wheelchair 
5 
 die