A Phase II, Prospective, Randomized, Open Label, Multi-center Study of Tislelizumab Combined With Anlotinib and Platinum Doublet Chemotherapy as Neoadjuvant/Adjuvant With Resectable Stage II-IIIB Non-Small Cell Lung Cancer
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer, Anti Angiogenesis
Sponsor: Tang-Du Hospital

 
 
 
 
A phase II, Prospective, Randomized, open label, multi-center study of Tislelizumab 
combined with Anlotinib and Platinum Doublet Chemotherapy as 
Neoadjuvant/Adjuvant with Resectable Stage II-IIIB Non-Small Cell Lung Cancer 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Plan version number: 2.0 version 
Version date: June 4th, 2024 
Applicant: Tangdu Hospital, Air Force Military Medical University 
Main researcher: Professor Yan Xiaolong 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Brief summary:  
This is a Phase II, prospective, randomized, open label, controlled, multi-center  study, 
aim to evaluate the activity of Tislelizumab and Anlotinib and chemotherapy compared with 
Tislelizumab and chemotherapy before surgery, followed by Tislelizumab alone as adjuvant 
therapy. in terms of pathological complete response. The primary objective of this study is to 
evaluate and compare pathological complete response rate(pCR). 
Study Type  : 
Interventional  (Clinical Trial) 
Actual Enrollment  : 178 participants 
Allocation: 
Randomized 
Intervention Model: Parallel Assignment 
Masking: 
open label 
Primary Purpose: Treatment 
Official Title: A phase II, Prospective, Randomized, open label, multi-center study of 
Tislelizumab combined with Anlotinib and Platinum Doublet Chemotherapy as 
Neoadjuvant/Adjuvant with Resectable Stage II-IIIB Non-Small Cell Lung Cancer 
Arms and Interventions 
Experimental A: Experimental Group: Tislelizumab with anlotinib and platinum-based 
chemotherapy + Adjuvant Tislelizumab （n=89） 
Intervention/treatment: 
Tislelizumab 200mg iv，d1，q3w， 
Anlotinib 10mg，po，qd1-14，q3w， 
Cisplatin 75 mg/m^2 by IV infusion Q3W, given on cycle day 1 
Carboplatin AUC of 5 on Day 1 of each 3-week cycle  
Paclitaxel 175mg/m2 on Day 1 of each 3-week cycle(SQ only) 
Albumin-bound paclitaxel 260mg/m2，on D1 IV infusion Q3W or 130mg/m2 on D1D8 IV 
infusion Q3W for each cycle(SQ only) 
Pemetrexed 500 mg/m2 on Day 1 of each 3-week cycle(NSQ only) 
Adjuvant: 4 weeks(±7 Days) following surgery, participants receive no more than 16 cycles 
(cycle length: 3 weeks) of Tislelizumab [200 mg, IV; given on cycle day 1]. 
Active Comparator B: Control group: Tislelizumab with platinum-based chemotherapy + 
Adjuvant Tislelizumab （n=89） 
Intervention/treatment: 
Tislelizumab 200mg iv，d1，q3w， 
Cisplatin 75 mg/m^2 by IV infusion Q3W, given on cycle day 1 
Carboplatin AUC of 5 on Day 1 of each 3-week cycle  
Paclitaxel 175mg/m2 on Day 1 of each 3-week cycle(SQ only) 
Albumin-bound paclitaxel 260mg/m2，on D1 IV infusion Q3W or 130mg/m2 on D1D8 IV 
infusion Q3W for each cycle(SQ only) 
Pemetrexed 500 mg/m2 on Day 1 of each 3-week cycle(NSQ only) 
Adjuvant: 4 weeks(±7 Days) following surgery, participants receive no more than 16 cycles 
(cycle length: 3 weeks) of Tislelizumab [200 mg, IV; given on cycle day 1]. 
Outcome Measures 
Primary Outcome Measures 
pathological complete response (pCR) in Intent-to-Treat (ITT) analysis set 

no residual tumor cells in the surgically resected tumor specimen and all sampled regional 
lymph nodes after neoadjuvant treatment. 
Secondary Outcome Measures 
main pathology rate (MPR) in ITT analysis set 
Major pathological response rate (MPR): defined as ≤ 10% of residual tumor cells in the 
surgically resected tumor specimen and sampled regional lymph nodes after neoadjuvant 
treatment. 
Event-free survival (EFS) in ITT analysis set: defined as the time from the randomization until 
the date of first documented RESCIST 1.1 disease progression or local or distant recurrence 
of lung cancer or date of death due to any cause, whichever came first. 
Objective Response Rate (ORR) in ITT analysis set 
defined as the proportion of participants with complete response (CR) and partial response 
(PR), as assessed by the RECIST v1.1 
Overall Survival (OS) 
defined as the time from randomization until the date of death due to any cause 
Adverse Events (AEs)  
The number of participants experiencing an AE will be assessed by CTCAE v5.0. 
Other Outcome Measures: 
Biomarker, R0 resection rate, type of surgery 
Eligibility Criteria 
Ages Eligible for Study:   
18 Years and older   (Adult, Older Adult) 
Sexes Eligible for Study:   All 
Accepts Healthy Volunteers:   No 
Criteria 
Key Inclusion Criteria: 
1. 
aged 18~75 years old 
2. 
histologically confirmed stage IIA to stage IIIB (IIIB term T2/3/4N2) non-small cell lung 
cancer (staging based on AJCC 9th edition) 
3. 
ECOG PS score of 0-1; 
4. 
patients are asked to provide an archived tumor tissue sample (FFPE tissue block or 
approximately ≥ 6 freshly cut unstained FFPE sections) and a pathology report of this 
baseline sample for PD-L1 and other biomarker analysis). Biopsy samples are requested 
at baseline if there are no available archival samples or samples are unavailable. 
5. 
Adequate organ and marrow function 
6. 
expected survival ≥ 3 months; 
7. 
be evaluated by a thoracic surgeon and confirmed to be eligible for R0 resection for the 
purpose of radical treatment 
8. 
At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 Target Lesion 
(TL) at baseline 
Key Exclusion Criteria: 
1. those with a known history of CNS metastases; 
2. patients with EGFR mutations or ALK translocations; 
3. those with imaging (CT or MRI) showing tumor invasion of a major blood vessel (e.g., 
pulmonary artery or superior vena cava) or those with a high likelihood of fatal 

hemorrhage due to tumor invasion of a major blood vessel during the follow-up study; 
4. prior treatment with immune checkpoint inhibitors, including but not limited to 
anti-CTLA-4, anti-PD-1 and anti-PD-L1 therapeutic antibodies, and OX-40; 
5. previous systemic antivascular therapy; 
6. current participation in an interventional clinical trial or receipt of another investigational 
drug or medical intervention within 4 weeks;  
7. presence of active hemoptysis, active diverticulitis, abdominal abscess, gastrointestinal 
obstruction (or other factors affecting the absorption of oral medications such as 
inability to swallow, nausea and vomiting, abnormal physiologic function, malabsorption 
syndrome, etc.) that require clinical intervention 
8. the presence of any signs or history of bleeding constitution; the presence of unhealed 
wounds, ulcers, or fractures in patients who have experienced any bleeding or 
hemorrhagic event ≥ CTCAE Grade 3 within 4 weeks prior to enrollment; 
9. class III-IV congestive heart failure with poorly controlled and clinically significant 
arrhythmias (including QTcF ≥450ms in men and ≥470ms in women); 
10. difficult-to-control hypertension; 
11. history of severe allergy to amlotinib or its prophylactic agents; 
12. any arterial thrombosis, embolism, or ischemia, such as myocardial infarction, unstable 
angina, cerebrovascular accident, or transient cerebral ischemic attack, that has occurred 
within 6 months prior to enrollment in therapy 
13. patients whose medical history or test results indicate a hereditary predisposition to 
bleeding or coagulation disorders that may increase the risk of bleeding 
14. active autoimmune disease requiring systemic treatment or history of autoimmune 
disease with potential for relapse 
15. patients requiring long-term systemic glucocorticosteroids (patients requiring inhaled or 
locally injected glucocorticosteroids due to COPD, asthma may be enrolled) or who have 
received immunosuppressive therapy within 7 days prior to treatment 
16. have an active infection requiring treatment or have used systemic anti-infective 
medications within one week prior to the first dose; 
17. a history of interstitial lung disease, non-infectious pneumonia, or poorly controlled 
disease, including pulmonary fibrosis, acute lung disease 
18. a known history of human immunodeficiency virus (HIV) infection, untreated active 
hepatitis B (defined as HBsAg positivity along with a detectable HBV-DNA copy number 
greater than 2,000 IU/ml, and active HCV-infected subjects (HCV antibody positivity with 
HCV-RNA levels above the lower limit of detection); 
19. previous allogeneic stem cell transplantation or organ transplantation. 
20. have received a live vaccine within 30 days prior to the first dose (Cycle 1, Day 1); 
21. pregnant or lactating women; 
22. patients with hypersensitivity to the study drug or excipients; 
23. history or evidence of disease that may interfere with the results of the trial, prevent the 
subject from participating in the study in its entirety, abnormal values of therapeutic or 
laboratory tests, or other conditions that, in the opinion of the investigator, make 
enrollment inappropriate The investigator believes that there are other potential risks 
that make participation in the study inappropriate; 

24. stage IIIB exclusion of patients with TxN3 non-small cell lung cancer (staging based on 
AJCC 9th edition); 
25. renal insufficiency: routine urinalysis suggestive of urinary protein ≥++ or confirmed 
24-hour urinary protein volume ≥1.0 g; 
26. patients with central squamous cell carcinoma confirmed by imaging and pathology; 
 
Locations 
China, Shannxi 
The Second Affiliated Hospital of Air Force Medical University  
Xi'an, Shannxi, China 
Sponsors and Collaborators 
Tang-Du Hospital 
Investigators 
Principal Investigator: Xiaolong Yan, PhD