Neoadjuvant of Tislelizumab Combined With Chemotherapy Followed by Surgery in Unresectable Stage Ⅲ NSCLC

Study Overview
=================
Brief Summary
-----------------
The purpose of this conversion therapy study is to evaluate the safety and efficacy of neoadjuvant of Tislelizumab combined with platinum doublet for stage III unresectable locally advanced NSCLC.

Official Title
-----------------
Efficacy and Safety of Tislelizumab With Platinum Doublet Chemotherapy as Neoadjuvant Therapy for Participants With Initially Unresectable Stage III Non-small Cell Lung Cancer: A Single-arm, Phase II Trial

Conditions
-----------------
NSCLC, Stage III

Intervention / Treatment
-----------------
* Drug: Tislelizumab
* Drug: Pemetrexed (Nonsquamous NSCLC) or Paclitaxel/Nab-paclitaxel(Squamous NSCLC)
* Drug: Carboplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent provided. Unresectable stage III non-small cell lung cancer confirmed by histopathology or cytology. ECOG score is 0 or 1. Adequate hematological function, liver function and renal function. Exclusion Criteria: Previously received systemic anti-tumor therapy for non-small cell lung cancer. history or current (non-infectious) pneumonia/interstitial pneumonia requiring steroid treatment. History or active pulmonary tuberculosis. Active infections that require systemic treatment. History or suspected autoimmune disease or immune deficiency who, in the judgment of the investigator, cannot tolerate immunotherapy. Untreated active Hepatitis B. Has a known history of human immunodeficiency virus (HIV) infection (HIV 1/2 antibody positive). Grade 3 or above peripheral neuropathy. Severe allergic history to pemetrexed, paclitaxel, albumin-bound paclitaxel, carboplatin or other preventive drugs. Underlying severe or uncontrolled disease. Malignant tumors other than NSCLC within 5 years. Any medical condition requiring systemic treatment with corticosteroids (prednisone or equivalent at a dose of >10mg/ day) or other immunosuppressive agents within 14 days prior to treatment.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant therapy of Tislelizumab with chemotherapy+surgery<br>Participants will receive neoadjuvant Tislelizumab plus double platinum based chemotherapy for 3 cycles, followed by surgical resection. | Drug: Tislelizumab<br>* Tislelizumab: 200mg, IV, day 1 of each 21-day cycle, Neoadjuvant therapy : 3 cycles<br>Drug: Pemetrexed (Nonsquamous NSCLC) or Paclitaxel/Nab-paclitaxel(Squamous NSCLC)<br>* Pemetrexed: 500 mg/m^2, IV, day 1 of each 21-day cycle, 3 cycles. Paclitaxel: 60-75mg/m^2, IV, day 1 of each 21-day cycle, 3 cycles. Nab-paclitaxel: 260mg/m^2, IV, day 1 of each 21-day cycle, 3 cycles.<br>Drug: Carboplatin<br>* AUC 5 mg/mL/min by IV infusion Q3W, given on cycle day 2.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resectability rate | Resectability rate is defined as the percentage of patients who were able to undergo surgery after neoadjuvant therapy. | At time of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major pathological response rate (MPR) | MPR rate is defined as the percentage of participants having ≤10% viable tumor cells in the resected primary tumor and all resected lymph nodes following completion of neoadjuvant therapy. | At time of surgery | 
| Pathology complete response rate(pCR) | pCR rate is defined as the percentage of participants lacking of evidence of viable tumor cells in the pathological examination of resected specimens. | At time of surgery | 
| R0 Resection rate | R0 Resection rate is defined as the percentage of patients who were able to undergo R0 Resection surgery after neoadjuvant therapy. | At time of surgery | 
| Perioperative G3-4 Adverse Events (AEs) | The number of participants experiencing an perioperative G3-4 AE will be assessed. | Up to 1 month post surgery |