A Single-arm Exploratory Study of Neoadjuvant Therapy

Study Overview
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Brief Summary
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Neoadjuvant EGFR TKI therapy targeting EGFR mutation has some problems failure to fulfill clinical requirements such as low MPR rate, tissue fibrosis and other major surgical impacts and unmet clinical needs.This study hypothesized that Tisleizumab combined with chemotherapy in the neoadjuvant treatment of stage II-IIIA non-squamous NSCLC with EGFR-mutant PD-L1 expression ≥1% could significantly improve the pathological response rate after neoadjuvant therapy, improve the surgical complete resection rate, reduce perioperative complications and do not increase the surgical difficulty.In this study, biomarker analysis is going to explore the possible direction of neoadjuvant therapy population screening, and to explore a possible method for the efficacy and safety of neoadjuvant immunotherapy in clinical stage II-IIIA non-squamous non-small cell lung cancer with EGFR mutation and expression of PD-L1.

Official Title
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Neoadjuvant Tislelizumab and Platinum-Based Doublet Chemotherapy in Stage II-IIIB EGFR-Mutated Lung Adenocarcinoma With PD-L1 Positive Expression -- A Phase II Study (DuoVitality)

Conditions
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Lung Adenocarcinoma

Intervention / Treatment
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* Drug: Tislelizumab
* Drug: pemetrexed
* Drug: cis-platemum
* Drug: or carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Volunteer to participate in clinical research;Fully understand and be Informed of the study and sign the Informed Consent Form (ICF);Willing to follow and able to complete all test procedures; Age 18-75 (boundary value included), no gender limitation; Histologically proven stage II-IIIB Lung Adenocarcinoma (as defined by the American Joint Commission on Cancer, 8th Edition); EGFR gene mutation positive (can be tested by tissue or blood samples); PD-L1 ≥ 1% ECOG PS score 0-1 (including boundary value); Cardiopulmonary function is good, and the requirements for surgical resection for radical treatment are confirmed; Meet the conditions for receiving platinum containing two-drug chemotherapy; The expected survival time is ≥3 months, and feasible surgery is planned; Exclusion Criteria: Any previous treatment for current lung cancer, including systemic therapy or radiotherapy; there are locally advanced unresectable diseases (regardless of disease stage) and metastatic diseases (stage IV). A history of interstitial lung disease, non-infectious pneumonia or uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung disease, etc.Patients with any severe and/or uncontrolled disease or symptom

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant ICI combined with chemotherory<br>intravenous injection :Tislelizumab + pemetrexed + platinum Q3W 2-4 cycles | Drug: Tislelizumab<br>* 200 mg ,intravenous injection ,Q3W 2-4 cycles<br>Drug: pemetrexed<br>* 500 mg/m2,intravenous injection ,Q3W 2-4 cycles<br>Drug: cis-platemum<br>* 60-75mg/m2 ,intravenous injection ,Q3W 2-4 cycles<br>Drug: or carboplatin<br>* AUC(4-5) ,intravenous injection ,Q3W 2-4 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major pathologic response rate (MPR) （proportion of patients with no more than 10% remaining live tumor cells in the resected primary tumor and in all resected lymph nodes） | MPR of surgical specimens from patients who were operable after neoadjuvant therapy was evaluated | 15-18 weeks after enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR: Proportion of patients who achieved complete response (CR) or partial response (PR) among all randomized patients with measurable disease at baseline assessed according to RECIST version 1.1 | To evaluate objective response rate (ORR) in neoadjuvant treatment | 6-12weeks after enrollment | 
| pCR: proportion of patients with no residual tumor in resected primary tumor and lymph nodes | pCR of surgical specimens from patients who were operable after neoadjuvant therapy was evaluated | 15-18 weeks after enrollment | 
| Descending rate of lymph nodes | Proportion of patients whose pathologic lymph node stage was reduced to N1/N0 by baseline radiographic assessment of N2 or N1 | 15-18 weeks after enrollment | 
| Number of Participants with Adverse Events | To evaluate the safety profile(Number of Participants with Adverse Events) | through study completion, an average of 35weeks | 
| The time of surgery delay | evaluate the interval time from the completation of last neoadjuvant therapy to surgery | 4-6weeks after completation of the last neoadjuvant therapy | 
| minimally invasive surgery rate | explore different surgery manner rate after neoadjuvant | 4-6weeks after completation of the last neoadjuvant therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Resectable II-IIIB, EGFR mutation and PD-L1≥1%, NSCLC, Neoadjuvant immunotherapy