Mechanism of Response to IMFINZI Neoadjuvant Therapy in Non-small Cell Lung Cancer Patients Based on Multiple-omics Models

Study Overview
=================
Brief Summary
-----------------
A single-center prospective exploratory single-arm neoadjuvant therapy study, based on a prospective cohort study, according to patients' blood and tumor samples before and after neoadjuvant treatment, WES, GEP gene expression profiling, TCR sequencing and ctDNA dynamic monitoring were used to explore the intratumoral immune consequences of PD-1 monoclonal antibody administration and identify potential Response biomarker.

Detailed Description
-----------------
To explore the safety and immunobiological effects of 2 cycles of duvalumab combined with albumin paclitaxel + cisplatin/carboplatin for patients with stage IB-IIIA non-small cell lung cancer; use whole exome sequencing , GEP gene expression profile detection based on NanoString platform and other methods to predict the efficacy of IMFINZI neoadjuvant therapy, looking for potential biomarkers; study the impact of neoadjuvant therapy of I drug on the tumor microenvironment at multiple levels such as genome, transcriptome, PD-1/PD-L1 protein transcription and expression, T cell TCR immune groupthe library and T cell subsets, and provide comprehensive exploratory research evidence for finding the biomarker for the neoadjuvant anti-PD-L1 therapy of lung cancer .

Official Title
-----------------
Mechanism of Response to IMFINZI Neoadjuvant Therapy in Non-small Cell Lung Cancer Patients Based on Multiple-omics Models

Conditions
-----------------
Non-small Cell Lung Cancer

Intervention / Treatment
-----------------
* Drug: Durvalumab
* Drug: Albumin Paclitaxel
* Drug: Carboplatin/Cisplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18-80 years old Male or female (no fertility requirement) Meet NCCN lung cancer diagnostic criteria No radical mastectomy, radiotherapy, chemotherapy, targeted therapy and immunotherapy Resectable stage Ib-IIIa non-small cell lung cancer (NSCLC) patients confirmed by imaging and biopsy; clear lung histopathological sample results have been obtained during screening, and all molecular biological tests can be completed. Patients without serious comorbidities, including but not limited to basic cardiovascular and cerebrovascular diseases, and patients whose clinical conditions allow to tolerate thoracic surgery Female and male subjects of childbearing age must use appropriate contraceptive measures during the study period and 6 months after the last study medication. Female subjects of childbearing age must have a negative pregnancy test Pathologically confirmed as lung adenocarcinoma or squamous cell carcinoma Exclusion Criteria: Patients with unstable vital signs, need vasoactive drugs, or need intensive care unit (ICU) support Patients with active infections (including infections such as bacteria, fungi, viruses, tuberculosis, and various types of hepatitis) within 3 months before the first study medication Symptoms and signs of severe or uncontrolled liver, kidney, gastrointestinal, endocrine, lung, heart, neuropsychiatric, or brain disease Patients with a history of autoimmune diseases (inflammation or insufficiency of glands such as thyroid, pituitary, adrenal gland, etc., immunological diseases with positive autoantibodies) Is participating in other drug trials One month before the enrollment plan to receive immunotherapy, he had used any anti-systemic antibiotic therapy, hormone therapy, immunosuppressive therapy, etc. The pathology is small cell lung cancer or other neuroendocrine tumors or sarcomas, rare tumors or lung adenocarcinoma/squamous cell carcinoma containing the above components. The patient has a history of malignant tumors other than lung cancer Patients with sensitive gene mutations in EGFR (E19del/E21 L858R) and ALK (various types of fusion mutations)

Ages Eligible for Study
-----------------
Minimum Age: 80 Years
Maximum Age: 80 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: Experimental Arm<br>Durvalumab 1000 mg IV Q3W + Paclitaxel 200mg/m2 + Carboplatin AUC 6 IV Q3W in resectable stage IB-IIIA NSCLC adult patients followed by adjuvant treatment for 1 year with Durvalumab 1000 mg IV Q3W for 4 months and Durvalumab 15000mg Q4W for 8 months | Drug: Durvalumab<br>* Durvalumab 1000 mg IV Q3W for 2 cycle + Followed by adjuvant treatment for 1 year with Durvalumab 1000 mg IV Q3W for 4 months and Durvalumab 1500mg Q4W for 8 months<br>* Other names: IMFINZI;Drug: Albumin Paclitaxel<br>* Albumin Paclitaxel 200-260 mg, depending on the patient's physical condition, for 2 cycle<br>Drug: Carboplatin/Cisplatin<br>* Carboplatin AUC 6 IV Q3W or Cisplatin 80mg/㎡ for 2 cycle<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MPR | Major pathologic response is defined as the presence of 10% or less of vital tumor cells in the sections of the primary lesion and/or mediastinal lymph nodes presenting focal microscopic disease after surgery | At the date of tumor assessment after surgery, estimated at approximately 24 weeks post-baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | The progression free survival is the time until the patients disease progresses | at 24 months from the first dose of neadjuvant treatment | 
| Overall survival | Time when the patient is still alive | at 3 years from the first dose of neoadjuvant treatment | 
| Toxicity profile | Toxicities caused by the drug during the study | from the first dose of neoadjuvant treatment until 90 days after the last dose of adjuvant treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
neoadjuvant immunotherapy, IMFINZI, multiple-omics