Correlation Between Specific Gene Mutationand Local Immune Microenvironment and Immunotherapy Efficacy in NSCLC

Immunotherapy for PD-L1 positive patients is still ineffective in some patients，which may be related to the complex immune microenvironment.In view of this bottleneck, further refinement of immunotyping and in-depth study of drug resistance mechanism are the most important tasks. In this observational study, we evaluated the difference of gene mutation and immune microenvironment and therapeutic effect in primary NSCLC.

Study Overview

• Status: Unknown
• Conditions: NSCLC

Detailed Description

There are still some patients with PD-L1 positive who are ineffective in immunotherapy, which may be related to the complex immune microenvironment. In view of this bottleneck, further refinement of immunotyping and in-depth study of drug resistance mechanism are the most important tasks.

Recently, studies have shown that the core elements of tumor microenvironment that have a significant impact on immunotherapy are:1. Infiltration abundance of specific killer T cells; 2. PD-L1 expression dependent on IFN - γ pathway, down-regulation of various active molecules and up-regulation of inhibitory molecules; 3. Activation and clearance of various inhibitory T cells.

Although the classification has achieved further refinement of immune cells and molecular level, there are still some problems to be solved urgently: first, the classification of TIL cells needs further refinement, and different types of TIL infiltration have different guiding significance for prognosis; second, the subjective second-order semi quantitative scoring is often used for til count scoring, with low repeatability and different centers It is not easy for different pathologists to reach an agreement on the results of reading and interpretation. Thirdly, conventional methods are difficult to meet the requirements of tumor microenvironment analysis. In conclusion, it is urgent to develop a multi molecular marker landscape analysis system for tumor microenvironment, and establish a standardized detection process for each molecule to meet the needs of clinical positioning, quantitative and qualitative analysis for key molecular markers of immune microenvironment.

In this observational study, we evaluated the difference of gene mutation and immune microenvironment and therapeutic effect in primary NSCLC.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: chengzhi zhou, PHD; Phone Number: +8613560351186; Email: doctorzcz@163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Recruiting
      • Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University
      • Contact: Chengzhi Zhou, MD; Phone Number: +8613560351186896; Email: doctorzcz@163.com
      • Principal Investigator: Chengzhi Zhou, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Chinese

Description

Inclusion Criteria:

• Non small cell lung cancer was diagnosed by cytology or histopathology;
• Patients to be treated with PD-1 / PD-L1 inhibitors;
• Who signed the informed consent for participating in the research plan

Exclusion Criteria:

• History of other malignancies
• Cancer meningitis in subjects
• Incomplete clinical follow-up data
• Failure to sign informed consent to participate in the research program

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between specific gene mutation and immune microenvironment	Correlation between specific gene mutation and immune microenvironment	up to 1year
Correlation between specific gene mutations and ORR and PFS in immunotherapy patients with lung cancerof lung cancer patients with immunotherapy	Correlation between specific gene mutations and ORR and PFS in immunotherapy patients with lung cancer	up to 1year
Correlation between immune microenvironment and ORR and PFS in immunotherapy lung cancer patients	Correlation between immune microenvironment and ORR and PFS in immunotherapy lung cancer patients	up to 1year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of OS with specific gene mutation in immunotherapy of lung cancer	Correlation of OS with specific gene mutation in immunotherapy of lung cancer	up to 1year
Correlation between immune microenvironment and OS in immunotherapy lung cancer patients	Correlation between immune microenvironment and OS in immunotherapy lung cancer patients	up to 1year

Collaborators and Investigators

• Sponsor: Guangzhou Institute of Respiratory Disease
• Collaborators: GeneCast Biotechnology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2020
• Primary Completion (Anticipated): May 31, 2021
• Study Completion (Anticipated): May 30, 2022

Study Registration Dates

• First Submitted: May 22, 2020
• First Submitted That Met QC Criteria: May 27, 2020
• First Posted (Actual): May 28, 2020

Study Record Updates

• Last Update Posted (Actual): May 28, 2020
• Last Update Submitted That Met QC Criteria: May 27, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Biomarker; NSCLC; mutation; PD-L1; sequencing; immune microenvironment; mIHC
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: NSCLC-202005

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No