Investigation on Predictive Molecular Markers of Efficacy for Front-line Immunochemotherapy in Advanced NSCLC

Investigation on Molecular Markers Associated With the Clinical Efficacy of Immunotherapy Combined With Chemotherapy in the First-line Treatment of Patients With Advanced Non-small-cell Lung Cancer

This project is a real-world exploratory study aiming to explore potential molecular markers detectable at baseline that can enable the prediction of clinical efficacy of front-line immunotherapy combined with chemotherapy in advanced non-small cell lung cancer (NSCLC). This study aims to include a total of 200 treatment-naïve patients initially diagnosed with advanced NSCLC. Paired tissue and blood samples collected from all patients before the start of immunochemotherapy treatment (baseline) will be analyzed. The patient samples will be submitted for molecular analysis, including next-generation sequencing (NGS)-based gene expression profiling (GEP) and inflammation-related T-cell receptor (TCR) repertoire profiling. The molecular assay results will include but will not be limited to tumor mutation burden (TMB), microsatellite instability (MSI) status, DNA damage repair (DDR)-related gene mutation status, and programmed death-ligand 1 (PD-L1) expression level. Patients will be followed-up for treatment responses until radiological confirmation of disease progression to first-line immunochemotherapy. The molecular assay results will then be analyzed with clinical data including objective responses and progression-free survival outcomes, among others, to identify molecular markers at baseline that are associated with clinical efficacy of immunochemotherapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Biomarkers

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Chengzhi Zhou; Phone Number: 13560351186; Email: doctorzcz@163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Zhou Chengzhi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with advanced NSCLC eligible for front-line treatment of immunotherapy combined with chemotherapy.

Description

Inclusion Criteria:

1. Patients who are clinically diagnosed with stage IV NSCLC;
2. Patients who submitted samples for molecular testing using the OncoScreen Plus panel and PD-L1 (22C3) immunohistochemistry test at baseline;
3. Patients with negative results for sensitizing mutations for 6 genes, including EGFR, ALK, ROS1, BRAF, MET exon 14 skipping, and RET;
4. Patients without contraindications for immunotherapy;
5. Patients who are 18 years or older at the time of signing the informed consent form;
6. Patients with life expectancy of at least 12 weeks;
7. Patients with ECOG score of 0 or 1;

8. Patients with adequate organ function defined by the following criteria:

   1. Absolute neutrophil count ≥ 1.5109/L;
   2. Platelets ≥ 90109/L;
   3. Hemoglobin ≥ 9.0g/dL;
   4. Albumin levels ≥2.8 g/L;
   5. Total serum bilirubin ≤ 1.5 the upper limit of normal (ULN); for patients with liver metastases, total bilirubin ≤ 2 ULN;
   6. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 ULN; for patients with liver metastases, ALT and AST ≤ 5ULN;
   7. Serum creatinine ≤ 1.5 ULN;
   8. International normalized ratio (INR) or plasma prothrombin time (PT) ≤1.5ULN.

Exclusion Criteria:

1. Patients with other concurrent tumors;
2. Patients with other concurrent medical conditions that may affect their follow-up and short-term survival;
3. Patients with any history of immunotherapy;
4. Patients with any history of chemotherapy, radiotherapy or other anti-tumor treatments;
5. Patients with heart function classified as New York Heart Association (NYHA) class III or IV;
6. Patients with peripheral nerve disease;
7. Patients with confirmed hearing loss;
8. Patients with other conditions deemed unsuitable for enrollment by the researchers.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigation on molecular markers associated with the clinical efficacy of immunotherapy combined with chemotherapy in the first-line treatment of patients with advanced non-small-cell lung cancer	Next-generation sequencing (NGS)-based gene expression profiling (GEP) and inflammation-related T-cell receptor (TCR) repertoire profiling. The molecular assay results will include but will not be limited to tumor mutation burden (TMB), microsatellite instability (MSI) status, DNA damage repair (DDR)-related gene mutation status, and programmed death-ligand 1 (PD-L1) expression level.	June 2021 - March 2024

Collaborators and Investigators

• Sponsor: Zhou Chengzhi

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2021
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): March 1, 2024

Study Registration Dates

• First Submitted: April 22, 2021
• First Submitted That Met QC Criteria: April 22, 2021
• First Posted (Actual): April 26, 2021

Study Record Updates

• Last Update Posted (Actual): April 26, 2021
• Last Update Submitted That Met QC Criteria: April 22, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: CROC2101

Drug and device information, study documents

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