NGS-based Comprehensive Genomic ctDNA Panel in NSCLC With Immunotherapy

A Prospective Study on NGS-based Comprehensive Genomic ctDNA Panel in NSCLC Treated With Immunotherapy

Liquid biopsy based on next-generation sequencing (NGS) method has become an increasingly powerful detection tool for clinical research and practice. As a companion diagnostic panel, circulating tumor DNA (ctDNA) assay has the considerable potential to detect the blood tumor mutation burden (bTMB), and bTMB calculated by ctDNA assay is regarded as a novel and promising biomarker for immunotherapy nowadays. Though immune checkpoint inhibitors (ICIs) in immunotherapy are highly effective but can induce severe immune-related adverse events (irAEs), which cannot be better predicted in advance. Meanwhile adoptive transfer of T cells transgenic for tumor-reactive T-cell receptors (TCR) is an attractive immunotherapeutic approach. However, clinical translation is so far limited due to challenges in the identification of suitable target antigens as well as TCRs that are concurrent safe and efficient. Definition of key characteristics relevant for effective and specific tumor rejection is essential to improve current TCR-based immunotherapy. This research is to characterize in-depth TCRs derived from HLA-mismatched allogeneic repertoire targeting different myeloperoxidase (MPO)-derived peptides presented by the same HLA-restriction element. Overall the purpose of this trial is to investigate the combined predictive biomarkers (including bTMB and HLA) related to the immunotherapy effects and the biomarker (TCR) associated with adverse reactions during immunotherapy and hold a predictive role, thus further benefit patients receiving immunotherapy, especially in the advanced stage lung cancer patients where tissue samples are unavailable.

Study Overview

• Status: Recruiting
• Conditions: Lung Cancer
• Intervention / Treatment: Other: The method of gene mutation detection

Detailed Description

Blood samples including the plasma and PBMC (peripheral blood mononuclear cell) from immunotherapy-naive lung cancer patients will be analyzed by CGP panel (OrigiMed, Inc.) for multiple molecular biomarkers including mutations with sensitivity/resistance to targeted therapies, bTMB, HLA, etc. Treatment methods and outcomes will be followed-up to inspect the clinical benefit and safety with CGP-panel analysis.

• Study Type: Observational
• Enrollment (Anticipated): 450

Contacts and Locations

• Study Contact: Name: Xiaomin Niu; Phone Number: 021-22200000-3403; Email: ar_tey@hotmail.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Recruiting
      • Shanghai Chest Hospital
      • Contact: Xiaomin Niu; Email: ar_tey@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

patients in Shanghai Chest Hospital

Description

Inclusion Criteria:

• Participant aged 18 or above, and gender unrestricted
• Individual with pathologically diagnosed lung cancer

Exclusion Criteria:

• Patients with concomitant other tumors
• Individual with severe cardiopulmonary insufficiency and hypoproteinemia
• Women who were pregnant and were during their lactation

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	PFS will be defined as the time from initial treatment to the time of disease progression or death	through the whole study period, an average of 3 years
Blood Tumor Mutational Burden (bTMB)	bTMB will be defined as the total number of detected somatic mutation counts in coding regions per million bases in plasma ctDNA	halfway of the study, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Other biomarkers	The distribution and clinical applications including benefit and adverse reaction of biomarkers such as HLA, TCR and gene mutations in Chinese non-small cell lung cancer patients	halfway of the study, an average of 1 year
Clonality	The tumor clonality in Chinese non-small cell lung cancer	halfway of the study, an average of 1 year
Overall survival (OS)	OS will be defined as the time from cancer diagnosed time to the time of death	through the whole study period, an average of 3 years

Collaborators and Investigators

• Sponsor: Shanghai Chest Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2020
• Primary Completion (Anticipated): February 1, 2023
• Study Completion (Anticipated): August 1, 2023

Study Registration Dates

• First Submitted: September 28, 2020
• First Submitted That Met QC Criteria: November 14, 2020
• First Posted (Actual): November 19, 2020

Study Record Updates

• Last Update Posted (Actual): November 19, 2020
• Last Update Submitted That Met QC Criteria: November 14, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: ShanghaiChest0016

Drug and device information, study documents

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