NGS-based Comprehensive Genomic ctDNA Panel in NSCLC With Immunotherapy

Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04636047
• Other study ID #: ShanghaiChest0016
• Status: Recruiting
• Start date: November 2020
• Est. completion date: August 2023

Study information

• Verified date: November 2020
• Source: Shanghai Chest Hospital
• Contact: Xiaomin Niu
• Phone: 021-22200000-3403
• Email: ar_tey[@]hotmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 450
• Est. completion date: August 2023
• Est. primary completion date: February 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Lung Cancer

Intervention

Other:
• The method of gene mutation detection
All samples were detected by NGS CGP panel.

Locations

Country	Name	City	State
China	Shanghai Chest Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Chest Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	Clonality	The tumor clonality in Chinese non-small cell lung cancer	halfway of the study, an average of 1 year
Secondary	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