Therapeutic ResistAnce and Clonal Evolution Assessed With Liquid Biopsy in ICIs Treated NSCLC Patients

Therapeutic ResistAnce and Clonal Evolution Assessed With Liquid Biopsy of NSCLC Patients Treated With Immune Checkpoint Inhibitors (ICIs) or Targeted Therapy

To evaluate the predictive value of ctDNA in response, relapse for patients treated with immune checkpoint inhibitors or targeted therapy for ALK, ROS1, MET ex14 skipping.

Study Overview

• Status: Recruiting
• Conditions: Lung Neoplasms; Adenocarcinoma of Lung; Lung Cancer, Nonsmall Cell; Squamous Cell Lung Cancer
• Intervention / Treatment: Other: Observation

Detailed Description

In the study, 250 advanced NSCLC patients will be recruited. All the patients will receive tissue biopsy and circultating tumor DNA (ctDNA) liquid biopsy before entry the study. Patients who have no actionable mutations in EGFR or ALK and receive ICIs treatment and patients who carry actionable ROS1 fusion, ALK fusion or MET exon 14 skipping mutation and receive TKI treatment according to guidelines will take liquid biopsy assay to monitor the mutation status. The study will be ended when over 70% of the patients had a progressive disease (PD) in their targeted lesion.

• Study Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

• Study Contact: Name: Rongrong Chen, MD, PhD; Phone Number: 8302 86-10-53955678; Email: chenrr@geneplus.org.cn
• Study Contact Backup: Name: Lianpeng Chang, MS; Phone Number: 8301 86-10-53955678; Email: changlp@geneplus.org.cn

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Shanghai Chest Hospital
    • Contact: Shun Lu, MD; Phone Number: 86-13601813062; Email: shun_lu@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

treatment naïve Stage IIIB or Stage IV NSCLC patients, adenocarcinoma or squamous cell carcinoma

Description

Inclusion Criteria:

• Provision of informed consent
• Newly diagnosed and histological or cytological confirmed stage IIIB-IV lung adenocarcinoma or squamous cell carcinoma patients according to the AJCC staging system. The stage IV lung cancer and brain metastasis can be diagnosed by imaging and enhanced CT respectively
• No EGFR mutation in tissue and ctDNA
• Received immune checkpoint inhibitors as the first line therapy
• ECOG performance status 0-2 with expected more than 6 months of survival time
• Willingness to comply with required protocols and give permission to use the data for clinical research and products development

Exclusion Criteria:

• Patients have other primary cancers
• Patients have symptomatic brain metastasis, complications that are associated with brain metastasis or cognitive disorders
• Patients failed in either plasma or tissue sample QC

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Immune checkpoint inhibitors	Other: Observation; observe the association of ctDNA with efficacy of treatment
Targeted therapy; Targeting ALK, ROS1, MET ex14 skipping	Other: Observation; observe the association of ctDNA with efficacy of treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the evolution of ctDNA mutation profile during treatment	ctDNA mutation will be detected, PyClone based clonal analysis will be performed to analyze the clonal dominance	every 2-3 cycles of treatment upon physicians' request, ctDNA mutation analysis and clonal analysis (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resistant mechanisms of targeted therapy	Resistant mutations will be identified from ctDNA or tissue mutations	At the time of disease progression (through study completion, an average of 1.5 years)

Collaborators and Investigators

• Sponsor: Geneplus-Beijing Co. Ltd.
• Collaborators: Shanghai Chest Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: July 23, 2020
• First Submitted That Met QC Criteria: September 22, 2020
• First Posted (Actual): September 28, 2020

Study Record Updates

• Last Update Posted (Actual): May 26, 2023
• Last Update Submitted That Met QC Criteria: May 25, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Liquid biopsy; Immune Checkpoint Inhibitor; Next Generation Sequencing (NGS); Whole Transcriptome Sequencing
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma of Lung
• Other Study ID Numbers: TRACELib002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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