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

Sponsor

Geneplus-Beijing Co. Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04566432

Collaborator

Shanghai Chest Hospital (Other)

250

Enrollment

Location

35.9

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Lung Neoplasms Lung Cancer, Nonsmall Cell Adenocarcinoma of Lung Squamous Cell Lung Cancer	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 Design

Study Type:

Observational

Anticipated Enrollment :

250 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Jul 1, 2020

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Jun 30, 2023

Arms and Interventions

Arm	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

Arm

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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