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

Recruiting

• Conditions: Lung Neoplasms; Lung Cancer, Nonsmall Cell; Adenocarcinoma of Lung; Squamous Cell Lung Cancer
• Interventions: Other: Observation

• Registration Number: NCT04566432
• Lead Sponsor: Geneplus-Beijing Co. Ltd.

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.

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 Timeline

• Study Start: 2020-07-01
• Study First Submitted: 2020-07-23
• Study First Submitted QC: 2020-09-22
• Study First Posted: 2020-09-28
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-16
• Last Update Posted: 2024-07-18
• Primary Completion: 2024-12-31
• Study Completion: 2025-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 250

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Targeted therapy	Observation	Targeting ALK, ROS1, MET ex14 skipping
Immune checkpoint inhibitors	Observation	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

Shanghai Chest Hospital; 🇨🇳 Shanghai, China