The Feasibility of Dynamic Liquid Biopsy Monitoring During Neoadjuvant Treatment for EGFR-mutated NSCLC

This study aimed to assess the value of dynamic ctDNA monitoring in guiding the development of personalized neoadjuvant treatment strategies for EGFR-mutated NSCLC patients.

Study Overview

• Status: Not yet recruiting
• Conditions: EGF-R Positive Non-Small Cell Lung Cancer
• Intervention / Treatment: Other: ctDNA monitoring

Detailed Description

This study aimed to prospectively enroll approximately 300 resectable stage II-IIIB (T1-4N0-2M0, excluding T4 with invasion of vital structures and bulky or infiltrative N2) NSCLC patients with histologically confirmed EGFR 19del or L858R mutations. Peripheral blood samples will be collected at baseline before neoadjuvant 3rd-generationEGFR TKI therapy, and ctDNA levels will be quantitatively assessed. For patients with positive baseline ctDNA, peripheral blood will be collected again after 3 weeks of neoadjuvant TKI therapy to assess if ctDNA has turned negative, and HRCT will be performed to evaluate the treatment efficiency simultaneously.

In patients with positive baseline ctDNA, for ctDNA-negative patients after 3 weeks of neoadjuvant TKI treatment, radical resection surgery will be performed after continuing TKI treatment for 9-12 weeks (Group A). For ctDNA-positive patients after 3 weeks of neoadjuvant TKI treatment, in combination with imaging changes in the lesions, a multidisciplinary team (MDT) evaluation will be conducted. After discussion between the attending physicians and the patient, the subsequent treatment will either continue TKI treatment for 9-12 weeks (Group B), undergo 3 cycles of TKI plus chemotherapy (Group C), or undergo sequential neoadjuvant immunotherapy plus chemotherapy for 3 cycles (Group D) before radical resection surgery.The study intends to evaluate the correlation between the rate of major pathological response (MPR) and ctDNA levels at 3 weeks after TKI treatment, to compare the difference in pathological response between ctDNA-negative and ctDNA-positive groups after 3 weeks of neoadjuvant TKI treatment and to evaluate the guiding value of dynamic ctDNA monitoring during neoadjuvant therapy for optimizing subsequent treatments.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xuqi Sun, MD; Phone Number: +86-18767186629; Email: sunxq@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients should voluntarily join this study and sign the informed consent form
2. Patients diagnosed with resectable stage II-IIIB (T1-4N0-2M0, excluding T4 with invasion of vital structures and bulky or infiltrative N2) NSCLC
3. Patients with EGFR 19del or L858R mutations.
4. Age from 18 to 75 years old, both male and female
5. ECOG score 0-1
6. According to the RECIST v1.1 , patients should have at least one measurable lesion
7. For suspicious mediastinal lymph nodes (including pathological enlargement or PET-CT indicating malignancy, etc.), further sampling is required for pathological diagnosis by EUBS, thoracoscopy, or mediastinoscopy
8. According clinical evaluation, the lung function of patients (such as FVC, FEV1, TLC, FRC, DLco, etc.) should be sufficient for pneumonectomy

9. The function of important organs should meet the following requirements: absolute count of neutrophils ≥ 1.5 × 109/L# Platelets

   ≥ 100 × 109/L# Hemoglobin ≥ 90g/L; Serum albumin ≥ 35g/L; Thyroid hormone (TSH) ≤ 1 × ULN# Serum bilirubin ≤ 1.5 × ULN# ALT and AST ≤ 3 × ULN# International standardized ratio (INR) ≤ 1.5 or prothrombin time (PT) ≤ 1.5 × ULN# Serum creatinine ≤ 1.5 × ULN

10. Female patients at childbearing age are required to use contraceptive measures; for male patients whose partners are women at childbearing age, effective methods of contraception should be used during the trial period

Exclusion Criteria:

1. Patients with other primary malignancies within the past 3 years (excluding cured skin basal cell carcinoma and cervical carcinoma in situ)
2. Patients with active hepatitis B/C
3. Patients with any active autoimmune diseases or a history of autoimmune diseases
4. Patients who are using immunosuppressive agents or require systemic hormone therapy
5. Patients with hypertension but without good control even through antihypertensive medication treatment ; patients with clinical symptoms or diseases related to unsatisfying cardiac function
6. Patients with abnormal coagulation function (INR>2.0, PT>16s)
7. Arterial/venous thrombotic events occurred before screening within 6 months
8. Patients with active infection
9. Patients with congenital or acquired immune dysfunction (such as HIV infection)
10. According to the judgment of the researchers, patients have other factors that may affect the results of the research or cause the research to be terminated

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: group A; For patients with negative ctDNA after 3 weeks of neoadjuvant TKI treatment, radical resection surgery will be performed after continuing TKI treatment for 9-12 weeks.	Other: ctDNA monitoring; Patients will receive ctDNA monitoring before and after 3 weeks of neoadjuvant 3rd TKI treatment and optimize the neoadjuvant treatment plan based on this.
Other: group B; For patients with positive ctDNA after 3 weeks of neoadjuvant TKI treatment, radical resection surgery will be performed after continuing TKI treatment for 9-12 weeks.	Other: ctDNA monitoring; Patients will receive ctDNA monitoring before and after 3 weeks of neoadjuvant 3rd TKI treatment and optimize the neoadjuvant treatment plan based on this.
Other: group C; For patients with positive ctDNA after 3 weeks of neoadjuvant TKI treatment, radical resection surgery will be performed after 3 cycles of TKI plus chemotherapy.	Other: ctDNA monitoring; Patients will receive ctDNA monitoring before and after 3 weeks of neoadjuvant 3rd TKI treatment and optimize the neoadjuvant treatment plan based on this.
Other: group D; For patients with positive ctDNA after 3 weeks of neoadjuvant TKI treatment, radical resection surgery will be performed after 3 cycles of sequential neoadjuvant PD-1 blockades plus chemotherapy.	Other: ctDNA monitoring; Patients will receive ctDNA monitoring before and after 3 weeks of neoadjuvant 3rd TKI treatment and optimize the neoadjuvant treatment plan based on this.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the rate of major pathological response (MPR)	the proportion of patients who achieve MRP among those receiving pneumonectomy	up to 17 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the rate of pathological complete response (pCR)	the proportion of patients who achieve pCR among those receiving pneumonectomy	up to 17 weeks

Collaborators and Investigators

• Sponsor: Zhejiang University
• Investigators: Principal Investigator: Weijia Fang, MD, The First Affiliated Hospital, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Estimated): April 15, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: February 23, 2024
• First Submitted That Met QC Criteria: February 23, 2024
• First Posted (Actual): March 1, 2024

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: ctDNA; EGFR positive resectable NSCLC
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: NeoLiq

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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