Exploring the Mechanism of Primary Resistance to Third-generation EGFR-TKIs as First-line Treatment in EGFR-positive Advanced NSCLC (PRECISE Study)

A Multicenter Clinical Study to Explore the Mechanism of Primary Resistance to Third-generation EGFR-TKIs as First-line Treatment in EGFR-positive Advanced NSCLC (PRECISE Study)

Status

Recruiting

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT05598528

Acronym

PRECISE

Enrollment

210

Registered

2022-10-28

Start date

2021-09-28

Completion date

2026-12-31

Last updated

2024-12-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Circulating Tumor DNA, EGFR Gene Mutation, EGFR-TKI Resistant Mutation, Lung Cancer, Non-small Cell, Primary Resistance

Brief summary

Lung cancer is currently the world's largest malignant tumor for cancer-related deaths with non-small cell lung cancer (NSCLC) accounting for 80%-85%. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), especially the 3rd-generation EGFR-TKIs have demonstrated strong antitumor effects in EGFR-positive patients. However, approximately 20% of EGFR-positive were primarily resistant to 3rd generation EGFR-TKIs, i.e., clinical non-response or disease progression in the short term. This study aimed to clarify the molecular indicators that predict the benefits of 3-rd EGFR-TKIs as first-line therapy in NSCLCpatients with EGFR-positive. Further, to clarify their primary drug resistance mechanisms, which is of great significance for the treatment and clinical decision-making of NSCLC disease.

Interventions

OTHERGenomic profiles detection

The Paraffin-embedded tumor tissue at diagnosis is collected and assessed by Next- generation gene sequencing

OTHERcirculating tumor DNA detection

The Plasma at diagnosis and at 1-month treatment are collected and assessed by Next-generation gene sequencing

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Age \>18 years; 2. Histological or cytopathological diagnosed NSCLC; 3. According to the American Joint Committee on Cancer (AJCC) eighth edition of the Lung Cancer Staging Manual, the clinical stage is unresectable IIIB-IV or recurrence and metastasis after surgery; 4. At least one measurable lesion can be evaluated according to the Response Evaluation Criteria In Solid Tumours v1.1 (RECIST1.1) criteria; 5. Positive EGFR mutation confirmed by tissue or cytology (pleural fluid, cerebrospinal fluid, etc.); 6. Use of third-generation EGFR-TKIs approved by the NMPA for NSCLC as first-line therapy; 7. Cooperate with the provision of clinicopathological data, imaging data, sample collection, and follow-up required for the research process, and agree to use the test data for subsequent research and product development; 8. Agree to participate in this study and sign an informed consent form.

Exclusion criteria

1. Patients who cannot understand the content of the experiment and cannot cooperate, and those who refuse to sign the informed consent form; 2. Pregnant and lactating women; 3. Other malignant neoplastic diseases within 3 years; 4. Patients who have undergone other clinical drug trials; 5. Received systemic anti-tumor therapy within 2 years;

Design outcomes

Primary

Measure	Time frame	Description
Objective Response Rate (ORR)	2 years	The proportion of patients with a complete response or partial response to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Progression-free survival (PFS)	3 years	Time from the beginning of treatment to the first disease progression (PD) in patients with advanced NSCLC
Differences in genomic profiles of tumor tissues and ctDNA clearance of third-generation EGFR-TKIs sensitive and primary drug-resistant NSCLC.	3 years	The patients who don't achieve partial response or progress within 6 months are defined as the primary resistant group. The genomic profiles and ctDNA clearance detected by Next-generation gene sequencing will be compared between the primary drug-resistant group and sensitive-drug group.

Secondary

Measure	Time frame	Description
Overall survival (OS)	5 years	Overall survival (OS) is defined as the duration from the beginning of first-line immunotherapy until death due to any cause. Subjects who are still alive at the end of the study observation period will be censored at the time of last known vital status
Disease Control Rate (DCR)	3 years	The proportion of patients with a complete response or partial response or stable desease to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1)

Other

Measure	Time frame	Description
The correlation between tumor microenvironment signature and efficacy of 3rd EGFR-TKIs	3 years	The baseline paraffin-embedded tissue is collected and assessed by multiplex immunohistochemistry, including T lymphocytes, B lymphocytes, NK lymphocytes, macrophagocyte, and DC cells. And explore the association between tumor microenvironment signature and primary resistance and the efficacy of 3rd EGFR-TKIs during the enrolled observation process.

Countries

China

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026