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

• ClinicalTrials.gov Identifier: NCT05598528
• Recruitment Status: Recruiting
• First Posted: October 28, 2022
• Last Update Posted: August 2, 2023
• Sponsor: Second Xiangya Hospital of Central South University
• Collaborators: Xiangya Hospital of Central South University; Shanghai Chest Hospital; West China Hospital; Hunan Cancer Hospital; The Third Xiangya Hospital of Central South University; The First Affiliated Hospital of Xiamen University; Second Affiliated Hospital, School of Medicine, Zhejiang University; China-Japan Friendship Hospital; Fudan University; First Affiliated Hospital of Kunming Medical University; Loudi Central Hospital; ZhuZhou Central Hospital; Xiangtan Central Hospital; First People's Hospital of Chenzhou; Yueyang Central Hospital; Yongzhou Central Hospital; The First Affiliated Hospital of University of South China; Hunan Provincial People's Hospital; Shaoyang Central Hospital; Yiyang Central Hospital; Changsha Central Hospital; The first people's hospital of Guiyang; Wuhan Union Hospital, China; Renmin Hospital of Wuhan University; The First People's Hospital of Changde; Zhuzhou Second Hospital; First Hospital of Changsha; Hengyang Central Hospital; Huaihua first people's Hospital; The First People's Hospital of Xiangtan; University of South China Affiliated Nanhua Hospital; Xiangxi Autonomous Prefecture People's Hospital; People's Hospital of Zhangjiajie; Second People's Hospital Of Huaihua; Hunan Academy of Traditional Chinese Medicine Affiliated Hospital; The Third Hospital of Changsha; Xiangya Changde Hospital; Changsha County first People's Hospital; Hunan Provincial Straight Hospital of Traditional Chinese Medicine; Liuyang Hospital of traditional Chinese Medicine; Second People's Hospital of Hunan; First Affiliated Hospital of Guangxi Medical University; Guiyang Public Health Treatment Center; The Affiliated Bethune Hospital of Shanxi Medical University; The First Affiliated Hospital of Hunan University of Chinese Medicine; Tongji Hospital; The First Affiliated Hospital of Nanchang University
• Information provided by (Responsible Party): Fang Wu, Second Xiangya Hospital of Central South University

Study Description

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.

Condition or disease	Intervention/treatment
Lung Cancer, Non-small Cell; EGFR Gene Mutation; EGFR-TKI Resistant Mutation; Primary Resistance; Circulating Tumor DNA	Other: Genomic profiles detection; Other: circulating tumor DNA detection

Study Design

• Study Type: Observational [Patient Registry]
• Estimated Enrollment: 210 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Target Follow-Up Duration: 5 Years
• Official Title: 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)
• Actual Study Start Date: September 28, 2021
• Estimated Primary Completion Date: December 31, 2024
• Estimated Study Completion Date: December 31, 2025

Groups and Cohorts

Group/Cohort	Intervention/treatment
EGFR-positive lung patients recieving 3rd generation EGFR-TKIs as first-line therapy; Stage III-IV EGFR-positive lung patients receiving 3rd generation EGFR-TKIs (Osimertinib 80mg/Qd or Almonertinib 110mg/Qd or Furmonertinib 80mg/Qd) as first-line therapy.	Other: Genomic profiles detection; The Paraffin-embedded tumor tissue at diagnosis is collected and assessed by Next- generation gene sequencing; Other: circulating tumor DNA detection; The Plasma at diagnosis and at 1-month treatment are collected and assessed by Next-generation gene sequencing

Outcome Measures

Primary Outcome Measures :

1. Objective Response Rate (ORR) [ Time Frame: 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)
2. Progression-free survival (PFS) [ Time Frame: 3 years ]
   Time from the beginning of treatment to the first disease progression (PD) in patients with advanced NSCLC
3. Differences in genomic profiles of tumor tissues and ctDNA clearance of third-generation EGFR-TKIs sensitive and primary drug-resistant NSCLC. [ Time Frame: 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 Outcome Measures :

1. Overall survival (OS) [ Time Frame: 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
2. Disease Control Rate (DCR) [ Time Frame: 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 Outcome Measures:

1. The correlation between tumor microenvironment signature and efficacy of 3rd EGFR-TKIs [ Time Frame: 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.

Biospecimen Retention:   Samples With DNA

1. The paraffin embeds tumor tissue at diognosis
2. Peripheral venous blood

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Stage IIIB-IV EGFR-positive lung patients receiving 3rd generation EGFR-TKIs (Osimertinib 80mg/Qd or Almonertinib 110mg/Qd or Furmonertinib 80mg/Qd) as first-line therapy.

Criteria

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;

Contacts and Locations

Locations

China, Hunan

Department of Oncology, The Second Xiangya Hospital, Central South University; Recruiting

Changsha, Hunan, China, 410011

Contact: Fang Wu, MD, PhD +86 13574858332 wufang4461@csu.edu.cn

Sponsors and Collaborators

Second Xiangya Hospital of Central South University

Xiangya Hospital of Central South University

Shanghai Chest Hospital

West China Hospital

Hunan Cancer Hospital

The Third Xiangya Hospital of Central South University

The First Affiliated Hospital of Xiamen University

Second Affiliated Hospital, School of Medicine, Zhejiang University

China-Japan Friendship Hospital

Fudan University

First Affiliated Hospital of Kunming Medical University

Loudi Central Hospital

ZhuZhou Central Hospital

Xiangtan Central Hospital

First People's Hospital of Chenzhou

Yueyang Central Hospital

Yongzhou Central Hospital

The First Affiliated Hospital of University of South China

Hunan Provincial People's Hospital

Shaoyang Central Hospital

Yiyang Central Hospital

Changsha Central Hospital

The first people's hospital of Guiyang

Wuhan Union Hospital, China

Renmin Hospital of Wuhan University

The First People's Hospital of Changde

Zhuzhou Second Hospital

First Hospital of Changsha

Hengyang Central Hospital

Huaihua first people's Hospital

The First People's Hospital of Xiangtan

University of South China Affiliated Nanhua Hospital

Xiangxi Autonomous Prefecture People's Hospital

People's Hospital of Zhangjiajie

Second People's Hospital Of Huaihua

Hunan Academy of Traditional Chinese Medicine Affiliated Hospital

The Third Hospital of Changsha

Xiangya Changde Hospital

Changsha County first People's Hospital

Hunan Provincial Straight Hospital of Traditional Chinese Medicine

Liuyang Hospital of traditional Chinese Medicine

Second People's Hospital of Hunan

First Affiliated Hospital of Guangxi Medical University

Guiyang Public Health Treatment Center

The Affiliated Bethune Hospital of Shanxi Medical University

The First Affiliated Hospital of Hunan University of Chinese Medicine

Tongji Hospital

The First Affiliated Hospital of Nanchang University

More Information

• Responsible Party: Fang Wu, Associate Professor, Second Xiangya Hospital of Central South University
• ClinicalTrials.gov Identifier: NCT05598528
• Other Study ID Numbers: XYEYY20220928
• First Posted: October 28, 2022
• Last Update Posted: August 2, 2023
• Last Verified: July 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases