Real-world Observational Study of Targeted Therapy in Patients With Advanced ROS1-positive NSCLC

The purpose of this project is to conduct an observational study on the efficacy and safety of entrectinib in real-world patients with ROS1-positive NSCLC who have received entrectinib treatment, while exploring the mechanism of entrectinib's brain protection and resistance mechanism. Because this study is a non-interventional study, it will not interfere with your usual treatment. However, your medical data will be analyzed, and the results will help improve future treatment options for ROS1 positive NSCLC patients and improve their quality of life.This study was divided into three cohorts. Cohort 1: For patients with advanced ROS1-positive NSCLC who met the inclusion criteria and had not received TKI treatment, they were treated with entrectinib until disease progression or intolerance (N=15); Cohort 2: For patients with advanced ROS1-positive NSCLC who met the inclusion criteria and had received first-generation ROS1 TKI treatment with disease progression on crizotinib, they were treated with entrectinib until disease progression or intolerance (N=15); Cohort 3: For patients with ROS1-positive NSCLC who had failed multiple lines of treatment, they were treated with entrectinib until disease progression or intolerance (N=10). Regular follow-up was conducted and relevant clinical data were recorded, followed by Cox regression analysis and survival analysis. The information that needs to be recorded includes baseline and treatment genetic testing, demographic information, anti-cancer history, and concomitant medication use, as well as the use of study drugs and adverse events during treatment visits, survival and subsequent drug use after discharge, and the follow-up frequency consistent with clinical practice. Subjects are eligible for a complimentary NGS test upon the development of entrectinib resistance.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-Small Cell Lung Cancer; Targeted Therapy; ROS1 Gene Rearrangement; Resistance
• Intervention / Treatment: Drug: Entrectinib

Detailed Description

The purpose of this project is to conduct an observational study on the efficacy and safety of entrectinib in real-world patients with ROS1-positive NSCLC who have received entrectinib treatment, while exploring the mechanism of entrectinib's brain protection and resistance mechanism. Because this study is a non-interventional study, it will not interfere with your usual treatment. However, your medical data will be analyzed, and the results will help improve future treatment options for ROS1 positive NSCLC patients and improve their quality of life.This study was divided into three cohorts. Cohort 1: For patients with advanced ROS1-positive NSCLC who met the inclusion criteria and had not received TKI treatment, they were treated with entrectinib until disease progression or intolerance (N=15); Cohort 2: For patients with advanced ROS1-positive NSCLC who met the inclusion criteria and had received first-generation ROS1 TKI treatment with disease progression on crizotinib, they were treated with entrectinib until disease progression or intolerance (N=15); Cohort 3: For patients with ROS1-positive NSCLC who had failed multiple lines of treatment, they were treated with entrectinib until disease progression or intolerance (N=10). Regular follow-up was conducted and relevant clinical data were recorded, followed by Cox regression analysis and survival analysis. The information that needs to be recorded includes baseline and treatment genetic testing, demographic information, anti-cancer history, and concomitant medication use, as well as the use of study drugs and adverse events during treatment visits, survival and subsequent drug use after discharge, and the follow-up frequency consistent with clinical practice. Subjects are eligible for a complimentary NGS test upon the development of entrectinib resistance.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Puyuan Xing; Phone Number: +86 135 2100 5935; Email: xingpuyuan@cicams.ac.cn

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with non-small cell lung cancer exhibiting ROS1 rearrangement.

Description

Inclusion Criteria:

• 1) Histologically or cytologically confirmed non-small cell lung cancer;
• 2) TNM stage of the ninth edition is IIIB, IIIC, or IV;
• 3) ROS1 fusion positive confirmed by one of the following qualified results: next-generation sequencing technology, fluorescence in situ hybridization, reverse transcription polymerase chain reaction;
• 4) No prior systemic chemotherapy, radiation therapy, or surgery;
• 5) Aged 18 years or older;
• 6) ECOG PS score of 0-1.

Exclusion Criteria:

• 1) any prior history of NSCLC and/or any prior treatment for NSCLC;
• 2) prior systemic chemotherapy or radiation therapy or surgical treatment;
• 3) the presence of a second primary tumor;
• 4) hypersensitivity to ROS1-TKI or intolerance to it.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1; For eligible patients with advanced ROS1-positive NSCLC who have not received TKI treatment, receive entrectinib therapy until disease progression or intolerance.	Drug: Entrectinib; Patients in each cohort were treated with Entrectinib.; Other Names: Rozlytrek
Cohort 2; For patients with NSCLC who have progressed after receiving first-generation ROS1 TKI crizotinib and meet the eligibility criteria, they can receive entrectinib treatment until disease progression or intolerance.	Drug: Entrectinib; Patients in each cohort were treated with Entrectinib.; Other Names: Rozlytrek
Cohort 3; For patients with ROS1-positive NSCLC who have failed multi-line therapy, receive entrectinib until disease progression or intolerance.	Drug: Entrectinib; Patients in each cohort were treated with Entrectinib.; Other Names: Rozlytrek

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression free survival	From enrollment to the end of treatment at 1 year.

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective remission rate	From enrollment to the end of treatment at 1 year.
Time to CNS progression	From enrollment to the end of treatment at 1 year.
Overall survival	From enrollment to the end of treatment at 1 year.

Other Outcome Measures

Outcome Measure	Time Frame
Exploratory biomarker analysis	From enrollment to the end of treatment at 1 year.

Collaborators and Investigators

• Sponsor: National Cancer Center, China

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: November 3, 2024
• First Submitted That Met QC Criteria: November 16, 2024
• First Posted (Estimated): November 19, 2024

Study Record Updates

• Last Update Posted (Estimated): November 19, 2024
• Last Update Submitted That Met QC Criteria: November 16, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Non-Small Cell Lung Cancer; Targeted therapy; ROS1 Gene Rearrangement
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Entrectinib
• Other Study ID Numbers: NCC4601

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: It involves patient privacy and cannot be disclosed at will.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No