DREAM Study: DNA/RNA-NGS Co-Testing in Driver-Negative, Treatment-Resistant NSCLC

Real-world Study of DNA + RNA-NGS Co-testing in Patients with Driver Gene-negative, First-line Non-targeted Therapy-resistant Primary NSCLC (Dream Study)

The study is divided into two parts, Part A and Part B. The purpose of Part A is to reveal the proportion of NSCLC patients who are primarily resistant to first-line non-targeted therapy due to the omission of driver genes (especially fusion variations) by DNA-NGS, the median PFS of patients in the first line, and clinical characteristics through synchronous co-testing of DNA and RNA NGS. The purpose of Part B is to compare the difference in ORR between patients with driver gene positivity identified through synchronous co-testing of DNA and RNA NGS who receive and do not receive targeted therapy.

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Other: This study did not include intervention between the two cohorts

• Study Type: Observational
• Enrollment (Estimated): 508

Contacts and Locations

• Study Contact: Name: Yuqing Lou; Phone Number: 13917197711; Email: louyq@hotmail.com

Study Locations

• China
  • Shanghai
    • ShangHai, Shanghai, China, 200030
      • Recruiting
      • Shanghai Chest Hospital
      • Contact: Yuqing Lou; Phone Number: 13917197711; Email: louyq@hotmail.com
      • Contact: Jun Lu; Phone Number: 13601887656

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

NSCLC patients who are primarily resistant to first-line non-targeted therapy due to the omission of driver genes (especially fusion variations) by DNA-NGS.

Description

Inclusion Criteria:

1. Aged 18 and above, male or female
2. Pathologically diagnosed with advanced or metastatic inoperable non-small cell lung cancer
3. Prior genetic testing [DNA-NGS] results show no mutations in EGFR, BRAF, MET, HER2, KRAS, FGFR2/3，no amplifications in MET and HER2 and no fusions in ALK, ROS1, RET, NTRK, NRG1, EGFR, MET, BRAF, FGFR2/3
4. Based on negative driver gene results, received first-line non-targeted therapy with rapid progression or intolerance, with a progression-free survival (PFS) of ≤6 months (regardless of drug exposure time, calculated from the first day of medication)
5. Have retained tumor tissue samples prior to first-line treatment
6. Patients are from medical centers that can ethically affiliate and have accessible clinical follow-up data.

Exclusion Criteria:

1. Patients who do not meet any of the necessary inclusion criteria
2. Presence of other pulmonary diseases that require treatment or are severe, including but not limited to active pulmonary tuberculosis, interstitial lung disease, etc.
3. Presence of active infections that require systemic treatment
4. History of drug abuse or alcohol abuse, or mental illness, or suspected allergy or intolerance to the study drug or any of its components
5. Any other conditions deemed unsuitable for entry into this study by the investigator.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Driver gene-positive patients with targeted therapy.; Patients who tested positive by DNA+RNA-NGS voluntarily choose to receive targeted therapy	Other: This study did not include intervention between the two cohorts; The study is divided into two parts, Part A and Part B. The purpose of Part A is to reveal the proportion of NSCLC patients who are primarily resistant to first-line non-targeted therapy due to the omission of driver genes (especially fusion variations) by DNA-NGS, the median PFS of patients in the first line, and clinical characteristics through synchronous co-testing of DNA and RNA NGS. The purpose of Part B is to compare the difference in ORR between patients with driver gene positivity identified through synchronous co-testing of DNA and RNA NGS who receive and do not receive targeted therapy, with subsequent treatment regimens determined at the discretion of the patients without any intervention measures.
Driver gene-positive patients without targeted therapy.; Patients who tested positive by DNA+RNA-NGS voluntarily choose to receive non-targeted therapy	Other: This study did not include intervention between the two cohorts; The study is divided into two parts, Part A and Part B. The purpose of Part A is to reveal the proportion of NSCLC patients who are primarily resistant to first-line non-targeted therapy due to the omission of driver genes (especially fusion variations) by DNA-NGS, the median PFS of patients in the first line, and clinical characteristics through synchronous co-testing of DNA and RNA NGS. The purpose of Part B is to compare the difference in ORR between patients with driver gene positivity identified through synchronous co-testing of DNA and RNA NGS who receive and do not receive targeted therapy, with subsequent treatment regimens determined at the discretion of the patients without any intervention measures.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The proportion of patients with advanced or metastatic inoperable NSCLC who test positive for driver genes upon re-testing with DNA+RNA NGS	2026.1
ORR	2027.1

Collaborators and Investigators

• Sponsor: Baohui Han

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2025
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: February 20, 2025
• First Submitted That Met QC Criteria: February 20, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 20, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: NSCLC; Targeted Therapy; Primary Resistance; DNA+RNA-NGS; Driver Gene Testing
• 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
• Other Study ID Numbers: ShanghaiChestIS25009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

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