Clinical trial NCT06846762: DREAM Study: DNA/RNA-NGS Co-Testing in Driver-Negative, Treatment-Resistant NSCLC
Official title: 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)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Non-Small Cell Lung Cancer
Keywords: NSCLC
Primary Resistance
DNA+RNA-NGS
Driver Gene Testing
Targeted Therapy
Lead sponsor: Shanghai Chest Hospital
Sponsor class: OTHER
First posted: 2025-02-26
Enrollment: 508
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: The proportion of patients with advanced or metastatic inoperable NSCLC who test positive for driver genes upon re-testing with DNA+RNA NGS
timeFrame: 2026.1
measure: ORR
timeFrame: 2027.1
Secondary outcomes:
Other outcomes:
Locations:
city: ShangHai
country: China
facility: Shanghai Chest Hospital
state: Shanghai
Study officials:
References: