DNA and RNA testing for treatment-resistant lung cancer

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)

This study is trying to see how many patients with advanced lung cancer are resistant to standard treatments because of hidden gene issues and how those with known gene problems respond to targeted therapies compared to those without.

Quick facts

• Study type: Observational
• Enrollment: 508 (estimated)
• Sex: All
• Sponsor: Shanghai Chest Hospital (other)
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06846762 on ClinicalTrials.gov

What this trial studies

This observational study investigates the prevalence of primary resistance to first-line non-targeted therapy in patients with advanced non-small cell lung cancer (NSCLC) who lack driver gene mutations. It consists of two parts: Part A assesses the proportion of patients resistant due to undetected driver genes through DNA and RNA next-generation sequencing (NGS), while Part B compares the outcomes of patients with identified driver gene positivity who receive targeted therapy versus those who do not. The study aims to enhance understanding of treatment resistance and improve patient management strategies.

Who should consider this trial

Good fit: Ideal candidates are adults diagnosed with advanced or metastatic inoperable NSCLC who have previously tested negative for common driver mutations and experienced rapid disease progression after first-line non-targeted therapy.

Not a fit: Patients with other significant pulmonary diseases or those who do not meet the inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to better-targeted therapies for patients with treatment-resistant NSCLC.

How similar studies have performed: While the approach of using DNA and RNA NGS for identifying treatment resistance is gaining traction, this specific study's methodology is relatively novel and untested.

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.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai Chest Hospital — Shanghai, Shanghai Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Yuqing Lou

Conditions: Non-Small Cell Lung Cancer, NSCLC, Primary Resistance, DNA+RNA-NGS, Driver Gene Testing, Targeted Therapy