Analyzing Drug Resistance in Lung Cancer Immunotherapy

Molecular Landscape of Primary and Acquired Resistance to Immune Checkpoint Inhibitors in Patients With Chinese Advanced Non-small Cell Lung Cancer

This study is testing how certain genetic markers in patients with advanced lung cancer might affect their response to immunotherapy treatments.

Quick facts

• Study type: Observational
• Enrollment: 250 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Shanghai Chest Hospital (Academic / other)
• Drugs / interventions: immunotherapy
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT04977791 on ClinicalTrials.gov

What this trial studies

This observational study aims to investigate the molecular markers associated with both primary and acquired resistance to immune checkpoint inhibitors in patients with advanced non-small cell lung cancer (NSCLC). It focuses on understanding factors such as PD-L1 expression, tumor mutation burden, and other genetic characteristics that may influence treatment outcomes. Patients will provide fresh tumor tissue samples and blood samples to facilitate comprehensive analysis of their immune response to therapy. The goal is to identify reasons for treatment resistance and improve future therapeutic strategies.

Who should consider this trial

Good fit: Ideal candidates for this study are patients with advanced non-small cell lung cancer who are receiving anti-PD-1/PD-L1 monoclonal antibody treatment.

Not a fit: Patients with neuroendocrine cancer or those unable to provide the required tumor and blood samples may not benefit from this study.

Why it matters

Potential benefit: If successful, this research could lead to improved patient selection for immunotherapy and enhanced treatment outcomes for those with non-small cell lung cancer.

How similar studies have performed: Other studies have shown success in identifying resistance mechanisms in cancer therapies, making this approach promising but still requiring further validation.

Eligibility criteria

Inclusion Criteria:

* Be able to provide informed consent, and understand and agree to follow the research requirements;
* Advanced non-small cell lung cancer;
* Patients receiving immune checkpoint inhibitor treatment represented by anti-PD-1/PD-L1 monoclonal antibody;
* The patient must be able to provide fresh tumor tissue before- and after- ICIs (50mg of tumor tissue sample/ 2 needles of 18G thick needle puncture) or tumor tissue archived within one year (FFPE tissue block or about 15 pieces \[10- 15 sheets\] Freshly cut, unstained FFPE slides) and pathology reports (except for advanced non-small cell lung cancer other than neuroendocrine cancer); provide matched 10mL peripheral whole blood samples at the same time;
* ECOG physical fitness status ≤1;
* The patient must have at least one measurable lesion (assessed according to RECIST v1.1);
* Life expectancy ≥ 12 weeks;
* The patient must have adequate organ function, and must be reached absolute neutrophil count (ANC) ≥1.5x10\^9/L, platelets ≥100x10\^9/L, hemoglobin ≥90g/L, international normalized ratio (INR) or prothrombin time ≤ 1.5x ULN , activated partial thromboplastin time (aPTT)≤1.5x ULN, serum total bilirubin≤1.5x ULN (Patients with Gilbert syndrome can be enrolled if total bilirubin\<3x ULN), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤2.5x ULN(Patient with liver metastases, this standard is AST and ALT≤5x ULN) within 7 days before treatment;

Exclusion Criteria:

* Patients with other tumors. Except for basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin or cervical cancer in situ, subjects who have received potential radical treatment and have not relapsed within 5 years before the start of treatment can be included in the study;
* Have received any approved systemic anti-tumor immunotherapy before starting the research treatment;
* A history of interstitial lung disease, non-infectious pneumonia or uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung disease, etc.;
* Severe chronic or active infections that require systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection;
* Known human immunodeficiency virus infection; previous allogeneic stem cell transplantation or organ transplantation;
* The investigator judged that the patient's compliance during the study period was insufficient

Where this trial is running

Shanghai, Shanghai Municipality

• Xiaomin Niu — Shanghai, Shanghai Municipality, China (Recruiting)

Conditions Non-Small Cell Lung Cancer; PD-L1; Resistance; Next-Generation Sequencing