Metabolic Biomarkers Predicting Response to Neoadjuvant Immunotherapy in Non-Small Cell Lung Cancer

Condition(s) studied

Investigational drug(s) / intervention(s)

Nivolumab 3 mg/kg + platinum-based chemotherapy (2 cycles, neoadjuvant): Patients will receive neoadjuvant treatment with nivolumab (3 mg/kg, IV) combined with platinum-based chemotherapy (cisplatin 75 mg/m² or carboplatin AUC 5, plus pemetrexed 500 mg/m² for non-squamous or paclitaxel 175 mg/m² for squamous tumors) every 21 days for two cycles. All patients will undergo invasive mediastinal staging before treatment and will be treated with robotic-assisted anatomical lung resection and mediastinal lymphadenectomy after neoadjuvant therapy.

Study summary

This study investigates metabolic glycolytic biomarkers obtained from radiological imaging (18F-FDG PET/CT), immunohistochemistry (IHC), and molecular analyses, and their association with response to neoadjuvant immunotherapy in early-stage non-small cell lung cancer (NSCLC).

Objective: To evaluate the relationship between glycolytic biomarkers measured by PET/CT (metabolic tumor volume and SUVmax), IHC markers (GLUT-1, Ki-67, PD-L1), and molecular oncogenic alterations, with the pathological response after two cycles of neoadjuvant nivolumab (3 mg/kg) combined with platinum-based chemotherapy in patients with early-stage NSCLC \[stage IB (tumor ≥4 cm) to IIIA\], negative for EGFR and ALK mutations.

Methods: This is a prospective, single-arm clinical study at a single institution, enrolling 30 patients. Baseline metabolic tumor volume (MTV) and SUVmax will be measured by PET/CT, while IHC markers and molecular profiling will be performed on pre-treatment biopsy samples. Patients will receive neoadjuvant treatment with nivolumab (3 mg/kg, IV) combined with platinum-based chemotherapy (cisplatin 75 mg/m² or carboplatin AUC 5, plus pemetrexed 500 mg/m² for non-squamous or paclitaxel 175 mg/m² for squamous tumors) every 21 days for two cycles. All patients will undergo invasive mediastinal staging before treatment and will be treated with robotic-assisted anatomical lung resection and mediastinal lymphadenectomy after neoadjuvant therapy. Primary outcomes include major pathological response (≤10% viable tumor cells) and immune profile characterization (IHC for CD8, CD4, FOXP3, PD-1, CD68, CD163). Secondary outcomes include event-free survival and treatment toxicity.

Standard of Care: Neoadjuvant chemotherapy regimens and PET/CT scans are part of the institutional standard of care for NSCLC patients.

Conclusion: The study aims to develop a practical diagnostic approach using metabolic glycolytic biomarkers to improve selection of patients likely to benefit from neoadjuvant immunotherapy. It is expected that patients with lower glycolytic activity will have higher rates of major pathological response after two cycles of neoadjuvant nivolumab (3 mg/kg) combined with chemotherapy. These findings may support a more cost-effective immunotherapy regimen for early-stage NSCLC.

Eligibility

Primary outcome measure(s)

• Major pathological response (MPR) rate — At the time of surgery, approximately 6 to 8 weeks after the beginning of neoadjuvant treatment
  MPR will be defined as ≤10% of viable tumor cells in the resected surgical specimen, assessed by standardized pathological examination after lung resection.

Trial sites (1)

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