Real-World Comparison of Chemo-Immunotherapy Regimens in Metastatic NSCLC With PD-L1 <50% (ALCG-01)

This is a prospective, observational cohort study conducted in patients with metastatic non-small cell lung cancer (NSCLC) and programmed death-ligand 1 (PD-L1) expression below 50% who are treated in routine clinical practice.

Eligible patients will receive systemic treatment according to standard-of-care decisions made by their treating physicians. Two commonly used treatment approaches will be observed: chemotherapy combined with pembrolizumab, and nivolumab plus ipilimumab administered in combination with chemotherapy. No randomization, protocol-driven treatment assignment, or experimental intervention will be performed as part of the study.

The primary objectives of the study are to compare progression-free survival (PFS) and overall survival (OS) between the two treatment approaches. Survival outcomes will be assessed using standard clinical and radiological follow-up data collected during routine care.

Secondary objectives include the evaluation of health-related quality of life and patient-reported outcomes. Quality of life will be assessed using validated questionnaires administered during routine follow-up visits, including global quality of life, functional status, cognitive function, and psychological well-being.

In addition to the primary and secondary objectives, exploratory analyses are planned to investigate the association between treatment outcomes and selected patient-related factors. These include biological age metrics, exposure to antibiotics during treatment, and dietary patterns assessed through patient questionnaires. These analyses will be conducted in subsets of patients with available and complete data for the relevant variables.

As an observational real-world study, missing data are anticipated for some variables, particularly patient-reported and lifestyle-related measures. All analyses will be performed using appropriate statistical methods, and results from exploratory analyses will be interpreted as hypothesis-generating.

This study is designed to provide prospective real-world evidence on the comparative effectiveness and patient-reported outcomes of widely used chemo-immunotherapy regimens in metastatic NSCLC patients with PD-L1 expression below 50%.

Inclusion criteria

• Age ≥18 years.
• Histologically or cytologically confirmed non-small cell lung cancer.
• Metastatic (stage IV) disease at the time of study entry.
• Tumor PD-L1 expression <50%.
• Initiation of first-line systemic treatment with either chemotherapy plus pembrolizumab or nivolumab plus ipilimumab in combination with chemotherapy, according to routine clinical practice.
• Ability to provide informed consent.

Exclusion criteria

• Prior systemic therapy for metastatic non-small cell lung cancer.
• Participation in an interventional clinical trial that mandates treatment assignment.
• Presence of another active malignancy requiring systemic treatment.
• Inability to comply with routine clinical follow-up or data collection.