Comparing chemo‑immunotherapy options for metastatic NSCLC with PD‑L1 <50%

A Prospective Observational Study Comparing Chemotherapy Plus Pembrolizumab Versus Nivolumab Plus Ipilimumab With Chemotherapy in Patients With Metastatic Non-Small Cell Lung Cancer and PD-L1 Expression Below 50%

This project will see if two common first‑line chemo‑immunotherapy approaches give different survival and quality‑of‑life results for adults with metastatic NSCLC whose tumors have PD‑L1 under 50%.

Quick facts

• Study type: Observational
• Enrollment: 400 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Gazi University (Academic / other)
• Drugs / interventions: pembrolizumab, nivolumab, ipilimumab, chemotherapy, immunotherapy
• Locations: 2 sites (Ankara and 1 other locations)
• Trial ID: NCT07394062 on ClinicalTrials.gov

What this trial studies

This is a prospective observational cohort that follows adults with stage IV NSCLC and tumor PD‑L1 <50% treated in routine clinical practice. Two commonly used approaches—chemotherapy plus pembrolizumab, and chemotherapy combined with nivolumab plus ipilimumab—will be recorded based on treating physicians' choices without randomization. The main outcomes are progression‑free survival and overall survival measured from standard clinical and radiological follow‑up; health‑related quality of life will be collected with validated patient‑reported questionnaires. Exploratory analyses will examine associations between outcomes and patient factors such as biological age metrics and recent antibiotic exposure.

Who should consider this trial

Good fit: Adults (≥18 years) with histologically confirmed stage IV NSCLC, tumor PD‑L1 <50%, starting first‑line systemic treatment with either chemotherapy plus pembrolizumab or chemotherapy with nivolumab plus ipilimumab, and able to give informed consent.

Not a fit: Patients who have received prior systemic therapy for metastatic NSCLC, have another active cancer needing systemic treatment, cannot comply with routine follow‑up, or are treated outside the participating sites are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the results could help doctors choose the chemo‑immunotherapy approach most likely to prolong life or preserve quality of life for patients with PD‑L1 <50% metastatic NSCLC.

How similar studies have performed: Randomized trials have shown benefit for pembrolizumab plus chemotherapy and for nivolumab‑ipilimumab combinations in various NSCLC populations, but direct real‑world head‑to‑head comparisons like this are limited.

Eligibility criteria

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.

Where this trial is running

Ankara and 1 other locations

• Ankara Etlik City Hospital — Ankara, Turkey (Türkiye) (Recruiting)
• Gazi University Faculty of Medicine, Department of Medical Oncology — Ankara, Turkey (Türkiye) (Recruiting)

Study contacts

• Study coordinator: Orhun Akdogan, MD

Conditions Nonsmall Cell Lung Cancer, Stage IV; Metastatic Nonsmall Cell Lung Cancer; NSCLC; Metastatic Lung Cancer; Chemo-Immunotherapy; PD-L1; Progression-Free Survival; Overall Survival