Large Granular Lymphocytes in mNSCLC Treated With Nivolumab

January 23, 2026 updated by: Mehmet Artac, Necmettin Erbakan University

Large Granular Lymphocytes as a Prognostic Factor in Metastatic Non-small Cell Lung Cancer Treated With Nivolumab

Large granular lymphocytes (LGLs), which constitute 10-15% of peripheral blood mononuclear cells, are large lymphocytes with a round nucleus, large cytoplasm, and azurophilic granules in the cytoplasm.

Most normal LGLs in peripheral blood are natural killer (NK) cells, but some are T lymphocytes. These cells cannot be measured by a standard complete blood count (CBC) test. These cells, which can be detected by peripheral smear, are expressed numerically and as a percentage relative to other cells. The aim of this study is to determine the relationship between the percentage of LGLs at baseline and at three months and the response and clinical parameters in participants with metastatic non-small cell lung cancer treated with nivolumab in second-line therapy.

Study Overview

Status

Recruiting

Conditions

Detailed Description

Non-small cell lung cancer ranks first worldwide in 2022 in terms of both incidence and mortality when both genders are considered . Historically, the 5-year survival rate for patients with advanced non-small cell lung cancer (NSCLC) receiving chemotherapy was 5%. Effective treatment options for patients without targetable molecular alterations, especially those who progressed after first-line chemotherapy, were limited until recently. Immunotherapy checkpoint inhibitors, with clinically meaningful survival benefits, long-term responses, and favorable safety profiles compared to chemotherapy, have become the standard of care for patients who progress during or after platinum-based chemotherapy. Immune checkpoint inhibitors are also effective as first-line therapy and are recommended as standard treatment for untreated advanced NSCLC patients, either in combination with chemotherapy or without chemotherapy.

Nivolumab, a fully human, monoclonal, anti-programmed death-1 (PD-1) antibody, is the first PD-1 inhibitor to demonstrate clinically meaningful efficacy in NSCLC. Nivolumab is approved for second-line treatment of advanced NSCLC in patients with advanced squamous (CheckMate 017; NCT01642004) and non-squamous (CheckMate 057; NCT01673867) NSCLC, following platinum-based chemotherapy, compared to docetaxel, showing improved overall survival and a favorable safety profile. Pembrolizumab is a humanized IgG4 monoclonal antibody against programmed cell death protein 1 (PD-1). Phase 1 KEYNOTE-0018 and phase 2/3 KEYNOTE-0109 studies demonstrated a correlation between increased expression of the PD-1 ligand PD-L1 in patients with advanced non-small cell lung cancer and the benefit achieved with pembrolizumab treatment. KEYNOTE-024 is a study comparing pembrolizumab monotherapy as first-line treatment with platinum-based chemotherapy in 305 patients with metastatic non-small cell lung cancer and a PD-L1 tumor proportion score (TPS) of 50% or higher. Both progression-free survival and overall survival were significantly longer in the pembrolizumab group compared to the standard chemotherapy group (median 10.3 months and 6.0 months vs. 30.0 months and 14.2 months).

Large granular lymphocytes (LGLs) are large lymphocytes with a round or kidney-shaped nucleus, a large cytoplasm, and azurophilic granules in the cytoplasm. They constitute 10-15% of peripheral blood mononuclear cells. Most normal LGLs in peripheral blood are natural killer (NK) cells, but some are T lymphocytes. These cells cannot be measured by a normal hemogram test. These cells, which can be detected by peripheral smear, are expressed both numerically and as a percentage relative to other cells. It has been shown that an absolute decrease in lymphocyte count reduces the response to immunotherapy. However, there are no studies in the literature showing the relationship between LGL and immunotherapy response.

In this prospectively planned study, the investigators aim to investigate the relationship between LGL (large granular lymphocyte) levels at the start of treatment and at 3 months in participants with non-small cell lung cancer treated with anti-PD-1 (programmed cell death-1) and survival and clinical parameters.

Study Type

Observational

Enrollment (Estimated)

50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Turkey (Türkiye)
    • Meram
      • Konya, Meram, Turkey (Türkiye), 42090
        • Recruiting
        • Necmettin Erbakan University Faculty of Medicine, Department of Medical Oncology
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients diagnosed with metastatic non-small cell lung cancer who were followed up at the Medical Oncology Clinic of Necmettin Erbakan University Hospital and treated with nivolumab as second-line therapy.

Description

Inclusion Criteria:

  • Histological and staging diagnosis of metastatic non-small cell lung cancer
  • ECOG performance score between 0 and 2
  • No contraindications for nivolumab

Exclusion Criteria:

  • Patients diagnosed with mNSCLC who received nivolumab as adjuvant or perioperative therapy
  • Those with a second primary malignancy undergoing active treatment
  • Those who have not signed the informed consent form
  • Those with additional hematological malignancies such as leukemia, lymphoma, or myelodysplastic syndrome
  • Those who have undergone palliative or curative radiotherapy within the last three months
  • Those with active viral/bacterial infections before nivolumab treatment
  • Patients who have used steroids in the last three months

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate according to RECIST 1.1 Evaluation of target lesions
Time Frame: From enrollment to the end of treatment at 12 weeks

Complete Response (CR):

Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.

Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this may include the baseline sum). The sum must also demonstrate an absolute increase of at least 5 mm.

Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
From enrollment to the end of treatment at 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival
Time Frame: From July 2025 to July 2027
It was defined as the time from the initiation of nivolumab treatment until disease progression or death, whichever occurred first. For patients without progression, PFS was calculated from the date of data entry onwards.
From July 2025 to July 2027
Overall survival
Time Frame: From July 2025 to July 2027
It was defined as the time from the start of nivolumab treatment until death from any cause, or until the last follow-up date for patients still alive.
From July 2025 to July 2027

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Necmettin Erbakan University

Investigators

  • Study Director: Mehmet Artaç, Necmettin Erbakan University Faculty of Medicine, Department of Medical Oncology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2025

Primary Completion (Estimated)

June 1, 2026

Study Completion (Estimated)

June 1, 2027

Study Registration Dates

First Submitted

January 15, 2026

First Submitted That Met QC Criteria

January 15, 2026

First Posted (Actual)

January 23, 2026

Study Record Updates

Last Update Posted (Actual)

January 26, 2026

Last Update Submitted That Met QC Criteria

January 23, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 26105/2025/5927

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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