Pharmacokinetically-guided on the Individualization of Pembrolizumab Administration in the Treatment of Lung Cancer

Study Overview
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Brief Summary
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Pembrolizumab with or without chemotherapy has become the standard therapy in advanced non-small cell lung cancer (NSCLC), with a fixed dose of 200mg every 3 weeks. The investigators performed this study to explore the clinical efficacy and safety of pharmacokinetic (PK)-guided pembrolizumab administration in advanced NSCLC.

Detailed Description
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In this prospective, open-label, single-arm exploratory study, the investigators enrolled advanced NSCLC patients without sensitizing EGFR or ALK mutation in Sun yat-sen university cancer center. Eligible patients received pembrolizumab 200mg every 3 weeks with or without chemotherapy for four cycles, then for patients without progressive disease, pembrolizumab was administrated in new dose-intervals according to steady state plasma-concentration (Css) of pembrolizumab until disease progression. Primary endpoint was the progression-free survival. Patients with Css of pembrolizumab also underthe investigatorsnt genetic polymorphism analysis of variable number of tandem repeats region (VNTR) in neonatal Fc receptor (FcRn).

Official Title
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Clinical Efficacy and Safety of Individual Pembrolizumab Administration Based on Pharmacokinetic in Advanced Non-small Cell Lung Cancer: an Open-label, Single Arm, Exploratory Clinical Trial

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: cytologically or histologically confirmed primary NSCLC; Stage IV primary NSCLC according to the International Association for the Study of Lung Cancer (IASLC) TNM Eighth Edition; There must be at least one evaluable lesion judged according to RECIST1.1; No sensitive mutation in EGFR and negative ALK rearrangement; ≥18 years old; The Eastern Cooperative Oncology Group (ECOG) physical status score was 0-2; Life expectancy of more than 3 months; Bone marrow and organs (liver and kidney) function well, which can meet the conventional conditions for chemotherapy: neutrophil count ≥1.5×109/ L, platelet count ≥75×109/ L, hemoglobin ≥9g/ dL, total bilirubin ≤1.5×ULN, transaminase ≤2.5×ULN, serum creatinine ≤1.5×ULN or creatinine clearance ≥45ml/min. (ULN: upper limit of normal value); For female subjects of reproductive age, urine or serum pregnancy test should be negative within 7 days prior to receiving the first study drug administration (cycle 1, day 1).If a urine pregnancy test is not confirmed negative, a blood pregnancy test is required;For men, consent must be given to use appropriate methods of contraception or surgical sterilization during the trial and for 8 weeks after the last administration of the experimental drug; Signing the informed consent; Good compliance, follow-up, and voluntary compliance with relevant regulations of the study.- Exclusion Criteria: Small cell lung cancer; Brain metastases with hemorrhage; Currently participating in interventional clinical research and treatment; Past anti-tumor immunotherapy with other anti-PD-1 /PD-L1 monoclonal antibodies; Have received solid organ or blood system transplantation; An active autoimmune disease requiring systemic treatment (e.g., use of palliative drugs, corticosteroids, or immunosuppressants) occurred within 2 years prior to initial administration.Alternative therapies (such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) are not considered systemic; having been diagnosed with immunodeficiency or receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 7 days prior to the first administration of the study;Physiological dose of glucocorticoids (≤10 mg/ day of prednisone or its equivalent) is allowed; A history of non-infectious pneumonia requiring glucocorticoid therapy or current interstitial lung disease within 1 year prior to initial administration; A known history of human immunodeficiency virus (HIV 1/2 antibody positive); untreated active hepatitis B

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pharmacokinetic-guided pembrolizumab cohort<br>Eligible patients received pembrolizumab 200mg every 3 weeks with or without chemotherapy for four cycles, then for patients without progressive disease, pembrolizumab was administrated in new dose-intervals according to steady state plasma-concentration (Css) of pembrolizumab until disease progression. | Drug: pembrolizumab<br>* Eligible patients received pembrolizumab 200mg every 3 weeks with or without chemotherapy for four cycles, then for patients without progressive disease, pembrolizumab was administrated in new dose-intervals according to steady state plasma-concentration (Css) of pembrolizumab until disease progression<br>* Other names: keytruda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | median progression-free survival | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pembrolizumab, Pharmacokinetics, Non-small Cell Lung Cancer