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

Sponsor

Sun Yat-sen University (Other)

Overall Status

Completed

CT.gov ID

NCT05226728

Collaborator

(none)

Enrollment

Location

Arm

27.8

Actual Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Drug: pembrolizumab	Phase 1

Detailed Description

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).

Study Design

Study Type:

Interventional

Actual Enrollment :

33 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 10, 2018

Actual Primary Completion Date :

Feb 1, 2021

Actual Study Completion Date :

Feb 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: pharmacokinetic-guided pembrolizumab cohort 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 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 Other Names: keytruda

Arm

Intervention/Treatment

Experimental: pharmacokinetic-guided pembrolizumab cohort

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

Other Names:

keytruda

Outcome Measures

Primary Outcome Measures

PFS [18 months]
median progression-free survival

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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