Clinical trial NCT05226728: Pharmacokinetically-guided on the Individualization of Pembrolizumab Administration in the Treatment of Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-small Cell Lung Cancer
Keywords: Pembrolizumab
Pharmacokinetics
Non-small Cell Lung Cancer
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2022-02-07
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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).

Eligibility criteria: Inclusion Criteria:

1. cytologically or histologically confirmed primary NSCLC;
2. Stage IV primary NSCLC according to the International Association for the Study of Lung Cancer (IASLC) TNM Eighth Edition;
3. There must be at least one evaluable lesion judged according to RECIST1.1;
4. No sensitive mutation in EGFR and negative ALK rearrangement;
5. ≥18 years old;
6. The Eastern Cooperative Oncology Group (ECOG) physical status score was 0-2;
7. Life expectancy of more than 3 months;
8. 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);
9. 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;
10. Signing the informed consent;
11. Good compliance, follow-up, and voluntary compliance with relevant regulations of the study.-

Exclusion Criteria:

1. Small cell lung cancer;
2. Brain metastases with hemorrhage;
3. Currently participating in interventional clinical research and treatment;
4. Past anti-tumor immunotherapy with other anti-PD-1 /PD-L1 monoclonal antibodies;
5. Have received solid organ or blood system transplantation;
6. 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;
7. 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;
8. A history of non-infectious pneumonia requiring glucocorticoid therapy or current interstitial lung disease within 1 year prior to initial administration;
9. A known history of human immunodeficiency virus (HIV 1/2 antibody positive);
10. untreated active hepatitis B

Primary outcomes:
measure: PFS
timeFrame: 18 months
Secondary outcomes:
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Likun Chen
role: STUDY_CHAIR
References: