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

Phase 1

Completed

• Conditions: Non-small Cell Lung Cancer
• Interventions: Drug: pembrolizumab

• Registration Number: NCT05226728
• Lead Sponsor: Sun Yat-sen University

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).

Study Timeline

• Study Start: 2018-10-10
• Primary Completion: 2021-02-01
• Study Completion: 2021-02-01
• Study First Submitted: 2021-06-27
• Status Verified: 2022-02
• Study First Submitted QC: 2022-02-03
• Last Update Submitted: 2022-02-03
• Study First Posted: 2022-02-07
• Last Update Posted: 2022-02-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 33

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
pharmacokinetic-guided pembrolizumab cohort	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.

Primary Outcome Measures

Name	Time	Method
PFS	18 months	median progression-free survival

Trial Locations

Locations (1)

Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China