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

Non-small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05226728
• Other study ID #: GASTO 1054
• Status: Completed
• Phase: Phase 1
• Start date: October 10, 2018
• Est. completion date: February 1, 2021

Study information

• Verified date: February 2022
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: February 1, 2021
• Est. primary completion date: February 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

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

Locations

Country	Name	City	State
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PFS	median progression-free survival	18 months