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

NCT ID: NCT05226728

Last Updated: 2022-02-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-10
• Study Completion Date: 2021-02-01

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).

Conditions

Non-small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

pembrolizumab

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

keytruda

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Li-kun Chen

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Likun Chen

Role: STUDY_CHAIR

Sun Yat-sen University

Locations

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Countries

China

References

Wang N, Zheng L, Li M, Hou X, Zhang B, Chen J, Li S, Chen L. Clinical efficacy and safety of individualized pembrolizumab administration based on pharmacokinetic in advanced non-small cell lung cancer: A prospective exploratory clinical trial. Lung Cancer. 2023 Apr;178:183-190. doi: 10.1016/j.lungcan.2023.02.009. Epub 2023 Feb 15.

Reference Type: DERIVED

PMID: 36868179 (View on PubMed)

Other Identifiers

GASTO 1054

Identifier Type: -

Identifier Source: org_study_id