Pharmacokinetic Profiling of Pembrolizumab and Nivolumab in Patients With Melanoma and/or Non-Small Cell Lung Cancer

Completed

• Conditions: Lung Non-Small Cell Carcinoma; Melanoma
• Interventions: Procedure: Biospecimen Collection; Other: Electronic Health Record Review; Other: Questionnaire Administration

• Registration Number: NCT05740501
• Lead Sponsor: Mayo Clinic

Brief Summary

This early phase I study collects blood samples and monitors the levels of pembrolizumab and nivolumab as they move through the body in patients with melanoma and/or non-small cell lung cancer. Pembrolizumab and nivolumab are a monoclonal antibodies that may interfere with the ability of cancer cells to grow and spread. Studying samples of blood in the laboratory from patients receiving pembrolizumab and nivolumab may help doctors learn more about the effects of pembrolizumab and nivolumab on cells. It may also help doctors understand how well patients respond to treatment. Information from this study may be used in the future to guide physicians to make dosage adjustments based on serum concentrations of drug to minimize adverse side effects and maximize the effect of the drug.

Detailed Description

PRIMARY OBJECTIVE:

I. To perform a steady-state PK study on patients who are taking monoclonal antibody therapy (25 patients starting pembrolizumab and 25 patients starting nivolumab for melanoma or non-small cell lung cancer).

II. Develop and validate a liquid chromatography tandem mass spectrometry (LC-MS/MS) assay to measure pembrolizumab and nivolumab in serum.

III. Measure patient samples for pembrolizumab/nivolumab at various clinical time points.

IV. Use the pharmacokinetic data (drug concentrations) to determine the area under the curve (AUC), maximum observed serum concentration (Cmax), clearance, half-life (t1/2), and trough steady-state drug concentrations.

V. Compare the data to the clinical efficacy (defined using Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 criteria)1, as well as, presence of auto-immune side effects using multiple variable regression modeling in Statistical Analysis System (SAS) version (v)9.4 or other statistical software.

OUTLINE:

Patients undergo collection of blood samples and have medical records reviewed on study.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2017-04-26
• Primary Completion: 2020-01-03
• Study Completion: 2020-01-03
• Study First Submitted: 2023-02-03
• Study First Submitted QC: 2023-02-13
• Study First Posted: 2023-02-23
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-02
• Last Update Posted: 2023-08-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

• Adults who are at steady-state and taking monoclonal antibody therapy with pembrolizumab or nivolumab for melanoma or non-small cell lung cancer. Steady-state for pembrolizumab is week 21 or later and for nivolumab is week 14 or later from the initial infusion

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Exclusion Criteria

• Patients not taking pembrolizumab or nivolumab or taking pembrolizumab or nivolumab for other indications (not melanoma or non-small cell lung cancer).

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Observational (biospecimen collection, chart review)	Biospecimen Collection	Patients undergo collection of blood samples and have medical records reviewed on study.
Observational (biospecimen collection, chart review)	Questionnaire Administration	Patients undergo collection of blood samples and have medical records reviewed on study.
Observational (biospecimen collection, chart review)	Electronic Health Record Review	Patients undergo collection of blood samples and have medical records reviewed on study.

Primary Outcome Measures

Name	Time	Method
Measurement of patient samples for pembrolizumab	Through study completion at several time points, an average of 3 weeks after taking pembrolizumab for at least 21 weeks.	Using a validated LDT liquid chromatography tandem mass spectrometry assay measure the concentration of pembrolizumab in serum.
Measurement of patient samples for nivolumab	Through study completion at several time points, an average of 1 month after taking nivolumab for at least 14 weeks	Using a validated LDT liquid chromatography tandem mass spectrometry assay measure the concentration of nivolumab in serum.
Correlation of steady-state concentrations of nivolumab correlate with clinical efficacy	Through study completion, an average of 1 month after taking nivolumab for at least 14 weeks	Will assess if therapeutic drug monitoring correlates with efficacy and/or toxicity of nivolumab. Concentrations in serum will be determined using a LDT mass spectrometry assay.
Clinical efficacy	After 6 months (24 weeks or more) of treatment	Tumor response will be determined using Response Evaluation Criteria in Solid Tumors1.1 criteria. Clinical efficacy defined as achieving an objective response (complete response or partial response) versus stable disease, or disease progression.
Development and validation of a laboratory developed test (LDT) using liquid chromatography tandem mass spectrometry to measure pemborlizumab and nivolumab.	Up to 1 year	Verify the accuracy, precision, linearity, sensitivity and specificity of a mass spectrometry assay for pembrolizumab and nivolumab in serum
Correlation of steady-state concentrations of pembrolizumab correlate with clinical efficacy and/or toxicity	Through study completion, an average of 3 weeks after taking pembrolizumab for at least 21 weeks.	Will assess if therapeutic drug monitoring correlates with efficacy and/or toxicity of pembrolizumab. Concentrations in serum will be determined using a LDT mass spectrometry assay.
Presence of auto-immune side effects	Through study completion, an average of 1 month	Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse events, version 4.0. Investigators will indicate if it was potentially immune related (i.e. grade 3-4 adverse events such as pneumonitis, diarrhea/colitis, hypophysitis/adrenal insufficiency, hyper/hypothyroidism, autoimmune hepatitis, severe skin reactions, nephritis/kidney failure, uveitis, myositis) in combination with other basic laboratory tests that are routinely monitored. Will use multiple variable regression modeling in Statistical Analysis System version 9.4 or other statistical software.

Trial Locations

Locations (1)

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States