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

August 2, 2023 updated by: Paul Jannetto, Mayo Clinic

Pharmacokinetic Profiling of Pembrolizumab (Keytruda&Amp;Reg;) and Nivolumab (Opdiva&Amp;Reg;) in Patients With Melanoma and/or Non-Small Cell Lung Cancer: Clinical Validation of a Mass Spectrometry-based Assay

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Actual)

13

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Adults with melanoma or non-small cell lung cancer who are taking monoclonal antibody therapy at Mayo Clinic Cancer Center

Description

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

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Observational (biospecimen collection, chart review)
Patients undergo collection of blood samples and have medical records reviewed on study.
Other: Questionnaire Administration
Ancillary studies
Procedure: Biospecimen Collection
Undergo collection of blood samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Other: Electronic Health Record Review
Medical records are reviewed

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Development and validation of a laboratory developed test (LDT) using liquid chromatography tandem mass spectrometry to measure pemborlizumab and nivolumab.
Time Frame: Up to 1 year
Verify the accuracy, precision, linearity, sensitivity and specificity of a mass spectrometry assay for pembrolizumab and nivolumab in serum
Up to 1 year
Measurement of patient samples for pembrolizumab
Time Frame: 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.
Through study completion at several time points, an average of 3 weeks after taking pembrolizumab for at least 21 weeks.
Measurement of patient samples for nivolumab
Time Frame: 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.
Through study completion at several time points, an average of 1 month after taking nivolumab for at least 14 weeks
Correlation of steady-state concentrations of pembrolizumab correlate with clinical efficacy and/or toxicity
Time Frame: 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.
Through study completion, an average of 3 weeks after taking pembrolizumab for at least 21 weeks.
Correlation of steady-state concentrations of nivolumab correlate with clinical efficacy
Time Frame: 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.
Through study completion, an average of 1 month after taking nivolumab for at least 14 weeks
Clinical efficacy
Time Frame: 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.
After 6 months (24 weeks or more) of treatment
Presence of auto-immune side effects
Time Frame: 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.
Through study completion, an average of 1 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Investigators

  • Principal Investigator: Paul J Jannetto, Mayo Clinic in Rochester

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 26, 2017

Primary Completion (Actual)

January 3, 2020

Study Completion (Actual)

January 3, 2020

Study Registration Dates

First Submitted

February 3, 2023

First Submitted That Met QC Criteria

February 13, 2023

First Posted (Actual)

February 23, 2023

Study Record Updates

Last Update Posted (Actual)

August 4, 2023

Last Update Submitted That Met QC Criteria

August 2, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17-002103
  • NCI-2023-00069 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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