Evaluation of Anti-PD-1 Therapy by Monitoring T Cell Responses in Melanoma, Lung and Other Cancer Types

October 4, 2023 updated by: Mayo Clinic

Maximizing Anti-PD-1 Therapy by Monitoring T Cell Responses in Melanoma, Lung and Other Cancer Types

This study explores the role of T cells in monitoring disease status and response during anti-PD-1/PD-L1 treatment in patients with melanoma, lung and other cancer types. Measuring levels of specific targets such as Bim and soluble PD-L1 during therapy may help track treatment resistance and clinical outcomes. This information may also help researchers determine why some people with melanoma, lung and other cancer types respond to PD-1/PD-L1 treatment and others do not.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. Establish the role of Bim for monitoring disease status during anti-PD-1 therapy.

II. Identify the mechanisms of resistance to anti-PD-1 blockade. III. Quantify and modulate levels of NKG7 messenger ribonucleic acid (mRNA) in CD8+ T cells.

OUTLINE: This is an observational study.

Patients undergo blood sample collection throughout the study. Patients also undergo optional stool sample collection and have their medical records reviewed on study. In addition, patients provide previously-collected tissue sample, if available.

Study Type

Observational

Enrollment (Estimated)

500

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
        • Recruiting
        • Mayo Clinic in Rochester
        • Contact:
          • Svetomir N. Markovic
          • Phone Number: 507-284-2511
        • Principal Investigator:
          • Svetomir N. Markovic

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients with metastatic melanoma, lung or other cancer recruited from the clinical practice in the Department of Oncology at Mayo Clinic in Rochester, Minnesota who are considered appropriate for starting therapy with an open-label commercially available, FDA approved anti-PD-1 monoclonal antibody by their treating provider.

Description

Inclusion Criteria:

  • Are 18 years of age or older
  • Have histologic evidence of locally or regionally advanced or stage IV malignancy
  • Are considered appropriate for starting therapy with anti-PD-1/anti-PD-L1 monoclonal antibody by their treating physician (prior therapy with immune checkpoint inhibitor (ICI) is allowed)
  • Have an understanding of the protocol and its requirements, risks, and discomforts
  • Are willing to undergo peripheral blood collection at the time points mentioned in the protocol
  • Are able and willing to sign an informed consent

Exclusion Criteria:

  • Inability on the part of the patient to understand the informed consent or be compliant with the protocol
  • Patients receiving any concurrent anti-cancer therapy or investigational agents (with the exception of an anti-PD-1/anti-PD-L1 agent as mentioned above)
  • Patients who are pregnant, nursing, or are of childbearing potential and are unwilling to employ adequate contraception

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 (Blood and stool sample collection)
Patients undergo blood sample collection throughout the study. Patients also undergo optional stool sample collection and have their medical records reviewed on study. In addition, patients provide previously-collected tissue sample, if available.
Other: Electronic Health Record Review
Medical records are reviewed
Procedure: Biospecimen Collection
Undergo blood and optional stool/tissue sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Role of Bim for monitoring disease status during anti-PD-1 therapy
Time Frame: Up to 10 samples: at baseline; 6 weeks after initiation of therapy; subsequently at each radiographic tumor assessment (starting at approx. 9-12 weeks) including at confirmed disease progression.
Will be assessed by serial measurements of Bim levels in tumor-reactive CD8+ T cells from the peripheral blood of patients with advanced cancer undergoing therapy with an anti-PD-1 monoclonal antibody and correlate them with clinical outcome.
Up to 10 samples: at baseline; 6 weeks after initiation of therapy; subsequently at each radiographic tumor assessment (starting at approx. 9-12 weeks) including at confirmed disease progression.
Mechanisms of resistance to anti-PD-1 blockade
Time Frame: Up to 10 samples: at baseline; 6 weeks after initiation of therapy; subsequently at each radiographic tumor assessment (starting at approx. 9-12 weeks) including at confirmed disease progression.
Will be assessed by reviewing blood samples to determine whether high sPD-L1 levels are associated with higher Bim levels in CD11ahigh PD-1+CD8+ T cells and decreased response to single-agent anti-PD1 blocking antibody in patients with cancer.
Up to 10 samples: at baseline; 6 weeks after initiation of therapy; subsequently at each radiographic tumor assessment (starting at approx. 9-12 weeks) including at confirmed disease progression.
Quantify and modulate levels of NKG7 mRNA in CD8+ T cells
Time Frame: Up to 10 samples: at baseline; 6 weeks after initiation of therapy; subsequently at each radiographic tumor assessment (starting at approx. 9-12 weeks) including at confirmed disease progression.
CD8+ T cells will be isolated from the peripheral blood of patients with advanced cancer, and messenger ribonucleic acid (mRNA) will be isolated. Qualitative and quantitative reverse transcription polymerase chain reaction (RT-PCR) assays will be performed on these samples in order to determine the levels of six different mRNA splice variants of NKG7. Results will be compared to clinical outcome.
Up to 10 samples: at baseline; 6 weeks after initiation of therapy; subsequently at each radiographic tumor assessment (starting at approx. 9-12 weeks) including at confirmed disease progression.

Collaborators and Investigators

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

Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Svetomir N Markovic, Mayo Clinic in Rochester

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

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)

June 15, 2015

Primary Completion (Estimated)

August 31, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

September 27, 2023

First Submitted That Met QC Criteria

October 4, 2023

First Posted (Actual)

October 10, 2023

Study Record Updates

Last Update Posted (Actual)

October 10, 2023

Last Update Submitted That Met QC Criteria

October 4, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MC200706 (Other Identifier: Mayo Clinic in Rochester)
  • P30CA015083 (U.S. NIH Grant/Contract)
  • NCI-2022-08127 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • 15-000934 (Other Identifier: Mayo Clinic Institutional Review Board)

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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