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

Sponsor

Mayo Clinic (Other)

Overall Status

Recruiting

CT.gov ID

NCT06075524

Collaborator

National Cancer Institute (NCI) (NIH)

500

Enrollment

Location

126.6

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Clinical Stage III Cutaneous Melanoma AJCC v8 Clinical Stage IV Cutaneous Melanoma AJCC v8 Locally Advanced Lung Carcinoma Locally Advanced Malignant Solid Neoplasm Locally Advanced Melanoma Metastatic Lung Carcinoma Metastatic Malignant Solid Neoplasm Metastatic Melanoma Stage III Lung Cancer AJCC v8 Stage IV Lung Cancer AJCC v8	Procedure: Biospecimen Collection Other: Electronic Health Record Review

Detailed Description

PRIMARY OBJECTIVES:

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

Study Type:

Observational

Anticipated Enrollment :

500 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Jun 15, 2015

Anticipated Primary Completion Date :

Aug 31, 2025

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

Arm	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.	Procedure: Biospecimen Collection Undergo blood and optional stool/tissue sample collection Other Names: Biological Sample Collection Biospecimen Collected Specimen Collection Other: Electronic Health Record Review Medical records are reviewed

Arm

Intervention/Treatment

Observational (Blood and stool sample collection)

Procedure: Biospecimen Collection

Undergo blood and optional stool/tissue sample collection

Other Names:

Biological Sample Collection

Biospecimen Collected

Specimen Collection

Other: Electronic Health Record Review

Medical records are reviewed

Outcome Measures

Primary Outcome Measures

Role of Bim for monitoring disease status during anti-PD-1 therapy [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.
Mechanisms of resistance to anti-PD-1 blockade [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.
Quantify and modulate levels of NKG7 mRNA in CD8+ T cells [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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