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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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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

Intervention / Treatment
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* Procedure: Biospecimen Collection
* Other: Electronic Health Record Review


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Observational (Blood and stool sample collection)<br>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<br>* Undergo blood and optional stool/tissue sample collection<br>* Other names: Specimen Collection;Other: Electronic Health Record Review<br>* Medical records are reviewed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Role of Bim for monitoring disease status during anti-PD-1 therapy | 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 | 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 | 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. |