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

Recruiting

• Conditions: Metastatic Malignant Solid Neoplasm; Metastatic Melanoma; Locally Advanced Melanoma; Stage IV Lung Cancer AJCC v8; Clinical Stage III Cutaneous Melanoma AJCC v8; Locally Advanced Lung Carcinoma; Metastatic Lung Carcinoma; Clinical Stage IV Cutaneous Melanoma AJCC v8; Locally Advanced Malignant Solid Neoplasm; Stage III Lung Cancer AJCC v8
• Interventions: Procedure: Biospecimen Collection; Other: Electronic Health Record Review

• Registration Number: NCT06075524
• Lead Sponsor: Mayo Clinic

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.

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 Timeline

• Study Start: 2015-06-15
• Study First Submitted: 2023-09-27
• Study First Submitted QC: 2023-10-04
• Study First Posted: 2023-10-10
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-03
• Last Update Posted: 2025-02-05
• Primary Completion: 2025-08-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 500

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Observational (Blood and stool sample collection)	Electronic Health Record Review	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.
Observational (Blood and stool sample collection)	Biospecimen 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.

Primary Outcome Measures

Name	Time	Method
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.
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.

Trial Locations

Locations (1)

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