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

Metastatic Melanoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06075524
• Other study ID #: MC200706
• Secondary ID: NCI-2022-0812715
• Status: Recruiting
• Start date: June 15, 2015
• Est. completion date: December 31, 2025

Study information

• Verified date: October 2023
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: December 31, 2025
• Est. primary completion date: August 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• 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
• Lung Neoplasms
• Melanoma
• Metastatic Lung Carcinoma
• Metastatic Malignant Solid Neoplasm
• Metastatic Melanoma
• Neoplasms
• Skin Neoplasms
• Stage III Lung Cancer AJCC v8
• Stage IV Lung Cancer AJCC v8

Intervention

Procedure:
• Biospecimen Collection
Undergo blood and optional stool/tissue sample collection

Other:
• Electronic Health Record Review
Medical records are reviewed

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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.

External Links

•   Mayo Clinic Clinical Trials