Peripheral T Cell Determinants of Response and Resistance to Pembrolizumab in Melanoma

NCT ID: NCT05105100

Last Updated: 2025-09-17

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 25 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-10-29
• Study Completion Date: 2025-09-15

Brief Summary

This is a non-therapeutic study assessing peripheral T cell determinants of response and resistance to immunotherapy in patients with advanced melanoma.The hypothesis is that systemic T cells traffic into the tumor microenvironment (TME) can predict response and resistance to immunotherapy. These systemic tumor directed T cells can be defined by tumor/blood small conditional RNA (scRNA) using T cell receptor (TCR) as a barcode and can help predict response to PD-1 therapy.

Detailed Description

Primary Objective:

To understand how the systemic immune profile (T cell activation and expansion in TME) changes in response to pembrolizumab therapy in patients with advanced melanoma on pembrolizumab monotherapy.

Exploratory Objectives :

I. To correlate the peripheral T cell profiles with the objective response rate (ORR) at 24 weeks in patients with advanced melanoma on pembrolizumab monotherapy.

II. To correlate the peripheral T cell profiles with progression free survival (PFS) in patients with advanced melanoma on pembrolizumab monotherapy.

III. To correlate the peripheral T cell profiles with overall survival (OS) in patients with advanced melanoma on pembrolizumab monotherapy.

IV. To correlate the peripheral T cell profiles with toxicity profile. V. Transcriptional and phenotypic features of tumor directed T cells in blood using a combination of phenotypic markers derived from COMET and cite-seq.

Patients will be followed for 6 months from time of treatment initiation. After 6 months, patients do not need to be followed but standard of care scans and survival status can be assessed for up to 5 years.

Conditions

Melanoma; Advanced Melanoma

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Participants with Melanoma

Participants will undergo a pre-treatment tumor core biopsy and Peripheral blood mononuclear cell (PBMC) collection. Then, patients will be started on pembrolizumab per standard of care and PBMCs will be collected every 3 weeks (1 cycle)

Biopsy

Intervention Type: PROCEDURE

Tumor tissue collection

Biospecimen Collection

Intervention Type: PROCEDURE

Intravenously Blood draw

Interventions

Biopsy

Tumor tissue collection

Intervention Type: PROCEDURE

Biospecimen Collection

Intravenously Blood draw

Intervention Type: PROCEDURE

Other Intervention Names

Excisional Biopsy; Specimen Collection

Eligibility Criteria

Inclusion Criteria

1. Patients must have histologically confirmed locally advanced or metastatic melanoma and be starting on standard of care pembrolizumab monotherapy. Patients may have received any or no prior anti-cancer therapy without limitation.

2. Must have one or more sites of disease amenable to biopsy (tumor, skin, lymph node, pleural fluid, peritoneal fluid, cerebral spinal fluid (CSF)).

3. Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

4. Participants must be age 18 years or older on the day of signing informed consent.

5. Have the ability to provide written informed consent for the trial.

6. Be able and willing to comply with study procedures including provision of basic demographic information and medical history.

7. Be willing to receive periodic follow up phone calls to monitor health status and survival status.

Exclusion Criteria

1. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX 40, Cluster of Differentiation 137 (CD137)).

2. Has received prior systemic anti-cancer therapy including investigational agents within the prior 2 weeks.

3. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.

4. Has a contraindication to tissue biopsy for minimally-invasive research-procedure

5. Contraindication to phlebotomy (up to 20 milliliters (mL)) per phlebotomy every three weeks).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Adil Daud, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

University of California, San Francisco

San Francisco, California, United States

Countries

United States

Other Identifiers

21853

Identifier Type: -

Identifier Source: org_study_id