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

NCT05105100 | Completed

• 1 other identifier: 21853
• Study Type: observational
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Melanoma; Advanced Melanoma

Keywords

Peripheral T Cell; Pembrolizumab

Outcome Measures

Primary Outcomes (6)

• Number of genes predictive of response at Baseline

  The investigators will identify the genes predictive of response to anti-PD-1 therapy by testing for significant associations across expression rates of each gene and response/resistance, within a hurdle-Gaussian mixed-effect framework that accounts for variance across patients and technical noise present in single-cell data.

  Baseline

• Number of genes predictive of response at 24 weeks

  The investigators will identify the genes predictive of response to anti-PD-1 therapy by testing for significant associations across expression rates of each gene and response/resistance, within a hurdle-Gaussian mixed-effect framework that accounts for variance across patients and technical noise present in single-cell data.

  24 weeks

• Number of T-cell sub-populations

  The investigators will identify T cell sub-populations in the tumor-directed component in blood whose relative frequency is indicative of response to anti-PD-1 therapy, using a negative binomial regression model. We will test for predictive differences in relative frequencies before and after treatment initiation separately, as well as when combining both time points with appropriate interaction terms

  Baseline and 24 weeks

• Proportion of participants with a change in clonal expansion of T cells associated with response to anti-PD-1 therapy

  The investigators will build a novel computational framework to identify T-cell clonal behavior associated with response to anti-PD-1 therapy using profiling of TCR sequences at single-cell resolution to compare clonal expansion in each of the sub-populations for their association with response to anti-PD-1 therapy.

  24 weeks

• Proportion of participants with a change in distribution of T cells associated with response to anti-PD-1 therapy

  The investigators will build a novel computational framework to identify T-cell clonal behavior associated with response to anti-PD-1 therapy using profiling of TCR sequences at single-cell resolution to compare distribution of T cells in each of the sub-populations for their association with response to anti-PD-1 therapy.

  24 weeks

• Number of transcriptional migration events

  The investigators will search for "transcriptional migration" events, in which T cell clones change their transcriptional profile following treatment and will assess the predictive power of such events to the success of anti-PD-1 therapy.

  24 weeks

Study Arms (1)

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)

Procedure: Biopsy; Procedure: Biospecimen Collection

Interventions

Biopsy PROCEDURE

Tumor tissue collection

Also known as: Excisional Biopsy

Participants with Melanoma

Biospecimen Collection PROCEDURE

Intravenously Blood draw

Also known as: Specimen Collection

Participants with Melanoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Participants will be recruited from the Melanoma and Cutaneous Oncology Program at the Helen Diller Family Comprehensive Cancer Center at University of California San Francisco.

You may qualify if:

• 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.
• Must have one or more sites of disease amenable to biopsy (tumor, skin, lymph node, pleural fluid, peritoneal fluid, cerebral spinal fluid (CSF)).
• 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.
• Participants must be age 18 years or older on the day of signing informed consent.
• Have the ability to provide written informed consent for the trial.
• Be able and willing to comply with study procedures including provision of basic demographic information and medical history.
• Be willing to receive periodic follow up phone calls to monitor health status and survival status.

You may not qualify if:

• 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)).
• Has received prior systemic anti-cancer therapy including investigational agents within the prior 2 weeks.
• 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.
• Has a contraindication to tissue biopsy for minimally-invasive research-procedure
• Contraindication to phlebotomy (up to 20 milliliters (mL)) per phlebotomy every three weeks).

Sponsors & Collaborators

• University of California, San Francisco: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Tumor tissue and blood samples

MeSH Terms

Conditions

Melanoma

Interventions

Biopsy; Specimen Handling

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Adil Daud, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2021
• First Posted: November 3, 2021
• Study Start: October 29, 2021
• Primary Completion: September 15, 2025
• Study Completion: September 15, 2025
• Last Updated: September 17, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)