Clinical trial NCT05105100: Peripheral T Cell Determinants of Response and Resistance to Pembrolizumab in Melanoma
Official title: Peripheral T Cell Determinants of Response and Resistance to Pembrolizumab in Melanoma
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Melanoma
Advanced Melanoma
Keywords: Peripheral T Cell
Pembrolizumab
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2021-11-03
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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).

Primary outcomes:
measure: Number of genes predictive of response at Baseline
timeFrame: Baseline
measure: Number of genes predictive of response at 24 weeks
timeFrame: 24 weeks
measure: Number of T-cell sub-populations
timeFrame: Baseline and 24 weeks
measure: Proportion of participants with a change in clonal expansion of T cells associated with response to anti-PD-1 therapy
timeFrame: 24 weeks
measure: Proportion of participants with a change in distribution of T cells associated with response to anti-PD-1 therapy
timeFrame: 24 weeks
measure: Number of transcriptional migration events
timeFrame: 24 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Adil Daud, MD
role: PRINCIPAL_INVESTIGATOR
References: