MelanomaNCT05105100
Peripheral T Cell Determinants of Response and Resistance to Pembrolizumab in Melanoma
An observational study of Melanoma and Advanced Melanoma, run by University of California, San Francisco at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma, Advanced Melanoma
- What is being tested?
- Biopsy and Biospecimen Collection
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Oct 2021to 15 Sep 2025
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- Participants must have histologically confirmed locally advanced or metastatic melanoma and be starting on standard of care pembrolizumab monotherapy. Participants 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.
Who cannot join
- 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 40 milliliters (mL)) per phlebotomy every three weeks).
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94143
About this study
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 Programmed death-1 (PD-1) therapy.
Read the 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 :
- 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.
- Transcriptional and phenotypic features of tumor directed T cells in blood using a combination of phenotypic markers derived from COMET and cite-seq.
Outline:
Participants will have blood drawn and tumor biopsied. Participants will be followed for 6 months from time of treatment initiation. After 6 months, participants 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
- Being tested
- Biopsy, Biospecimen Collection
- Keywords
- Peripheral T Cell, Pembrolizumab
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BiopsyProcedure or surgery
Also called Excisional Biopsy
Tumor tissue collection
Biospecimen CollectionProcedure or surgery
Also called Specimen Collection
Intravenously Blood draw
| Study group | Role | What they receive |
|---|---|---|
| Participants with Melanoma | Participants will undergo a pre-treatment tumor core biopsy and Peripheral blood mononuclear cell (PBMC) collection. Then, participants will be started on non-investigational pembrolizumab per standard of care and PBMCs will be collected every 3 weeks (1 cycle). Receives: Procedure: Biopsy; Procedure: Biospecimen Collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Genes Predictive of Response at Baseline
The investigators will identify the genes predictive of response to anti-programmed death-1(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. The overall number of genes predictive of response at baseline will be reported.
Measured: At Baseline, 1 day
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. The overall number of genes predictive of response at week 24 will be reported.
Measured: 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. The overall number of t-cell sub-populations will be reported.
Measured: Up to 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 T-Cell Receptor (TCR) sequences at single-cell resolution to compare clonal expansion in each of the sub-population's association with response to anti-PD-1 therapy. The proportion of participants with a change in clonal expansion of T-cells associated with a response to anti-PD-1 therapy will be reported.
Measured: Up to 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. The proportion of participants with a change in distribution of T cells associated with response to anti-PD-1 therapy will be reported.
Measured: Up to 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. The overall number of transcriptional migration events will be reported.
Measured: Up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2021
- Study start29 Oct 2021
- Primary completion15 Sep 2025
- Study completion15 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Adil Daud, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05105100
- Sponsor's protocol ID
- 21853
- Status last verified
- Mar 2026
- First submitted
- 12 Oct 2021
- Last updated
- 6 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Peripheral T Cell Determinants of Response and Resistance to Pembrolizumab in Melanoma
- ClinicalTrials.gov ID
- NCT05105100
- Acronym / sponsor ID
- 21853
- Conditions
- Melanoma, Advanced Melanoma
- Keywords
- Peripheral T Cell, Pembrolizumab
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 29 Oct 2021 (actual)
- Primary completion
- 15 Sep 2025 (actual)
- Study completion
- 15 Sep 2025 (actual)
- First posted
- 3 Nov 2021 (actual)
- Results
- Posted 6 Apr 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 Programmed death-1 (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 :
- 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.
- Transcriptional and phenotypic features of tumor directed T cells in blood using a combination of phenotypic markers derived from COMET and cite-seq.
Outline:
Participants will have blood drawn and tumor biopsied. Participants will be followed for 6 months from time of treatment initiation. After 6 months, participants do not need to be followed but standard of care scans and survival status can be assessed for up to 5 years.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Participants with Melanoma | – | Procedure: Biopsy, Procedure: Biospecimen CollectionParticipants will undergo a pre-treatment tumor core biopsy and Peripheral blood mononuclear cell (PBMC) collection. Then, participants will be started on non-investigational pembrolizumab per standard of care and PBMCs will be collected every 3 weeks (1 cycle). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (7 listed)
- Participants must have histologically confirmed locally advanced or metastatic melanoma and be starting on standard of care pembrolizumab monotherapy. Participants 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.
Key exclusion criteria (5 listed)
- 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 40 milliliters (mL)) per phlebotomy every three weeks).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BiopsyAlso: Excisional BiopsyTumor tissue collection | Procedure or surgery | Participants with Melanoma |
| Biospecimen CollectionAlso: Specimen CollectionIntravenously Blood draw | Procedure or surgery | Participants with Melanoma |
Primary outcome
Number of Genes Predictive of Response at Baseline
Time frame: At Baseline, 1 day
The investigators will identify the genes predictive of response to anti-programmed death-1(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. The overall number of genes predictive of response at baseline will be reported.
Number of Genes Predictive of Response at 24 Weeks
Time frame: 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. The overall number of genes predictive of response at week 24 will be reported.
Number of T-cell Sub-populations
Time frame: Up to 24 weeks
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. The overall number of t-cell sub-populations will be reported.
Proportion of Participants With a Change in Clonal Expansion of T Cells Associated With Response to Anti-PD-1 Therapy
Time frame: Up to 24 weeks
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 T-Cell Receptor (TCR) sequences at single-cell resolution to compare clonal expansion in each of the sub-population's association with response to anti-PD-1 therapy. The proportion of participants with a change in clonal expansion of T-cells associated with a response to anti-PD-1 therapy will be reported.
Proportion of Participants With a Change in Distribution of T Cells Associated With Response to Anti-PD-1 Therapy
Time frame: Up to 24 weeks
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. The proportion of participants with a change in distribution of T cells associated with response to anti-PD-1 therapy will be reported.
Number of Transcriptional Migration Events
Time frame: Up to 24 weeks
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. The overall number of transcriptional migration events will be reported.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adil Daud, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Melanoma and Advanced Melanoma, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Apr 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Genes Predictive of Response at Baseline (time frame: At Baseline, 1 day). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2026.