Trial Outcomes & Findings for Peripheral T Cell Determinants of Response and Resistance to Pembrolizumab in Melanoma (NCT NCT05105100)
NCT ID: NCT05105100
Last Updated: 2026-04-06
Results Overview
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.
COMPLETED
25 participants
At Baseline, 1 day
2026-04-06
Participant Flow
Participant milestones
| Measure |
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).
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|---|---|
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Overall Study
STARTED
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25
|
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Overall Study
COMPLETED
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25
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Peripheral T Cell Determinants of Response and Resistance to Pembrolizumab in Melanoma
Baseline characteristics by cohort
| Measure |
Participants With Melanoma
n=25 Participants
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).
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|---|---|
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Age, Customized
30-39 years old
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1 Participants
n=5 Participants
|
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Age, Customized
40-49 years old
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2 Participants
n=5 Participants
|
|
Age, Customized
50-59 years old
|
5 Participants
n=5 Participants
|
|
Age, Customized
60-69 years old
|
1 Participants
n=5 Participants
|
|
Age, Customized
70-79 years old
|
10 Participants
n=5 Participants
|
|
Age, Customized
80-89 years old
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6 Participants
n=5 Participants
|
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Sex: Female, Male
Female
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9 Participants
n=5 Participants
|
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Sex: Female, Male
Male
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16 Participants
n=5 Participants
|
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Ethnicity (NIH/OMB)
Hispanic or Latino
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1 Participants
n=5 Participants
|
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Ethnicity (NIH/OMB)
Not Hispanic or Latino
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24 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
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1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
22 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
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Region of Enrollment
United States
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25 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: At Baseline, 1 dayThe 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.
Outcome measures
| Measure |
Participants With Melanoma
n=25 Participants
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).
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|---|---|
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Number of Genes Predictive of Response at Baseline
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52 genes
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PRIMARY outcome
Timeframe: 24 weeksThe 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.
Outcome measures
| Measure |
Participants With Melanoma
n=25 Participants
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).
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|---|---|
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Number of Genes Predictive of Response at 24 Weeks
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52 genes
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PRIMARY outcome
Timeframe: Up to 24 weeksThe 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.
Outcome measures
| Measure |
Participants With Melanoma
n=25 Participants
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).
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|---|---|
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Number of T-cell Sub-populations
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12 t-cell sub-populations
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PRIMARY outcome
Timeframe: Up to 24 weeksThe 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.
Outcome measures
| Measure |
Participants With Melanoma
n=25 Participants
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).
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|---|---|
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Proportion of Participants With a Change in Clonal Expansion of T Cells Associated With Response to Anti-PD-1 Therapy
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.08 proportion of participants
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PRIMARY outcome
Timeframe: Up to 24 weeksThe 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.
Outcome measures
| Measure |
Participants With Melanoma
n=25 Participants
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).
|
|---|---|
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Proportion of Participants With a Change in Distribution of T Cells Associated With Response to Anti-PD-1 Therapy
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.08 proportion of participants
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PRIMARY outcome
Timeframe: Up to 24 weeksThe 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.
Outcome measures
| Measure |
Participants With Melanoma
n=25 Participants
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).
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|---|---|
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Number of Transcriptional Migration Events
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2 transcriptional migration events
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Adverse Events
Participants With Melanoma
Serious adverse events
| Measure |
Participants With Melanoma
n=25 participants at risk
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).
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|---|---|
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Cardiac disorders
Chest Pain
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4.0%
1/25 • Number of events 1 • Up to 24 weeks
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Other adverse events
| Measure |
Participants With Melanoma
n=25 participants at risk
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).
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|---|---|
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Endocrine disorders
Hypothyroidism
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8.0%
2/25 • Up to 24 weeks
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Investigations
Aspartate aminotransferase increased
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4.0%
1/25 • Up to 24 weeks
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Musculoskeletal and connective tissue disorders
Arthralgia
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4.0%
1/25 • Up to 24 weeks
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General disorders
Fever
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4.0%
1/25 • Up to 24 weeks
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General disorders
Chills
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4.0%
1/25 • Up to 24 weeks
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Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, specify
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4.0%
1/25 • Up to 24 weeks
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Gastrointestinal disorders
Colitis
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8.0%
2/25 • Up to 24 weeks
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General disorders
Fatigue
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24.0%
6/25 • Up to 24 weeks
|
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Musculoskeletal and connective tissue disorders
Myalgia
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8.0%
2/25 • Up to 24 weeks
|
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Respiratory, thoracic and mediastinal disorders
Dyspnea
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4.0%
1/25 • Up to 24 weeks
|
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Respiratory, thoracic and mediastinal disorders
Pleural effusion
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4.0%
1/25 • Up to 24 weeks
|
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Skin and subcutaneous tissue disorders
Rash
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20.0%
5/25 • Up to 24 weeks
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Skin and subcutaneous tissue disorders
Eczema
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4.0%
1/25 • Up to 24 weeks
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Investigations
Neutrophil count decreased
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4.0%
1/25 • Up to 24 weeks
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Nervous system disorders
Neuropathy
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4.0%
1/25 • Up to 24 weeks
|
|
Skin and subcutaneous tissue disorders
Pruritic rash
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4.0%
1/25 • Up to 24 weeks
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Additional Information
Dr. Adil Daud, MD
University of California, San Francisco
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place