In this study, participants with advanced melanoma will be treated with pembrolizumab (MK-3475) and their tumors and blood will be analyzed for changes related to pembrolizumab therapy. The primary hypotheses are that participants who respond to pembrolizumab have: 1. a higher fraction of cytotoxic tumor-infiltrating T-lymphocytes (FCT) at baseline compared to those who do not respond to pembrolizumab 2. a higher fold-increase in FCT compared to baseline than those who do not respond to pembrolizumab 3. a higher Average Specific Cytotoxic T-lymphocyte Frequency Ratio (ASCTFR) compared to those who do not respond to pembrolizumab
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
1
200 mg by IV infusion Q3W for up to 24 months
Massachusetts General Hospital ( Site 0102)
Boston, Massachusetts, United States
Dana Farber Cancer Institute ( Site 0101)
Boston, Massachusetts, United States
Mean Fraction of Cytotoxic T-lymphocytes (FCT) for Participants With Response Versus Participants With Progression
FCT is defined as the fraction of CD8+ T-cells expressing a predefined single-cell ribonucleic acid (RNA) gene signature to the total tumor infiltrating CD8+T-cells isolated from tumor biopsies.
Time frame: Up to approximately 59 weeks
Average Specific Cytotoxic T-lymphocyte Frequency Ratio (ASCTFR) for Participants With Response Versus Participants With Progression
ASCTFR is defined as the arithmetic average of the log10 ratio of the frequency of individual specific cytotoxic T-Cell Receptor (TCR) clones of on-treatment to pre-treatment.
Time frame: Up to approximately 59 weeks
Change in Baseline of Fraction of Cytotoxic T-lymphocytes (FCT) for Participants With Response Versus Participants With Progression
The fold change from baseline in FCT. FCT is defined as the fraction of CD8+ T-cells expressing a predefined single-cell RNA gene signature to the total tumor infiltrating CD8+T-cells isolated from tumor biopsies.
Time frame: Up to approximately 59 weeks
Number of Participants Who Experienced an Adverse Event (AE)
An AE is any untoward medical occurrence in a participant temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experienced an AE is presented.
Time frame: Up to approximately 59 weeks
Number of Participants Who Discontinued Any Study Drug Due to an Adverse Event (AE)
The number of participants who discontinued any study treatment due to an AE is presented.
Time frame: Up to approximately 59 weeks
Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST Version 1.1 as assessed by the investigator.
Time frame: Up to approximately 59 weeks
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
PFS is defined as the time from start of treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurs first, per RECIST Version 1.1 as assessed by the investigator.
Time frame: Up to approximately 59 weeks
Overall Survival (OS)
OS is defined as the time from the start of treatment to death due to any cause.
Time frame: Up to approximately 59 weeks
Neoepitope Burden
Neoepitope sequencing will be generated based on single cell ribonucleic acid (RNA) sequencing (scRNAseq), whole exome sequencing, and an epitope prediction algorithm to obtain neoepitope burden.
Time frame: Up to approximately 59 weeks
Antigenic Determinants of Highly-functional CD8 + T-cell Clones
T-cell receptors (TCRs) from CD8+ T-cell clones will be identified by single cell ribonucleic acid (RNA) sequencing (scRNAseq) and their killing function will be confirmed by TCR-transduced T-cells recognizing autologous tumor-derived cell lines.
Time frame: Up to approximately 59 weeks
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