A Phase 2 interventional study of pembrolizumab in Advanced Melanoma, sponsored by Merck Sharp & Dohme LLC. Terminated at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-07-15.
Sponsored by Merck Sharp & Dohme LLC · Phase 2, Interventional, and Treatment
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:
Exclusion Criteria:
Participants receive pembrolizumab 200 mg by intravenous (IV) infusion every 3 weeks (Q3W) for up to 24 months
Biological: pembrolizumab
200 mg by IV infusion Q3W for up to 24 months
Also known as: KEYTRUDA®, MK-3475
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
| Milestone | Pembrolizumab |
|---|---|
| Started | 1 |
| Completed | 0 |
| Not completed | 1 |
| Withdrew: Adverse event | 1 |
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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.
| Participants | Pembrolizumab |
|---|---|
| Number of Participants Who Experienced an Adverse Event (AE) | 1 |
The number of participants who discontinued any study treatment due to an AE is presented.
| Participants | Pembrolizumab |
|---|---|
| Number of Participants Who Discontinued Any Study Drug Due to an Adverse Event (AE) | 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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
OS is defined as the time from the start of treatment to death due to any cause.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
Collected over Up to approximately 59 weeks. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Pembrolizumab | — | — | — |
Zero participants are reported due to the risk of identification of a person.
| Age, Categorical(Participants) | Pembrolizumab |
|---|---|
| <=18 years | — |
| Between 18 and 65 years | — |
| >=65 years | — |
| Sex: Female, Male(Participants) | Pembrolizumab |
|---|---|
| Female | — |
| Male | — |
| Ethnicity (NIH/OMB)(Participants) | Pembrolizumab |
|---|---|
| Hispanic or Latino | — |
| Not Hispanic or Latino | — |
| Unknown or Not Reported | — |
| Race (NIH/OMB)(Participants) | Pembrolizumab |
|---|---|
| American Indian or Alaska Native | — |
| Asian | — |
| Native Hawaiian or Other Pacific Islander | — |
| Black or African American | — |
| White | — |
| More than one race | — |
| Unknown or Not Reported | — |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
This study is terminated, as verified in Jun 2020. You cannot join it, but the record below documents what was studied.
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Merck Sharp & Dohme LLC