Immunologic Determinants of Response to Pembrolizumab (MK-3475) in Advanced Melanoma (MK-3475-161/KEYNOTE-161)
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|ClinicalTrials.gov Identifier: NCT03407170|
Recruitment Status : Recruiting
First Posted : January 23, 2018
Last Update Posted : June 8, 2018
|Condition or disease||Intervention/treatment||Phase|
|Advanced Melanoma||Biological: pembrolizumab||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-Label, Phase II Study to Determine the Immunologic Correlates of Pembrolizumab-Mediated Tumor Regression in Subjects With Advanced Melanoma (KEYNOTE-161)|
|Estimated Study Start Date :||June 15, 2018|
|Estimated Primary Completion Date :||December 13, 2021|
|Estimated Study Completion Date :||December 13, 2021|
Participants receive pembrolizumab 200 mg by intravenous (IV) infusion every 3 weeks (Q3W) for up to 24 months
200 mg by IV infusion Q3W for up to 24 months
- Mean Fraction of Cytotoxic T-lymphocytes (FCT) for Participants with Response versus Participants with Progression [ Time Frame: Up to 24 months ]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.
- Average Specific Cytotoxic T-lymphocyte Frequency Ratio (ASCTFR) for Participants with Response vs Participants with Progression [ Time Frame: Up to 24 months ]ASCTFR is defined as the arithmetic average of the log^10 ratio of the frequency of individual specific cytotoxic T-Cell Receptor (TCR) clones of on-treatment to pre-treatment.
- Change in Baseline of FCT for Participants With Response Versus Participants With Progression [ Time Frame: Baseline and Month 24 ]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.
- Adverse Events (AEs) [ Time Frame: Up to 27 months ]Number of participants experiencing an AE defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.
- Treatment Discontinuations due to AEs [ Time Frame: Up to 24 months ]Number of participants discontinuing study drug due to an AE.
- Overall Response Rate (ORR) per Immune-related Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [ Time Frame: Up to 24 months ]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.
- Progression-free Survival (PFS) per RECIST Version 1.1 [ Time Frame: Up to 24 months ]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..
- Overall Survival (OS) [ Time Frame: Up to 24 months ]OS is defined as the time from the start of treatment to death due to any cause.
- Neoepitope Burden [ Time Frame: Up to 24 months ]Neoepitope sequencing will be generated based on single cell RNA sequencing (scRNAseq), whole exome sequencing, and an epitope prediction algorithm to obtain neoepitope burden.
- Antigenic Determinants of Highly-functional CD8 + T-cell Clones [ Time Frame: Up to 24 months ]TCRs from CD8+ T-cell clones will be identified by scRNAseq and their killing function will be confirmed by TCR-transduced T-cells recognizing autologous tumor-derived cell lines.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03407170
|Contact: Toll Free Number||1-888-577-8839||Trialsites@merck.com|
|United States, Massachusetts|
|Massachusetts General Hospital ( Site 0102)||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Contact: Study Coordinator 617-724-4800|
|Dana Farber Cancer Institute ( Site 0101)||Recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: Study Coordinator 617-582-9992|
|Study Director:||Medical Director||Merck Sharp & Dohme Corp.|