Immunologic Determinants of Response to Pembrolizumab (MK-3475) in Advanced Melanoma (MK-3475-161/KEYNOTE-161)

NCT03407170 | Terminated Phase 2 Results FDA Drug

• 3 other identifiers: 3475-161MK-3475-161KEYNOTE-161
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 2

Brief Summary

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. 1.a higher fraction of cytotoxic tumor-infiltrating T-lymphocytes (FCT) at baseline compared to those who do not respond to pembrolizumab
2. 2.a higher fold-increase in FCT compared to baseline than those who do not respond to pembrolizumab
3. 3.a higher Average Specific Cytotoxic T-lymphocyte Frequency Ratio (ASCTFR) compared to those who do not respond to pembrolizumab

Conditions

Advanced Melanoma

Keywords

Programmed Cell Death-1 (PD-1); PD1; Programmed Cell Death-Ligand 1 (PD-L1); Programmed Cell Death-Ligand 2 (PD-L2); PDL1; PDL2

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  Up to approximately 59 weeks

Secondary Outcomes (7)

• Number of Participants Who Experienced an Adverse Event (AE)

  Up to approximately 59 weeks

• Number of Participants Who Discontinued Any Study Drug Due to an Adverse Event (AE)

  Up to approximately 59 weeks

• Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

  Up to approximately 59 weeks

• Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

  Up to approximately 59 weeks

• Overall Survival (OS)

  Up to approximately 59 weeks

Study Arms (1)

Pembrolizumab

EXPERIMENTAL

Participants receive pembrolizumab 200 mg by intravenous (IV) infusion every 3 weeks (Q3W) for up to 24 months

Biological: pembrolizumab

Interventions

pembrolizumab BIOLOGICAL

200 mg by IV infusion Q3W for up to 24 months

Also known as: KEYTRUDA®, MK-3475

Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has a histologically confirmed diagnosis of unresectable stage III or metastatic melanoma not amenable to local therapy
• Has testing for a BRAF mutation prior to study entry
• Has measurable disease per RECIST 1.1 as assessed by the investigator/radiology
• Has resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 or less (except alopecia). If the participant received major surgery or radiation therapy of \>30 Gray units, they must have recovered from the toxicity and/or complications from the intervention
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days of study start
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP) OR is a WOCBP and agrees to use a contraceptive method, consistent with local regulations regarding the methods of contraception for those participating in clinical studies, during the treatment period and for at least 120 days after the last dose of study treatment
• A male participant is eligible to participate if he agrees not to donate sperm PLUS to be abstinent from heterosexual intercourse as their preferred and usual lifestyle OR agree to use contraception, consistent with local regulations regarding the methods of contraception for those participating in clinical studies, during the treatment period and for at least 120 days after the last dose of study treatment

You may not qualify if:

• Has disease that is suitable for local therapy administered with curative intent
• Has a history of interstitial lung disease
• Has a positive pregnancy test within 72 hours before the first dose of study therapy
• Has received prior therapy with an anti-Programmed Cell Death Protein 1 (PD-1), anti-Programmed Cell Death-Ligand 1 (PD-L1), anti-Programmed Cell Death-Ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 \[CTLA-4\], OX-40, CD137)
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to study start
• Has received prior radiotherapy within 2 weeks of start of study therapy
• Has received a live vaccine within 30 days prior to the first dose of study therapy
• Has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte colony stimulating factor \[G-CSF\], granulocyte macrophage colony stimulating factor \[GMCSF\] or recombinant erythropoietin) within 4 weeks prior to study start
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study therapy
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study therapy
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years with the exception of basal cell and squamous cell carcinoma of the skin, transitional cell carcinoma of urothelial cancer, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (2)

Massachusetts General Hospital ( Site 0102)

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute ( Site 0101)

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Interventions

pembrolizumab

Limitations and Caveats

Study was stopped early due to lack of accrual.

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2018
• First Posted: January 23, 2018
• Study Start: June 28, 2018
• Primary Completion: August 14, 2019
• Study Completion: August 14, 2019
• Last Updated: July 15, 2020
• Results First Posted: July 15, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will share

Locations

US (2)