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Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-158/KEYNOTE-158)

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ClinicalTrials.gov Identifier: NCT02628067
Recruitment Status : Recruiting
First Posted : December 11, 2015
Last Update Posted : September 24, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE December 9, 2015
First Posted Date  ICMJE December 11, 2015
Last Update Posted Date September 24, 2020
Actual Study Start Date  ICMJE December 18, 2015
Estimated Primary Completion Date June 18, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 26, 2020)
Objective Response Rate (ORR) [ Time Frame: Up to approximately 2 years ]
ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ at any time during the trial. Responses will be determined by independent central radiologic review, with confirmatory assessment as required per RECIST 1.1. Participants with unknown or missing response information will be treated as non-responders. The percentage of participants who experience a CR or PR based on modified RECIST 1.1 will be presented.
Original Primary Outcome Measures  ICMJE
 (submitted: December 9, 2015)
Objective Response Rate (ORR) [ Time Frame: Up to 5 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 26, 2020)
  • Duration of Response (DOR) [ Time Frame: Up to approximately 2 years ]
    DOR, defined in the subset of participants with a CR or PR, based on RECIST 1.1 as assessed by independent central radiologic review, as the time from first documented evidence of CR or PR until the first documented sign of disease progression or death due to any cause, whichever occurs first. A Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. Participants who are alive, have not progressed, have not initiated new anti-cancer treatment, and have not been determined to be lost to follow-up are considered ongoing responders at the time of analysis.
  • Progression Free Survival (PFS) [ Time Frame: Up to approximately 2 years ]
    PFS is defined as the time from allocation to the first documented disease progression according to RECIST 1.1 as assessed by independent central radiologic review, or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions is also considered PD. If a participant does not have a documented date of progression or death, PFS will be censored at the date of the last adequate assessment.
  • Overall Survival (OS) [ Time Frame: Up to approximately 2 years ]
    OS was defined as the time from randomization to death due to any cause. OS is presented. Censoring will be performed using the date of last known contact for those who are alive at the time of analysis.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-158/KEYNOTE-158)
Official Title  ICMJE A Clinical Trial of Pembrolizumab (MK-3475) Evaluating Predictive Biomarkers in Subjects With Advanced Solid Tumors (KEYNOTE 158)
Brief Summary In this study, participants with multiple types of advanced (unresectable and/or metastatic) solid tumors who have progressed on standard of care therapy will be treated with pembrolizumab (MK-3475).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Cancer
  • Anal Carcinoma
  • Anal Cancer
  • Biliary Cancer
  • Cholangiocarcinoma
  • Bile Duct Cancer
  • Neuroendocrine Tumor
  • Carcinoid Tumor
  • Endometrial Carcinoma
  • Endometrial Cancer
  • Cervical Carcinoma
  • Cervical Cancer
  • Vulvar Carcinoma
  • Vulvar Cancer
  • Small Cell Lung Carcinoma
  • Small Cell Lung Cancer (SCLC)
  • Mesothelioma
  • Thyroid Carcinoma
  • Thyroid Cancer
  • Salivary Gland Carcinoma
  • Salivary Gland Cancer
  • Salivary Cancer
  • Parotid Gland Cancer
  • Advanced Solid Tumors
  • Colorectal Carcinoma
Intervention  ICMJE Biological: pembrolizumab
intravenous infusion
Other Names:
  • MK-3475
  • SCH 900475
  • KEYTRUDA®
Study Arms  ICMJE
  • Experimental: Pembrolizumab 200 mg
    Participants receive pembrolizumab 200 mg intravenously on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years of treatment).
    Intervention: Biological: pembrolizumab
  • Experimental: Pembrolizumab 400 mg
    Participants with any advanced solid tumor that has failed at least one line of therapy and is Tumor- Mutational Burden-High (TMB-H), excluding participants with mismatch repair deficient (dMMR/MSI-H) tumors. The dosing regimen for this cohort will be 400 mg every 6 weeks (Q6W) for up to 18 administrations (up to approximately 2 years of treatment).
    Intervention: Biological: pembrolizumab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 26, 2020)
1595
Original Estimated Enrollment  ICMJE
 (submitted: December 9, 2015)
1100
Estimated Study Completion Date  ICMJE June 18, 2026
Estimated Primary Completion Date June 18, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

- Histologically or cytologically-documented, advanced solid tumor of one of the following types:

  • Anal Squamous Cell Carcinoma
  • Biliary Adenocarcinoma (gallbladder or biliary tree (intrahepatic or extrahepatic cholangiocarcinoma) except Ampulla of Vater cancers)
  • Neuroendocrine Tumors (well- and moderately-differentiated) of the lung, appendix, small intestine, colon, rectum, or pancreas
  • Endometrial Carcinoma (sarcomas and mesenchymal tumors are excluded)
  • Cervical Squamous Cell Carcinoma
  • Vulvar Squamous Cell Carcinoma
  • Small Cell Lung Carcinoma
  • Mesothelioma
  • Thyroid Carcinoma
  • Salivary Gland Carcinoma (sarcomas and mesenchymal tumors are excluded)
  • Any advanced solid tumor, with the exception of colorectal carcinoma (CRC), which is Microsatellite Instability (MSI)-High (MSI-H) OR
  • Any advanced solid tumor (including Colorectal Carcinoma [CRC]) which is Mismatch Repair Deficient (dMMR)/MSI-H in participants from mainland China who are of Chinese descent. (CRC participants will have a histologically proven locally advanced unresectable or metastatic CRC which is dMMR/MSI-H that has received 2 prior lines of therapy.) OR
  • Any advanced solid tumor that has failed at least one line of therapy and is TMB-H (≥10 mut/Mb, F1CDx assay), excluding dMMR/MSI-H tumors.

Note: For participants to be eligible for enrollment they must have failed at least one line of standard of care systemic therapy (ie, not treatment naïve), with the exception of CRC participants who must have failed at least 2 lines of standard of care systemic therapy, as per CRC specific eligibility criteria. Participants must not have melanoma or NSCLC.

  • Progression of tumor or intolerance to therapies known to provide clinical benefit. There is no limit to the number of prior treatment regimens
  • Can supply tumor tissue for study analyses (dependent on tumor type)
  • Radiologically-measurable disease
  • Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale within 3 days prior to first dose of pembrolizumab
  • Life expectancy of at least 3 months
  • Adequate organ function
  • Female participants of childbearing potential must be willing to use adequate contraception for the course of the study through 120 days after the last dose of study treatment
  • Male participants with partners of must childbearing potential must be willing to use adequate contraception for the course of the study through 120 days after the last dose of study treatment

Exclusion Criteria:

  • Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study treatment
  • Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
  • Active autoimmune disease that has required systemic treatment in the past 2 years
  • Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or not recovered from an adverse event caused by mAbs administered more than 4 weeks earlier
  • Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks of study Day 1 or not recovered from adverse events caused by a previously administered agent
  • Known additional malignancy within 2 years prior to enrollment with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ cancers
  • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has known glioblastoma multiforme of the brain stem
  • History of non-infectious pneumonitis that required steroids or current pneumonitis
  • Active infection requiring systemic therapy
  • Known psychiatric or substance abuse disorders that would interfere with the participant's ability to cooperate with the requirements of the study
  • Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
  • Previously participated in any other pembrolizumab (MK-3475) study, or received prior therapy with an anti-programmed cell death (PD)-1, anti-PD-Ligand 1 (anti-PD-L1), anti-PD-Ligand 2 (anti-PD-L2), or any other immunomodulating mAb or drug specifically targeting T-cell co-stimulation or checkpoint pathways
  • Known history of Human Immunodeficiency Virus (HIV)
  • Known active Hepatitis B or C
  • Received live vaccine within 30 days of planned start of study treatment
  • Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
  • Known history of active tuberculosis (TB, Bacillus tuberculosis)
  • Has had an allogenic tissue/solid organ transplant.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Toll Free Number 1-888-577-8839
Listed Location Countries  ICMJE Japan,   Australia,   Brazil,   Canada,   China,   Colombia,   Denmark,   France,   Germany,   Israel,   Italy,   Korea, Republic of,   Mexico,   Netherlands,   Norway,   Philippines,   Russian Federation,   South Africa,   Spain,   Taiwan,   United States
Removed Location Countries United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT02628067
Other Study ID Numbers  ICMJE 3475-158
2015-002067-41 ( EudraCT Number )
163196 ( Registry Identifier: JAPIC-CTI )
MK-3475-158 ( Other Identifier: Merck )
KEYNOTE-158 ( Other Identifier: Merck )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP