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

April 4, 2024 updated by: Merck Sharp & Dohme LLC

A Clinical Trial of Pembrolizumab (MK-3475) Evaluating Predictive Biomarkers in Subjects With Advanced Solid Tumors (KEYNOTE 158)

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

1609

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Toll Free Number
  • Phone Number: 1-888-577-8839

Study Locations

  • Australia
      • North Ryde, Australia
        • Recruiting
        • MSD Australia
        • Contact:
          • Australian Medical Information Centre
          • Phone Number: 61 2 8988 8428
  • Brazil
      • Sao Paulo, Brazil
        • Recruiting
        • MSD Brasil
        • Contact:
          • MSD Online
          • Phone Number: 0800 012 22 32
  • Canada
    • Quebec
      • Kirkland, Quebec, Canada, H9H 4M7
        • Recruiting
        • Merck Canada
        • Contact:
          • Medical Information Centre Centre d'information medicale Merck Canada Inc.
          • Phone Number: 514-428-8600 / 1-800-567-2594
  • Chile
      • Santiago, Chile
        • Recruiting
        • Merck Sharp & Dohme (I.A.) Corp.
        • Contact:
          • Maria Elena Azara Hernandez
          • Phone Number: 56 2 6558958
  • Colombia
      • Bogota, Colombia
        • Recruiting
        • MDS Colombia SAS
        • Contact:
          • Francesca Carvajal
          • Phone Number: 57 1219109011090
  • Denmark
      • Glostrup, Denmark
        • Recruiting
        • MSD Denmark
        • Contact:
          • Artur Fijolek
          • Phone Number: 45 21387145
  • France
      • Paris, France
        • Recruiting
        • MSD France
        • Contact:
          • Dominique Blazy
          • Phone Number: 33 147548990
  • Germany
      • Haar, Germany
        • Recruiting
        • MSD Sharp & Dohme GmbH
        • Contact:
          • German Medical Information Center
          • Phone Number: 49 800 673 673 673
  • Israel
      • Hod Hasharon, Israel
        • Recruiting
        • Merck Sharp & Dohme Co. Ltd.
        • Contact:
          • Gally Teper
          • Phone Number: 972-9-9533310
  • Italy
      • Rome, Italy
        • Recruiting
        • MSD Italia S.r.l.
        • Contact:
          • Barbara Capaccetti
          • Phone Number: 39 06361911
  • Korea, Republic of
      • Seoul, Korea, Republic of, 4130
        • Recruiting
        • MSD Korea LTD
        • Contact:
          • Jongho Ahn
          • Phone Number: 82-2-331-2000 2015
  • Mexico
      • Mexico City, Mexico
        • Recruiting
        • MSD
        • Contact:
          • Juan Marques
          • Phone Number: 52 55254819608
  • Netherlands
      • Haarlem, Netherlands
        • Recruiting
        • Merck Sharp & Dohme BV
        • Contact:
          • Caroline Doornebos
          • Phone Number: 31 23 515 3362
  • Norway
      • Drammen, Norway
        • Recruiting
        • MSD Norge A/S
        • Contact:
          • Tony Johansson
          • Phone Number: 47 32 20 75 20
  • Peru
      • Lima, Peru
        • Recruiting
        • Merck Sharp & Dohme, Peru S.R.L.
        • Contact:
          • Oscar Espinoza
          • Phone Number: (51-1) 411-5100
  • Philippines
      • Makati, Philippines
        • Recruiting
        • Merck Sharp & Dohme (I.A.) Corporation
        • Contact:
          • Cesar Recto
          • Phone Number: 632 784 9500
  • Poland
      • Warsaw, Poland
        • Recruiting
        • MSD Polska Sp. Z o.o.
        • Contact:
          • Thomas Johansson
          • Phone Number: 48 22ý478 43 24
  • Portugal
      • Paco D'arcos, Portugal
        • Recruiting
        • Merck Sharp & Dohme Lda.
        • Contact:
          • Paula Martins de Jesus
          • Phone Number: 00351-214465803
  • Russian Federation
      • Moscow, Russian Federation
        • Recruiting
        • Merck Sharp & Dohme IDEA, Inc.
        • Contact:
          • Tatiana Serebriakova
          • Phone Number: 74959167100, EXT.366
  • South Africa
      • Midrand, South Africa
        • Recruiting
        • MSD (Pty) LTD South Africa
        • Contact:
          • Khanyi Mzolo
          • Phone Number: 27 11 655 3140
  • Spain
      • Madrid, Spain
        • Recruiting
        • Merck Sharp and Dohme de Espana S.A.
        • Contact:
          • Lourdes Lopez-Bravo
          • Phone Number: (0034) 913210654
  • Taiwan
      • Taipei, Taiwan
        • Recruiting
        • Merck Sharp & Dohme (I.A.) Corp.
        • Contact:
          • I-Hua Su
          • Phone Number: 886-2-66316000
  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Call for Information (Investigational Site 0010)
    • New Jersey
      • New Brunswick, New Jersey, United States, 08903
        • Recruiting
        • Call for Information (Investigational Site 0008)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The length of time required to continue contraception for each study intervention is as follows: MK-3475 (120 days)

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
  • Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pembrolizumab 200 mg
Participants will 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).
Biological: pembrolizumab
intravenous infusion
Other Names:
  • MK-3475
  • SCH 900475
  • KEYTRUDA®
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).
Biological: pembrolizumab
intravenous infusion
Other Names:
  • MK-3475
  • SCH 900475
  • KEYTRUDA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: Up to approximately 10.5 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.
Up to approximately 10.5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants with Adverse Events (AEs)
Time Frame: Up to approximately 27 months
An adverse event (AE) is defined as any untoward medical occurrence in a study participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this intervention. The percentage of participants with AEs will be reported.
Up to approximately 27 months
Percentage of Participants who Discontinue Study Intervention due to AEs
Time Frame: Up to approximately 2 years
An AE is defined as any untoward medical occurrence in a study participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The percentage of participants who discontinue study intervention due to AEs will be reported.
Up to approximately 2 years
Duration of Response (DOR)
Time Frame: Up to approximately 10.5 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.
Up to approximately 10.5 years
Progression Free Survival (PFS)
Time Frame: Up to approximately 10.5 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, progressive disease (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.
Up to approximately 10.5 years
Overall Survival (OS)
Time Frame: Up to approximately 10.5 years
OS is defined as the time from randomization to death due to any cause. OS will be presented. Censoring will be performed using the date of last known contact for those who are alive at the time of analysis.
Up to approximately 10.5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Investigators

  • Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 18, 2015

Primary Completion (Estimated)

October 2, 2026

Study Completion (Estimated)

October 2, 2026

Study Registration Dates

First Submitted

December 9, 2015

First Submitted That Met QC Criteria

December 9, 2015

First Posted (Estimated)

December 11, 2015

Study Record Updates

Last Update Posted (Actual)

April 5, 2024

Last Update Submitted That Met QC Criteria

April 4, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3475-158
  • 163196 (Registry Identifier: JAPIC-CTI)
  • MK-3475-158 (Other Identifier: Merck)
  • KEYNOTE-158 (Other Identifier: Merck)
  • 2022-500397-34-00 (Registry Identifier: EU CT)
  • 2015-002067-41 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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