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Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-028/KEYNOTE-28)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02054806
Recruitment Status : Completed
First Posted : February 4, 2014
Results First Posted : October 30, 2023
Last Update Posted : October 30, 2023
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Tracking Information
First Submitted Date  ICMJE February 3, 2014
First Posted Date  ICMJE February 4, 2014
Results First Submitted Date  ICMJE April 19, 2022
Results First Posted Date  ICMJE October 30, 2023
Last Update Posted Date October 30, 2023
Actual Study Start Date  ICMJE February 17, 2014
Actual Primary Completion Date April 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 6, 2023)		 Overall Response Rate (ORR) [ Time Frame: Up to approximately 86 months ]
Overall response rate (ORR) was defined as the percentage of participants who experienced 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) and was assessed using modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by the investigator.
Original Primary Outcome Measures  ICMJE
 (submitted: February 3, 2014)		 Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) [ Time Frame: Up to 24 monoths ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 6, 2023)
  • Number of Participants Who Experienced an Adverse Event (AE) [ Time Frame: Up to approximately 28 months ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants with at least one AE was assessed.
  • Number of Participants Who Discontinued From Study Treatment Due to an AE [ Time Frame: Up to approximately 25 months ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued treatment due to an AE was assessed.
  • Progression Free Survival (PFS) [ Time Frame: Up to approximately 86 months ]
    PFS was defined as the time from the date of allocation to the date of the first documentation of disease progression, as determined by investigator per modified RECIST 1.1 or death due to any cause (whichever occurred first). Disease progression was defined as at least 20 percent (%) increase (including an absolute increase of at least 5 millimeter [mm]) in the sum of diameter of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.
  • Overall Survival (OS) [ Time Frame: Up to approximately 86 months ]
    OS was defined as the time from the date of allocation to the date of death due to any cause. Participants who were lost to follow-up and those who were alive at the end of the trial were censored at the date of last assessment.
  • Duration of Response (DOR) [ Time Frame: Up to approximately 86 months ]
    For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per modified RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per modified RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. DOR assessments were based on investigator with confirmation. The DOR according to modified RECIST 1.1 for all participants who experienced a confirmed CR or PR was reported. Per protocol, participants were analyzed according to disease type.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 3, 2014)
  • Progression Free Survival (PFS) [ Time Frame: Up to 24 months ]
  • Overall Survival (OS) [ Time Frame: Up to 24 months ]
  • Duration of Response (DOR) in Participants Who Achieve Partial Response (PR) or Better [ Time Frame: Up to 24 months ]
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-3475-028/KEYNOTE-28)
Official Title  ICMJE Phase IB Study of Pembrolizumab (MK-3475) in Subjects With Select Advanced Solid Tumors
Brief Summary

This study will assess the efficacy and safety of pembrolizumab (MK-3475) administered to participants with incurable advanced biomarker-positive solid tumors that have not responded to current therapy or for which current therapy is not appropriate.

The study hypothesis is that administration of pembrolizumab to participants with some types of solid tumors will result in a clinically meaningful response rate.
Detailed Description Qualified participants who complete up to ~2 years of pembrolizumab treatment but progress after discontinuation may be eligible for a second course of pembrolizumab for up to ~1 additional year, at the Investigator's discretion. Per protocol, response or progression during this second course will not count towards efficacy outcome measures and adverse events during this second course will not count towards safety outcome measures.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumor
Intervention  ICMJE Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Study Arms  ICMJE Experimental: Pembrolizumab
Participants receive pembrolizumab 10 mg/kg, intravenously (IV), once every 2 weeks (Q2W) for up to ~2 years
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 Completed
Actual Enrollment  ICMJE
 (submitted: August 12, 2016)		 477
Original Estimated Enrollment  ICMJE
 (submitted: February 3, 2014)		 320
Actual Study Completion Date  ICMJE April 30, 2021
Actual Primary Completion Date April 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically documented locally-advanced and/or metastatic solid malignancy that is incurable, and has failed prior standard therapy or for which standard therapy is not appropriate
  • Have biomarker-positive solid tumor
  • Have measurable disease based on Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
  • Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1
  • Adequate organ function
  • Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication
  • Male participants of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study medication through 120 days after the last dose of study medication

Exclusion Criteria:

  • Is 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 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 trial treatment
  • Prior anti-cancer therapy with a monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or not recovered from adverse events due to mAbs administered more than 4 weeks earlier
  • Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks (12 weeks for measurable sites of central nervous system [CNS] disease) prior to study Day 1 or not recovered from adverse events due to a previously administered agent
  • Known additional malignancy that is progressing or requires active treatment excepting basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer
  • Known active CNS metastases and/or carcinomatous meningitis
  • Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Has evidence of interstitial lung disease or a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
  • Active infection requiring systemic therapy
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Has previously participated in any other pembrolizumab (MK-3475) trial, or received prior therapy with an anti-PD-1, anti-PD-L1, and anti-PD-L2 (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
  • Known history of human immunodeficiency virus (HIV)
  • Known active Hepatitis B or Hepatitis C
  • Has received a live vaccine within 30 days of planned start of study medication. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist®) are live attenuated vaccines and are not allowed.
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 information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Canada,   France,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Spain,   Taiwan,   United Kingdom,   United States
 
Administrative Information
NCT Number  ICMJE NCT02054806
Other Study ID Numbers  ICMJE 3475-028
142515 ( Registry Identifier: JAPIC-CTI )
MK-3475-028 ( Other Identifier: Merck )
KEYNOTE-28 ( Other Identifier: Merck )
2013-004507-39 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
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
Current Responsible Party Merck Sharp & Dohme LLC
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Merck Sharp & Dohme LLC
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme LLC
PRS Account Merck Sharp & Dohme LLC
Verification Date February 2023

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