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Trial record 1 of 1 for:    KEYNOTE-040
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Pembrolizumab (MK-3475) Versus Standard Treatment for Recurrent or Metastatic Head and Neck Cancer (MK-3475-040/KEYNOTE-040)

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: NCT02252042
Recruitment Status : Active, not recruiting
First Posted : September 29, 2014
Results First Posted : August 13, 2018
Last Update Posted : July 29, 2021
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE September 25, 2014
First Posted Date  ICMJE September 29, 2014
Results First Submitted Date  ICMJE May 4, 2018
Results First Posted Date  ICMJE August 13, 2018
Last Update Posted Date July 29, 2021
Actual Study Start Date  ICMJE November 17, 2014
Actual Primary Completion Date May 15, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 10, 2018)
  • Initial Overall Survival (OS) for All Participants [ Time Frame: Up to approximately 2 years (Database lock on 04-Jun-2017) ]
    OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. The OS for all participants is presented. These initial OS results are based on a data cutoff date of 15-May-2017 with a database lock date of 04-Jun-2017. At the time of the database lock of 04-Jun-2017, there was incomplete collection of survival data for 12 participants.
  • Updated Final OS for All Participants [ Time Frame: Up to approximately 2 years (Database update on 13-Oct-2017) ]
    OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. The updated OS for all participants is presented. These OS results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
Original Primary Outcome Measures  ICMJE
 (submitted: September 25, 2014)
  • Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) for All Participants [ Time Frame: Up to 2 years ]
  • Overall Survival (OS) for All Participants [ Time Frame: Up to 2 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 10, 2018)
  • OS for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Expression Defined by ≥1% Combined Positive Score (CPS)(PD-L1 ≥1% CPS) [ Time Frame: Up to approximately 2 years ]
    OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis will be censored at the date of the last follow-up. The OS for all participants with PD-L1 expression ≥1% CPS is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
  • Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 for All Participants [ Time Frame: Up to approximately 2 years ]
    PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease 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. Note: The appearance of one or more new lesions was also considered progression. The PFS per RECIST 1.1 for all participants is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
  • PFS Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS [ Time Frame: Up to approximately 2 years ]
    PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease 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. Note: The appearance of one or more new lesions was also considered progression. The PFS per RECIST 1.1 for all participants with PD-L1 expression ≥1% CPS is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
  • Objective Response Rate (ORR) Per RECIST 1.1 in All Participants [ Time Frame: Up to approximately 2 years ]
    ORR was defined as the percentage of the participants in the analysis population who had 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 based on blinded central imaging vendor review with or without confirmation. The ORR per RECIST 1.1 for all participants is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
  • ORR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS [ Time Frame: Up to approximately 2 years ]
    ORR was defined as the percentage of the participants in the analysis population who had 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 based on blinded central imaging vendor review with or without confirmation. The ORR per RECIST 1.1 for all participants with PD-L1 expression ≥1% CPS is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
  • Duration of Response (DOR) Per RECIST 1.1 in All Participants [ Time Frame: Up to approximately 2 years ]
    For participants who demonstrated a confirmed CR or PR per RECIST 1.1, DOR was defined as the time from first documented evidence of a confirmed CR or PR per RECIST 1.1 until disease progression per RECIST 1.1 or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease 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. Note: The appearance of one or more new lesions was also considered progression. DOR assessments were based on blinded central imaging vendor review with confirmation. The DOR per RECIST 1.1 for all participants who experienced a confirmed CR or PR is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
  • DOR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS [ Time Frame: Up to approximately 2 years ]
    For participants who demonstrated a confirmed CR or PR per RECIST 1.1, DOR was defined as the time from first documented evidence of a confirmed CR or PR per RECIST 1.1 until disease progression per RECIST 1.1 or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease 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. Note: The appearance of one or more new lesions was also considered progression. DOR assessments were based on blinded central imaging vendor review with confirmation. The DOR per RECIST 1.1 for all participants with PD-L1 ≥1% CPS who experienced a confirmed CR or PR is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
  • Time to Progression (TTP) Per RECIST 1.1 in All Participants [ Time Frame: Up to approximately 2 years ]
    TTP was defined as the time from randomization to the first documented disease progression based on assessments by the blinded central imaging vendor review per RECIST 1.1. Per RECIST 1.1, progressive disease 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. Note: The appearance of one or more new lesions was also considered progression. The TTP per RECIST 1.1 for all participants is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
  • TTP Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS [ Time Frame: Up to approximately 2 years ]
    TTP was defined as the time from randomization to the first documented disease progression based on assessments by the blinded central imaging vendor review per RECIST 1.1. Per RECIST 1.1, progressive disease 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. Note: The appearance of one or more new lesions was also considered progression. The TTP per RECIST 1.1 for all participants with PD-L1 ≥1% CPS is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
  • PFS Per Modified RECIST in All Participants [ Time Frame: Up to approximately 2 years ]
    PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥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 ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. Modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (>4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1. The PFS per modified RECIST for all participants is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
  • PFS Per Modified RECIST 1.1 in Participants With PD-L1 ≥1% CPS [ Time Frame: Up to approximately 2 years ]
    PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥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 ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. Modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (>4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1. The PFS per modified RECIST for all participants with PD-L1 ≥1% CPS is presented. These efficacy results are after complete acquisition of all outstanding survival data using a 15-May-2017 data cutoff date with a database update date of 13-Oct-2017.
  • Number of Participants Who Experienced At Least One Adverse Event (AE) in All Participants [ Time Frame: Up to approximately 27 months ]
    An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants who experienced at least one AE is presented.
  • Number of Participants Who Experienced At Least One AE in Participants With PD-L1 ≥1% CPS [ Time Frame: Up to approximately 27 months ]
    An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants with PD-L1 ≥1% CPS who experienced at least one AE is presented.
  • Number of Participants Who Discontinued Study Treatment Due to an AE in All Participants [ Time Frame: Up to approximately 2 years ]
    The number of all participants who discontinued study treatment due to an AE is presented.
  • Number of Participants Who Discontinued Study Treatment Due to an AE in Participants With PD-L1 ≥1% CPS [ Time Frame: Up to approximately 2 years ]
    The number of all participants with PD-L1 ≥1% CPS who discontinued study treatment due to an AE is presented.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 25, 2014)
  • PFS per Modified RECIST 1.1 for All Participants [ Time Frame: Up to 2 years ]
  • Objective Response Rate (ORR) per RECIST 1.1 for All Participants [ Time Frame: Up to 2 years ]
  • ORR per Modified RECIST 1.1 for All Participants [ Time Frame: Up to 2 years ]
  • PFS per RECIST 1.1 in Programmed Cell Death Ligand 1 (PD-L1)-Positive Participants [ Time Frame: Up to 2 years ]
  • OS in PD-L1-Positive Participants [ Time Frame: Up to 2 years ]
  • ORR in PD-L1-Positive Participants [ Time Frame: Up to 2 years ]
  • Time to First Grade 3-5 Adverse Event (AE) [ Time Frame: Up to 2 years ]
  • Percentage of Participants Experiencing Grade 3-5 AEs [ Time Frame: Up to 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pembrolizumab (MK-3475) Versus Standard Treatment for Recurrent or Metastatic Head and Neck Cancer (MK-3475-040/KEYNOTE-040)
Official Title  ICMJE A Phase III Randomized Trial of MK-3475 (Pembrolizumab) Versus Standard Treatment in Subjects With Recurrent or Metastatic Head and Neck Cancer
Brief Summary This is a study of pembrolizumab (MK-3475, KEYTRUDA®) versus standard treatment (methotrexate, docetaxel or cetuximab) for the treatment of recurrent or metastatic head and neck squamous cell cancer (HNSCC). Participants will be randomly assigned to receive either pembrolizumab or Investigator's choice of standard treatment. The primary study hypothesis is that pembrolizumab treatment prolongs Overall Survival (OS) when compared to standard treatment.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Head and Neck Squamous Cell Cancer
Intervention  ICMJE
  • Biological: pembrolizumab
    Other Names:
    • MK-3475
    • KEYTRUDA®
  • Drug: methotrexate
  • Drug: docetaxel
  • Biological: cetuximab
Study Arms  ICMJE
  • Experimental: Pembroliziumab
    Participants receive pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle.
    Intervention: Biological: pembrolizumab
  • Active Comparator: Active Comparator
    Participants receive methotrexate 40 mg/m^2 IV (may be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
    Interventions:
    • Drug: methotrexate
    • Drug: docetaxel
    • Biological: cetuximab
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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 14, 2017)
495
Original Estimated Enrollment  ICMJE
 (submitted: September 25, 2014)
466
Estimated Study Completion Date  ICMJE August 15, 2022
Actual Primary Completion Date May 15, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Has histologically- or cytologically-confirmed recurrent disease not amenable to curative treatment with local or systemic therapy, or metastatic (disseminated) head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx that is considered incurable by local therapies
  • Failure of prior platinum therapy
  • Radiographically-measurable disease based on RECIST 1.1
  • Tumor tissue available for PD-L1 biomarker analysis
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Adequate organ function
  • Female participants of childbearing potential must be willing to use 2 methods of birth control or abstain from heterosexual activity for the course of the study through 120 days after last dose of pembrolizumab or through 120-180 days after the last dose of docetaxel, methotrexate or cetuximab, acccording to local standard of care
  • Male participants must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after last dose of pembrolizumab or through 120-180 days after the last dose of docetaxel, methotrexate or cetuximab, acccording to local standard of care

Exclusion Criteria

  • Disease is suitable for local therapy administered with curative intent
  • Currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks prior to randomization
  • Previously treated with 3 or more systemic regimens given for recurrent and/or metastatic disease
  • 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 therapy
  • Not recovered from adverse events due to therapy more than 4 weeks earlier
  • Prior anti-cancer monoclonal antibody (mAb) therapy within 4 weeks prior to study Day 1, or not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1
  • Diagnosed and/or treated additional malignancy within 5 years of randomization, with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin, and/or curatively-resected in situ cervical and/or breast cancers
  • Active autoimmune disease that has required systemic therapy in the past 2 years with modifying agents, corticosteroids, or immunosuppressive agents
  • Active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Active, non-infectious pneumonitis
  • Active infection requiring systemic therapy
  • Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial therapy according to local standard of care
  • Prior therapy with an anti-PD-1 or anti-PD1-L1 or -L2 therapy or previously participated in a Merck pembrolizumab (MK-3475) trial
  • Human immunodeficiency virus (HIV)
  • Hepatitis B or C
  • Live vaccine within 30 days of planned start of study therapy
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 Australia,   Belgium,   Canada,   France,   Germany,   Hungary,   Ireland,   Italy,   Korea, Republic of,   Lithuania,   Mexico,   Netherlands,   Poland,   Portugal,   Puerto Rico,   Russian Federation,   Spain,   Sweden,   Switzerland,   United Kingdom,   United States
 
Administrative Information
NCT Number  ICMJE NCT02252042
Other Study ID Numbers  ICMJE 3475-040
2014-001749-26 ( EudraCT Number )
MK-3475-040 ( Other Identifier: Merck Protocol Number )
Has Data Monitoring Committee Yes
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 July 2021

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