Back to resultsPembrolizumab (MK-3475) Versus Standard Treatment for Recurrent or Metastatic Head and Neck Cancer (MK-3475-040/KEYNOTE-040)
Primary Purpose
Head and Neck Squamous Cell Cancer
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Pembrolizumab
Methotrexate
Docetaxel
Cetuximab
Sponsored by
About this trial
This is an interventional treatment trial for Head and Neck Squamous Cell Cancer focused on measuring Squamous cell carcinoma, Head and neck carcinoma, Programmed Cell Death-1 (PD1, PD-1),, Programmed Death-Ligand 1 (PDL1, PD-L1), Programmed Cell Death Receptor Ligand 2 (PDL2, PD-L2)
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Pembroliziumab
Standard Treatment
Arm Description
Participants will receive pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle for up to approximately 24 months. Eligible participants who stop pembrolizumab with Stable Disease (SD) or better but progress after discontinuation may be able to initiate a second course of pembrolizumab for up to approximately 1 additional year at the investigator's discretion.
Participants will receive standard treatment of either 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.
Outcomes
Primary Outcome Measures
Initial Overall Survival (OS) for All Participants
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
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 were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Secondary Outcome Measures
OS for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Expression Defined by ≥1% Combined Positive Score (CPS)(PD-L1 ≥1% CPS)
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 censored at the date of the last follow-up. The OS for all participants with PD-L1 expression ≥1% CPS was presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off 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
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 were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
PFS Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
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 were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Objective Response Rate (ORR) Per RECIST 1.1 in All Participants
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 were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
ORR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
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 were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Duration of Response (DOR) Per RECIST 1.1 in All Participants
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 were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
DOR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
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 were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Time to Progression (TTP) Per RECIST 1.1 in All Participants
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 were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
TTP Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
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 were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
PFS Per Modified RECIST in All Participants
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 were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
PFS Per Modified RECIST 1.1 in Participants With PD-L1 ≥1% CPS
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 were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Number of Participants Who Experienced At Least One Adverse Event (AE) in All Participants
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
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
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 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
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 discontinued study treatment due to an AE is presented.
Full Information
NCT ID
NCT02252042
First Posted
September 25, 2014
Last Updated
June 30, 2023
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT02252042
Brief Title
Pembrolizumab (MK-3475) Versus Standard Treatment for Recurrent or Metastatic Head and Neck Cancer (MK-3475-040/KEYNOTE-040)
Official Title
A Phase III Randomized Trial of MK-3475 (Pembrolizumab) Versus Standard Treatment in Subjects With Recurrent or Metastatic Head and Neck Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
November 17, 2014 (Actual)
Primary Completion Date
May 15, 2017 (Actual)
Study Completion Date
August 15, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Squamous Cell Cancer
Keywords
Squamous cell carcinoma, Head and neck carcinoma, Programmed Cell Death-1 (PD1, PD-1),, Programmed Death-Ligand 1 (PDL1, PD-L1), Programmed Cell Death Receptor Ligand 2 (PDL2, PD-L2)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
495 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pembroliziumab
Arm Type
Experimental
Arm Description
Participants will receive pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle for up to approximately 24 months. Eligible participants who stop pembrolizumab with Stable Disease (SD) or better but progress after discontinuation may be able to initiate a second course of pembrolizumab for up to approximately 1 additional year at the investigator's discretion.
Arm Title
Standard Treatment
Arm Type
Active Comparator
Arm Description
Participants will receive standard treatment of either 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.
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
MK-3475, KEYTRUDA®
Intervention Description
200 mg intravenous (IV) on Day 1 of each 3-week cycle.
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Intervention Description
75 mg/m^2 IV on Day 1 of each 3- week cycle
Intervention Type
Biological
Intervention Name(s)
Cetuximab
Intervention Description
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 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
Primary Outcome Measure Information:
Title
Initial Overall Survival (OS) for All Participants
Description
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.
Time Frame
Up to approximately 2 years
Title
Updated Final OS for All Participants
Description
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 were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Time Frame
Up to approximately 2 years
Secondary Outcome Measure Information:
Title
OS for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Expression Defined by ≥1% Combined Positive Score (CPS)(PD-L1 ≥1% CPS)
Description
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 censored at the date of the last follow-up. The OS for all participants with PD-L1 expression ≥1% CPS was presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Time Frame
Up to approximately 2 years
Title
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 for All Participants
Description
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 were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Time Frame
Up to approximately 2 years
Title
PFS Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
Description
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 were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Time Frame
Up to approximately 2 years
Title
Objective Response Rate (ORR) Per RECIST 1.1 in All Participants
Description
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 were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Time Frame
Up to approximately 2 years
Title
ORR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
Description
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 were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Time Frame
Up to approximately 2 years
Title
Duration of Response (DOR) Per RECIST 1.1 in All Participants
Description
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 were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Time Frame
Up to approximately 2 years
Title
DOR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
Description
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 were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Time Frame
Up to approximately 2 years
Title
Time to Progression (TTP) Per RECIST 1.1 in All Participants
Description
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 were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Time Frame
Up to approximately 2 years
Title
TTP Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
Description
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 were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Time Frame
Up to approximately 2 years
Title
PFS Per Modified RECIST in All Participants
Description
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 were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Time Frame
Up to approximately 2 years
Title
PFS Per Modified RECIST 1.1 in Participants With PD-L1 ≥1% CPS
Description
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 were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
Time Frame
Up to approximately 2 years
Title
Number of Participants Who Experienced At Least One Adverse Event (AE) in All Participants
Description
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.
Time Frame
Up to approximately 33 months
Title
Number of Participants Who Experienced At Least One AE in Participants With PD-L1 ≥1% CPS
Description
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.
Time Frame
Up to approximately 33 months
Title
Number of Participants Who Discontinued Study Treatment Due to an AE in All Participants
Description
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 discontinued study treatment due to an AE is presented.
Time Frame
Up to approximately 30 months
Title
Number of Participants Who Discontinued Study Treatment Due to an AE in Participants With PD-L1 ≥1% CPS
Description
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 discontinued study treatment due to an AE is presented.
Time Frame
Up to approximately 30 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
33371020
Citation
Xin W, Ding H, Fang Q, Zheng X, Tong Y, Xu G, Yang G. Cost-effectiveness of pembrolizumab for treatment of platinum-resistant recurrent or metastatic head and neck squamous cell carcinoma in China: an economic analysis based on a randomised, open-label, phase III trial. BMJ Open. 2020 Dec 18;10(12):e038867. doi: 10.1136/bmjopen-2020-038867.
Results Reference
derived
PubMed Identifier
33239737
Citation
Emancipator K, Huang L, Aurora-Garg D, Bal T, Cohen EEW, Harrington K, Soulieres D, Le Tourneau C, Licitra L, Burtness B, Swaby R. Comparing programmed death ligand 1 scores for predicting pembrolizumab efficacy in head and neck cancer. Mod Pathol. 2021 Mar;34(3):532-541. doi: 10.1038/s41379-020-00710-9. Epub 2020 Nov 25.
Results Reference
derived
PubMed Identifier
30944020
Citation
Pai SI, Faivre S, Licitra L, Machiels JP, Vermorken JB, Bruzzi P, Gruenwald V, Giglio RE, Leemans CR, Seiwert TY, Soulieres D. Comparative analysis of the phase III clinical trials of anti-PD1 monotherapy in head and neck squamous cell carcinoma patients (CheckMate 141 and KEYNOTE 040). J Immunother Cancer. 2019 Apr 3;7(1):96. doi: 10.1186/s40425-019-0578-0.
Results Reference
derived
PubMed Identifier
30509740
Citation
Cohen EEW, Soulieres D, Le Tourneau C, Dinis J, Licitra L, Ahn MJ, Soria A, Machiels JP, Mach N, Mehra R, Burtness B, Zhang P, Cheng J, Swaby RF, Harrington KJ; KEYNOTE-040 investigators. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet. 2019 Jan 12;393(10167):156-167. doi: 10.1016/S0140-6736(18)31999-8. Epub 2018 Nov 30. Erratum In: Lancet. 2019 Jan 12;393(10167):132.
Results Reference
derived
PubMed Identifier
25979390
Citation
Guo T, Califano JA. Molecular biology and immunology of head and neck cancer. Surg Oncol Clin N Am. 2015 Jul;24(3):397-407. doi: 10.1016/j.soc.2015.03.002. Epub 2015 Apr 20.
Results Reference
derived
Links:
URL
https://www.merckclinicaltrials.com/
Description
Merck Clinical Trials Information
Learn more about this trial
Pembrolizumab (MK-3475) Versus Standard Treatment for Recurrent or Metastatic Head and Neck Cancer (MK-3475-040/KEYNOTE-040)
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