Safety and Efficacy Study of Pembrolizumab (MK-3475) in Chinese Participants With Locally Advanced or Metastatic Melanoma (MK-3475-151/KEYNOTE-151)

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02821000
Collaborator
(none)
103
1
76.7

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety, tolerability, and objective response rate (ORR) of pembrolizumab (MK-3475) in Chinese participants with locally advanced or metastatic melanoma, with disease progression following first line chemotherapy or targeted therapy. ORR will be based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

With Amendment 6 (effective date 18-Mar-2022), once the study objectives have been met or the study has ended, participants will be discontinued from this study and may be enrolled in an extension study to continue protocol-defined assessments and treatment.

Condition or Disease Intervention/Treatment Phase
  • Biological: Pembrolizumab
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
103 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase Ib Study of Pembrolizumab (MK-3475) in Chinese Subjects With Locally Advanced or Metastatic Melanoma (Keynote-151)
Actual Study Start Date :
Jul 8, 2016
Actual Primary Completion Date :
Dec 27, 2017
Anticipated Study Completion Date :
Nov 30, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Pembrolizumab

Participants receive pembrolizumab 2 mg/kg intravenously on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).

Biological: Pembrolizumab
Intravenous infusion
Other Names:
  • MK-3475
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participants Who Experienced At Least One Adverse Event (AE) [Up to approximately 17 months (through data cutoff date of 27-December-2017)]

      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. These safety results are based on a 27- Dec-2017 data cutoff date.

    2. Number of Participants Who Discontinued Study Treatment Due to an AE [Up to approximately 17 months (through data cutoff date of 27-December-2017)]

      The number of all participants who discontinued study treatment due to an AE is presented. These results are based on a 27- Dec-2017 data cutoff date.

    3. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [Up to approximately 17 months (through data cutoff date of 27-December-2017)]

      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 assessed by blinded independent central review (BICR). The ORR per RECIST 1.1 for participants is presented. Participants without response data were treated as non-responders. ORR was analyzed using an exact method based on binomial distribution (Clopper-Pearson method) and is reported as percentage of participants. These efficacy results are based on a 27- Dec-2017 data cutoff date.

    Secondary Outcome Measures

    1. Overall Survival (OS) [Up to approximately 17 months (through data cutoff date of 27-December-2017)]

      OS was defined as the time from randomization to death due to any cause. OS was analyzed using the Kaplan-Meier method and is reported in months. The OS for participants is presented. These efficacy results are based on a 27-Dec-2017 data cutoff date.

    2. Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [Up to approximately 17 months (through data cutoff date of 27-December-2017)]

      PFS was defined as the time from the first day of study treatment to the first documented disease progression per RECIST 1.1 based on blinded independent central review (BICR) or death due to any cause, whichever occurred first. Using RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. PFS was analyzed using the Kaplan-Meier method and is reported in months. The PFS per RECIST 1.1 for participants is presented. These efficacy results are based on a 27-Dec-2017 data cutoff date.

    3. Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [Up to approximately 17 months (through data cutoff date of 27-December-2017)]

      DOR was defined as the time from first documented evidence of 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 until disease progression or death due to any cause, whichever occurred first. Using RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must have demonstrated an absolute increase of at least 5 mm. DOR assessments were based on blinded independent central review (BICR). DOR was analyzed using the Kaplan-Meier method and is reported in months. DOR for participants who experienced a confirmed CR or PR is presented. These efficacy results are based on a 27-Dec-2017 data cutoff date.

    4. Objective Response Rate (ORR) Per Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) [Up to approximately 17 months (through data cutoff date of 27-December-2017)]

      ORR was defined as the percentage of the participants in the analysis population who had a Complete Response (CR: disappearance of all lesions and no new lesions confirmed by a consecutive assessment at least 4 weeks after first documentation) or a Partial Response (PR: at least a 50% decrease in tumor burden relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation) per irRECIST assessed by blinded independent central review (BICR). The ORR per irRECIST for participants is presented. Participants without response data were treated as non-responders. ORR was analyzed using an exact method based on binomial distribution (Clopper-Pearson method) and is reported as percentage of participants. These efficacy results are based on a 27-Dec-2017 data cutoff date.

    5. Progression-free Survival (PFS) Per Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) [Up to approximately 17 months (through data cutoff date of 27-December-2017)]

      PFS was defined as the time from the first day of study treatment to the first documented disease progression per irRECIST based on blinded independent central review (BICR) or death due to any cause, whichever occurred first. Using irRECIST, progressive disease was defined as at least a 25% increase in tumor burden relative the minimum recorded tumor burden confirmed by a consecutive assessment at least 4 weeks after first documentation. PFS was analyzed using the Kaplan-Meier method and is reported in months. The PFS per irRECIST for participants is presented. These efficacy results are based on a 27-Dec-2017 data cutoff date.

    6. Duration of Response (DOR) by Immune-related Response Evaluation Criteria in Solid Tumors Version (irRECIST) [Up to approximately 17 months (through data cutoff date of 27-December-2017)]

      DOR was defined as the time from first documented evidence of Complete Response (CR: disappearance of all lesions and no new lesions confirmed by a consecutive assessment at least 4 weeks after first documentation) or Partial Response (PR: at least a 50% decrease in tumor burden relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation) per irRECIST until disease progression or death due to any cause, whichever occurred first. Using irRECIST, progressive disease was defined as at least a 25% increase in tumor burden relative the minimum recorded tumor burden confirmed by a consecutive assessment at least 4 weeks after first documentation. DOR assessments were based on blinded independent central review (BICR). DOR was analyzed using the Kaplan-Meier method and is reported in months. DOR for participants who experienced a confirmed CR or PR is presented. These efficacy results are based on a 27-Dec-2017 data cutoff date.

    7. Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 2 (21-day Cycle) [Day 21: Prior to the Cycle 2 (21-day cycle) Dose]

      Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 2 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 2 is presented. These PK results are based on a 20-Jul-2017 data cutoff date.

    8. Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 4 (21-day Cycle) [Day 63: Prior to the Cycle 4 (21-day cycle) Dose]

      Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 4 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 4 is presented. These PK results are based on a 20-Jul-2017 data cutoff date.

    9. Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 6 (21-day Cycle) [Day 105: Prior to the Cycle 6 (21-day cycle) Dose]

      Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 6 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 6 is presented. These PK results are based on a 20-Jul-2017 data cutoff date.

    10. Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 8 (21-day Cycle) [Day 147: Prior to the Cycle 8 (21-day cycle) Dose]

      Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 8 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 8 is presented. These PK results are based on a 20-Jul-2017 data cutoff date.

    11. Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 12 (21-day Cycle) [Day 231: Prior to the Cycle 12 (21-day cycle) Dose]

      Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 12 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 12 is presented. These PK results are based on a 20-Jul-2017 data cutoff date.

    12. Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 16 (21-day Cycle) [Day 315: Prior to the Cycle 16 (21-day cycle) Dose]

      Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 16 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 16 is presented. These PK results are based on a 20-Jul-2017 data cutoff date.

    13. Observed Maximum Serum Concentration (Cmax) of Pembrolizumab 30 Minutes After The End of Infusion During Cycle 1 (21-day Cycle) [Day 0: 30 minutes after the end of infusion during Cycle 1 (21-day cycle)]

      Blood samples were obtained for PK analysis of the Cmax of pembrolizumab 30 minutes after the end of infusion during Cycle 1 (21-day cycle). The Cmax of pembrolizumab is presented. These PK results are based on a 20-Jul-2017 data cutoff date.

    14. Observed Maximum Serum Concentration (Cmax) of Pembrolizumab 30 Minutes After The End of Infusion During Cycle 8 (21-day Cycle) [Day 147: 30 minutes after the end of infusion during Cycle 8 (21-day cycle)]

      Blood samples were obtained for PK analysis of the Cmax of pembrolizumab 30 minutes after the end of infusion during Cycle 8 (21-day cycle). The Cmax of pembrolizumab is presented. These PK results are based on a 20-Jul-2017 data cutoff date.

    15. Observed Serum Concentration of Pembrolizumab 1 Day After The End of Infusion During Cycle 1 (21-day Cycle) [Day 2: 1 day after the end of infusion during Cycle 1 (21-day cycle)]

      Blood samples were obtained for PK analysis of the serum concentration of pembrolizumab 1 day after the end of infusion during Cycle 1 (21-day cycle). The serum concentration of pembrolizumab is presented. These PK results are based on a 20-Jul-2017 data cutoff date.

    16. Observed Serum Concentration of Pembrolizumab 5 Days After The End of Infusion During Cycle 1 (21-day Cycle) [Day 6: 5 days after the end of infusion during Cycle 1 (21-day cycle)]

      Blood samples were obtained for PK analysis of the serum concentration of pembrolizumab 5 days after the end of infusion during Cycle 1 (21-day cycle). The serum concentration of pembrolizumab is presented. These PK results are based on a 20-Jul-2017 data cutoff date.

    17. Observed Serum Concentration of Pembrolizumab 14 Days After The End of Infusion During Cycle 1 (21-day Cycle) [Day 15: 14 days after the end of infusion during Cycle 1 (21-day cycle)]

      Blood samples were obtained for PK analysis of the serum concentration of pembrolizumab 14 days after the end of infusion during Cycle 1 (21-day cycle). The serum concentration of pembrolizumab is presented. These PK results are based on a 20-Jul-2017 data cutoff date.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Is of the Chinese descent, was born in China, and has a Chinese home address.

    • Has histologically confirmed diagnosis of locally advanced (unresectable Stage III) or metastatic (Stage IV) melanoma not amenable to local therapy.

    • Participant may not have a diagnosis of uveal or ocular melanoma.

    • Overall proportion of participants with mucosa melanoma will be no more than 22%.

    • Has failed the first line chemotherapy (excluding adjuvant or neoadjuvant therapy) or targeted therapy for melanoma.

    • Has at least one measurable lesion as defined by RECIST 1.1 on imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]).

    • Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.

    • Has an anticipated life expectancy of at least 3 months.

    • Demonstrates adequate organ function.

    • Has provided tissue for anti-programmed cell death ligand-1 (PD-L1) expression evaluation from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.

    • Has documented BRAF mutation status or is willing to provide a tumor tissue for BRAF genotyping.

    • Females may be enrolled in the study if they are:

    • Of non-childbearing potential which is defined as:

    • Is ≥45 years of age and has not had menses for greater than 2 years.

    • Is amenorrheic for <2 years without a hysterectomy and oophorectomy and has a follicle stimulating hormone (FSH) value in the postmenopausal range upon screening evaluation, and/or,

    • Is status post hysterectomy, oophorectomy or tubal ligation.

    • Female and male 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 treatment. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the participant.

    Exclusion Criteria:
    • Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-PD-L1, anti-PD-L2 agents.

    • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of study drug.

    • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the first dose of study drug or who has not recovered (i.e., ≤ Grade 1 or baseline) from AEs due to agents administered more than 4 weeks earlier.

    • Has had chemotherapy, targeted small molecule therapy, radiotherapy within 2 weeks prior to the first dose of study drug, or who has not recovered (i.e., ≤ Grade 1 or baseline) from AEs due to a previously administered agent.

    • Has a known history of another (including unknown primary) malignancy within 5 years prior to first dose of study drug. (Exceptions include adequately treated Stage 1 or Stage 2 basal/squamous cell carcinoma of the skin, superficial bladder cancer, or cancer in situ which has undergone potentially curative therapy.)

    • Is expected to require any other form of systemic or localized antineoplastic therapy while in study.

    • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.

    • Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).

    • Is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 1 week prior to the first dose of study drug.

    • Has an active infection requiring intravenous systemic therapy.

    • Has received a live vaccine within 4 weeks prior to the first dose of study drug.

    • Has a known hypersensitivity to the components of the study drug or another mAb.

    • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.

    • Is known to be Human Immunodeficiency Virus (HIV) positive.

    • Has known active Hepatitis B or C.

    • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.

    • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit (Visit 1) through 120 days after the last dose of study treatment.

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Merck Sharp & Dohme LLC

    Investigators

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

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT02821000
    Other Study ID Numbers:
    • 3475-151
    • MK-3475-151
    • KEYNOTE-151
    First Posted:
    Jul 1, 2016
    Last Update Posted:
    Aug 17, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by Merck Sharp & Dohme LLC
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail This results disclosure is based on a data cutoff date of 27-December-2017 for the efficacy and safety analyses; at which time 58 participants were ongoing in the study. The data cutoff date for the pharmacokinetics analysis was 20-July-2017.
    Arm/Group Title Pembrolizumab
    Arm/Group Description Participants received pembrolizumab 2 mg/kg intravenous (IV) on Day 1 of each 21-day cycle.
    Period Title: Overall Study
    STARTED 103
    Treated 103
    COMPLETED 0
    NOT COMPLETED 103

    Baseline Characteristics

    Arm/Group Title Pembrolizumab
    Arm/Group Description Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
    Overall Participants 103
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    50.5
    (14.2)
    Sex: Female, Male (Count of Participants)
    Female
    59
    57.3%
    Male
    44
    42.7%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    103
    100%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    0
    0%
    White
    0
    0%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Programmed Cell Death-Ligand 1 (PD-L1) Expression Status (Count of Participants)
    Positive for PD-L1
    53
    51.5%
    Negative for PD-L1
    45
    43.7%
    Unknown PD-L1 Status
    5
    4.9%
    Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (Count of Participants)
    ECOG PS=0
    45
    43.7%
    ECOG PS=1
    58
    56.3%
    BRAF Mutation Expression Status (Count of Participants)
    Wild Type
    82
    79.6%
    Mutant
    20
    19.4%
    Unknown
    1
    1%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants Who Experienced At Least One Adverse Event (AE)
    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. These safety results are based on a 27- Dec-2017 data cutoff date.
    Time Frame Up to approximately 17 months (through data cutoff date of 27-December-2017)

    Outcome Measure Data

    Analysis Population Description
    The safety population consisted of all participants who received at least one dose of study treatment.
    Arm/Group Title Pembrolizumab
    Arm/Group Description Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
    Measure Participants 103
    Count of Participants [Participants]
    101
    98.1%
    2. Primary Outcome
    Title Number of Participants Who Discontinued Study Treatment Due to an AE
    Description The number of all participants who discontinued study treatment due to an AE is presented. These results are based on a 27- Dec-2017 data cutoff date.
    Time Frame Up to approximately 17 months (through data cutoff date of 27-December-2017)

    Outcome Measure Data

    Analysis Population Description
    The safety population consisted of all participants who received at least one dose of study treatment.
    Arm/Group Title Pembrolizumab
    Arm/Group Description Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
    Measure Participants 103
    Count of Participants [Participants]
    4
    3.9%
    3. Primary Outcome
    Title Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
    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 assessed by blinded independent central review (BICR). The ORR per RECIST 1.1 for participants is presented. Participants without response data were treated as non-responders. ORR was analyzed using an exact method based on binomial distribution (Clopper-Pearson method) and is reported as percentage of participants. These efficacy results are based on a 27- Dec-2017 data cutoff date.
    Time Frame Up to approximately 17 months (through data cutoff date of 27-December-2017)

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of all participants who received at least one dose of study treatment and had measurable disease at baseline.
    Arm/Group Title Pembrolizumab
    Arm/Group Description Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
    Measure Participants 102
    Number (95% Confidence Interval) [Percentage of Participants]
    16.7
    16.2%
    4. Secondary Outcome
    Title Overall Survival (OS)
    Description OS was defined as the time from randomization to death due to any cause. OS was analyzed using the Kaplan-Meier method and is reported in months. The OS for participants is presented. These efficacy results are based on a 27-Dec-2017 data cutoff date.
    Time Frame Up to approximately 17 months (through data cutoff date of 27-December-2017)

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of all participants who received at least one dose of study treatment.
    Arm/Group Title Pembrolizumab
    Arm/Group Description Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
    Measure Participants 103
    Median (95% Confidence Interval) [Months]
    12.1
    5. Secondary Outcome
    Title Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
    Description PFS was defined as the time from the first day of study treatment to the first documented disease progression per RECIST 1.1 based on blinded independent central review (BICR) or death due to any cause, whichever occurred first. Using RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. PFS was analyzed using the Kaplan-Meier method and is reported in months. The PFS per RECIST 1.1 for participants is presented. These efficacy results are based on a 27-Dec-2017 data cutoff date.
    Time Frame Up to approximately 17 months (through data cutoff date of 27-December-2017)

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of all participants who received at least one dose of study treatment and had measurable disease at baseline.
    Arm/Group Title Pembrolizumab
    Arm/Group Description Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
    Measure Participants 102
    Median (95% Confidence Interval) [Months]
    2.8
    6. Secondary Outcome
    Title Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
    Description DOR was defined as the time from first documented evidence of 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 until disease progression or death due to any cause, whichever occurred first. Using RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must have demonstrated an absolute increase of at least 5 mm. DOR assessments were based on blinded independent central review (BICR). DOR was analyzed using the Kaplan-Meier method and is reported in months. DOR for participants who experienced a confirmed CR or PR is presented. These efficacy results are based on a 27-Dec-2017 data cutoff date.
    Time Frame Up to approximately 17 months (through data cutoff date of 27-December-2017)

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of all participants who received at least one dose of study treatment, had measurable disease at baseline, and had confirmed CR or PR.
    Arm/Group Title Pembrolizumab
    Arm/Group Description Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
    Measure Participants 17
    Median (Full Range) [Months]
    8.4
    7. Secondary Outcome
    Title Objective Response Rate (ORR) Per Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
    Description ORR was defined as the percentage of the participants in the analysis population who had a Complete Response (CR: disappearance of all lesions and no new lesions confirmed by a consecutive assessment at least 4 weeks after first documentation) or a Partial Response (PR: at least a 50% decrease in tumor burden relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation) per irRECIST assessed by blinded independent central review (BICR). The ORR per irRECIST for participants is presented. Participants without response data were treated as non-responders. ORR was analyzed using an exact method based on binomial distribution (Clopper-Pearson method) and is reported as percentage of participants. These efficacy results are based on a 27-Dec-2017 data cutoff date.
    Time Frame Up to approximately 17 months (through data cutoff date of 27-December-2017)

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of all participants who received at least one dose of study treatment and had measurable disease at baseline.
    Arm/Group Title Pembrolizumab
    Arm/Group Description Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
    Measure Participants 102
    Number (95% Confidence Interval) [Percentage of Participants]
    16.7
    16.2%
    8. Secondary Outcome
    Title Progression-free Survival (PFS) Per Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
    Description PFS was defined as the time from the first day of study treatment to the first documented disease progression per irRECIST based on blinded independent central review (BICR) or death due to any cause, whichever occurred first. Using irRECIST, progressive disease was defined as at least a 25% increase in tumor burden relative the minimum recorded tumor burden confirmed by a consecutive assessment at least 4 weeks after first documentation. PFS was analyzed using the Kaplan-Meier method and is reported in months. The PFS per irRECIST for participants is presented. These efficacy results are based on a 27-Dec-2017 data cutoff date.
    Time Frame Up to approximately 17 months (through data cutoff date of 27-December-2017)

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of all participants who received at least one dose of study treatment and had measurable disease at baseline.
    Arm/Group Title Pembrolizumab
    Arm/Group Description Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
    Measure Participants 102
    Median (95% Confidence Interval) [Months]
    2.8
    9. Secondary Outcome
    Title Duration of Response (DOR) by Immune-related Response Evaluation Criteria in Solid Tumors Version (irRECIST)
    Description DOR was defined as the time from first documented evidence of Complete Response (CR: disappearance of all lesions and no new lesions confirmed by a consecutive assessment at least 4 weeks after first documentation) or Partial Response (PR: at least a 50% decrease in tumor burden relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation) per irRECIST until disease progression or death due to any cause, whichever occurred first. Using irRECIST, progressive disease was defined as at least a 25% increase in tumor burden relative the minimum recorded tumor burden confirmed by a consecutive assessment at least 4 weeks after first documentation. DOR assessments were based on blinded independent central review (BICR). DOR was analyzed using the Kaplan-Meier method and is reported in months. DOR for participants who experienced a confirmed CR or PR is presented. These efficacy results are based on a 27-Dec-2017 data cutoff date.
    Time Frame Up to approximately 17 months (through data cutoff date of 27-December-2017)

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of all participants who received at least one dose of study treatment, had measurable disease at baseline, and had confirmed CR or PR.
    Arm/Group Title Pembrolizumab
    Arm/Group Description Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
    Measure Participants 17
    Median (Full Range) [Months]
    8.4
    10. Secondary Outcome
    Title Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 2 (21-day Cycle)
    Description Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 2 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 2 is presented. These PK results are based on a 20-Jul-2017 data cutoff date.
    Time Frame Day 21: Prior to the Cycle 2 (21-day cycle) Dose

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of participants who received 1 dose of study treatment, completed Cycle 1 (21-day cycle), and had blood samples drawn for Ctrough analysis.
    Arm/Group Title Pembrolizumab
    Arm/Group Description Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
    Measure Participants 30
    Mean (Standard Deviation) [μg/mL]
    8.70
    (2.4)
    11. Secondary Outcome
    Title Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 4 (21-day Cycle)
    Description Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 4 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 4 is presented. These PK results are based on a 20-Jul-2017 data cutoff date.
    Time Frame Day 63: Prior to the Cycle 4 (21-day cycle) Dose

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of participants who received 3 doses of study treatment, completed Cycle 3 (21-day cycle), and had blood samples drawn for Ctrough analysis.
    Arm/Group Title Pembrolizumab
    Arm/Group Description Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
    Measure Participants 26
    Mean (Standard Deviation) [μg/mL]
    16.2
    (6.7)
    12. Secondary Outcome
    Title Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 6 (21-day Cycle)
    Description Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 6 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 6 is presented. These PK results are based on a 20-Jul-2017 data cutoff date.
    Time Frame Day 105: Prior to the Cycle 6 (21-day cycle) Dose

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of participants who received 5 doses of study treatment, completed Cycle 5 (21-day cycle), and had blood samples drawn for Ctrough analysis.
    Arm/Group Title Pembrolizumab
    Arm/Group Description Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
    Measure Participants 17
    Mean (Standard Deviation) [μg/mL]
    22.9
    (6.4)
    13. Secondary Outcome
    Title Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 8 (21-day Cycle)
    Description Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 8 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 8 is presented. These PK results are based on a 20-Jul-2017 data cutoff date.
    Time Frame Day 147: Prior to the Cycle 8 (21-day cycle) Dose

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of participants who received 7 doses of study treatment, completed Cycle 7 (21-day cycle), and had blood samples drawn for Ctrough analysis.
    Arm/Group Title Pembrolizumab
    Arm/Group Description Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
    Measure Participants 13
    Mean (Standard Deviation) [μg/mL]
    26.9
    (6.5)
    14. Secondary Outcome
    Title Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 12 (21-day Cycle)
    Description Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 12 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 12 is presented. These PK results are based on a 20-Jul-2017 data cutoff date.
    Time Frame Day 231: Prior to the Cycle 12 (21-day cycle) Dose

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of participants who received 11 doses of study treatment, completed Cycle 11 (21-day cycle), and had blood samples drawn for Ctrough analysis.
    Arm/Group Title Pembrolizumab
    Arm/Group Description Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
    Measure Participants 8
    Mean (Standard Deviation) [μg/mL]
    33.8
    (4.5)
    15. Secondary Outcome
    Title Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 16 (21-day Cycle)
    Description Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 16 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 16 is presented. These PK results are based on a 20-Jul-2017 data cutoff date.
    Time Frame Day 315: Prior to the Cycle 16 (21-day cycle) Dose

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of participants who received 15 doses of study treatment, completed Cycle 15 (21-day cycle), and had blood samples drawn for Ctrough analysis.
    Arm/Group Title Pembrolizumab
    Arm/Group Description Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
    Measure Participants 4
    Mean (Standard Deviation) [μg/mL]
    34.6
    (5.0)
    16. Secondary Outcome
    Title Observed Maximum Serum Concentration (Cmax) of Pembrolizumab 30 Minutes After The End of Infusion During Cycle 1 (21-day Cycle)
    Description Blood samples were obtained for PK analysis of the Cmax of pembrolizumab 30 minutes after the end of infusion during Cycle 1 (21-day cycle). The Cmax of pembrolizumab is presented. These PK results are based on a 20-Jul-2017 data cutoff date.
    Time Frame Day 0: 30 minutes after the end of infusion during Cycle 1 (21-day cycle)

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of participants who received 1 dose of study treatment in Cycle 1 (21-day cycle) and had blood samples drawn for Cmax analysis.
    Arm/Group Title Pembrolizumab
    Arm/Group Description Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
    Measure Participants 28
    Mean (Standard Deviation) [μg/mL]
    45.9
    (10.9)
    17. Secondary Outcome
    Title Observed Maximum Serum Concentration (Cmax) of Pembrolizumab 30 Minutes After The End of Infusion During Cycle 8 (21-day Cycle)
    Description Blood samples were obtained for PK analysis of the Cmax of pembrolizumab 30 minutes after the end of infusion during Cycle 8 (21-day cycle). The Cmax of pembrolizumab is presented. These PK results are based on a 20-Jul-2017 data cutoff date.
    Time Frame Day 147: 30 minutes after the end of infusion during Cycle 8 (21-day cycle)

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of participants who received 8 doses of study treatment and had blood samples drawn for Cmax analysis.
    Arm/Group Title Pembrolizumab
    Arm/Group Description Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
    Measure Participants 12
    Mean (Standard Deviation) [μg/mL]
    68.7
    (12.5)
    18. Secondary Outcome
    Title Observed Serum Concentration of Pembrolizumab 1 Day After The End of Infusion During Cycle 1 (21-day Cycle)
    Description Blood samples were obtained for PK analysis of the serum concentration of pembrolizumab 1 day after the end of infusion during Cycle 1 (21-day cycle). The serum concentration of pembrolizumab is presented. These PK results are based on a 20-Jul-2017 data cutoff date.
    Time Frame Day 2: 1 day after the end of infusion during Cycle 1 (21-day cycle)

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of participants who received 1 dose of study treatment in Cycle 1 (21-day cycle) and had blood samples drawn for serum concentration of pembrolizumab.
    Arm/Group Title Pembrolizumab
    Arm/Group Description Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
    Measure Participants 30
    Mean (Standard Deviation) [μg/mL]
    34.0
    (4.6)
    19. Secondary Outcome
    Title Observed Serum Concentration of Pembrolizumab 5 Days After The End of Infusion During Cycle 1 (21-day Cycle)
    Description Blood samples were obtained for PK analysis of the serum concentration of pembrolizumab 5 days after the end of infusion during Cycle 1 (21-day cycle). The serum concentration of pembrolizumab is presented. These PK results are based on a 20-Jul-2017 data cutoff date.
    Time Frame Day 6: 5 days after the end of infusion during Cycle 1 (21-day cycle)

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of participants who received 1 dose of study treatment in Cycle 1 (21-day cycle) and had blood samples drawn for serum concentration of pembrolizumab.
    Arm/Group Title Pembrolizumab
    Arm/Group Description Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
    Measure Participants 30
    Mean (Standard Deviation) [μg/mL]
    18.4
    (4.6)
    20. Secondary Outcome
    Title Observed Serum Concentration of Pembrolizumab 14 Days After The End of Infusion During Cycle 1 (21-day Cycle)
    Description Blood samples were obtained for PK analysis of the serum concentration of pembrolizumab 14 days after the end of infusion during Cycle 1 (21-day cycle). The serum concentration of pembrolizumab is presented. These PK results are based on a 20-Jul-2017 data cutoff date.
    Time Frame Day 15: 14 days after the end of infusion during Cycle 1 (21-day cycle)

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of participants who received 1 dose of study treatment in Cycle 1 (21-day cycle) and had blood samples drawn for serum concentration of pembrolizumab.
    Arm/Group Title Pembrolizumab
    Arm/Group Description Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
    Measure Participants 30
    Mean (Standard Deviation) [μg/mL]
    11.9
    (2.5)

    Adverse Events

    Time Frame Up to approximately 17 months through the data cutoff date of 27-December-2017.
    Adverse Event Reporting Description The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs.
    Arm/Group Title Pembrolizumab
    Arm/Group Description Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.
    All Cause Mortality
    Pembrolizumab
    Affected / at Risk (%) # Events
    Total 44/103 (42.7%)
    Serious Adverse Events
    Pembrolizumab
    Affected / at Risk (%) # Events
    Total 8/103 (7.8%)
    Cardiac disorders
    Sinus tachycardia 1/103 (1%) 1
    Hepatobiliary disorders
    Autoimmune hepatitis 1/103 (1%) 1
    Infections and infestations
    Pneumonia 1/103 (1%) 1
    Injury, poisoning and procedural complications
    Rib fracture 1/103 (1%) 1
    Metabolism and nutrition disorders
    Decreased appetite 1/103 (1%) 1
    Musculoskeletal and connective tissue disorders
    Arthritis 1/103 (1%) 1
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism 1/103 (1%) 1
    Vascular disorders
    Shock 1/103 (1%) 1
    Venous thrombosis limb 1/103 (1%) 1
    Other (Not Including Serious) Adverse Events
    Pembrolizumab
    Affected / at Risk (%) # Events
    Total 98/103 (95.1%)
    Blood and lymphatic system disorders
    Anaemia 25/103 (24.3%) 28
    Endocrine disorders
    Hyperthyroidism 6/103 (5.8%) 6
    Hypothyroidism 24/103 (23.3%) 30
    Gastrointestinal disorders
    Abdominal distension 6/103 (5.8%) 6
    Abdominal pain upper 7/103 (6.8%) 7
    Constipation 7/103 (6.8%) 8
    Diarrhoea 7/103 (6.8%) 9
    Nausea 7/103 (6.8%) 8
    Vomiting 11/103 (10.7%) 11
    General disorders
    Asthenia 8/103 (7.8%) 11
    Fatigue 16/103 (15.5%) 18
    Pyrexia 10/103 (9.7%) 12
    Infections and infestations
    Upper respiratory tract infection 14/103 (13.6%) 16
    Investigations
    Alanine aminotransferase increased 19/103 (18.4%) 24
    Aspartate aminotransferase increased 15/103 (14.6%) 19
    Bilirubin conjugated increased 9/103 (8.7%) 14
    Blood alkaline phosphatase increased 8/103 (7.8%) 9
    Blood bilirubin increased 16/103 (15.5%) 26
    Blood bilirubin unconjugated increased 6/103 (5.8%) 10
    Blood cholesterol increased 6/103 (5.8%) 11
    Blood creatine phosphokinase increased 9/103 (8.7%) 11
    Blood lactate dehydrogenase increased 16/103 (15.5%) 25
    Gamma-glutamyltransferase increased 13/103 (12.6%) 14
    Neutrophil count decreased 10/103 (9.7%) 16
    Weight decreased 11/103 (10.7%) 11
    White blood cell count decreased 13/103 (12.6%) 23
    White blood cells urine positive 7/103 (6.8%) 7
    Metabolism and nutrition disorders
    Decreased appetite 18/103 (17.5%) 19
    Hypercholesterolaemia 6/103 (5.8%) 12
    Hyperglycaemia 12/103 (11.7%) 23
    Hypertriglyceridaemia 27/103 (26.2%) 58
    Hyperuricaemia 13/103 (12.6%) 21
    Hypoalbuminaemia 9/103 (8.7%) 11
    Hyponatraemia 8/103 (7.8%) 8
    Musculoskeletal and connective tissue disorders
    Back pain 9/103 (8.7%) 9
    Pain in extremity 6/103 (5.8%) 8
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain 18/103 (17.5%) 24
    Psychiatric disorders
    Insomnia 8/103 (7.8%) 8
    Respiratory, thoracic and mediastinal disorders
    Cough 9/103 (8.7%) 10
    Dyspnoea 6/103 (5.8%) 6
    Skin and subcutaneous tissue disorders
    Pruritus 14/103 (13.6%) 16
    Rash 18/103 (17.5%) 20

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.

    Results Point of Contact

    Name/Title Senior Vice President, Global Clinical Development
    Organization Merck Sharp & Dohme LLC
    Phone 1-800-672-6372
    Email ClinicalTrialsDisclosure@merck.com
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT02821000
    Other Study ID Numbers:
    • 3475-151
    • MK-3475-151
    • KEYNOTE-151
    First Posted:
    Jul 1, 2016
    Last Update Posted:
    Aug 17, 2022
    Last Verified:
    Aug 1, 2022