Safety and Efficacy Study of Pembrolizumab (MK-3475) in Chinese Participants With Locally Advanced or Metastatic Melanoma (MK-3475-151/KEYNOTE-151)
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 |
---|---|---|
|
Phase 1 |
Study Design
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:
|
Outcome Measures
Primary Outcome Measures
- 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.
- 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.
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
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.- 3475-151
- MK-3475-151
- KEYNOTE-151
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
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%
|
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%
|
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%
|
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
|
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
|
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
|
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%
|
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
|
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
|
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)
|
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)
|
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)
|
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)
|
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)
|
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)
|
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)
|
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)
|
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)
|
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)
|
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
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 |
ClinicalTrialsDisclosure@merck.com |
- 3475-151
- MK-3475-151
- KEYNOTE-151