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Study of the Safety, Tolerability, Pharmacokinetics and Efficacy of Pembrolizumab (MK-3475) in Chinese Participants With Non-Small-Cell Lung Cancer (MK-3475-032/KEYNOTE-032)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02835690
Recruitment Status : Active, not recruiting
First Posted : July 18, 2016
Results First Posted : October 7, 2019
Last Update Posted : June 9, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Non-Small-Cell Lung Cancer
Intervention Biological: Pembrolizumab
Enrollment 44
Recruitment Details  
Pre-assignment Details Of 44 participants enrolled, 42 received treatment. As of the 19-Sept-2017 database cut-off, 26 participants were ongoing in the study for long-term safety and survival follow-up.
Arm/Group Title Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Pembrolizumab 200 mg Fixed Dose
Hide Arm/Group Description Participants receive pembrolizumab 2 mg/kg administered intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days. Participants receive pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days. Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Period Title: Overall Study
Started 14 15 15
Treated 14 13 15
Completed 0 0 0
Not Completed 14 15 15
Reason Not Completed
Death             4             6             6
Ongoing in Study (Follow-up)             10             7             9
Not Treated             0             2             0
Arm/Group Title Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Pembrolizumab 200 mg Fixed Dose Total
Hide Arm/Group Description Participants receive pembrolizumab 2 mg/kg administered intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days. Participants receive pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days. Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days. Total of all reporting groups
Overall Number of Baseline Participants 14 13 15 42
Hide Baseline Analysis Population Description
All randomized participants that received at least one dose of study treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 14 participants 13 participants 15 participants 42 participants
53.2  (9.5) 56.2  (11.5) 56.7  (8.8) 55.4  (9.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 13 participants 15 participants 42 participants
Female
5
  35.7%
4
  30.8%
6
  40.0%
15
  35.7%
Male
9
  64.3%
9
  69.2%
9
  60.0%
27
  64.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 13 participants 15 participants 42 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
14
 100.0%
13
 100.0%
15
 100.0%
42
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Chinese Number Analyzed 14 participants 13 participants 15 participants 42 participants
14 13 15 42
1.Primary Outcome
Title Number of Participants Who Experienced an Adverse Event (AE)
Hide Description An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to be a causal relationship with this treatment. An AE could therefore be any unfavourable 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 medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants who experienced at least one AE was reported.
Time Frame Up to ~13 months (through database cut-off date of 19-Sept-2017)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants that received at least one dose of study treatment.
Arm/Group Title Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Pembrolizumab 200 mg Fixed Dose
Hide Arm/Group Description:
Participants receive pembrolizumab 2 mg/kg administered intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Overall Number of Participants Analyzed 14 13 15
Measure Type: Count of Participants
Unit of Measure: Participants
14
 100.0%
13
 100.0%
14
  93.3%
2.Primary Outcome
Title Number of Participants Who Discontinued Study Drug Due to an AE
Hide Description An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to be a causal relationship with this treatment. An AE could therefore be any unfavourable 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 medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants who discontinued study treatment due to an AE was reported.
Time Frame Up to ~13 months (through database cut-off date of 19-Sept-2017)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants that received at least one dose of study treatment.
Arm/Group Title Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Pembrolizumab 200 mg Fixed Dose
Hide Arm/Group Description:
Participants receive pembrolizumab 2 mg/kg administered intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Overall Number of Participants Analyzed 14 13 15
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
1
   7.7%
3
  20.0%
3.Primary Outcome
Title Single Dose PK: Area Under the Plasma Concentration Curve From 0-28 Days (AUC[0-28 Days]) of Pembrolizumab
Hide Description AUC was defined as a measure of pembrolizumab exposure that was calculated as the product of plasma drug concentration and time. Blood samples were collected pre-dose and post-dose at multiple time points up to 28 days during cycle 1 to estimate AUC(0-28 days) following single dose administration.
Time Frame Cycle 1 Day 1: pre-dose [-1 to 0 hour] and post-dose at 0 [up to 0.5], 6 [±0.5], 24, 48, 168, 336, and 504 [±2 for 24 to 504] hours after completion of pembrolizumab infusion. Cycle 1= 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received a pembrolizumab dose, with available pharmacokinetic (PK) data, and who did not have any protocol deviation interfering with PK.
Arm/Group Title Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Pembrolizumab 200 mg Fixed Dose
Hide Arm/Group Description:
Participants receive pembrolizumab 2 mg/kg administered intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Overall Number of Participants Analyzed 14 13 15
Geometric Mean (95% Confidence Interval)
Unit of Measure: μg•day/mL
437.10
(388.94 to 491.22)
1979.62
(1737.75 to 2255.15)
637.22
(569.89 to 712.51)
4.Primary Outcome
Title Single-Dose PK: Maximum Plasma Concentration (Cmax) of Pembrolizumab
Hide Description Cmax was defined as the maximum concentration of pembrolizumab observed in plasma following a single dose. Blood samples were collected pre-dose and post-dose at multiple time points up to 28 days during cycle 1 to estimate Cmax following single dose administration.
Time Frame Cycle 1 Day 1: pre-dose [-1 to 0 hour] and post-dose at 0 [up to 0.5], 6 [±0.5], 24, 48, 168, 336, and 504 [±2 for 24 to 504] hours after completion of pembrolizumab infusion. Cycle 1= 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received a pembrolizumab dose, with available PK data, and who did not have any protocol deviation interfering with PK.
Arm/Group Title Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Pembrolizumab 200 mg Fixed Dose
Hide Arm/Group Description:
Participants receive pembrolizumab 2 mg/kg administered intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Overall Number of Participants Analyzed 14 13 15
Geometric Mean (95% Confidence Interval)
Unit of Measure: μg/mL
50.62
(42.34 to 60.52)
213.12
(191.45 to 237.25)
76.21
(63.59 to 91.32)
5.Primary Outcome
Title Single Dose PK: Time to Cmax (Tmax) of Pembrolizumab
Hide Description Tmax was defined as the time required post dosing to reach a maximum plasma concentration of pembrolizumab. Blood samples were collected pre-dose and post-dose at multiple time points up to 28 days at cycle 1 to estimate Tmax following single dose administration.
Time Frame Cycle 1 Day 1: pre-dose [-1 to 0 hour] and post-dose at 0 [up to 0.5], 6 [±0.5], 24, 48, 168, 336, and 504 [±2 for 24 to 504] hours after completion of pembrolizumab infusion. Cycle 1= 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received a pembrolizumab dose, with available PK data, and who did not have any protocol deviation interfering with PK.
Arm/Group Title Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Pembrolizumab 200 mg Fixed Dose
Hide Arm/Group Description:
Participants receive pembrolizumab 2 mg/kg administered intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Overall Number of Participants Analyzed 14 13 15
Median (Full Range)
Unit of Measure: day
0.06
(0.03 to 2.02)
0.05
(0.02 to 0.27)
0.04
(0.02 to 0.27)
6.Primary Outcome
Title Single Dose PK: Apparent Terminal Half-Life (t1/2) of Pembrolizumab
Hide Description t½ was defined as the time required to divide the pembrolizumab plasma concentration by two after reaching pseudo-equilibrium, following a single dose of pembrolizumab. Blood samples were collected pre-dose and post-dose at multiple time points up to 28 days at cycle 1 to estimate t½ following single dose administration.
Time Frame Cycle 1 Day 1: pre-dose [-1 to 0 hour] and post-dose at 0 [up to 0.5], 6 [±0.5], 24, 48, 168, 336, and 504 [±2 for 24 to 504] hours after completion of pembrolizumab infusion. Cycle 1= 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received a pembrolizumab dose, with available PK data, and who did not have any protocol deviation interfering with PK.
Arm/Group Title Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Pembrolizumab 200 mg Fixed Dose
Hide Arm/Group Description:
Participants receive pembrolizumab 2 mg/kg administered intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Overall Number of Participants Analyzed 14 13 15
Median (Full Range)
Unit of Measure: Day
14.10
(9.56 to 31.60)
16.00
(10.50 to 23.80)
12.70
(4.15 to 24.50)
7.Primary Outcome
Title Multiple Dose PK: Trough Plasma Concentration (Ctrough) of Pembrolizumab
Hide Description Ctrough was defined as the minimum concentration that occurred immediately prior to the administration of pembrolizumab in Cycle 8. Blood samples were collected pre-dose at Cycle 8 to estimate Ctrough following multiple dose administrations of pembrolizumab.
Time Frame Cycle 8 Day 1: pre-dose [-1 to 0 hour]. Cycle 8 up to 175 days (Cycle 1 = 28 days, Cycles 2-8 = 21 days).
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received a pembrolizumab dose, had available Ctrough data, and who did not have any protocol deviation interfering with PK.
Arm/Group Title Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Pembrolizumab 200 mg Fixed Dose
Hide Arm/Group Description:
Participants receive pembrolizumab 2 mg/kg administered intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Overall Number of Participants Analyzed 8 5 5
Geometric Mean (95% Confidence Interval)
Unit of Measure: μg/mL
21.53
(15.76 to 29.41)
78.35
(56.09 to 109.45)
25.46
(17.70 to 36.63)
8.Primary Outcome
Title Multiple Dose PK: AUC(0-21 Days) of Pembrolizumab at Steady State
Hide Description AUC was defined as a measure of pembrolizumab exposure that was calculated as the product of plasma drug concentration and time at steady state following multiple doses. Blood samples were collected pre-dose and post-dose at multiple time points up to 21 days during cycle 8 for AUC(0-21 days) assessment at steady state.
Time Frame Cycle 8 Day 1: pre-dose [-1 to 0 hour] and post-dose at 0 [up to 0.5], 6 [up to 0.5], 24, 48, 168, 336, and 504 [±2 for 24 to 504] hours after completion of pembrolizumab infusion. Cycle 8 up to 175 days (Cycle 1 = 28 days, Cycles 2-8 = 21 days).
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received a pembrolizumab dose, had available AUC(0-21 days) data, and who did not have any protocol deviation interfering with PK.
Arm/Group Title Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Pembrolizumab 200 mg Fixed Dose
Hide Arm/Group Description:
Participants receive pembrolizumab 2 mg/kg administered intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Overall Number of Participants Analyzed 7 5 4
Geometric Mean (95% Confidence Interval)
Unit of Measure: μg•day/mL
730.94
(627.38 to 851.60)
2819.19
(2009.36 to 3955.43)
930.99
(724.37 to 1196.56)
9.Primary Outcome
Title Multiple Dose PK: Cmax of Pembrolizumab at Steady State
Hide Description Cmax was defined as the maximum concentration of pembrolizumab observed in plasma at steady state following multiple doses. Blood samples were collected pre-dose and post-dose at multiple time points up to 21 days during cycle 8 for Cmax assessment at steady state.
Time Frame Cycle 8 Day 1: pre-dose [-1 to 0 hour] and post-dose at 0 [up to 0.5], 6 [up to 0.5], 24, 48, 168, 336, and 504 [±2 for 24 to 504] hours after completion of pembrolizumab infusion. Cycle 8 up to 175 days (Cycle 1 = 28 days, Cycles 2-8 = 21 days).
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received a pembrolizumab dose, had available Cmax data, and who did not have any protocol deviation interfering with PK.
Arm/Group Title Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Pembrolizumab 200 mg Fixed Dose
Hide Arm/Group Description:
Participants receive pembrolizumab 2 mg/kg administered intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Overall Number of Participants Analyzed 8 5 5
Geometric Mean (95% Confidence Interval)
Unit of Measure: g/mL
66.67
(56.90 to 78.10)
268.59
(217.81 to 331.21)
92.22
(81.66 to 104.16)
10.Secondary Outcome
Title Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Central Radiologists' Review
Hide Description ORR was defined as the percentage of participants who had a Complete Response (CR: disappearance of all lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions, without evidence of progression based on non-target or new lesions) as assessed by central radiologists' review per RECIST 1.1 which is modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced a confirmed CR or PR per RECIST 1.1 as assessed by central radiologists' review was reported for each arm.
Time Frame Up to ~13 months (through database cut-off date of 19-Sept-2017)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants that received at least one dose of study treatment and with measurable disease at baseline as assessed by central radiology review.
Arm/Group Title Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Pembrolizumab 200 mg Fixed Dose
Hide Arm/Group Description:
Participants receive pembrolizumab 2 mg/kg administered intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Overall Number of Participants Analyzed 14 13 15
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
0.0
(0.0 to 23.2)
23.1
(5.0 to 53.8)
20.0
(4.3 to 48.1)
11.Secondary Outcome
Title ORR Per Immune-related RECIST (irRECIST) as Assessed by Central Radiologists' Review
Hide Description ORR was defined as the percentage of participants who had confirmed responses assessed using RECIST 1.1 before PD or an immune-related Complete Response (irCR: Disappearance of all target lesions and non-target) or an immune-related Partial Response (irPR: At least a 30% decrease in the sum of diameters of target lesions, stability of non-target lesions no new lesions) after a single PD per irRECIST as assessed by central radiologists' review. Per RECIST 1.1, CR or PR was confirmed by repeated radiographic assessment no less than 4 weeks from the first documented response. If site-assessed PD was verified by the central imaging vendor, the site could elect to continue treatment, repeat imaging ≥4 weeks later and assess tumor response or confirmed progression per irRECIST. The percentage of participants who experienced a CR or PR per RECIST 1.1 or irCR or irPR per irRECIST as assessed by central radiologists' review was reported for each arm.
Time Frame Up to ~13 months (through database cut-off date of 19-Sept-2017)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants that received at least one dose of study treatment and with measurable disease at baseline as assessed by central radiology review.
Arm/Group Title Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Pembrolizumab 200 mg Fixed Dose
Hide Arm/Group Description:
Participants receive pembrolizumab 2 mg/kg administered intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Overall Number of Participants Analyzed 14 13 15
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
0.0
(0.0 to 23.2)
23.1
(5.0 to 53.8)
20.0
(4.3 to 48.1)
12.Secondary Outcome
Title Duration of Response (DOR) Per RECIST 1.1 as Assessed by Central Radiologists' Review
Hide Description For participants who demonstrated a confirmed CR (disappearance of all lesions) or confirmed PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by central radiologists' review, DOR was defined as the time from first documented evidence of a CR or PR until disease progression or death. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The DOR per RECIST 1.1 as assessed by central radiologists' review for all participants who experienced a confirmed CR or PR was reported for each arm.
Time Frame Up to ~13 months (through database cut-off date of 19-Sept-2017)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants that received at least one dose of study treatment, had measurable disease at baseline as assessed by central radiology review, and who demonstrated a confirmed response (CR or PR). No participants in the Pembrolizumab 2 mg/kg group had a CR or PR and thus were not included in this analysis.
Arm/Group Title Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Pembrolizumab 200 mg Fixed Dose
Hide Arm/Group Description:
Participants receive pembrolizumab 2 mg/kg administered intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Overall Number of Participants Analyzed 0 3 3
Median (Full Range)
Unit of Measure: Months
6.28
(2.00 to 6.28)
4.1
(2.00 to 4.11)
13.Secondary Outcome
Title DOR Per irRECIST as Assessed by Central Radiologists' Review
Hide Description For participants who demonstrated a confirmed CR (disappearance of all target lesions and non-target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 or CR or PR after a single PD, DOR was defined as the time from the first documented CR or PR, or irCR or irPR, until an immune-related progressive disease (irPD) or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per irRECIST, irPD was defined as after a single PD, ≥20% increase in the sum of diameters of target lesions, or unequivocal worsening of non-target lesions or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The DOR per irRECIST as assessed by central radiologists' review for all participants who experienced a confirmed CR or PR or irCR or irPR was reported for each arm.
Time Frame Up to ~13 months (through database cut-off date of 19-Sept-2017)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants that received at least one dose of study treatment, had measurable disease at baseline as assessed by central radiology review, and who demonstrated a confirmed response (iCR or iPR). No participants in the Pembrolizumab 2 mg/kg group had a CR or PR and thus were not included in this analysis.
Arm/Group Title Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Pembrolizumab 200 mg Fixed Dose
Hide Arm/Group Description:
Participants receive pembrolizumab 2 mg/kg administered intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Overall Number of Participants Analyzed 0 3 3
Median (Full Range)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
NA=The median of DOR and the lower and upper ranges of DOR were not reached (no progressive disease by time of last disease assessment).
14.Secondary Outcome
Title Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Central Radiologists' Review
Hide Description PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as either a 20% increase from nadir in target lesions, unequivocal progression of nontarget lesions, or the appearance of new lesions. PFS per RECIST 1.1 as assessed by central radiologists' review was reported for each arm.
Time Frame Up to ~13 months (through database cut-off date of 19-Sept-2017)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants that received at least one dose of study treatment.
Arm/Group Title Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Pembrolizumab 200 mg Fixed Dose
Hide Arm/Group Description:
Participants receive pembrolizumab 2 mg/kg administered intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Overall Number of Participants Analyzed 14 13 15
Median (95% Confidence Interval)
Unit of Measure: Months
2.1
(2.0 to 4.2)
2.7
(2.1 to 8.2)
2.1
(1.3 to 6.4)
15.Secondary Outcome
Title PFS Per irRECIST as Assessed by Central Radiologists' Review
Hide Description PFS was defined as the time from randomization to the first documented immune-based confirmed progressive disease (iCPD) or death due to any cause, whichever occurred first. Per iRECIST, iCPD is defined as worsening of any existing cause of progression, or the appearance of any other cause of progression, relative to the initial appearance of progressive disease by RECIST 1.1. PFS per irRECIST as assessed by central radiologists' review is reported for each arm.
Time Frame Up to ~13 months (through database cut-off date of 19-Sept-2017)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants that received at least one dose of study treatment.
Arm/Group Title Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Pembrolizumab 200 mg Fixed Dose
Hide Arm/Group Description:
Participants receive pembrolizumab 2 mg/kg administered intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Overall Number of Participants Analyzed 14 13 15
Median (95% Confidence Interval)
Unit of Measure: Months
2.2
(2.0 to 4.4)
6.2 [1] 
(2.1 to NA)
6.4 [1] 
(1.3 to NA)
[1]
NA=The upper limit of the PFS 95% confidence interval (CI) was not reached by the time of the 19-Sept-2017 data cut-off.
16.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS was reported for each arm using a 19-Sept-2017 data cut-off date.
Time Frame Up to ~13 months (through database cut-off date of 19-Sept-2017)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants that received at least one dose of study treatment.
Arm/Group Title Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Pembrolizumab 200 mg Fixed Dose
Hide Arm/Group Description:
Participants receive pembrolizumab 2 mg/kg administered intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
Overall Number of Participants Analyzed 14 13 15
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(4.4 to NA)
9.4 [2] 
(6.2 to NA)
NA [1] 
(1.3 to NA)
[1]
NA=The median of OS and the upper limit of the OS 95% CI were not reached by the time of the 19-Sept-2017 data cut-off.
[2]
NA=The upper limit of the OS 95% CI was not reached by the time of the 19-Sept-2017 data cut-off.
Time Frame Up to ~13 months (through database cut-off date of 19-Sept-2017)
Adverse Event Reporting Description

All-Cause Mortality was reported for all randomized participants.

Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.

 
Arm/Group Title Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Pembrolizumab 200 mg Fixed Dose
Hide Arm/Group Description Participants receive pembrolizumab 2 mg/kg administered intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations. Cycle 1 is 28 days instead of 21 days. Participants receive pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days instead of 21 days. Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days instead of 21 days.
All-Cause Mortality
Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Pembrolizumab 200 mg Fixed Dose
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/14 (28.57%)      6/15 (40.00%)      6/15 (40.00%)    
Hide Serious Adverse Events
Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Pembrolizumab 200 mg Fixed Dose
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/14 (7.14%)      1/13 (7.69%)      3/15 (20.00%)    
Eye disorders       
Eyelid ptosis  1  0/14 (0.00%)  0 0/13 (0.00%)  0 1/15 (6.67%)  1
Gastrointestinal disorders       
Abdominal pain upper  1  0/14 (0.00%)  0 1/13 (7.69%)  1 0/15 (0.00%)  0
Infections and infestations       
Pneumonia  1  1/14 (7.14%)  1 0/13 (0.00%)  0 0/15 (0.00%)  0
Nervous system disorders       
Cerebral infarction  1  0/14 (0.00%)  0 0/13 (0.00%)  0 1/15 (6.67%)  1
Skin and subcutaneous tissue disorders       
Dermatitis acneiform  1  0/14 (0.00%)  0 0/13 (0.00%)  0 1/15 (6.67%)  1
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Pembrolizumab 200 mg Fixed Dose
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/14 (100.00%)      13/13 (100.00%)      14/15 (93.33%)    
Blood and lymphatic system disorders       
Lymph node pain  1  0/14 (0.00%)  0 1/13 (7.69%)  1 0/15 (0.00%)  0
Thrombocytopenia  1  1/14 (7.14%)  1 0/13 (0.00%)  0 0/15 (0.00%)  0
Cardiac disorders       
Atrial fibrillation  1  0/14 (0.00%)  0 1/13 (7.69%)  1 0/15 (0.00%)  0
Endocrine disorders       
Hyperthyroidism  1  0/14 (0.00%)  0 1/13 (7.69%)  1 0/15 (0.00%)  0
Hypothyroidism  1  1/14 (7.14%)  1 1/13 (7.69%)  1 0/15 (0.00%)  0
Gastrointestinal disorders       
Abdominal discomfort  1  0/14 (0.00%)  0 1/13 (7.69%)  1 0/15 (0.00%)  0
Abdominal distension  1  0/14 (0.00%)  0 1/13 (7.69%)  1 1/15 (6.67%)  1
Abdominal pain  1  0/14 (0.00%)  0 1/13 (7.69%)  1 0/15 (0.00%)  0
Aphthous ulcer  1  1/14 (7.14%)  1 0/13 (0.00%)  0 0/15 (0.00%)  0
Constipation  1  2/14 (14.29%)  2 0/13 (0.00%)  0 3/15 (20.00%)  3
Diarrhoea  1  0/14 (0.00%)  0 2/13 (15.38%)  3 2/15 (13.33%)  2
Dysphagia  1  0/14 (0.00%)  0 0/13 (0.00%)  0 1/15 (6.67%)  1
Faeces hard  1  0/14 (0.00%)  0 1/13 (7.69%)  1 0/15 (0.00%)  0
Gingival pain  1  0/14 (0.00%)  0 0/13 (0.00%)  0 1/15 (6.67%)  1
Lower gastrointestinal haemorrhage  1  0/14 (0.00%)  0 0/13 (0.00%)  0 1/15 (6.67%)  1
Nausea  1  2/14 (14.29%)  2 2/13 (15.38%)  2 0/15 (0.00%)  0
Toothache  1  0/14 (0.00%)  0 2/13 (15.38%)  2 0/15 (0.00%)  0
Vomiting  1  1/14 (7.14%)  1 1/13 (7.69%)  1 1/15 (6.67%)  1
General disorders       
Asthenia  1  0/14 (0.00%)  0 1/13 (7.69%)  1 0/15 (0.00%)  0
Chest pain  1  1/14 (7.14%)  1 0/13 (0.00%)  0 1/15 (6.67%)  1
Fatigue  1  5/14 (35.71%)  7 4/13 (30.77%)  4 3/15 (20.00%)  3
Oedema peripheral  1  0/14 (0.00%)  0 1/13 (7.69%)  1 1/15 (6.67%)  1
Pain  1  1/14 (7.14%)  1 0/13 (0.00%)  0 1/15 (6.67%)  1
Pyrexia  1  0/14 (0.00%)  0 2/13 (15.38%)  2 2/15 (13.33%)  2
Immune system disorders       
Anaphylactic reaction  1  0/14 (0.00%)  0 1/13 (7.69%)  1 0/15 (0.00%)  0
Infections and infestations       
Conjunctivitis  1  0/14 (0.00%)  0 1/13 (7.69%)  1 0/15 (0.00%)  0
Herpes zoster  1  1/14 (7.14%)  1 0/13 (0.00%)  0 0/15 (0.00%)  0
Upper respiratory tract infection  1  4/14 (28.57%)  6 3/13 (23.08%)  3 1/15 (6.67%)  1
Injury, poisoning and procedural complications       
Hip fracture  1  0/14 (0.00%)  0 0/13 (0.00%)  0 1/15 (6.67%)  1
Spinal compression fracture  1  0/14 (0.00%)  0 0/13 (0.00%)  0 1/15 (6.67%)  1
Investigations       
Alanine aminotransferase increased  1  3/14 (21.43%)  3 1/13 (7.69%)  2 1/15 (6.67%)  1
Aspartate aminotransferase increased  1  2/14 (14.29%)  2 1/13 (7.69%)  4 0/15 (0.00%)  0
Blood albumin decreased  1  1/14 (7.14%)  1 1/13 (7.69%)  1 0/15 (0.00%)  0
Blood creatinine increased  1  1/14 (7.14%)  1 0/13 (0.00%)  0 0/15 (0.00%)  0
Blood pressure increased  1  0/14 (0.00%)  0 0/13 (0.00%)  0 1/15 (6.67%)  2
Haemoglobin decreased  1  3/14 (21.43%)  3 1/13 (7.69%)  1 2/15 (13.33%)  2
Heart rate increased  1  1/14 (7.14%)  1 0/13 (0.00%)  0 0/15 (0.00%)  0
Neutrophil count increased  1  0/14 (0.00%)  0 0/13 (0.00%)  0 2/15 (13.33%)  2
Platelet count decreased  1  1/14 (7.14%)  1 0/13 (0.00%)  0 0/15 (0.00%)  0
White blood cell count decreased  1  1/14 (7.14%)  1 0/13 (0.00%)  0 0/15 (0.00%)  0
White blood cell count increased  1  0/14 (0.00%)  0 0/13 (0.00%)  0 2/15 (13.33%)  2
Metabolism and nutrition disorders       
Decreased appetite  1  0/14 (0.00%)  0 4/13 (30.77%)  4 4/15 (26.67%)  5
Hypercalcaemia  1  0/14 (0.00%)  0 1/13 (7.69%)  1 0/15 (0.00%)  0
Hyperkalaemia  1  0/14 (0.00%)  0 0/13 (0.00%)  0 1/15 (6.67%)  1
Hypoalbuminaemia  1  1/14 (7.14%)  1 1/13 (7.69%)  1 2/15 (13.33%)  2
Hypokalaemia  1  0/14 (0.00%)  0 0/13 (0.00%)  0 2/15 (13.33%)  2
Hyponatraemia  1  1/14 (7.14%)  1 0/13 (0.00%)  0 1/15 (6.67%)  1
Musculoskeletal and connective tissue disorders       
Back pain  1  1/14 (7.14%)  1 0/13 (0.00%)  0 2/15 (13.33%)  2
Muscular weakness  1  0/14 (0.00%)  0 0/13 (0.00%)  0 1/15 (6.67%)  1
Musculoskeletal chest pain  1  2/14 (14.29%)  2 0/13 (0.00%)  0 1/15 (6.67%)  1
Musculoskeletal pain  1  1/14 (7.14%)  1 0/13 (0.00%)  0 0/15 (0.00%)  0
Nervous system disorders       
Ataxia  1  1/14 (7.14%)  1 0/13 (0.00%)  0 0/15 (0.00%)  0
Dizziness  1  0/14 (0.00%)  0 3/13 (23.08%)  3 2/15 (13.33%)  2
Headache  1  0/14 (0.00%)  0 0/13 (0.00%)  0 1/15 (6.67%)  1
Psychiatric disorders       
Insomnia  1  1/14 (7.14%)  1 0/13 (0.00%)  0 0/15 (0.00%)  0
Renal and urinary disorders       
Dysuria  1  1/14 (7.14%)  1 0/13 (0.00%)  0 0/15 (0.00%)  0
Pollakiuria  1  1/14 (7.14%)  1 0/13 (0.00%)  0 0/15 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Cough  1  2/14 (14.29%)  2 0/13 (0.00%)  0 1/15 (6.67%)  1
Dyspnoea  1  0/14 (0.00%)  0 1/13 (7.69%)  1 3/15 (20.00%)  3
Haemoptysis  1  1/14 (7.14%)  1 2/13 (15.38%)  2 0/15 (0.00%)  0
Hiccups  1  1/14 (7.14%)  1 0/13 (0.00%)  0 0/15 (0.00%)  0
Productive cough  1  1/14 (7.14%)  1 0/13 (0.00%)  0 0/15 (0.00%)  0
Skin and subcutaneous tissue disorders       
Dry skin  1  1/14 (7.14%)  1 0/13 (0.00%)  0 0/15 (0.00%)  0
Palmar-plantar erythrodysaesthesia syndrome  1  0/14 (0.00%)  0 0/13 (0.00%)  0 1/15 (6.67%)  1
Pruritus  1  1/14 (7.14%)  1 2/13 (15.38%)  3 1/15 (6.67%)  1
Rash  1  5/14 (35.71%)  7 2/13 (15.38%)  2 4/15 (26.67%)  5
Skin swelling  1  1/14 (7.14%)  1 0/13 (0.00%)  0 0/15 (0.00%)  0
Swelling face  1  0/14 (0.00%)  0 0/13 (0.00%)  0 1/15 (6.67%)  1
Vascular disorders       
Hypertension  1  1/14 (7.14%)  1 0/13 (0.00%)  0 1/15 (6.67%)  1
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02835690    
Other Study ID Numbers: 3475-032
MK-3475-032 ( Other Identifier: Merck Protocol Number )
KEYNOTE-032 ( Other Identifier: Merck )
First Submitted: June 29, 2016
First Posted: July 18, 2016
Results First Submitted: September 10, 2019
Results First Posted: October 7, 2019
Last Update Posted: June 9, 2020