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A Study of Pembrolizumab Plus Epacadostat With Platinum-based Chemotherapy Versus Pembrolizumab Plus Platinum-based Chemotherapy Plus Placebo in Metastatic Non-Small Cell Lung Cancer (KEYNOTE-715-06/ECHO-306-06)

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ClinicalTrials.gov Identifier: NCT03322566
Recruitment Status : Completed
First Posted : October 26, 2017
Results First Posted : January 29, 2020
Last Update Posted : January 6, 2021
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Incyte Corporation

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Lung Cancer
Interventions Drug: Pembrolizumab
Drug: Epacadostat
Drug: Platinum-based chemotherapy
Drug: Placebo
Enrollment 233
Recruitment Details Participants took part in the study at 65 investigative sites in 14 countries from 09 January 2018 to 13 December 2018.
Pre-assignment Details  
Arm/Group Title Pembrolizumab + Chemotherapy + Epacadostat Pembrolizumab + Chemotherapy + Placebo Pembrolizumab + Epacadostat
Hide Arm/Group Description Participant received pembrolizumab 200 mg intravenous (IV) infusion, every 3 weeks (Q3W) on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat 100 mg tablets, orally, twice daily (BID) in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m^2 IV infusion, Q3W + cisplatin 75 mg/m^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles). Participant received pembrolizumab 200 mg IV infusion, Q3W on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat matching placebo tablets, orally, BID in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m^2 IV infusion, Q3W + cisplatin 75 mg/m^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles). Participant received pembrolizumab 200 mg IV infusion, Q3W on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat 100 mg tablets, orally, BID in each 21 day cycle for up to 35 cycles.
Period Title: Overall Study
Started 91 87 55
Completed 0 0 0
Not Completed 91 87 55
Reason Not Completed
Death             20             12             13
Physician Decision             0             0             1
Withdrawal by Subject             3             1             5
On-going at clinical cut off date             68             74             36
Arm/Group Title Pembrolizumab + Chemotherapy + Epacadostat Pembrolizumab + Chemotherapy + Placebo Pembrolizumab + Epacadostat Total
Hide Arm/Group Description Participant received pembrolizumab 200 mg intravenous (IV) infusion, every 3 weeks (Q3W) on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat 100 mg tablets, orally, twice daily (BID) in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m^2 IV infusion, Q3W + cisplatin 75 mg/m^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles). Participant received pembrolizumab 200 mg IV infusion, Q3W on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat matching placebo tablets, orally, BID in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m^2 IV infusion, Q3W + cisplatin 75 mg/m^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles). Participant received pembrolizumab 200 mg IV infusion, Q3W on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat 100 mg tablets, orally, BID in each 21 day cycle for up to 35 cycles. Total of all reporting groups
Overall Number of Baseline Participants 91 87 55 233
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) population included all participants who were randomized to study intervention.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 91 participants 87 participants 55 participants 233 participants
63.0  (11.7) 63.6  (8.8) 62.8  (8.4) 63.2  (9.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 91 participants 87 participants 55 participants 233 participants
Female
33
  36.3%
30
  34.5%
16
  29.1%
79
  33.9%
Male
58
  63.7%
57
  65.5%
39
  70.9%
154
  66.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 91 participants 87 participants 55 participants 233 participants
American Indian Or Alaska Native
1
   1.1%
0
   0.0%
0
   0.0%
1
   0.4%
Asian
11
  12.1%
10
  11.5%
2
   3.6%
23
   9.9%
Black Or African American
1
   1.1%
1
   1.1%
0
   0.0%
2
   0.9%
White
78
  85.7%
75
  86.2%
53
  96.4%
206
  88.4%
Missing
0
   0.0%
1
   1.1%
0
   0.0%
1
   0.4%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Ethnicity Number Analyzed 91 participants 87 participants 55 participants 233 participants
Hispanic or Latino
3
   3.3%
1
   1.1%
1
   1.8%
5
   2.1%
Not Hispanic or Latino
86
  94.5%
85
  97.7%
52
  94.5%
223
  95.7%
Unknown
2
   2.2%
1
   1.1%
1
   1.8%
4
   1.7%
Not Reported
0
   0.0%
0
   0.0%
1
   1.8%
1
   0.4%
1.Primary Outcome
Title Objective Response Rate (ORR) of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo
Hide Description ORR is defined as the percentage of participants who have a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) based on blinded independent central review (BICR).
Time Frame Assessed after a minimum of 12 weeks of follow-up ( Data Cut Off of 13-Dec 18).
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population consisted of all participants randomized in arms Pembrolizumab+Epacadostat+Chemotherapy and Pembrolizumab+Chemothrapy. This was no longer a primary outcome for arm pembrolizumab+epacadostat as the study was amended prospectively from a phase 3 to phase 2 study with different objectives as per amendment 5; this study arm was dropped.
Arm/Group Title Pembrolizumab + Chemotherapy + Epacadostat Pembrolizumab + Chemotherapy + Placebo
Hide Arm/Group Description:
Participant received pembrolizumab 200 mg intravenous (IV) infusion, every 3 weeks (Q3W) on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat 100 mg tablets, orally, twice daily (BID) in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m^2 IV infusion, Q3W + cisplatin 75 mg/m^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles).
Participant received pembrolizumab 200 mg IV infusion, Q3W on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat matching placebo tablets, orally, BID in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m^2 IV infusion, Q3W + cisplatin 75 mg/m^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles).
Overall Number of Participants Analyzed 91 87
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
26.4
(17.7 to 36.7)
44.8
(34.1 to 55.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + Chemotherapy + Epacadostat, Pembrolizumab + Chemotherapy + Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9948
Comments One-sided p-value for testing. H0: difference in % = 0 versus H1: difference in % > 0.
Method Stratified Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value -18.5
Confidence Interval (2-Sided) 95%
-32.0 to -4.3
Estimation Comments Stratified by PD-L1 TPS ( <50% vs. >=50% ) and predominant tumor histology (squamous vs non-squamous);because of small sample size, the strata 'TPS >= 50 percent Non-squamous' and 'TPS >= 50% Squamous' were combined into one stratum.
2.Secondary Outcome
Title Progression-free Survival of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo
Hide Description Defined as the time from randomization to the first documented progressive disease (PD) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurs first.
Time Frame Assessed from the start of the study until death or PD, whichever was earlier until the Data Cut Off of 13-Dec 18.
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population consisted of all participants randomized in arms Pembrolizumab+Epacadostat+Chemotherapy and Pembrolizumab+Chemothrapy. This was no longer a secondary outcome for arm pembrolizumab+epacadostat as the study was amended prospectively from a phase 3 to phase 2 with different objectives as per amendment 5; this study arm was dropped.
Arm/Group Title Pembrolizumab + Chemotherapy + Epacadostat Pembrolizumab + Chemotherapy + Placebo
Hide Arm/Group Description:
Participant received pembrolizumab 200 mg intravenous (IV) infusion, every 3 weeks (Q3W) on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat 100 mg tablets, orally, twice daily (BID) in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m^2 IV infusion, Q3W + cisplatin 75 mg/m^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles).
Participant received pembrolizumab 200 mg IV infusion, Q3W on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat matching placebo tablets, orally, BID in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m^2 IV infusion, Q3W + cisplatin 75 mg/m^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles).
Overall Number of Participants Analyzed 91 87
Median (95% Confidence Interval)
Unit of Measure: months
8.0
(4.2 to 10.2)
8.2 [1] 
(6.0 to NA)
[1]
Upper bound is not estimable
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + Chemotherapy + Epacadostat, Pembrolizumab + Chemotherapy + Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.94305
Comments One-sided p-value based on log-rank test stratified by TPS (<50% vs >=50%) and predominant histology (squamous vs non-squamous), because of small sample size, the strata 'TPS >= 50% Non-squamous' and 'TPS >= 50% Squamous' were combined into one.
Method Regression, Cox
Comments Efron's method of tie handling
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.47
Confidence Interval (2-Sided) 95%
0.91 to 2.36
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Overall Survival of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo
Hide Description Defined as the time from randomization to death due to any cause.
Time Frame Assessed from the start of study until the Data Cut Off of 13-Dec 18.
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population consisted of all participants randomized in arms Pembrolizumab+Epacadostat+Chemotherapy and Pembrolizumab+Chemothrapy. This was no longer a secondary outcome for arm pembrolizumab+epacadostat as the study was amended prospectively from a phase 3 to phase 2 with different objectives as per amendment 5; this study arm was dropped.
Arm/Group Title Pembrolizumab + Chemotherapy + Epacadostat Pembrolizumab + Chemotherapy + Placebo
Hide Arm/Group Description:
Participant received pembrolizumab 200 mg intravenous (IV) infusion, every 3 weeks (Q3W) on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat 100 mg tablets, orally, twice daily (BID) in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m^2 IV infusion, Q3W + cisplatin 75 mg/m^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles).
Participant received pembrolizumab 200 mg IV infusion, Q3W on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat matching placebo tablets, orally, BID in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m^2 IV infusion, Q3W + cisplatin 75 mg/m^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles).
Overall Number of Participants Analyzed 91 87
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Median could not be estimated because there were not enough events
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pembrolizumab + Chemotherapy + Epacadostat, Pembrolizumab + Chemotherapy + Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.96272
Comments One-sided p-value based on log-rank test stratified by TPS (<50% vs >=50%) and predominant histology (squamous vs non-squamous), because of small sample size, the strata 'TPS >= 50% Non-squamous' and 'TPS >= 50% Squamous' were combined into one.
Method Regression, Cox
Comments Efron's method of tie handling
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.90
Confidence Interval (2-Sided) 95%
0.93 to 3.90
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Duration of Response of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo
Hide Description Defined as the time from the earliest date of qualifying response until earliest date of disease progression, per RECIST v1.1, or death from any cause, whichever comes first.
Time Frame Assessed from the fist dose until the Data Cut Off of 13-Dec 18.
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population consisted of all participants randomized in arms Pembrolizumab+Epacadostat+Chemotherapy and Pembrolizumab+Chemothrapy. This was no longer a secondary outcome for arm pembrolizumab+epacadostat as the study was amended prospectively from a phase 3 to phase 2 with different objectives as per amendment 5; this study arm was dropped.
Arm/Group Title Pembrolizumab + Chemotherapy + Epacadostat Pembrolizumab + Chemotherapy + Placebo
Hide Arm/Group Description:
Participant received pembrolizumab 200 mg intravenous (IV) infusion, every 3 weeks (Q3W) on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat 100 mg tablets, orally, twice daily (BID) in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m^2 IV infusion, Q3W + cisplatin 75 mg/m^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles).
Participant received pembrolizumab 200 mg IV infusion, Q3W on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat matching placebo tablets, orally, BID in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m^2 IV infusion, Q3W + cisplatin 75 mg/m^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles).
Overall Number of Participants Analyzed 91 87
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(1.1 to 7.0)
7.0
(1.2 to 8.0)
[1]
Median could not be estimated because there were not enough events
5.Secondary Outcome
Title Safety and Tolerability of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo as Measured by the Number of Participants Experiencing Adverse Events (AEs)
Hide Description An AE is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Time Frame Assessed from the fist dose until the Data Cut Off of 13-Dec 18.
Hide Outcome Measure Data
Hide Analysis Population Description
All Subjects as Treated consists of all randomized participants who received at least one dose of study treatment. This was no longer a secondary outcome for arm pembrolizumab+epacadostat as the study was amended prospectively from a phase 3 to phase 2 with different objectives as per amendment 5; this study arm was dropped.
Arm/Group Title Pembrolizumab + Chemotherapy + Epacadostat Pembrolizumab + Chemotherapy + Placebo
Hide Arm/Group Description:
Participant received pembrolizumab 200 mg intravenous (IV) infusion, every 3 weeks (Q3W) on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat 100 mg tablets, orally, twice daily (BID) in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m^2 IV infusion, Q3W + cisplatin 75 mg/m^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles).
Participant received pembrolizumab 200 mg IV infusion, Q3W on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat matching placebo tablets, orally, BID in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m^2 IV infusion, Q3W + cisplatin 75 mg/m^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles).
Overall Number of Participants Analyzed 90 86
Measure Type: Count of Participants
Unit of Measure: Participants
89
  98.9%
82
  95.3%
6.Secondary Outcome
Title Safety and Tolerability of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo as Measured by the Number of Participants Discontinuing Study Drug Due to AEs
Hide Description An AE is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Time Frame Assessed from the fist dose until the Data Cut Off of 13-Dec 18.
Hide Outcome Measure Data
Hide Analysis Population Description
All Subjects as Treated consists of all randomized participants who received at least one dose of study treatment. This was no longer a secondary outcome for arm pembrolizumab+epacadostat as the study was amended prospectively from a phase 3 to phase 2 with different objectives as per amendment 5; this study arm was dropped.
Arm/Group Title Pembrolizumab + Chemotherapy + Epacadostat Pembrolizumab + Chemotherapy + Placebo
Hide Arm/Group Description:
Participant received pembrolizumab 200 mg intravenous (IV) infusion, every 3 weeks (Q3W) on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat 100 mg tablets, orally, twice daily (BID) in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m^2 IV infusion, Q3W + cisplatin 75 mg/m^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles).
Participant received pembrolizumab 200 mg IV infusion, Q3W on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat matching placebo tablets, orally, BID in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m^2 IV infusion, Q3W + cisplatin 75 mg/m^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles).
Overall Number of Participants Analyzed 90 86
Measure Type: Count of Participants
Unit of Measure: Participants
23
  25.6%
21
  24.4%
Time Frame Assessed from the fist dose until the Data Cut Off of 13-Dec 18 (Approximately 9 months).
Adverse Event Reporting Description All participants as treated (APaT) population included all randomized participants who received at least one dose of study treatment.
 
Arm/Group Title Pembrolizumab + Chemotherapy + Epacadostat Pembrolizumab + Chemotherapy + Placebo Pembrolizumab + Epacadostat
Hide Arm/Group Description Participant received pembrolizumab 200 mg intravenous (IV) infusion, every 3 weeks (Q3W) on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat 100 mg tablets, orally, twice daily (BID) in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m^2 IV infusion, Q3W + cisplatin 75 mg/m^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles). Participant received pembrolizumab 200 mg IV infusion, Q3W on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat matching placebo tablets, orally, BID in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m^2 IV infusion, Q3W + cisplatin 75 mg/m^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles). Participant received pembrolizumab 200 mg IV infusion, Q3W on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat 100 mg tablets, orally, BID in each 21 day cycle for up to 35 cycles.
All-Cause Mortality
Pembrolizumab + Chemotherapy + Epacadostat Pembrolizumab + Chemotherapy + Placebo Pembrolizumab + Epacadostat
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   21/90 (23.33%)   12/86 (13.95%)   14/52 (26.92%) 
Hide Serious Adverse Events
Pembrolizumab + Chemotherapy + Epacadostat Pembrolizumab + Chemotherapy + Placebo Pembrolizumab + Epacadostat
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   39/90 (43.33%)   32/86 (37.21%)   12/52 (23.08%) 
Blood and lymphatic system disorders       
Anaemia  1  1/90 (1.11%)  1/86 (1.16%)  0/52 (0.00%) 
Febrile neutropenia  1  4/90 (4.44%)  0/86 (0.00%)  0/52 (0.00%) 
Neutropenia  1  2/90 (2.22%)  0/86 (0.00%)  0/52 (0.00%) 
Pancytopenia  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Cardiac disorders       
Acute myocardial infarction  1  0/90 (0.00%)  1/86 (1.16%)  0/52 (0.00%) 
Atrial fibrillation  1  1/90 (1.11%)  1/86 (1.16%)  0/52 (0.00%) 
Atrioventricular block complete  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Cardiac arrest  1  0/90 (0.00%)  1/86 (1.16%)  0/52 (0.00%) 
Cardio-respiratory arrest  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Myocardial infarction  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Pericardial effusion  1  0/90 (0.00%)  0/86 (0.00%)  1/52 (1.92%) 
Endocrine disorders       
Hyperthyroidism  1  0/90 (0.00%)  0/86 (0.00%)  1/52 (1.92%) 
Gastrointestinal disorders       
Abdominal pain upper  1  0/90 (0.00%)  1/86 (1.16%)  0/52 (0.00%) 
Colitis  1  0/90 (0.00%)  2/86 (2.33%)  1/52 (1.92%) 
Constipation  1  0/90 (0.00%)  1/86 (1.16%)  0/52 (0.00%) 
Diarrhoea  1  2/90 (2.22%)  2/86 (2.33%)  0/52 (0.00%) 
Gastrointestinal toxicity  1  0/90 (0.00%)  0/86 (0.00%)  1/52 (1.92%) 
Pancreatitis acute  1  0/90 (0.00%)  1/86 (1.16%)  0/52 (0.00%) 
Stomatitis  1  1/90 (1.11%)  1/86 (1.16%)  0/52 (0.00%) 
Vomiting  1  2/90 (2.22%)  0/86 (0.00%)  0/52 (0.00%) 
General disorders       
Chest pain  1  0/90 (0.00%)  1/86 (1.16%)  1/52 (1.92%) 
Death  1  0/90 (0.00%)  0/86 (0.00%)  1/52 (1.92%) 
Mucosal inflammation  1  0/90 (0.00%)  1/86 (1.16%)  0/52 (0.00%) 
Pyrexia  1  2/90 (2.22%)  0/86 (0.00%)  1/52 (1.92%) 
Hepatobiliary disorders       
Hepatotoxicity  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Immune system disorders       
Hypersensitivity  1  0/90 (0.00%)  1/86 (1.16%)  0/52 (0.00%) 
Infections and infestations       
Bronchitis  1  1/90 (1.11%)  1/86 (1.16%)  0/52 (0.00%) 
Cellulitis  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Encephalitis  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Gastroenteritis  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Gingivitis  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Lower respiratory tract infection  1  3/90 (3.33%)  0/86 (0.00%)  0/52 (0.00%) 
Pneumocystis jirovecii pneumonia  1  0/90 (0.00%)  0/86 (0.00%)  1/52 (1.92%) 
Pneumonia  1  4/90 (4.44%)  11/86 (12.79%)  4/52 (7.69%) 
Sepsis  1  2/90 (2.22%)  0/86 (0.00%)  0/52 (0.00%) 
Urinary tract infection  1  1/90 (1.11%)  1/86 (1.16%)  0/52 (0.00%) 
Injury, poisoning and procedural complications       
Humerus fracture  1  0/90 (0.00%)  0/86 (0.00%)  1/52 (1.92%) 
Radiation necrosis  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Subdural haemorrhage  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Investigations       
Alanine aminotransferase increased  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Liver function test increased  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Pancreatic enzymes increased  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Platelet count decreased  1  0/90 (0.00%)  1/86 (1.16%)  0/52 (0.00%) 
Metabolism and nutrition disorders       
Decreased appetite  1  0/90 (0.00%)  1/86 (1.16%)  1/52 (1.92%) 
Dehydration  1  2/90 (2.22%)  0/86 (0.00%)  0/52 (0.00%) 
Hyperglycaemia  1  1/90 (1.11%)  0/86 (0.00%)  1/52 (1.92%) 
Hyponatraemia  1  0/90 (0.00%)  0/86 (0.00%)  1/52 (1.92%) 
Musculoskeletal and connective tissue disorders       
Arthropathy  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Myalgia  1  0/90 (0.00%)  1/86 (1.16%)  0/52 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Cancer pain  1  0/90 (0.00%)  1/86 (1.16%)  0/52 (0.00%) 
Hypopharyngeal neoplasm  1  0/90 (0.00%)  1/86 (1.16%)  0/52 (0.00%) 
Malignant pleural effusion  1  0/90 (0.00%)  1/86 (1.16%)  0/52 (0.00%) 
Paraneoplastic syndrome  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Prostate cancer  1  0/90 (0.00%)  1/86 (1.16%)  0/52 (0.00%) 
Nervous system disorders       
Cerebrovascular accident  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Embolic stroke  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Encephalopathy  1  0/90 (0.00%)  1/86 (1.16%)  0/52 (0.00%) 
Peripheral sensory neuropathy  1  0/90 (0.00%)  1/86 (1.16%)  0/52 (0.00%) 
Sciatica  1  0/90 (0.00%)  1/86 (1.16%)  0/52 (0.00%) 
Syncope  1  0/90 (0.00%)  0/86 (0.00%)  1/52 (1.92%) 
Transient ischaemic attack  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Vocal cord paralysis  1  0/90 (0.00%)  0/86 (0.00%)  1/52 (1.92%) 
Psychiatric disorders       
Agitation  1  0/90 (0.00%)  1/86 (1.16%)  0/52 (0.00%) 
Confusional state  1  0/90 (0.00%)  1/86 (1.16%)  0/52 (0.00%) 
Hallucination  1  0/90 (0.00%)  0/86 (0.00%)  1/52 (1.92%) 
Renal and urinary disorders       
Acute kidney injury  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Renal failure  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Chronic obstructive pulmonary disease  1  0/90 (0.00%)  1/86 (1.16%)  0/52 (0.00%) 
Dyspnoea  1  0/90 (0.00%)  1/86 (1.16%)  0/52 (0.00%) 
Haemoptysis  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Haemothorax  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Hypoxia  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Pleural effusion  1  1/90 (1.11%)  1/86 (1.16%)  2/52 (3.85%) 
Pneumonitis  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Pulmonary embolism  1  1/90 (1.11%)  1/86 (1.16%)  0/52 (0.00%) 
Respiratory failure  1  1/90 (1.11%)  1/86 (1.16%)  0/52 (0.00%) 
Skin and subcutaneous tissue disorders       
Exfoliative rash  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Purpura  1  0/90 (0.00%)  1/86 (1.16%)  0/52 (0.00%) 
Rash  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Skin ulcer  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Stevens-Johnson syndrome  1  0/90 (0.00%)  1/86 (1.16%)  0/52 (0.00%) 
Vascular disorders       
Embolism  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
Peripheral ischaemia  1  0/90 (0.00%)  1/86 (1.16%)  0/52 (0.00%) 
Superior vena cava syndrome  1  1/90 (1.11%)  0/86 (0.00%)  0/52 (0.00%) 
1
Term from vocabulary, MedDRA 21.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pembrolizumab + Chemotherapy + Epacadostat Pembrolizumab + Chemotherapy + Placebo Pembrolizumab + Epacadostat
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   86/90 (95.56%)   81/86 (94.19%)   50/52 (96.15%) 
Blood and lymphatic system disorders       
Anaemia  1  21/90 (23.33%)  32/86 (37.21%)  8/52 (15.38%) 
Leukopenia  1  5/90 (5.56%)  3/86 (3.49%)  0/52 (0.00%) 
Neutropenia  1  15/90 (16.67%)  15/86 (17.44%)  2/52 (3.85%) 
Thrombocytopenia  1  8/90 (8.89%)  2/86 (2.33%)  0/52 (0.00%) 
Endocrine disorders       
Hyperthyroidism  1  5/90 (5.56%)  5/86 (5.81%)  2/52 (3.85%) 
Hypothyroidism  1  8/90 (8.89%)  6/86 (6.98%)  7/52 (13.46%) 
Eye disorders       
Lacrimation increased  1  10/90 (11.11%)  8/86 (9.30%)  0/52 (0.00%) 
Gastrointestinal disorders       
Abdominal pain  1  5/90 (5.56%)  3/86 (3.49%)  5/52 (9.62%) 
Constipation  1  25/90 (27.78%)  21/86 (24.42%)  7/52 (13.46%) 
Diarrhoea  1  20/90 (22.22%)  18/86 (20.93%)  11/52 (21.15%) 
Dry mouth  1  1/90 (1.11%)  5/86 (5.81%)  0/52 (0.00%) 
Dyspepsia  1  5/90 (5.56%)  1/86 (1.16%)  3/52 (5.77%) 
Nausea  1  36/90 (40.00%)  36/86 (41.86%)  10/52 (19.23%) 
Vomiting  1  18/90 (20.00%)  8/86 (9.30%)  5/52 (9.62%) 
General disorders       
Asthenia  1  9/90 (10.00%)  13/86 (15.12%)  6/52 (11.54%) 
Chest pain  1  3/90 (3.33%)  8/86 (9.30%)  7/52 (13.46%) 
Fatigue  1  26/90 (28.89%)  23/86 (26.74%)  12/52 (23.08%) 
Mucosal inflammation  1  4/90 (4.44%)  6/86 (6.98%)  0/52 (0.00%) 
Oedema peripheral  1  8/90 (8.89%)  4/86 (4.65%)  4/52 (7.69%) 
Pyrexia  1  10/90 (11.11%)  7/86 (8.14%)  9/52 (17.31%) 
Infections and infestations       
Pneumonia  1  5/90 (5.56%)  0/86 (0.00%)  1/52 (1.92%) 
Urinary tract infection  1  5/90 (5.56%)  5/86 (5.81%)  3/52 (5.77%) 
Injury, poisoning and procedural complications       
Fall  1  1/90 (1.11%)  5/86 (5.81%)  0/52 (0.00%) 
Investigations       
Alanine aminotransferase increase  1  14/90 (15.56%)  8/86 (9.30%)  1/52 (1.92%) 
Amylase increased  1  8/90 (8.89%)  8/86 (9.30%)  5/52 (9.62%) 
Aspartate aminotransferase increased  1  14/90 (15.56%)  5/86 (5.81%)  3/52 (5.77%) 
Blood alkaline phosphatase increased  1  5/90 (5.56%)  3/86 (3.49%)  2/52 (3.85%) 
Blood creatinine increased  1  3/90 (3.33%)  4/86 (4.65%)  4/52 (7.69%) 
Gamma-glutamyltransferase increased  1  4/90 (4.44%)  5/86 (5.81%)  2/52 (3.85%) 
Lipase increased  1  3/90 (3.33%)  4/86 (4.65%)  4/52 (7.69%) 
Neutrophil count decreased  1  4/90 (4.44%)  13/86 (15.12%)  0/52 (0.00%) 
Platelet count decreased  1  4/90 (4.44%)  8/86 (9.30%)  0/52 (0.00%) 
Weight decreased  1  9/90 (10.00%)  7/86 (8.14%)  6/52 (11.54%) 
Metabolism and nutrition disorders       
Decreased appetite  1  16/90 (17.78%)  12/86 (13.95%)  8/52 (15.38%) 
Dehydration  1  2/90 (2.22%)  2/86 (2.33%)  3/52 (5.77%) 
Hypokalaemia  1  8/90 (8.89%)  4/86 (4.65%)  1/52 (1.92%) 
Hypomagnesaemia  1  7/90 (7.78%)  6/86 (6.98%)  1/52 (1.92%) 
Hyponatraemia  1  2/90 (2.22%)  5/86 (5.81%)  1/52 (1.92%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  6/90 (6.67%)  7/86 (8.14%)  3/52 (5.77%) 
Back pain  1  7/90 (7.78%)  8/86 (9.30%)  8/52 (15.38%) 
Bone pain  1  5/90 (5.56%)  0/86 (0.00%)  3/52 (5.77%) 
Muscular weakness  1  6/90 (6.67%)  2/86 (2.33%)  2/52 (3.85%) 
Musculoskeletal pain  1  5/90 (5.56%)  2/86 (2.33%)  3/52 (5.77%) 
Pain in extremity  1  10/90 (11.11%)  3/86 (3.49%)  2/52 (3.85%) 
Nervous system disorders       
Dizziness  1  10/90 (11.11%)  9/86 (10.47%)  5/52 (9.62%) 
Dysgeusia  1  9/90 (10.00%)  7/86 (8.14%)  0/52 (0.00%) 
Headache  1  8/90 (8.89%)  12/86 (13.95%)  5/52 (9.62%) 
Hypoaesthesia  1  5/90 (5.56%)  7/86 (8.14%)  0/52 (0.00%) 
Neuropathy peripheral  1  11/90 (12.22%)  9/86 (10.47%)  0/52 (0.00%) 
Paraesthesia  1  5/90 (5.56%)  1/86 (1.16%)  0/52 (0.00%) 
Psychiatric disorders       
Insomnia  1  10/90 (11.11%)  7/86 (8.14%)  2/52 (3.85%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  6/90 (6.67%)  6/86 (6.98%)  9/52 (17.31%) 
Dyspnoea  1  7/90 (7.78%)  9/86 (10.47%)  6/52 (11.54%) 
Epistaxis  1  5/90 (5.56%)  5/86 (5.81%)  1/52 (1.92%) 
Haemoptysis  1  3/90 (3.33%)  6/86 (6.98%)  2/52 (3.85%) 
Productive cough  1  3/90 (3.33%)  0/86 (0.00%)  3/52 (5.77%) 
Rhinorrhoea  1  7/90 (7.78%)  0/86 (0.00%)  1/52 (1.92%) 
Skin and subcutaneous tissue disorders       
Alopecia  1  11/90 (12.22%)  16/86 (18.60%)  0/52 (0.00%) 
Pruritus  1  10/90 (11.11%)  8/86 (9.30%)  3/52 (5.77%) 
Rash  1  22/90 (24.44%)  16/86 (18.60%)  8/52 (15.38%) 
1
Term from vocabulary, MedDRA 21.1
Indicates events were collected by systematic assessment
Data from the final analysis of KEYNOTE-715/ECHO-306 (data cutoff: 13-DEC-2018) indicated that the study did not meet the pre-specified endpoint of improvement in objective response rate (ORR).
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.
Clinical Study Agreement
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Incyte Corporation
Phone: 855-463-3463
EMail: medinfo@incyte.com
Layout table for additonal information
Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT03322566    
Other Study ID Numbers: KEYNOTE-715-06/ECHO-306-06
2017-001810-27 ( EudraCT Number )
First Submitted: October 24, 2017
First Posted: October 26, 2017
Results First Submitted: December 10, 2019
Results First Posted: January 29, 2020
Last Update Posted: January 6, 2021