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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)

Sponsor
Incyte Corporation (Industry)
Overall Status
Completed
CT.gov ID
NCT03322566
Collaborator
Merck Sharp & Dohme LLC (Industry)
233
Enrollment
94
Locations
3
Arms
33.2
Actual Duration (Months)
2.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study was to evaluate the efficacy and safety of pembrolizumab plus epacadostat with platinum-based chemotherapy versus pembrolizumab plus platinum-based chemotherapy plus placebo as first-line therapy in participants with metastatic non-small cell lung cancer (NSCLC).

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
233 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized Phase 2 Study of the Combination of Pembrolizumab (MK-3475) Plus Epacadostat (INCB024360) With Platinum-based Chemotherapy Versus Pembrolizumab Plus Platinum-based Chemotherapy Plus Placebo as First-Line Treatment in Patients With Metastatic Non-Small Cell Lung Cancer
Actual Study Start Date :
Jan 9, 2018
Actual Primary Completion Date :
Dec 13, 2018
Actual Study Completion Date :
Oct 16, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Pembrolizumab + Chemotherapy + Epacadostat

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).

Drug: Pembrolizumab
Pembrolizumab administered intravenously every 3 weeks.
Other Names:
  • MK-3475

    • Drug: Epacadostat
    Epacadostat administered orally twice daily.
    Other Names:
  • INCB024360

    • Drug: Platinum-based chemotherapy
    Investigator selected one of the following regimens: pemetrexed + cisplatin, pemetrexed + carboplatin, or paclitaxel + carboplatin, depending on histology.
    Experimental: Pembrolizumab + Chemotherapy + Placebo

    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).

    Drug: Pembrolizumab
    Pembrolizumab administered intravenously every 3 weeks.
    Other Names:
  • MK-3475

    • Drug: Platinum-based chemotherapy
    Investigator selected one of the following regimens: pemetrexed + cisplatin, pemetrexed + carboplatin, or paclitaxel + carboplatin, depending on histology.

    Drug: Placebo
    Matching placebo administered orally twice daily.
    Experimental: Pembrolizumab + Epacadostat

    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.

    Drug: Pembrolizumab
    Pembrolizumab administered intravenously every 3 weeks.
    Other Names:
  • MK-3475

    • Drug: Epacadostat
    Epacadostat administered orally twice daily.
    Other Names:
  • INCB024360

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Objective Response Rate (ORR) of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo [Assessed every 12 weeks up to 24 months]

      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).

    Secondary Outcome Measures

    1. Progression-free Survival of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo [Up to 24 months]

      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.

    2. Overall Survival of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo [Up to 24 months]

      Defined as the time from randomization to death due to any cause.

    3. Duration of Response of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo [Up to 24 months]

      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.

    4. Safety and Tolerability of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo as Measured by the Number of Participants Experiencing Adverse Events (AEs) [Up to 25 months]

      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.

    5. Safety and Tolerability of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo as Measured by the Number of Participants Discontinuing Study Drug Due to AEs [Up to 25 months]

      An AE is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of any study drug, whether or not considered related to the study drug.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Histologically or cytologically confirmed diagnosis of stage IV NSCLC without epidermal growth factor receptor (EGFR)-sensitizing mutation, ROS1 and/or anaplastic lymphoma kinase (ALK) translocation

    • Measurable disease based on RECIST 1.1

    • Life expectancy of at least 3 months.

    • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

    • Adequate organ function per protocol-defined criteria.

    • Provide tumor tissue sample.

    Exclusion Criteria:

    • Known untreated central nervous system metastases and/or carcinomatous meningitis

    • History of (non-infectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.

    • Symptomatic ascites or pleural effusion.

    • Known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.

    • Active autoimmune disease that has required systemic treatment in past 2 years.

    • Has had an allogeneic tissue/solid organ transplant.

    • Has a known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by the local health authority.

    • Has known history of or is positive for active Hepatitis B (HBsAg reactive) or has active Hepatitis C (HCV RNA). Note: Testing must be performed to determine eligibility.

    • History or presence of an abnormal electrocardiogram (ECG) that, in the Investigator's opinion, is clinically meaningful.

    • Use of protocol-defined prior/concomitant therapy.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Southern Cancer Center, PC Daphne Alabama United States 36526
    2 Western Regional Medical Center, Inc. Goodyear Arizona United States 85338
    3 Arizona Oncology Associates PC- HOPE Tucson Arizona United States 85704
    4 Lynn Cancer Institute Boca Raton Florida United States 33486
    5 Florida Cancer Specialists (South Region) Fort Myers Florida United States 33901-8101
    6 Florida Cancer Specialists (North Region) Saint Petersburg Florida United States 33705
    7 PPG-Oncology Fort Wayne Indiana United States 46845
    8 University of Michigan Ann Arbor Michigan United States 48109
    9 MMCORC Saint Louis Park Minnesota United States 55416
    10 St. Vincent Healthcare Frontier Cancer Center Billings Montana United States 59102
    11 New York Oncology Hematology P.C Albany New York United States 12208
    12 Oncology Hematology Care, Inc. Cincinnati Ohio United States 45242
    13 Southwestern Regional Medical Center, Inc. Tulsa Oklahoma United States 74133
    14 St. Luke's Hospital - Anderson Campus Easton Pennsylvania United States 18045
    15 Allegheny General Hospital Pittsburgh Pennsylvania United States 15224
    16 Tennessee Oncology, PLLC/The Sarah Cannon Research Institute Chattanooga Tennessee United States 37404
    17 Tennessee Oncology, PLLC/The Sarah Cannon Research Institute Nashville Tennessee United States 37203
    18 Texas Oncology-Denton South Denton Texas United States 76210
    19 Oncology & Hematology Assoc. SW Virginia, Inc., DBA Blue Ridge Cancer Care Blacksburg Virginia United States 24060
    20 Emily Couric Clinical Cancer Center Charlottesville Virginia United States 22908
    21 Seattle Cancer Care Alliance Seattle Washington United States 98109
    22 MNCCI Port Macquarie Base Hospital Port Macquarie New South Wales (Australia) Australia 2444
    23 Blacktown Hospital Blacktown New South Wales Australia 2148
    24 Chris OBrien Lifehouse Camperdown New South Wales Australia 2050
    25 The Crown Princess Mary Cancer Centre Westmead Westmead New South Wales Australia 2145
    26 Southern Medical Day Care Centre Wollongong New South Wales Australia 2500
    27 Cairns Base Hospital Cairns Queensland Australia 4870
    28 BCCA-Cancer Centre of the Southern Interior Kelowna British Columbia Canada V1Y 5L3
    29 Lions Gate Hospital North Vancouver British Columbia Canada V7L 2L7
    30 CISSS de la Monteregie-Centre Greenfield Park Quebec Canada J4V 2H1
    31 CSSS de Laval- Hopital de la Cite de la Sante Laval Quebec Canada H7M 3L9
    32 CIUSSS Ouest de l'Ile - St-Mary's Hospital Montréal Quebec Canada H3T 1M5
    33 CIUSSS du Nord-de-l'ILe-de-Montreal Hopital du Sacre-Coeur de Montreal Montréal Quebec Canada H4J 1C5
    34 CIUSSS de la Mauricie-et-du-Centre-du-Quebec Trois-Rivières Quebec Canada G8Z 3R9
    35 CHU de Quebec - Hotel-Dieu de Quebec Quebec Canada G1R 2J6
    36 Zala Megyei Korhaz Pozvai Telephely Pozva Zalaegerszeg Hungary 8900
    37 Orszagos Koranyi TBC es Pulmonologiai Intezet Budapest Hungary 1121
    38 Veszprem Megyei Tudogyogyintezet Farkasgyepű Hungary 8582
    39 Bekes Megyei Pandy Kalman Korhaz Gyula Hungary 5700
    40 CRU Hungary Kft. Miskolc Hungary 3529
    41 Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet Szolnok Hungary 5004
    42 St Vincents University Hospital Dublin Ireland Dublin 4
    43 Ha Emek Medical Center Afula Israel 1834111
    44 Soroka Medical Center Be'er Sheva Israel 8457108
    45 Rambam Medical Center Haifa Israel 3525408
    46 Meir Medical Center Kfar Saba Israel 4428164
    47 Rabin Medical Center Petah Tikva Israel 5262000
    48 Chaim Sheba Medcal Center Ramat Gan Israel 52621
    49 Centro Di Riferimento Oncologico Aviano Italy 33081
    50 A.O.U. Policlinico Vittorio Emanuele - Presidio Gaspare Rodolico Catania Italy 95123
    51 Fondazione IRCCS Istituto Nazionale dei Tumori Milano Italy 20133
    52 Istituto Europeo di Oncologia Milano Italy 20141
    53 Ospedale San Gerardo - ASST Monza Monza Italy 20900
    54 National Cancer Center Goyang-si Korea, Republic of 10408
    55 Severance Hospital Yonsei University Health System Seoul Korea, Republic of 03722
    56 Asan Medical Center Seoul Korea, Republic of 05505
    57 Samsung Medical Center Seoul Korea, Republic of 06351
    58 Medical Care Research S.A. de C.V. Mérida Yucatan Mexico 97070
    59 Oaxaca Site Management Organization S.C. Oaxaca Mexico 68000
    60 FAICIC Clinical Research Veracruz Mexico 91900
    61 Belgorod Regional Oncology Dispensary Belgorod Russian Federation 308010
    62 Udmurtia Republic Regional Clinical Oncology Dispensary Izhevsk Russian Federation 426067
    63 Republican Clinical Oncology Dispensary of Tatarstan MoH Kazan Russian Federation 420029
    64 Central Clinical Hospital with polyclinic Moscow Russian Federation 121359
    65 Moscow Research Oncology Institute Moscow Russian Federation 125284
    66 SBI of Stavropol region Pyatigorskiy Oncologic dispensary Pyatigorsk Russian Federation 357502
    67 SBHI Leningrad Regional Clinical Hospital Saint Petersburg Russian Federation 194291
    68 SBHI Samara Regional Clinical Oncology Dispensary Samara Russian Federation 443031
    69 Oncological Dispensary #2 of Ministry of Health of Krasnodar region Sochi Russian Federation 354057
    70 Tomsk Scientific Research Institute of Oncology Tomsk Russian Federation 634028
    71 Hospital Universitario Insular de Gran Canaria Las Palmas De Gran Canaria Gran Canaria Spain 35016
    72 Hospital Juan Ramón Jimenez Huelva Spain 21005
    73 Institut Catala Oncologia de Bellvitge - ICO L'Hospitalet De Llobregat Spain 08980
    74 Hospital Universitario La Paz Madrid Spain 28046
    75 Hospital Universitario La Fe Valencia Spain 46026
    76 Hospital Clinico Universitario Lozano Blesa Zaragoza Spain 50009
    77 Chang Gung Medical Foundation, Kaohsiung Branch Kaohsiung Taiwan 833
    78 China Medical University Hospital Taichung Taiwan 40447
    79 National Cheng Kung University Hospital Tainan Taiwan 70457
    80 National Taiwan University Hospital Taipei Taiwan 10048
    81 Chang Gung Medical Foundation, Linkou Branch Taoyuan Taiwan 33305
    82 Ege Universitesi Tip Fakultesi Hastanesi İzmir Bornova Turkey 35100
    83 Baskent Universitesi Adana Uygulama ve Arastirma Hastanesi Adana Turkey 01120
    84 Cukurova Universitesi Tıp Fakultesi Balcalı Hastanesi Adana Turkey 01330
    85 Hacettepe Universitesi Tip Fakultesi Hastanesi Ankara Turkey 06100
    86 Uludag Universitesi Tip Fakultesi Bursa Turkey 16059
    87 Pamukkale Unv. Tip Fak Denizli Turkey 20070
    88 Istanbul Universitesi Cerrahpasa Tip Fakultesi Istanbul Turkey 34098
    89 Samsun Medical Park Hastanesi Samsun Turkey 55200
    90 Namık Kemal University Medical Faculty Tekirdağ Turkey 59030
    91 Mount Vernon Cancer Centre Northwood Middlesex United Kingdom HA6 2RN
    92 Western General Hospital Edinburgh United Kingdom EH42XU
    93 North Middlesex Hospital London United Kingdom N18 1QX
    94 Freeman Hospital Newcastle upon Tyne Foundation NHS Trust Newcastle Upon Tyne United Kingdom NE7 7DN

    Sponsors and Collaborators

    • Incyte Corporation
    • Merck Sharp & Dohme LLC

    Investigators

    • Study Director: Lance Leopold, MD, Incyte Corporation

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Incyte Corporation
    ClinicalTrials.gov Identifier:
    NCT03322566
    Other Study ID Numbers:
    • KEYNOTE-715-06/ECHO-306-06
    • 2017-001810-27
    First Posted:
    Oct 26, 2017
    Last Update Posted:
    Jan 24, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Incyte Corporation
    Non-small cell lung cancer
    programmed cell death 1 (PD-1) inhibitor
    indoleamine 2
    3-dioxygenase 1 (IDO1) inhibitor
    chemotherapy
    Additional relevant MeSH terms:
    Lung Neoplasms
    Carcinoma, Non-Small-Cell Lung
    Pembrolizumab

    Study Results

    Participant Flow

    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 Detail Phase 3 design of the study has been amended soon after it had started to a prospectively randomized phase 2 study. At the time of amendment existing participants were given a choice to move/participate in the new phase 2 study, and some participants who chose to discontinue the study at phase 3 were assigned to "study terminated by sponsor" as the reason for not completing the study in disposition table. The results posted are combined in the prospectively redesigned phase 2 trial.
    Arm/Group Title Pembrolizumab + Chemotherapy + Epacadostat Pembrolizumab + Chemotherapy + Placebo Pembrolizumab + Epacadostat
    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 46 42 22
    NOT COMPLETED 45 45 33

    Baseline Characteristics

    Arm/Group Title Pembrolizumab + Chemotherapy + Epacadostat Pembrolizumab + Chemotherapy + Placebo Pembrolizumab + Epacadostat Total
    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 Participants 91 87 55 233
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    63.0
    (11.7)
    63.6
    (8.8)
    62.8
    (8.4)
    63.2
    (9.9)
    Sex: Female, Male (Count of 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 (Count of Participants)
    American Indian Or Alaska Native
    1
    1.1%
    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%
    2
    0.9%
    White
    78
    85.7%
    75
    86.2%
    53
    96.4%
    206
    88.4%
    Missing
    0
    0%
    1
    1.1%
    0
    0%
    1
    0.4%
    Race/Ethnicity, Customized (Count of 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%
    1
    1.8%
    1
    0.4%

    Outcome Measures

    1. Primary Outcome
    Title Objective Response Rate (ORR) of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo
    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 every 12 weeks up to 24 months

    Outcome Measure Data

    Analysis Population Description
    ITT population consisted of all participants randomized in treatment arm Pembrolizumab+Epacadostat+Chemotherapy and treatment arm Pembrolizumab+Chemothrapy. This is not a primary outcome measure for treatment arm Pembrolizumab+Epacadostat per protocol.
    Arm/Group Title Pembrolizumab + Chemotherapy + Epacadostat Pembrolizumab + Chemotherapy + Placebo
    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).
    Measure Participants 91 87
    Number (95% Confidence Interval) [percentage of participants]
    26.4
    29%
    44.8
    51.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pembrolizumab + Chemotherapy + Epacadostat, Pembrolizumab + Chemotherapy + Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    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
    Method of Estimation Estimation Parameter Difference in Percentages
    Estimated Value -18.5
    Confidence Interval (2-Sided) 95%
    -32.0 to -4.3
    Parameter Dispersion Type:
    Value:
    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
    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 Up to 24 months

    Outcome Measure Data

    Analysis Population Description
    ITT population consisted of all participants randomized in treatment arm Pembrolizumab+Epacadostat+Chemotherapy and treatment arm Pembrolizumab+Chemothrapy. This is not a secondary outcome measure for treatment arm Pembrolizumab+Epacadostat per protocol.
    Arm/Group Title Pembrolizumab + Chemotherapy + Epacadostat Pembrolizumab + Chemotherapy + Placebo
    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).
    Measure Participants 91 87
    Median (95% Confidence Interval) [months]
    8.0
    8.2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pembrolizumab + Chemotherapy + Epacadostat, Pembrolizumab + Chemotherapy + Placebo
    Comments
    Type of Statistical Test Other
    Comments
    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
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Overall Survival of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo
    Description Defined as the time from randomization to death due to any cause.
    Time Frame Up to 24 months

    Outcome Measure Data

    Analysis Population Description
    ITT population consisted of all participants randomized in treatment arm Pembrolizumab+Epacadostat+Chemotherapy and treatment arm Pembrolizumab+Chemothrapy. This is not a secondary outcome measure for treatment arm Pembrolizumab+Epacadostat per protocol.
    Arm/Group Title Pembrolizumab + Chemotherapy + Epacadostat Pembrolizumab + Chemotherapy + Placebo
    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).
    Measure Participants 91 87
    Median (95% Confidence Interval) [months]
    NA
    NA
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pembrolizumab + Chemotherapy + Epacadostat, Pembrolizumab + Chemotherapy + Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.96272
    Comments One-sided p-value based on log-rank test stratified by PD-L1 TPS (<50% vs >=50%) and predominant tumor histology (squamous vs non-squamous), because of small sample size, the strata (<50% vs >=50%) were combined into one stratum.
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.90
    Confidence Interval (2-Sided) 95%
    0.93 to 3.90
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Duration of Response of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo
    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 Up to 24 months

    Outcome Measure Data

    Analysis Population Description
    ITT population consisted of all participants randomized in treatment arm Pembrolizumab+Epacadostat+Chemotherapy and treatment arm Pembrolizumab+Chemothrapy. This is not a secondary outcome measure for treatment arm Pembrolizumab+Epacadostat per protocol.
    Arm/Group Title Pembrolizumab + Chemotherapy + Epacadostat Pembrolizumab + Chemotherapy + Placebo
    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).
    Measure Participants 91 87
    Median (95% Confidence Interval) [months]
    NA
    7.0
    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)
    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 Up to 25 months

    Outcome Measure Data

    Analysis Population Description
    All Subjects as Treated consists of all randomized participants who received at least one dose of study treatment. This is not a secondary outcome measure for treatment arm Pembrolizumab+Epacadostat per protocol.
    Arm/Group Title Pembrolizumab + Chemotherapy + Epacadostat Pembrolizumab + Chemotherapy + Placebo
    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).
    Measure Participants 90 86
    Count of Participants [Participants]
    89
    97.8%
    82
    94.3%
    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
    Description An AE is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of any study drug, whether or not considered related to the study drug.
    Time Frame Up to 25 months

    Outcome Measure Data

    Analysis Population Description
    All Subjects as Treated consists of all randomized participants who received at least one dose of study treatment. This is not a secondary outcome measure for treatment arm Pembrolizumab+Epacadostat per protocol.
    Arm/Group Title Pembrolizumab + Chemotherapy + Epacadostat Pembrolizumab + Chemotherapy + Placebo
    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).
    Measure Participants 90 86
    Count of Participants [Participants]
    37
    40.7%
    35
    40.2%

    Adverse Events

    Time Frame Up to 25 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 Total
    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
    All Cause Mortality
    Pembrolizumab + Chemotherapy + Epacadostat Pembrolizumab + Chemotherapy + Placebo Pembrolizumab + Epacadostat Total
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 38/90 (42.2%) 35/86 (40.7%) 26/52 (50%) 99/228 (43.4%)
    Serious Adverse Events
    Pembrolizumab + Chemotherapy + Epacadostat Pembrolizumab + Chemotherapy + Placebo Pembrolizumab + Epacadostat Total
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 47/90 (52.2%) 41/86 (47.7%) 20/52 (38.5%) 108/228 (47.4%)
    Blood and lymphatic system disorders
    Anaemia 1/90 (1.1%) 1 1/86 (1.2%) 1 0/52 (0%) 0 2/228 (0.9%) 2
    Febrile neutropenia 5/90 (5.6%) 5 0/86 (0%) 0 0/52 (0%) 0 5/228 (2.2%) 5
    Lymphadenopathy 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Neutropenia 2/90 (2.2%) 3 0/86 (0%) 0 0/52 (0%) 0 2/228 (0.9%) 3
    Pancytopenia 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Thrombocytopenia 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Cardiac disorders
    Acute coronary syndrome 0/90 (0%) 0 1/86 (1.2%) 1 1/52 (1.9%) 1 2/228 (0.9%) 2
    Acute myocardial infarction 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Atrial fibrillation 1/90 (1.1%) 1 2/86 (2.3%) 2 0/52 (0%) 0 3/228 (1.3%) 3
    Atrioventricular block complete 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Cardiac arrest 0/90 (0%) 0 2/86 (2.3%) 2 0/52 (0%) 0 2/228 (0.9%) 2
    Cardiac failure acute 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Cardio-respiratory arrest 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Myocardial infarction 1/90 (1.1%) 1 0/86 (0%) 0 1/52 (1.9%) 1 2/228 (0.9%) 2
    Pericardial effusion 0/90 (0%) 0 0/86 (0%) 0 1/52 (1.9%) 1 1/228 (0.4%) 1
    Endocrine disorders
    Hyperthyroidism 0/90 (0%) 0 0/86 (0%) 0 1/52 (1.9%) 1 1/228 (0.4%) 1
    Gastrointestinal disorders
    Abdominal pain upper 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Colitis 0/90 (0%) 0 2/86 (2.3%) 2 1/52 (1.9%) 1 3/228 (1.3%) 3
    Constipation 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Diarrhoea 2/90 (2.2%) 3 2/86 (2.3%) 2 0/52 (0%) 0 4/228 (1.8%) 5
    Gastrointestinal toxicity 0/90 (0%) 0 0/86 (0%) 0 1/52 (1.9%) 1 1/228 (0.4%) 1
    Odynophagia 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Pancreatitis acute 1/90 (1.1%) 1 1/86 (1.2%) 1 0/52 (0%) 0 2/228 (0.9%) 2
    Stomatitis 1/90 (1.1%) 1 1/86 (1.2%) 1 0/52 (0%) 0 2/228 (0.9%) 2
    Vomiting 2/90 (2.2%) 3 0/86 (0%) 0 0/52 (0%) 0 2/228 (0.9%) 3
    General disorders
    Breakthrough pain 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Chest pain 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Death 0/90 (0%) 0 0/86 (0%) 0 2/52 (3.8%) 2 2/228 (0.9%) 2
    General physical health deterioration 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Infusion site extravasation 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Malaise 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Mucosal inflammation 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Pyrexia 2/90 (2.2%) 2 0/86 (0%) 0 0/52 (0%) 0 2/228 (0.9%) 2
    Hepatobiliary disorders
    Autoimmune hepatitis 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Cholecystitis 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Cholecystitis acute 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Gallbladder rupture 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Hepatotoxicity 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Immune system disorders
    Hypersensitivity 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Infections and infestations
    Bronchitis 3/90 (3.3%) 3 1/86 (1.2%) 1 0/52 (0%) 0 4/228 (1.8%) 4
    Cellulitis 1/90 (1.1%) 3 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 3
    Encephalitis 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Gastroenteritis 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Gingivitis 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Herpes zoster 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Lower respiratory tract infection 3/90 (3.3%) 4 1/86 (1.2%) 1 0/52 (0%) 0 4/228 (1.8%) 5
    Ophthalmic herpes zoster 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Pneumocystis jirovecii pneumonia 0/90 (0%) 0 0/86 (0%) 0 1/52 (1.9%) 1 1/228 (0.4%) 1
    Pneumonia 5/90 (5.6%) 5 12/86 (14%) 12 4/52 (7.7%) 4 21/228 (9.2%) 21
    Sepsis 3/90 (3.3%) 3 0/86 (0%) 0 1/52 (1.9%) 1 4/228 (1.8%) 4
    Urinary tract infection 1/90 (1.1%) 1 1/86 (1.2%) 1 0/52 (0%) 0 2/228 (0.9%) 2
    Urosepsis 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Vascular device infection 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Injury, poisoning and procedural complications
    Femoral neck fracture 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Hip fracture 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Humerus fracture 0/90 (0%) 0 0/86 (0%) 0 1/52 (1.9%) 1 1/228 (0.4%) 1
    Radiation necrosis 1/90 (1.1%) 3 1/86 (1.2%) 1 0/52 (0%) 0 2/228 (0.9%) 4
    Spinal compression fracture 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Subdural haemorrhage 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Investigations
    Alanine aminotransferase increased 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Liver function test increased 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Pancreatic enzymes increased 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Platelet count decreased 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Metabolism and nutrition disorders
    Decreased appetite 0/90 (0%) 0 1/86 (1.2%) 1 1/52 (1.9%) 1 2/228 (0.9%) 2
    Dehydration 2/90 (2.2%) 2 0/86 (0%) 0 1/52 (1.9%) 1 3/228 (1.3%) 3
    Diabetes mellitus 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Diabetic ketoacidosis 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Hyperglycaemia 0/90 (0%) 0 0/86 (0%) 0 1/52 (1.9%) 1 1/228 (0.4%) 1
    Hyperkalaemia 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Hyponatraemia 0/90 (0%) 0 0/86 (0%) 0 1/52 (1.9%) 1 1/228 (0.4%) 1
    Musculoskeletal and connective tissue disorders
    Arthropathy 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Myalgia 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Pain in extremity 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Rhabdomyolysis 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Hypopharyngeal neoplasm 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Malignant neoplasm progression 5/90 (5.6%) 5 2/86 (2.3%) 2 8/52 (15.4%) 8 15/228 (6.6%) 15
    Malignant pleural effusion 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Pancreatic carcinoma 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Paraneoplastic syndrome 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Prostate cancer 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Nervous system disorders
    Cerebrovascular accident 2/90 (2.2%) 2 1/86 (1.2%) 1 0/52 (0%) 0 3/228 (1.3%) 3
    Embolic stroke 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Encephalopathy 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Peripheral sensory neuropathy 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Sciatica 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Syncope 0/90 (0%) 0 1/86 (1.2%) 1 1/52 (1.9%) 1 2/228 (0.9%) 2
    Transient ischaemic attack 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Vocal cord paralysis 0/90 (0%) 0 0/86 (0%) 0 1/52 (1.9%) 1 1/228 (0.4%) 1
    Psychiatric disorders
    Agitation 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Confusional state 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Hallucination 0/90 (0%) 0 0/86 (0%) 0 1/52 (1.9%) 1 1/228 (0.4%) 1
    Renal and urinary disorders
    Acute kidney injury 2/90 (2.2%) 2 0/86 (0%) 0 0/52 (0%) 0 2/228 (0.9%) 2
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Cough 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Dyspnoea 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Haemoptysis 2/90 (2.2%) 2 1/86 (1.2%) 1 0/52 (0%) 0 3/228 (1.3%) 3
    Haemothorax 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Hypoxia 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Pleural effusion 2/90 (2.2%) 2 1/86 (1.2%) 1 2/52 (3.8%) 2 5/228 (2.2%) 5
    Pneumonitis 1/90 (1.1%) 1 3/86 (3.5%) 3 0/52 (0%) 0 4/228 (1.8%) 4
    Pulmonary embolism 1/90 (1.1%) 1 1/86 (1.2%) 1 0/52 (0%) 0 2/228 (0.9%) 2
    Pulmonary oedema 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Respiratory failure 1/90 (1.1%) 1 1/86 (1.2%) 1 0/52 (0%) 0 2/228 (0.9%) 2
    Skin and subcutaneous tissue disorders
    Exfoliative rash 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Purpura 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Rash 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Skin ulcer 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Stevens-Johnson syndrome 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Vascular disorders
    Embolism 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Hypertension 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Peripheral ischaemia 0/90 (0%) 0 1/86 (1.2%) 1 0/52 (0%) 0 1/228 (0.4%) 1
    Superior vena cava syndrome 1/90 (1.1%) 1 0/86 (0%) 0 0/52 (0%) 0 1/228 (0.4%) 1
    Other (Not Including Serious) Adverse Events
    Pembrolizumab + Chemotherapy + Epacadostat Pembrolizumab + Chemotherapy + Placebo Pembrolizumab + Epacadostat Total
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 87/90 (96.7%) 81/86 (94.2%) 51/52 (98.1%) 219/228 (96.1%)
    Blood and lymphatic system disorders
    Anaemia 24/90 (26.7%) 34 37/86 (43%) 56 8/52 (15.4%) 11 69/228 (30.3%) 101
    Leukopenia 6/90 (6.7%) 25 4/86 (4.7%) 7 0/52 (0%) 0 10/228 (4.4%) 32
    Neutropenia 16/90 (17.8%) 24 15/86 (17.4%) 25 2/52 (3.8%) 3 33/228 (14.5%) 52
    Thrombocytopenia 9/90 (10%) 14 2/86 (2.3%) 3 0/52 (0%) 0 11/228 (4.8%) 17
    Endocrine disorders
    Hyperthyroidism 6/90 (6.7%) 8 6/86 (7%) 6 3/52 (5.8%) 3 15/228 (6.6%) 17
    Hypothyroidism 10/90 (11.1%) 10 9/86 (10.5%) 9 7/52 (13.5%) 8 26/228 (11.4%) 27
    Eye disorders
    Lacrimation increased 11/90 (12.2%) 13 8/86 (9.3%) 8 0/52 (0%) 0 19/228 (8.3%) 21
    Gastrointestinal disorders
    Abdominal pain 6/90 (6.7%) 8 3/86 (3.5%) 3 5/52 (9.6%) 5 14/228 (6.1%) 16
    Abdominal pain upper 3/90 (3.3%) 3 7/86 (8.1%) 8 0/52 (0%) 0 10/228 (4.4%) 11
    Constipation 26/90 (28.9%) 40 23/86 (26.7%) 35 8/52 (15.4%) 9 57/228 (25%) 84
    Diarrhoea 23/90 (25.6%) 36 23/86 (26.7%) 35 14/52 (26.9%) 19 60/228 (26.3%) 90
    Dry mouth 1/90 (1.1%) 1 5/86 (5.8%) 5 0/52 (0%) 0 6/228 (2.6%) 6
    Dyspepsia 6/90 (6.7%) 11 1/86 (1.2%) 2 3/52 (5.8%) 5 10/228 (4.4%) 18
    Dysphagia 5/90 (5.6%) 5 4/86 (4.7%) 4 0/52 (0%) 0 9/228 (3.9%) 9
    Nausea 38/90 (42.2%) 80 37/86 (43%) 101 10/52 (19.2%) 13 85/228 (37.3%) 194
    Vomiting 19/90 (21.1%) 29 11/86 (12.8%) 14 6/52 (11.5%) 6 36/228 (15.8%) 49
    General disorders
    Asthenia 12/90 (13.3%) 14 18/86 (20.9%) 24 6/52 (11.5%) 9 36/228 (15.8%) 47
    Chest pain 3/90 (3.3%) 3 13/86 (15.1%) 13 10/52 (19.2%) 11 26/228 (11.4%) 27
    Fatigue 28/90 (31.1%) 40 25/86 (29.1%) 32 14/52 (26.9%) 16 67/228 (29.4%) 88
    Mucosal inflammation 5/90 (5.6%) 7 7/86 (8.1%) 8 0/52 (0%) 0 12/228 (5.3%) 15
    Oedema peripheral 14/90 (15.6%) 20 10/86 (11.6%) 11 4/52 (7.7%) 4 28/228 (12.3%) 35
    Peripheral swelling 6/90 (6.7%) 9 2/86 (2.3%) 3 1/52 (1.9%) 1 9/228 (3.9%) 13
    Pyrexia 15/90 (16.7%) 21 10/86 (11.6%) 12 9/52 (17.3%) 13 34/228 (14.9%) 46
    Infections and infestations
    Nasopharyngitis 5/90 (5.6%) 8 5/86 (5.8%) 9 3/52 (5.8%) 3 13/228 (5.7%) 20
    Pneumonia 7/90 (7.8%) 7 1/86 (1.2%) 1 2/52 (3.8%) 2 10/228 (4.4%) 10
    Upper respiratory tract infection 11/90 (12.2%) 14 6/86 (7%) 7 1/52 (1.9%) 1 18/228 (7.9%) 22
    Urinary tract infection 5/90 (5.6%) 8 9/86 (10.5%) 10 4/52 (7.7%) 4 18/228 (7.9%) 22
    Viral infection 5/90 (5.6%) 6 2/86 (2.3%) 3 0/52 (0%) 0 7/228 (3.1%) 9
    Injury, poisoning and procedural complications
    Fall 3/90 (3.3%) 3 5/86 (5.8%) 6 1/52 (1.9%) 1 9/228 (3.9%) 10
    Investigations
    Alanine aminotransferase increased 15/90 (16.7%) 20 10/86 (11.6%) 12 1/52 (1.9%) 3 26/228 (11.4%) 35
    Amylase increased 10/90 (11.1%) 14 10/86 (11.6%) 10 7/52 (13.5%) 8 27/228 (11.8%) 32
    Aspartate aminotransferase increased 15/90 (16.7%) 22 8/86 (9.3%) 10 3/52 (5.8%) 5 26/228 (11.4%) 37
    Blood alkaline phosphatase increased 7/90 (7.8%) 7 3/86 (3.5%) 4 2/52 (3.8%) 2 12/228 (5.3%) 13
    Blood creatinine increased 7/90 (7.8%) 8 7/86 (8.1%) 11 4/52 (7.7%) 4 18/228 (7.9%) 23
    Gamma-glutamyltransferase increased 5/90 (5.6%) 5 7/86 (8.1%) 12 3/52 (5.8%) 3 15/228 (6.6%) 20
    Lipase increased 7/90 (7.8%) 9 6/86 (7%) 7 5/52 (9.6%) 5 18/228 (7.9%) 21
    Neutrophil count decreased 4/90 (4.4%) 8 14/86 (16.3%) 20 0/52 (0%) 0 18/228 (7.9%) 28
    Platelet count decreased 5/90 (5.6%) 9 9/86 (10.5%) 12 0/52 (0%) 0 14/228 (6.1%) 21
    Weight decreased 10/90 (11.1%) 10 8/86 (9.3%) 9 7/52 (13.5%) 7 25/228 (11%) 26
    Metabolism and nutrition disorders
    Decreased appetite 19/90 (21.1%) 23 20/86 (23.3%) 23 8/52 (15.4%) 11 47/228 (20.6%) 57
    Dehydration 4/90 (4.4%) 5 2/86 (2.3%) 2 3/52 (5.8%) 6 9/228 (3.9%) 13
    Hypercalcaemia 5/90 (5.6%) 6 1/86 (1.2%) 1 1/52 (1.9%) 1 7/228 (3.1%) 8
    Hyperglycaemia 4/90 (4.4%) 6 6/86 (7%) 6 2/52 (3.8%) 5 12/228 (5.3%) 17
    Hypoalbuminaemia 1/90 (1.1%) 3 5/86 (5.8%) 6 0/52 (0%) 0 6/228 (2.6%) 9
    Hypokalaemia 9/90 (10%) 13 8/86 (9.3%) 12 1/52 (1.9%) 1 18/228 (7.9%) 26
    Hypomagnesaemia 8/90 (8.9%) 12 7/86 (8.1%) 10 1/52 (1.9%) 1 16/228 (7%) 23
    Hyponatraemia 4/90 (4.4%) 4 6/86 (7%) 11 1/52 (1.9%) 1 11/228 (4.8%) 16
    Musculoskeletal and connective tissue disorders
    Arthralgia 14/90 (15.6%) 21 10/86 (11.6%) 13 5/52 (9.6%) 5 29/228 (12.7%) 39
    Back pain 14/90 (15.6%) 18 10/86 (11.6%) 10 8/52 (15.4%) 9 32/228 (14%) 37
    Bone pain 5/90 (5.6%) 8 0/86 (0%) 0 3/52 (5.8%) 3 8/228 (3.5%) 11
    Muscular weakness 6/90 (6.7%) 6 3/86 (3.5%) 3 2/52 (3.8%) 3 11/228 (4.8%) 12
    Myalgia 5/90 (5.6%) 5 3/86 (3.5%) 3 2/52 (3.8%) 2 10/228 (4.4%) 10
    Neck pain 5/90 (5.6%) 5 2/86 (2.3%) 2 1/52 (1.9%) 1 8/228 (3.5%) 8
    Pain in extremity 11/90 (12.2%) 12 5/86 (5.8%) 5 2/52 (3.8%) 3 18/228 (7.9%) 20
    Nervous system disorders
    Dizziness 16/90 (17.8%) 17 13/86 (15.1%) 17 5/52 (9.6%) 7 34/228 (14.9%) 41
    Dysgeusia 8/90 (8.9%) 9 5/86 (5.8%) 6 0/52 (0%) 0 13/228 (5.7%) 15
    Headache 14/90 (15.6%) 18 11/86 (12.8%) 13 5/52 (9.6%) 7 30/228 (13.2%) 38
    Hypoaesthesia 7/90 (7.8%) 7 7/86 (8.1%) 8 0/52 (0%) 0 14/228 (6.1%) 15
    Neuropathy peripheral 14/90 (15.6%) 14 10/86 (11.6%) 10 1/52 (1.9%) 2 25/228 (11%) 26
    Paraesthesia 6/90 (6.7%) 6 1/86 (1.2%) 1 0/52 (0%) 0 7/228 (3.1%) 7
    Psychiatric disorders
    Anxiety 3/90 (3.3%) 3 5/86 (5.8%) 5 2/52 (3.8%) 2 10/228 (4.4%) 10
    Insomnia 16/90 (17.8%) 16 7/86 (8.1%) 7 2/52 (3.8%) 2 25/228 (11%) 25
    Renal and urinary disorders
    Acute kidney injury 4/90 (4.4%) 4 6/86 (7%) 6 0/52 (0%) 0 10/228 (4.4%) 10
    Respiratory, thoracic and mediastinal disorders
    Cough 10/90 (11.1%) 10 11/86 (12.8%) 13 12/52 (23.1%) 14 33/228 (14.5%) 37
    Dyspnoea 12/90 (13.3%) 14 11/86 (12.8%) 11 7/52 (13.5%) 7 30/228 (13.2%) 32
    Epistaxis 7/90 (7.8%) 7 6/86 (7%) 8 1/52 (1.9%) 1 14/228 (6.1%) 16
    Haemoptysis 4/90 (4.4%) 4 7/86 (8.1%) 9 3/52 (5.8%) 3 14/228 (6.1%) 16
    Oropharyngeal pain 5/90 (5.6%) 5 2/86 (2.3%) 2 1/52 (1.9%) 1 8/228 (3.5%) 8
    Pneumonitis 2/90 (2.2%) 2 6/86 (7%) 7 0/52 (0%) 0 8/228 (3.5%) 9
    Productive cough 5/90 (5.6%) 5 1/86 (1.2%) 1 4/52 (7.7%) 4 10/228 (4.4%) 10
    Rhinorrhoea 10/90 (11.1%) 12 0/86 (0%) 0 2/52 (3.8%) 2 12/228 (5.3%) 14
    Skin and subcutaneous tissue disorders
    Alopecia 11/90 (12.2%) 11 16/86 (18.6%) 16 0/52 (0%) 0 27/228 (11.8%) 27
    Pruritus 12/90 (13.3%) 13 11/86 (12.8%) 14 6/52 (11.5%) 11 29/228 (12.7%) 38
    Rash 22/90 (24.4%) 35 18/86 (20.9%) 25 10/52 (19.2%) 13 50/228 (21.9%) 73
    Rash maculo-papular 5/90 (5.6%) 5 2/86 (2.3%) 2 0/52 (0%) 0 7/228 (3.1%) 7
    Vascular disorders
    Hypertension 5/90 (5.6%) 7 3/86 (3.5%) 4 0/52 (0%) 0 8/228 (3.5%) 11

    Limitations/Caveats

    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).

    More Information

    Certain Agreements

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

    Clinical Study Agreement

    Results Point of Contact

    Name/Title Study Director
    Organization Incyte Corporation
    Phone 855-463-3463
    Email medinfo@incyte.com
    Responsible Party:
    Incyte Corporation
    ClinicalTrials.gov Identifier:
    NCT03322566
    Other Study ID Numbers:
    • KEYNOTE-715-06/ECHO-306-06
    • 2017-001810-27
    First Posted:
    Oct 26, 2017
    Last Update Posted:
    Jan 24, 2022
    Last Verified:
    Jan 1, 2022