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Pembrolizumab in Combination With Epacadostat or Placebo in Cisplatin-ineligible Urothelial Carcinoma (KEYNOTE-672/ECHO-307)

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: NCT03361865
Recruitment Status : Completed
First Posted : December 5, 2017
Results First Posted : August 29, 2019
Last Update Posted : September 14, 2020
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: None (Open Label);   Primary Purpose: Treatment
Condition UC (Urothelial Cancer)
Interventions Drug: Pembrolizumab
Drug: Epacadostat
Drug: Placebo
Enrollment 93
Recruitment Details This study was conducted at 98 centers in 17 countries.
Pre-assignment Details  
Arm/Group Title Pembrolizumab 200 mg + Epacadostat 100 mg BID Pembrolizumab 200 mg + Placebo BID
Hide Arm/Group Description Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily. Pembrolizumab administered intravenously every 3 weeks. Matching placebo administered orally twice daily.
Period Title: Overall Study
Started 44 49
Intention-to-Treat (ITT) 44 49
All Participants as Treated (APaT) 43 49
Completed [1] 1 0
Not Completed 43 49
Reason Not Completed
Death             13             10
Physician Decision             1             0
On-going at clinical cut off date             29             39
[1]
Refers to participants that discontinued study with amendment 4, and didn't require follow-up.
Arm/Group Title Pembrolizumab 200 mg + Epacadostat 100 mg BID Pembrolizumab 200 mg + Placebo BID Total
Hide Arm/Group Description Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily. Pembrolizumab administered intravenously every 3 weeks. Matching placebo administered orally twice daily. Total of all reporting groups
Overall Number of Baseline Participants 44 49 93
Hide Baseline Analysis Population Description
The Intention-to-Treat (ITT) population consisted of all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 44 participants 49 participants 93 participants
73.3  (9.5) 72.4  (8.9) 72.8  (9.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 49 participants 93 participants
Female
11
  25.0%
11
  22.4%
22
  23.7%
Male
33
  75.0%
38
  77.6%
71
  76.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 49 participants 93 participants
Hispanic or Latino
2
   4.5%
0
   0.0%
2
   2.2%
Not Hispanic or Latino
35
  79.5%
42
  85.7%
77
  82.8%
Unknown or Not Reported
7
  15.9%
7
  14.3%
14
  15.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 49 participants 93 participants
Asian
9
  20.5%
8
  16.3%
17
  18.3%
White
33
  75.0%
37
  75.5%
70
  75.3%
Missing
2
   4.5%
4
   8.2%
6
   6.5%
Metastasis Status at Screening  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 49 participants 93 participants
Metastatic
38
  86.4%
45
  91.8%
83
  89.2%
Advanced/Unresectable
6
  13.6%
4
   8.2%
10
  10.8%
1.Primary Outcome
Title Objective Response Rate (ORR) With Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo
Hide Description

ORR was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 by investigator determination.

Responses are based on Investigator assessments per RECIST 1.1 without confirmation using all scans up to the cutoff date.

Time Frame Week 9
Hide Outcome Measure Data
Hide Analysis Population Description
The Intention-to-Treat (ITT) population consisted of all randomized participants.
Arm/Group Title Pembrolizumab 200 mg + Epacadostat 100 mg BID Pembrolizumab 200 mg + Placebo BID
Hide Arm/Group Description:
Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily.
Pembrolizumab administered intravenously every 3 weeks. Matching placebo administered orally twice daily.
Overall Number of Participants Analyzed 44 49
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
31.8
(22.46 to 55.24)
24.5
(15.33 to 43.67)
2.Secondary Outcome
Title Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Experiencing Adverse Events (AEs)
Hide Description AE is defined as any untoward medical occurrence in a patient 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 approximately 9 months at data cut-off 15-AUG-2018
Hide Outcome Measure Data
Hide Analysis Population Description
All Participants as Treated (APaT) population consisted of all randomized participants who received at least 1 dose of study treatment.
Arm/Group Title Pembrolizumab 200 mg + Epacadostat 100 mg BID Pembrolizumab 200 mg + Placebo BID
Hide Arm/Group Description:
Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily.
Pembrolizumab administered intravenously every 3 weeks. Matching placebo administered orally twice daily.
Overall Number of Participants Analyzed 43 49
Measure Type: Count of Participants
Unit of Measure: Participants
39
  90.7%
43
  87.8%
3.Secondary Outcome
Title Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Discontinuing Study Treatment Due to AE
Hide Description AE is defined as any untoward medical occurrence in a patient 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 approximately 9 months at data cut-off 15-AUG-2018
Hide Outcome Measure Data
Hide Analysis Population Description
All Participants as Treated (APaT) population consisted of all randomized participants who received at least 1 dose of study treatment.
Arm/Group Title Pembrolizumab 200 mg + Epacadostat 100 mg BID Pembrolizumab 200 mg + Placebo BID
Hide Arm/Group Description:
Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily.
Pembrolizumab administered intravenously every 3 weeks. Matching placebo administered orally twice daily.
Overall Number of Participants Analyzed 43 49
Measure Type: Count of Participants
Unit of Measure: Participants
6
  14.0%
7
  14.3%
Time Frame From start of study to data cutoff 15Aug2018, up to approximately 9 months. Non-serious adverse events up to 30 days of last dose and serious adverse events up to 90 days of last dose are included.
Adverse Event Reporting Description

The All Participants as Treated (APaT) population was used for the safety analysis and consisted of all randomized participants who received at least 1 dose of study treatment.

All-Cause Mortality was based on the ITT population and consisted of all randomized participants.

MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to the drug are excluded.

 
Arm/Group Title Pembrolizumab 200 mg + Epacadostat 100 mg BID Pembrolizumab 200 mg + Placebo BID
Hide Arm/Group Description Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily. Pembrolizumab administered intravenously every 3 weeks. Matching placebo administered orally twice daily.
All-Cause Mortality
Pembrolizumab 200 mg + Epacadostat 100 mg BID Pembrolizumab 200 mg + Placebo BID
Affected / at Risk (%) Affected / at Risk (%)
Total   13/44 (29.55%)   10/49 (20.41%) 
Hide Serious Adverse Events
Pembrolizumab 200 mg + Epacadostat 100 mg BID Pembrolizumab 200 mg + Placebo BID
Affected / at Risk (%) Affected / at Risk (%)
Total   13/43 (30.23%)   13/49 (26.53%) 
Blood and lymphatic system disorders     
Anaemia  1  1/43 (2.33%)  0/49 (0.00%) 
Cardiac disorders     
Left ventricular dysfunction  1  1/43 (2.33%)  0/49 (0.00%) 
Supraventricular tachycardia  1  1/43 (2.33%)  0/49 (0.00%) 
Congenital, familial and genetic disorders     
Huntington's disease  1  0/43 (0.00%)  1/49 (2.04%) 
Gastrointestinal disorders     
Nausea  1  1/43 (2.33%)  0/49 (0.00%) 
General disorders     
Death  1  1/43 (2.33%)  0/49 (0.00%) 
Hepatobiliary disorders     
Hepatitis cholestatic  1  0/43 (0.00%)  1/49 (2.04%) 
Immune system disorders     
Anaphylactic reaction  1  0/43 (0.00%)  1/49 (2.04%) 
Infections and infestations     
Encephalitis  1  1/43 (2.33%)  0/49 (0.00%) 
Enterococcal bacteraemia  1  0/43 (0.00%)  1/49 (2.04%) 
Gastroenteritis  1  1/43 (2.33%)  0/49 (0.00%) 
Herpes zoster  1  1/43 (2.33%)  0/49 (0.00%) 
Sepsis  1  0/43 (0.00%)  1/49 (2.04%) 
Septic shock  1  1/43 (2.33%)  0/49 (0.00%) 
Urinary tract infection  1  3/43 (6.98%)  4/49 (8.16%) 
Urosepsis  1  0/43 (0.00%)  1/49 (2.04%) 
Injury, poisoning and procedural complications     
Fall  1  0/43 (0.00%)  1/49 (2.04%) 
Infusion related reaction  1  0/43 (0.00%)  1/49 (2.04%) 
Urinary tract stoma complication  1  1/43 (2.33%)  0/49 (0.00%) 
Metabolism and nutrition disorders     
Hypercalcaemia  1  1/43 (2.33%)  1/49 (2.04%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenocarcinoma of colon  1  0/43 (0.00%)  1/49 (2.04%) 
Nervous system disorders     
Somnolence  1  1/43 (2.33%)  0/49 (0.00%) 
Transient ischaemic attack  1  0/43 (0.00%)  1/49 (2.04%) 
Product Issues     
Device occlusion  1  1/43 (2.33%)  0/49 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  0/43 (0.00%)  2/49 (4.08%) 
Autoimmune nephritis  1  0/43 (0.00%)  1/49 (2.04%) 
Chronic kidney disease  1  0/43 (0.00%)  1/49 (2.04%) 
Haematuria  1  1/43 (2.33%)  0/49 (0.00%) 
Nephropathy toxic  1  1/43 (2.33%)  0/49 (0.00%) 
Renal failure  1  1/43 (2.33%)  0/49 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Interstitial lung disease  1  0/43 (0.00%)  1/49 (2.04%) 
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pembrolizumab 200 mg + Epacadostat 100 mg BID Pembrolizumab 200 mg + Placebo BID
Affected / at Risk (%) Affected / at Risk (%)
Total   36/43 (83.72%)   38/49 (77.55%) 
Blood and lymphatic system disorders     
Anaemia  1  12/43 (27.91%)  8/49 (16.33%) 
Gastrointestinal disorders     
Abdominal pain  1  1/43 (2.33%)  5/49 (10.20%) 
Constipation  1  6/43 (13.95%)  6/49 (12.24%) 
Diarrhoea  1  7/43 (16.28%)  3/49 (6.12%) 
Dry mouth  1  0/43 (0.00%)  3/49 (6.12%) 
Nausea  1  4/43 (9.30%)  4/49 (8.16%) 
Vomiting  1  3/43 (6.98%)  5/49 (10.20%) 
General disorders     
Asthenia  1  7/43 (16.28%)  4/49 (8.16%) 
Fatigue  1  5/43 (11.63%)  7/49 (14.29%) 
Oedema peripheral  1  3/43 (6.98%)  6/49 (12.24%) 
Pyrexia  1  4/43 (9.30%)  5/49 (10.20%) 
Infections and infestations     
Urinary tract infection  1  4/43 (9.30%)  9/49 (18.37%) 
Investigations     
Blood alkaline phosphatase increased  1  0/43 (0.00%)  3/49 (6.12%) 
Blood creatinine increased  1  3/43 (6.98%)  3/49 (6.12%) 
Weight decreased  1  3/43 (6.98%)  3/49 (6.12%) 
Metabolism and nutrition disorders     
Decreased appetite  1  3/43 (6.98%)  5/49 (10.20%) 
Hypoalbuminaemia  1  3/43 (6.98%)  2/49 (4.08%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  3/43 (6.98%)  4/49 (8.16%) 
Psychiatric disorders     
Insomnia  1  3/43 (6.98%)  1/49 (2.04%) 
Renal and urinary disorders     
Haematuria  1  4/43 (9.30%)  4/49 (8.16%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  3/43 (6.98%)  5/49 (10.20%) 
Dyspnoea  1  3/43 (6.98%)  3/49 (6.12%) 
Skin and subcutaneous tissue disorders     
Pruritus  1  8/43 (18.60%)  4/49 (8.16%) 
Rash  1  8/43 (18.60%)  8/49 (16.33%) 
1
Term from vocabulary, MedDRA 21.0
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.
Following the first publication, the Institution and/or Principal Investigator may publish data or results from the Study, provided, however, that the Institution and/or Principal Investigator submits the proposed publication to the Sponsor for review at least sixty (60) days prior to the date of the proposed publication. Sponsor may remove from the proposed publication any information that is considered confidential and/or proprietary other than Study data and results.
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: NCT03361865    
Other Study ID Numbers: KEYNOTE-672/ECHO-307
First Submitted: November 29, 2017
First Posted: December 5, 2017
Results First Submitted: August 9, 2019
Results First Posted: August 29, 2019
Last Update Posted: September 14, 2020