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Pembrolizumab + Epacadostat vs Pembrolizumab + Placebo in Recurrent or Progressive Metastatic Urothelial Carcinoma

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ClinicalTrials.gov Identifier: NCT03374488
Recruitment Status : Active, not recruiting
First Posted : December 15, 2017
Results First Posted : August 26, 2019
Last Update Posted : August 26, 2019
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 84
Recruitment Details This study was conducted at 82 centers in 16 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 Day 1 of each cycle every 3 weeks. Epacadostat administered orally twice daily. Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks. Matching placebo administered orally twice daily.
Period Title: Overall Study
Started 42 42
Intention-to-Treat (ITT) 42 42
All Participants as Treated (APaT) 42 41
Completed [1] 1 5
Not Completed 41 37
Reason Not Completed
Death             10             8
Withdrawal by Subject             1             1
On-going at clinical cut off date             30             28
[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 Day 1 of each cycle every 3 weeks. Epacadostat administered orally twice daily. Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks. Matching placebo administered orally twice daily. Total of all reporting groups
Overall Number of Baseline Participants 42 42 84
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 42 participants 42 participants 84 participants
67.9  (8.7) 65.2  (10.0) 66.5  (9.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 42 participants 42 participants 84 participants
Female
7
  16.7%
5
  11.9%
12
  14.3%
Male
35
  83.3%
37
  88.1%
72
  85.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 42 participants 42 participants 84 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
38
  90.5%
37
  88.1%
75
  89.3%
Unknown or Not Reported
4
   9.5%
5
  11.9%
9
  10.7%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 42 participants 42 participants 84 participants
Asian
5
  11.9%
6
  14.3%
11
  13.1%
White
35
  83.3%
32
  76.2%
67
  79.8%
Missing
2
   4.8%
4
   9.5%
6
   7.1%
Metastasis Status at Screening  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 42 participants 42 participants 84 participants
Metastatic
35
  83.3%
40
  95.2%
75
  89.3%
Advanced/Unresectable
7
  16.7%
2
   4.8%
9
  10.7%
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 complete response (CR), disappearance of all target lesions or partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions per RECIST v1.1 by investigator determination.
Time Frame up to 9 weeks +14 days
Hide Outcome Measure Data
Hide Analysis Population Description

The Intention-to-Treat (ITT) population consisted of all randomized participants.

Responses are based on Investigator assessments per RECIST 1.1 without confirmation using all scans up to week 9 (day 63) + 14 days.

Arm/Group Title Pembrolizumab 200 mg + Epacadostat 100 mg BID Pembrolizumab 200 mg + Placebo BID
Hide Arm/Group Description:
Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks. Epacadostat administered orally twice daily.
Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks. Matching placebo administered orally twice daily.
Overall Number of Participants Analyzed 42 42
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
21.4
(12.49 to 43.26)
9.5
(3.11 to 26.06)
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 8 months
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 Day 1 of each cycle every 3 weeks. Epacadostat administered orally twice daily.
Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks. Matching placebo administered orally twice daily.
Overall Number of Participants Analyzed 42 41
Measure Type: Count of Participants
Unit of Measure: Participants
41
  97.6%
37
  90.2%
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 8 months
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 Day 1 of each cycle every 3 weeks. Epacadostat administered orally twice daily.
Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks. Matching placebo administered orally twice daily.
Overall Number of Participants Analyzed 42 41
Measure Type: Count of Participants
Unit of Measure: Participants
3
   7.1%
5
  12.2%
Time Frame Non-serious adverse events were reported from start of study, up to 30 days after last dose and serious adverse events up to 90 days after last dose are included, up to 8 months
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 Day 1 of each cycle every 3 weeks. Epacadostat administered orally twice daily. Pembrolizumab administered intravenously Day 1 of each cycle 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   10/42 (23.81%)   9/42 (21.43%) 
Show Serious Adverse Events Hide Serious Adverse Events
Pembrolizumab 200 mg + Epacadostat 100 mg BID Pembrolizumab 200 mg + Placebo BID
Affected / at Risk (%) Affected / at Risk (%)
Total   11/42 (26.19%)   12/41 (29.27%) 
Blood and lymphatic system disorders     
Anaemia  1  1/42 (2.38%)  1/41 (2.44%) 
Histiocytosis haematophagic  1  0/42 (0.00%)  1/41 (2.44%) 
Cardiac disorders     
Myocardial infarction  1  1/42 (2.38%)  1/41 (2.44%) 
Gastrointestinal disorders     
Diverticular perforation  1  1/42 (2.38%)  0/41 (0.00%) 
Gastrointestinal disorder  1  0/42 (0.00%)  1/41 (2.44%) 
Ileus  1  2/42 (4.76%)  0/41 (0.00%) 
Hepatobiliary disorders     
Cholecystitis acute  1  1/42 (2.38%)  0/41 (0.00%) 
Infections and infestations     
Bacteraemia  1  1/42 (2.38%)  0/41 (0.00%) 
Bronchitis  1  0/42 (0.00%)  1/41 (2.44%) 
Pneumonia  1  0/42 (0.00%)  1/41 (2.44%) 
Pyelonephritis  1  1/42 (2.38%)  0/41 (0.00%) 
Urinary tract infection  1  2/42 (4.76%)  3/41 (7.32%) 
Injury, poisoning and procedural complications     
Radius fracture  1  0/42 (0.00%)  1/41 (2.44%) 
Urinary tract stoma complication  1  0/42 (0.00%)  1/41 (2.44%) 
Investigations     
Amylase increased  1  1/42 (2.38%)  0/41 (0.00%) 
Nervous system disorders     
Ataxia  1  1/42 (2.38%)  0/41 (0.00%) 
Hypoxic-ischaemic encephalopathy  1  0/42 (0.00%)  1/41 (2.44%) 
Peripheral motor neuropathy  1  1/42 (2.38%)  0/41 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  0/42 (0.00%)  1/41 (2.44%) 
Chronic kidney disease  1  0/42 (0.00%)  1/41 (2.44%) 
Haematuria  1  2/42 (4.76%)  1/41 (2.44%) 
Hydronephrosis  1  1/42 (2.38%)  0/41 (0.00%) 
Urinary retention  1  0/42 (0.00%)  1/41 (2.44%) 
Reproductive system and breast disorders     
Pelvic pain  1  0/42 (0.00%)  1/41 (2.44%) 
Respiratory, thoracic and mediastinal disorders     
Pneumonia aspiration  1  1/42 (2.38%)  0/41 (0.00%) 
Pneumonitis  1  1/42 (2.38%)  0/41 (0.00%) 
Pulmonary embolism  1  1/42 (2.38%)  0/41 (0.00%) 
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events 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   37/42 (88.10%)   27/41 (65.85%) 
Blood and lymphatic system disorders     
Anaemia  1  9/42 (21.43%)  8/41 (19.51%) 
Gastrointestinal disorders     
Abdominal pain  1  4/42 (9.52%)  1/41 (2.44%) 
Constipation  1  10/42 (23.81%)  5/41 (12.20%) 
Diarrhoea  1  5/42 (11.90%)  3/41 (7.32%) 
Dry mouth  1  3/42 (7.14%)  1/41 (2.44%) 
Nausea  1  7/42 (16.67%)  5/41 (12.20%) 
Vomiting  1  4/42 (9.52%)  2/41 (4.88%) 
General disorders     
Asthenia  1  3/42 (7.14%)  7/41 (17.07%) 
Chest pain  1  1/42 (2.38%)  4/41 (9.76%) 
Fatigue  1  12/42 (28.57%)  5/41 (12.20%) 
Pyrexia  1  7/42 (16.67%)  3/41 (7.32%) 
Infections and infestations     
Urinary tract infection  1  6/42 (14.29%)  6/41 (14.63%) 
Metabolism and nutrition disorders     
Decreased appetite  1  9/42 (21.43%)  4/41 (9.76%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  3/42 (7.14%)  1/41 (2.44%) 
Groin pain  1  3/42 (7.14%)  0/41 (0.00%) 
Musculoskeletal pain  1  3/42 (7.14%)  1/41 (2.44%) 
Renal and urinary disorders     
Dysuria  1  4/42 (9.52%)  1/41 (2.44%) 
Haematuria  1  7/42 (16.67%)  1/41 (2.44%) 
Renal impairment  1  3/42 (7.14%)  0/41 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  3/42 (7.14%)  2/41 (4.88%) 
Skin and subcutaneous tissue disorders     
Pruritus  1  6/42 (14.29%)  3/41 (7.32%) 
Rash  1  5/42 (11.90%)  4/41 (9.76%) 
Rash maculo-papular  1  3/42 (7.14%)  0/41 (0.00%) 
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: NCT03374488     History of Changes
Other Study ID Numbers: KEYNOTE-698/ECHO-303
First Submitted: December 11, 2017
First Posted: December 15, 2017
Results First Submitted: July 26, 2019
Results First Posted: August 26, 2019
Last Update Posted: August 26, 2019