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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

Tracking Information
First Submitted Date  ICMJE November 29, 2017
First Posted Date  ICMJE December 5, 2017
Results First Submitted Date  ICMJE August 9, 2019
Results First Posted Date  ICMJE August 29, 2019
Last Update Posted Date September 14, 2020
Actual Study Start Date  ICMJE December 4, 2017
Actual Primary Completion Date August 9, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 27, 2019)
Objective Response Rate (ORR) With Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo [ Time Frame: Week 9 ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 29, 2017)
  • Progression-free survival (PFS) with pembrolizumab + epacadostat versus pembrolizumab + placebo [ Time Frame: Up to 36 months ]
    randomization until disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death from any cause, whichever occurs first.
  • Overall survival (OS) with pembrolizumab + epacadostat versus pembrolizumab + placebo [ Time Frame: Up to 36 months ]
    Defined as the time from the date of randomization to the date of death due to any cause.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 27, 2019)
  • Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to approximately 9 months at data cut-off 15-AUG-2018 ]
    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.
  • Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Discontinuing Study Treatment Due to AE [ Time Frame: Up to approximately 9 months at data cut-off 15-AUG-2018 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 29, 2017)
  • Safety and tolerability of pembrolizumab + epacadostat versus pembrolizumab + placebo as measured by number of participants experiencing adverse events (AEs) [ Time Frame: Up to 39 months ]
    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.
  • Safety and tolerability of pembrolizumab + epacadostat versus pembrolizumab + placebo as measured by number of participants discontinuing study treatment due to AEs [ Time Frame: Up to 39 months ]
    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.
  • Objective response rate with pembrolizumab + epacadostat versus pembrolizumab + placebo [ Time Frame: Approximately 24 months ]
    Defined as the proportion of participants who have complete response (CR) or partial response (PR) per RECIST v1.1.
  • Mean change from baseline in global health status/quality of life scales [ Time Frame: Up to 25 months ]
    Global health status/quality of life scales of the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC-QLQ)-C30 (items 29 and 30).
  • Time to true deterioration (TTD) [ Time Frame: Up to 25 months ]
    Defined as the time from baseline to first onset of patient-reported outcome (PRO) deterioration.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pembrolizumab in Combination With Epacadostat or Placebo in Cisplatin-ineligible Urothelial Carcinoma (KEYNOTE-672/ECHO-307)
Official Title  ICMJE A Phase 3 Randomized, Double-Blind Trial of Pembrolizumab (MK-3475) in Combination With Epacadostat (INCB024360) or Placebo in Participants With Cisplatin-ineligible Urothelial Carcinoma (KEYNOTE-672/ECHO-307)
Brief Summary The purpose of this study was to evaluate the efficacy and safety of pembrolizumab + epacadostat vs pembrolizumab + placebo in participants with cisplatin-ineligible urothelial carcinoma.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description:
The study will be unblinded after the last participant completes Week 9 imaging assessment for efficacy analysis and after appropriate EC/IRB approvals have been received.
Primary Purpose: Treatment
Condition  ICMJE UC (Urothelial Cancer)
Intervention  ICMJE
  • Drug: Pembrolizumab
    Pembrolizumab administered intravenously every 3 weeks.
    Other Name: MK-3475
  • Drug: Epacadostat
    Epacadostat administered orally twice daily.
    Other Name: INCB024360
  • Drug: Placebo
    Matching placebo administered orally twice daily.
Study Arms  ICMJE
  • Experimental: Pembrolizumab 200 mg + epacadostat 100 mg BID
    Pembrolizumab + epacadostat
    Interventions:
    • Drug: Pembrolizumab
    • Drug: Epacadostat
  • Active Comparator: Pembrolizumab 200 mg + placebo BID
    Pembrolizumab + placebo
    Interventions:
    • Drug: Pembrolizumab
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 27, 2019)
93
Original Estimated Enrollment  ICMJE
 (submitted: November 29, 2017)
650
Actual Study Completion Date  ICMJE August 4, 2020
Actual Primary Completion Date August 9, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically-confirmed diagnosis of advanced/unresectable (inoperable) or metastatic urothelial cancer of the renal pelvis, ureter, bladder, or urethra.
  • Measurable disease based on RECIST v1.1.
  • Be considered ineligible to receive cisplatin-based combination therapy, based on protocol-defined criteria.
  • Have provided tissue for PD-L1 analysis from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
  • Have received no prior systemic chemotherapy for advanced/unresectable (inoperable) or metastatic urothelial cancer.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 within 14 days prior to randomization.
  • Adequate organ function per protocol-defined criteria.

Exclusion Criteria:

  • Disease that is suitable for local therapy administered with curative intent.
  • Known additional malignancy that is progressing or has required active treatment within the past 3 years.
  • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, ie, without evidence of progression for at least 4 weeks by repeat imaging, clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
  • Active autoimmune disease that has required systemic treatment in past 2 years.
  • Known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by local health authority.
  • Known history of or is positive for active hepatitis B (hepatitis B surface antigen [HBsAg] reactive) or has active hepatitis C (HCV RNA). Note: Testing must be performed to determine eligibility.
  • History of a gastrointestinal condition that in the opinion of the Investigator may affect oral drug absorption.
  • History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful.
  • Use of protocol-defined prior/concomitant therapy.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   France,   Germany,   Ireland,   Israel,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Poland,   Russian Federation,   Spain,   Taiwan,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03361865
Other Study ID Numbers  ICMJE KEYNOTE-672/ECHO-307
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Incyte Corporation
Study Sponsor  ICMJE Incyte Corporation
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Study Director: Mark Jones, MD Incyte Corporation
PRS Account Incyte Corporation
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP