Clinical Trials /

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

NCT03361865

Description:

The purpose of this study is to evaluate the efficacy and safety of pembrolizumab + epacadostat vs pembrolizumab + placebo in participants with cisplatin-ineligible urothelial carcinoma.

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab in Combination With Epacadostat or Placebo in Cisplatin-ineligible Urothelial Carcinoma (KEYNOTE-672/ECHO-307)
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: 672-00/ECHO-307
  • NCT ID: NCT03361865

Conditions

  • Advanced/Unresectable (Inoperable) Urothelial Cancer
  • Metastatic Urothelial Cancer

Interventions

DrugSynonymsArms
PembrolizumabMK-3475Treatment Group 1
EpacadostatINCB024360Treatment Group 1
PlaceboTreatment Group 2

Purpose

The purpose of this study is to evaluate the efficacy and safety of pembrolizumab + epacadostat vs pembrolizumab + placebo in participants with cisplatin-ineligible urothelial carcinoma.

Trial Arms

NameTypeDescriptionInterventions
Treatment Group 1ExperimentalPembrolizumab + epacadostat
  • Pembrolizumab
  • Epacadostat
Treatment Group 2Active ComparatorPembrolizumab + placebo
  • Pembrolizumab
  • Placebo

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS) with pembrolizumab + epacadostat versus pembrolizumab + placebo
Time Frame:Up to 36 months
Safety Issue:
Description:randomization until disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death from any cause, whichever occurs first.

Secondary Outcome Measures

Measure:Number of participants experiencing adverse events (AEs) compared between pembrolizumab + epacadostat versus pembrolizumab + placebo [Safety and Tolerability]
Time Frame:Up to 39 months
Safety Issue:
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.
Measure:Number of participants discontinuing study treatment due to AEs compared between pembrolizumab + epacadostat versus pembrolizumab + placebo [Safety and Tolerability]
Time Frame:Up to 39 months
Safety Issue:
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.
Measure:Objective response rate with pembrolizumab + epacadostat versus pembrolizumab + placebo
Time Frame:Approximately 24 months
Safety Issue:
Description:Defined as the proportion of participants who have complete response (CR) or partial response (PR) per RECIST v1.1.
Measure:Mean change from baseline in global health status/quality of life scales
Time Frame:Up to 25 months
Safety Issue:
Description: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).
Measure:Time to true deterioration (TTD)
Time Frame:Up to 25 months
Safety Issue:
Description:Defined as the time from baseline to first onset of patient-reported outcome (PRO) deterioration.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Incyte Corporation

Trial Keywords

  • Urothelial cancer, programmed cell death 1 (PD-1) inhibitor
  • indoleamine 2,3-dioxygenase (IDO) inhibitor

Last Updated

January 4, 2018