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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
Last Update Posted : August 15, 2018
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Incyte Corporation

Brief Summary:
The purpose of this study is to evaluate the efficacy and safety of pembrolizumab + epacadostat vs pembrolizumab + placebo as a treatment for recurrent or progressive metastatic urothelial carcinoma in patients who have failed a first-line platinum-containing chemotherapy regimen for advanced/metastatic disease.

Condition or disease Intervention/treatment Phase
UC (Urothelial Cancer) Drug: Pembrolizumab Drug: Epacadostat Drug: Placebo Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 84 participants
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
Official Title: A Phase 3 Randomized, Double-Blind Clinical Study of Pembrolizumab + Epacadostat vs Pembrolizumab + Placebo as a Treatment for Recurrent or Progressive Metastatic Urothelial Carcinoma in Patients Who Have Failed a First-Line Platinum-containing Chemotherapy Regimen for Advanced/Metastatic Disease (KEYNOTE-698/ECHO-303)
Actual Study Start Date : December 22, 2017
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment Group 1
Pembrolizumab + epacadostat
Drug: Pembrolizumab
Pembrolizumab administered intravenously every 3 weeks.
Other Name: MK-3475

Drug: Epacadostat
Epacadostat administered orally twice daily.
Other Name: INCB024360

Active Comparator: Treatment Group 2
Pembrolizumab + placebo
Drug: Pembrolizumab
Pembrolizumab administered intravenously every 3 weeks.
Other Name: MK-3475

Drug: Placebo
Matching placebo administered orally twice daily.




Primary Outcome Measures :
  1. Objective response rate with pembrolizumab + epacadostat versus pembrolizumab + placebo [ Time Frame: Up to 8 months ]
    Defined as the proportion of participants who have a best response of complete response (CR) or partial response (PR) per RECIST v1.1 by investigator determination.


Secondary Outcome Measures :
  1. Number of participants experiencing adverse events (AEs) compared between pembrolizumab + epacadostat versus pembrolizumab + placebo [Safety and Tolerability] [ Time Frame: Up to 27 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.

  2. Number of participants discontinuing study treatment due to AEs compared between pembrolizumab + epacadostat versus pembrolizumab + placebo [Safety and Tolerability] [ Time Frame: Up to 27 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically-confirmed diagnosis of urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra, that is transitional cell, or mixed transitional/non-transitional (predominantly transitional) cell type.
  • Progression or recurrence of urothelial carcinoma following one prior platinum containing chemotherapy regimen for metastatic or unresectable locally advanced disease. A participant who receives a neoadjuvant or adjuvant platinum-containing regimen following cystectomy for localized muscle-invasive urothelial carcinoma is acceptable (without further systemic treatment), if recurrence/progression occurs ≤ 12 months following completion of therapy.
  • Measurable disease based on RECIST v1.1.
  • Have provided an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated for PD-L1 analysis.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Adequate organ function per protocol-defined criteria.

Exclusion Criteria:

  • Urothelial carcinoma that is suitable for local therapy with curative intent.
  • History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful.
  • 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.
  • 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 (HBsAg reactive) or has active hepatitis C (HCV RNA). Note: Testing must be performed to determine eligibility.
  • Use of protocol-defined prior/concomitant therapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03374488


  Show 136 Study Locations
Sponsors and Collaborators
Incyte Corporation
Merck Sharp & Dohme Corp.
Investigators
Study Director: Mark Jones, MD Incyte Corporation

Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT03374488     History of Changes
Other Study ID Numbers: 698-03/ECHO-303-03
First Posted: December 15, 2017    Key Record Dates
Last Update Posted: August 15, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
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:
Urothelial carcinoma
programmed cell death protein 1 (PD-1) inhibitor
indoleamine 2,3-dioxygenase (IDO) inhibitor

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Pembrolizumab
Antineoplastic Agents