Pembrolizumab (MK-3475) Plus Epacadostat vs Standard of Care in mRCC (KEYNOTE-679/ECHO-302)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study was to evaluate the efficacy and safety of pembrolizumab plus epacadostat compared to sunitinib or pazopanib in participants with locally advanced/metastatic renal cell carcinoma (mRCC) with a clear cell component who have not received prior systemic therapy for their mRCC.

Official Title
-----------------
A Randomized, Open-Label, Phase 3 Study to Evaluate Efficacy and Safety of Pembrolizumab (MK-3475) Plus Epacadostat vs Standard of Care (Sunitinib or Pazopanib) as First-Line Treatment for Locally Advanced or Metastatic Renal Cell Carcinoma (mRCC) (KEYNOTE-679/ECHO-302)

Conditions
-----------------
Renal Cell Carcinoma (RCC)

Intervention / Treatment
-----------------
* Drug: Pembrolizumab
* Drug: Epacadostat
* Drug: Sunitinib
* Drug: Pazopanib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologic confirmation of locally advanced or metastatic RCC with a clear-cell component with or without sarcomatoid features. Must not have received any prior systemic therapy for their mRCC. Measurable disease based on RECIST v1.1. Archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion as required. Karnofsky performance status ≥ 70%. Adequate organ function per protocol-defined criteria. Exclusion Criteria: Use of protocol-defined prior/concomitant therapy. Currently receiving or has received an investigational treatment as part of a study of an investigational agent or has used an investigational device within 4 weeks before randomization. History of severe hypersensitivity reaction to study treatments or their excipients. Active autoimmune disease that has required systemic treatment in past 2 years. Known additional malignancy that has progressed or has required active treatment in the last 3 years. Known active central nervous system metastases and/or carcinomatous meningitis. History of (noninfectious) pneumonitis that required steroids or current pneumonitis. History or presence of an abnormal electrocardiogram that, in the investigator's opinion, is clinically meaningful. Significant cardiac event within 12 months before Cycle 1 Day 1.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pembrolizumab + Epacadostat<br> | Drug: Pembrolizumab<br>* Pembrolizumab 200 mg administered intravenously every 3 weeks.<br>* Other names: MK-3475;Drug: Epacadostat<br>* Epacadostat 100 mg administered orally twice daily.<br>* Other names: INCB024360;|
| Active Comparator: SoC (Sunitinib or Pazopanib)<br>Standard of care (SoC) (sunitinib or pazopanib monotherapy). | Drug: Sunitinib<br>* Sunitinib 50 mg administered orally once daily; 4 weeks on, 2 weeks off for 6-wk cycle.<br>* Other names: SU11248;Drug: Pazopanib<br>* Pazopanib 800 mg administered orally once daily.<br>* Other names: Votrient;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) of Pembrolizumab + Epacadostat Versus Standard of Care (SOC) | ORR was defined as the percentage of participants who had complete response (CR) or partial response (PR) per RECIST v1.1 by investigator determination. | Minimum up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of Pembrolizumab + Epacadostat Versus SOC as Measured by the Number of Participants Experiencing Adverse Events (AEs) | 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. | Data reported from start of study to data cutoff 28-Feb-2019, up to 15 months. | 
| Safety and Tolerability of Pembrolizumab + Epacadostat Versus SOC as Measured by the Number of Participants Discontinuing Study Drug Due to AEs | 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. | Data reported from start of study to data cutoff 28-Feb-2019, up to 15 months. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Renal cell carcinoma, programmed cell death 1 (PD-1) inhibitor, indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitor