Pembrolizumab Plus Epacadostat vs Pembrolizumab Plus Placebo in Metastatic Non-Small Cell Lung Cancer (KEYNOTE-654-05/ECHO-305-05)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the efficacy and safety of pembrolizumab plus epacadostat compared to pembrolizumab plus placebo as first-line treatment in participants with metastatic non-small cell lung cancer (NSCLC) expressing high levels of programmed cell death ligand 1 (PD-L1).

Official Title
-----------------
A Phase 2, Randomized, Double-Blind Study of Pembrolizumab (MK-3475) Plus Epacadostat (INCB024360) Versus Pembrolizumab Plus Placebo as First-Line Treatment in Patients With Metastatic Non-Small Cell Lung Cancer Expressing High Levels of PD-L1

Conditions
-----------------
Lung Cancer

Intervention / Treatment
-----------------
* Drug: Pembrolizumab
* Drug: Epacadostat
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed diagnosis of stage IV NSCLC without epidermal growth factor receptor (EGFR)-sensitizing mutation, ROS1 and/or anaplastic lymphoma kinase (ALK) translocation. Measurable disease based on RECIST 1.1. Tumor tissue that demonstrates programmed cell death ligand 1 (PD-L1) expression in ≥ 50% of tumor cells (tumor proportion score [TPS] ≥ 50%) as assessed by immunohistochemistry at a central laboratory. Life expectancy of at least 3 months. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Adequate organ function per protocol-defined criteria. Exclusion Criteria: Known untreated central nervous system metastases and/or carcinomatous meningitis. History of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease. Symptomatic ascites or pleural effusion. Known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy. Active autoimmune disease that has required systemic treatment in past 2 years. Has had an allogeneic tissue/solid organ transplant. Has a known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by the local health authority. Has 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. History or presence of an abnormal electrocardiogram (ECG) that, in the Investigator's opinion, is clinically meaningful. Use of protocol-defined prior/concomitant therapy.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pembrolizumab + Epacadostat<br>Participants received pembrolizumab 200 mg as an intravenous (IV) infusion, every three weeks (Q3W) starting on Day 1 of each cycle for up to 35 administrations in combination with epacadostat 100 mg orally, twice daily. Epacodostat administration was discontinued after the implementation of protocol amendment 05. | Drug: Pembrolizumab<br>* Pembrolizumab administered intravenously every 3 weeks.<br>* Other names: MK-3475;Drug: Epacadostat<br>* Epacadostat administered orally twice daily.<br>* Other names: INCB024360;|
| Active Comparator: Pembrolizumab + Placebo<br>Participants received pembrolizumab 200 mg by IV infusion, Q3W starting on Day 1 of each cycle for up to 35 administrations in combination with matching placebo orally, twice daily. Placebo administration was discontinued after the implementation of protocol amendment 05. | Drug: Pembrolizumab<br>* Pembrolizumab administered intravenously every 3 weeks.<br>* Other names: MK-3475;Drug: Placebo<br>* Matching placebo administered orally twice daily.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) of Pembrolizumab Plus Epacadostat Versus Pembrolizumab Plus Placebo | ORR is defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 based on blinded independent central review (BICR). | Up to approximately 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo | PFS is defined as the time from randomization to the first documented progressive disease per RECIST v1.1 based on BICR or death due to any cause, whichever occurs first. | Up to approximately 36 months | 
| Overall Survival (OS) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo | OS is defined as the time from randomization to death due to any cause. | Up to approximately 36 months | 
| Duration of Response (DOR) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo | DOR is defined as the time from the earliest date of qualifying response until earliest date of disease progression per RECIST v1.1 or death from any cause, whichever comes first. | Up to approximately 36 months | 
| Number of Participants With 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. | Up to 37 months | 
| Number of Participants Who Discontinued 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. | Up to 37 months | 

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