A Study of Pembrolizumab Plus Epacadostat With Platinum-based Chemotherapy Versus Pembrolizumab Plus Platinum-based Chemotherapy Plus Placebo in Metastatic Non-Small Cell Lung Cancer (KEYNOTE-715-06/ECHO-306-06)

Study Overview
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Brief Summary
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The purpose of this study was to evaluate the efficacy and safety of pembrolizumab plus epacadostat with platinum-based chemotherapy versus pembrolizumab plus platinum-based chemotherapy plus placebo as first-line therapy in participants with metastatic non-small cell lung cancer (NSCLC).

Official Title
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A Randomized Phase 2 Study of the Combination of Pembrolizumab (MK-3475) Plus Epacadostat (INCB024360) With Platinum-based Chemotherapy Versus Pembrolizumab Plus Platinum-based Chemotherapy Plus Placebo as First-Line Treatment in Patients With Metastatic Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Pembrolizumab
* Drug: Epacadostat
* Drug: Platinum-based chemotherapy
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 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. Provide tumor tissue sample. Exclusion Criteria: Known untreated central nervous system metastases and/or carcinomatous meningitis History of (non-infectious) 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
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pembrolizumab + Chemotherapy + Epacadostat<br>Participant received pembrolizumab 200 mg intravenous (IV) infusion, every 3 weeks (Q3W) on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat 100 mg tablets, orally, twice daily (BID) in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m^2 IV infusion, Q3W + cisplatin 75 mg/m^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles). | 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;Drug: Platinum-based chemotherapy<br>* Investigator selected one of the following regimens: pemetrexed + cisplatin, pemetrexed + carboplatin, or paclitaxel + carboplatin, depending on histology.<br>|
| Experimental: Pembrolizumab + Chemotherapy + Placebo<br>Participant received pembrolizumab 200 mg IV infusion, Q3W on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat matching placebo tablets, orally, BID in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m^2 IV infusion, Q3W + cisplatin 75 mg/m^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles). | Drug: Pembrolizumab<br>* Pembrolizumab administered intravenously every 3 weeks.<br>* Other names: MK-3475;Drug: Platinum-based chemotherapy<br>* Investigator selected one of the following regimens: pemetrexed + cisplatin, pemetrexed + carboplatin, or paclitaxel + carboplatin, depending on histology.<br>Drug: Placebo<br>* Matching placebo administered orally twice daily.<br>|
| Experimental: Pembrolizumab + Epacadostat<br>Participant received pembrolizumab 200 mg IV infusion, Q3W on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat 100 mg tablets, orally, BID in each 21 day cycle for up to 35 cycles. | 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;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo | ORR is defined as the percentage of participants who have a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) based on blinded independent central review (BICR). | Assessed every 12 weeks up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo | Defined as the time from randomization to the first documented progressive disease (PD) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurs first. | Up to 24 months | 
| Overall Survival of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo | Defined as the time from randomization to death due to any cause. | Up to 24 months | 
| Duration of Response of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo | 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 24 months | 
| Safety and Tolerability of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo as Measured by the Number of Participants Experiencing Adverse Events (AEs) | An AE is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. | Up to 25 months | 
| Safety and Tolerability of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo as Measured by the Number of Participants Discontinuing Study Drug Due to AEs | An AE is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of any study drug, whether or not considered related to the study drug. | Up to 25 months | 

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