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

Phase 2

Completed

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).

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Pembrolizumab + Epacadostat	Epacadostat	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.
Pembrolizumab + Placebo	Placebo	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.
Pembrolizumab + Epacadostat	Pembrolizumab	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.
Pembrolizumab + Placebo	Pembrolizumab	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.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) of Pembrolizumab Plus Epacadostat Versus Pembrolizumab Plus Placebo	Up to approximately 6 months	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).

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events (AEs)	Up to 37 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.
Progression-free Survival (PFS) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo	Up to approximately 36 months	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.
Overall Survival (OS) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo	Up to approximately 36 months	OS is defined as the time from randomization to death due to any cause.
Duration of Response (DOR) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo	Up to approximately 36 months	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.
Number of Participants Who Discontinued Study Drug Due to AEs	Up to 37 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.

Locations (99): Pacific Cancer Medical Center, Inc.
🇺🇸
Anaheim, California, United States
Innovative Clinical Research Institute
🇺🇸
Whittier, California, United States
Florida Cancer Specialists (South Region)
🇺🇸
Fort Myers, Florida, United States
Florida Cancer Specialists (North Region)
🇺🇸
Saint Petersburg, Florida, United States
Southeastern Regional Medical Center, Inc.
🇺🇸
Newnan, Georgia, United States
Anne Arundel Health System Research Institute
🇺🇸
Annapolis, Maryland, United States
Weinberg Cancer Institute at Franklin Square
🇺🇸
Baltimore, Maryland, United States
Maryland Oncology Hematology, P.A.
🇺🇸
Rockville, Maryland, United States
UMass Memorial Medical Center
🇺🇸
Worcester, Massachusetts, United States
Minnesota Oncology Hematology, PA
🇺🇸
Coon Rapids, Minnesota, United States
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Pacific Cancer Medical Center, Inc.
🇺🇸Anaheim, California, United States