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

Incyte

Status and phase: Completed; Phase 2

Conditions: Lung Cancer

Treatments: Drug: Placebo; Drug: Pembrolizumab; Drug: Epacadostat

Study type: Interventional

Funder types: Industry

Identifiers

NCT03322540

2017-001841-28 (EudraCT Number)

KEYNOTE-654-05/ECHO-305-05

Details and patient eligibility

About

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).

Enrollment: 154 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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154 participants in 2 patient groups

Pembrolizumab + Epacadostat

Experimental group

Description:

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.

Treatment:

Drug: Epacadostat

Drug: Pembrolizumab

Pembrolizumab + Placebo

Active Comparator group

Description:

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.

Treatment:

Drug: Pembrolizumab

Drug: Placebo