Pembrolizumab Plus Epacadostat vs Pembrolizumab Plus Placebo in Metastatic Non-Small Cell Lung Cancer (KEYNOTE-654-05/ECHO-305-05)
Condition: Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Pembrolizumab; Epacadostat; Placebo
Intervention description: Pembrolizumab administered intravenously every 3 weeks.; Epacadostat administered orally twice daily.; Matching placebo administered orally twice daily.
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: With the implementation of Amendment 05 the study is no longer blinded.
Enrollment: 154.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: non-small cell lung cancer; programmed cell death 1 (PD-1) inhibitor; indoleamine 2; 3-dioxygenase 1 (IDO1) inhibitor

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).
    

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.