A Study of Pembrolizumab (MK-3475) Versus Paclitaxel for Participants With Advanced Gastric/Gastroesophageal Junction Adenocarcinoma That Progressed After Therapy With Platinum and Fluoropyrimidine (MK-3475-061/KEYNOTE-061)
Condition: Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma
MeSH terms: Adenocarcinoma; Esophageal Neoplasms
Intervention: pembrolizumab; paclitaxel
Intervention description: 200 mg administered as IV infusion on Day 1 of each 21-day cycle.; 80 mg/m^2 administered as IV infusion on Days 1, 8, and 15 of each 28-day cycle.
Intervention MeSH terms: Paclitaxel; Pembrolizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 592.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Gastric cancer; Gastroesophageal junction cancer; PD1; PD-1; PDL1; PD-L1

Summary:

      This is a study for participants with advanced gastric or gastroesophageal junction
      adenocarcinoma who have had tumor progression after first-line treatment with platinum and
      fluoropyrimidine doublet therapy. The primary study hypotheses are that pembrolizumab
      (MK-3475) prolongs progression free survival (PFS) and overall survival (OS) for participants
      with tumors that show positive programmed cell death ligand 1 (PD-L1) expression.

      As of 20-March-2016, enrollment will be limited to PD-L1 positive participants.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically- or cytologically-confirmed diagnosis of gastric or gastroesophageal
             junction adenocarcinoma

          -  Confirmed metastatic or locally advanced, unresectable disease (by computed tomography
             [CT] scan or clinical evidence)

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Progression on or after prior first-line therapy containing any
             platinum/fluoropyrimidine doublet

          -  Willing to provide tumor tissue for PD-L1 biomarker analysis (new or archived
             specimens with agreement of Sponsor). As of 20 March 2016, participants must be PD-L1
             positive to be enrolled.

          -  Human epidermal growth factor receptor 2 (HER-2/neu) status known and participants
             with HER2/neu positive tumors show documentation of disease progression on treatment
             containing trastuzumab

          -  Female participants of childbearing potential should be willing to use 2 methods of
             birth control or be surgically sterile, or abstain from heterosexual activity for the
             course of the study through 120 days after the last dose of pembrolizumab or through
             180 days after the last dose of paclitaxel.

          -  Male participants should agree to use an adequate method of contraception starting
             with the first dose of study therapy through 120 days after the last dose of
             pembrolizumab or through 180 days after the last dose of paclitaxel.

          -  Adequate organ function

        Exclusion Criteria:

          -  Currently participating and receiving study therapy, or participated in a study of an
             investigational agent and received study therapy or used an investigation device
             within 4 weeks of the first dose of medication

          -  Squamous cell or undifferentiated gastric cancer

          -  Active autoimmune disease that has required systemic treatment in past 2 years
             (replacement therapy is not considered a form of systemic treatment

          -  Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form
             of immunosuppressive therapy within 7 days prior to the first dose of study medication

          -  Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or not
             recovered from AEs due to agents administered more than 4 weeks earlier

          -  Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2
             weeks prior to study Day 1 or not recovered from adverse events due to a previously
             administered agent or surgery

          -  Known additional malignancy that is progressing or requires active treatment (with the
             exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or
             in situ cervical cancer that has undergone potentially curative therapy)

          -  Known active central nervous system (CNS) metastases and/or carcinomatous meningitis

          -  History of (noninfectious) pneumonitis that required steroids or current pneumonitis

          -  Active infection requiring systemic therapy

          -  Known psychiatric or substance abuse disorders that would interfere with cooperation
             with the requirements of the trial

          -  Pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the screening visit through 120 days
             after the last dose of pembrolizumab or through 180 days after the last dose of
             paclitaxel.

          -  Prior immunotherapy including anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or
             previously participated in Merck pembrolizumab (MK-3475) clinical trial

          -  Known history of human immunodeficiency virus (HIV)

          -  Known active Hepatitis B or Hepatitis C

          -  Live vaccine within 30 days of planned start of study therapy

          -  Known allergy or hypersensitivity to paclitaxel or any components used in the
             paclitaxel preparation or other contraindication for taxane therapy