Study of Pembrolizumab (MK-3475) Versus Investigator's Choice Standard Therapy for Participants With Advanced Esophageal/ Esophagogastric Junction Carcinoma That Progressed After First-Line Therapy (MK-3475-181/KEYNOTE-181)
Condition: Esophageal Carcinoma; Esophagogastric Junction Carcinoma
MeSH terms: Carcinoma; Esophageal Neoplasms
Intervention: pembrolizumab; paclitaxel; docetaxel; irinotecan
Intervention description: 200 mg administered as IV infusion on Day 1 of every 21-day cycle; 80-100 mg/m^2 administered as IV infusion on Days 1, 8, and 15 of each 28-day cycle; 75 mg/m^2 administered as IV infusion on Day 1 of every 21-day cycle; 180 mg/m^2 administered as IV infusion on Day 1 of every 14-day cycle
Intervention MeSH terms: Paclitaxel; Docetaxel; Pembrolizumab; Irinotecan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 628.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1); Programmed Death-Ligand 2 (PDL2, PD-L2); Gene expression profiling (GEP)

Summary:

      In this study, participants with advanced or metastatic adenocarcinoma or squamous cell
      carcinoma of the esophagus or Siewert type I adenocarcinoma of the esophagogastric junction
      (EGJ) that had progressed after first-line standard therapy were randomized to receive either
      pembrolizumab (MK-3475) OR the Investigator's choice of standard chemotherapy with
      paclitaxel, docetaxel, or irinotecan.

      The primary study hypothesis was that treatment with pembrolizumab would prolong overall
      survival (OS) as compared to treatment with standard chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically- or cytologically-confirmed diagnosis of adenocarcinoma or squamous
             cell carcinoma of the esophagus or Siewert type I adenocarcinoma of the EGJ

          -  Metastatic disease or locally advanced, unresectable disease

          -  Life expectancy of greater than 3 months

          -  Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1

          -  Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Scale

          -  Documented radiographic or clinical disease progression on no more or less than one
             previous line of standard therapy

          -  Can provide either a newly obtained or archival tumor tissue sample for intra-tumoral
             immune-related testing and for anti-programmed cell death (PD)-1

          -  Participants of reproductive potential must be willing to use adequate contraception
             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, docetaxel or irinotecan

          -  Adequate organ function

        Exclusion Criteria:

          -  Currently participating and receiving study therapy or has participated in a study of
             an investigational agent and received study therapy or used an investigational device
             within 4 weeks of the first dose of study treatment

          -  Active autoimmune disease that has required systemic treatment in past 2 years

          -  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 treatment

          -  Known central nervous system (CNS) metastases and/or carcinomatous meningitis
             (includes past history or current metastasis)

          -  Has received prior anti-cancer monoclonal antibody (mAb), 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

          -  Has had a severe hypersensitivity reaction to treatment with another mAb

          -  Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1), or anti-PD-L2 agent, or
             previously participated in Merck pembrolizumab (MK-3475) study

          -  Has a known additional malignancy that has progressed or required active treatment
             within the last 5 years with the exception of curatively treated basal cell and
             squamous cell carcinoma of the skin and/or curatively resected in-situ cervical and/or
             breast cancers, and in-situ or intra-mucosal pharyngeal cancer

          -  Received a live vaccine within 30 days of the first dose of study treatment

          -  Known history of human immunodeficiency virus (HIV) infection

          -  Known history of or is positive for hepatitis B or known active hepatitis C

          -  History of non-infectious 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 study

          -  Pregnant, breastfeeding, or expecting to conceive or father children within the
             projected duration of the study starting with the screening visit through 120 days
             after the last dose of pembrolizumab or through 180 days after the last dose of
             paclitaxel, docetaxel or irinotecan

          -  Known allergy, hypersensitivity, or contraindication to paclitaxel, docetaxel, or
             irinotecan or any components used in their preparation

          -  Experienced weight loss >10% over approximately 2 months prior to first dose of study
             treatment

          -  Has ascites or pleural effusion by physical exam

          -  Has experienced documented objective radiographic or clinical disease progression
             during or after receiving >1 line of therapy