Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Randomized, Open-label Clinical Trial of Pembrolizumab (MK-3475) Versus Paclitaxel in Subjects With Advanced Gastric or Gastroesophageal Junction Adenocarcinoma Who Progressed After First-Line Therapy With Platinum and Fluoropyrimidine
Brief 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.


Options:
A: Inclusion Criteria:

* Men \& women ≥20 years of age
* Unresectable advanced or recurrent gastric cancer (including esophagogastric junction cancer)
* Histologically confirmed adenocarcinoma
* Refractory to or intolerant of standard therapy
* ECOG Performance Status score 0 or 1
* A life expectancy of at least 3 months

Exclusion Criteria:

* Current or past history of severe hypersensitivity to any other antibody products
* Patients with multiple primary cancers
* Patients with any metastasis in the brain or meninx that is symptomatic or requires treatment
* Patients with active, known or suspected autoimmune disease
B: 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
C: Inclusion Criteria:

* Histologically proven inoperable advanced gastric adenocarcinoma (including adenocarcinoma of the gastroesophageal junction) or relapse gastric adenocarcinoma
* Subjects must be able to take orally
* Subjects must be confirmed to be PD status by picture diagnosis after first-line chemotherapy using S-1 alone, S-1 + Cisplatinum or S-1 + taxane, except S-1 + CPT-11
* Within 4 weeks from the diagnosis of PD
* Total dosage of S-1 at the first-line is over 2,240mg/m2 in S-1 alone treatment, 1,680mg/m2 in the S-1 combination
* ECOG performance status ≤ 1
* Follow up Age 20 or over
* Life expectancy estimated more than 12 weeks
* Hgb ≥ 8 g/dL, WBC 4,000-12,000/mm3, ANC ≥ 2,000/mm3, platelets ≥ 100,000/mm3
* Creatinine ≤ upper normal limit (UNL)
* Total bilirubin ≤ 1.5 X UNL
* Written informed consent

Exclusion Criteria:

* S-1 + CPT-11 was employed as a first-line
* Any other cytotoxic agents therapy, immuno-therapy, radiation-therapy
* After S-1 adjuvant
* Suspended cases by adverse events by S-1 or S-1 combination
* Excessive amounts of ascites require drainage
* Known brain metastases
* History of hypersensitivity to fluoropyrimidines and CPT-11
* Pregnancy or lactation women, or women with suspected pregnancy or men with willing to get pregnant
* Active double cancer
* Gastrointestinal bleeding
* Any subject judged by the investigator to be unfit for any reason to participate in the study
D: 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

Answer: B