<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03281369</url>
  </required_header>
  <id_info>
    <org_study_id>YO39609</org_study_id>
    <secondary_id>2016-004529-17</secondary_id>
    <nct_id>NCT03281369</nct_id>
  </id_info>
  <brief_title>A Study of Multiple Immunotherapy-Based Treatment Combinations in Patients With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Cancer (G/GEJ) or Esophageal Cancer (Morpheus-Gastric and Esophageal Cancer)</brief_title>
  <official_title>A Phase Ib/II, Open-Label, Multicenter, Randomized, Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Cancer or Esophageal Cancer (Morpheus-Gastric and Esophageal Cancer)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Halozyme Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>BioLineRx, Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A Phase Ib/II, open label, multi-center, randomized study designed to assess the safety,&#xD;
      tolerability, pharmacokinetics and preliminary anti-tumor activity of immunotherapy-based&#xD;
      treatment combinations in patients with locally advanced unresectable or metastatic G/GEJ&#xD;
      cancer (hereafter referred to as gastric cancer) and esophageal cancer. Two cohorts of&#xD;
      patients with gastric cancer have been enrolled in parallel in this study: the second-line&#xD;
      (2L) Gastric Cancer Cohort consists of patients with gastric cancer who have progressed after&#xD;
      receiving a platinum-containing or fluoropyrimide-containing chemotherapy regimen in the&#xD;
      first-line setting, and the first-line (1L) Gastric Cancer Cohort consists of patients with&#xD;
      gastric cancer who have not received prior chemotherapy in this setting. In each cohort,&#xD;
      eligible patients will be assigned to one of several treatment arms. Additionally, a cohort&#xD;
      of patients with esophageal cancer who have not received prior systemic treatment for their&#xD;
      disease will be enrolled in this study. Eligible patients will be randomized to chemotherapy&#xD;
      or the combination of chemotherapy with checkpoint inhibitor immunotherapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 13, 2017</start_date>
  <completion_date type="Anticipated">February 8, 2025</completion_date>
  <primary_completion_date type="Anticipated">August 24, 2024</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants With Objective Response, as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1)</measure>
    <time_frame>From Randomization until disease progression or loss of clinical benefit (up to approximately 3-6 years)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants with Adverse Events (AEs)</measure>
    <time_frame>From first study treatment administration until 30 days after the last dose or until initiation of new systemic anti-cancer therapy, whichever occurs first (up to approximately 3-6 years)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>For Arm 1L-A : Percentage of Participants with Serious and Non-serious Treatment-related AEs</measure>
    <time_frame>During the safety run-in phase up to 28 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1</measure>
    <time_frame>From randomization up to the first occurrence of disease (up to approximately 3-6 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>From randomization up to death from any cause (up to approximately 3-6 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Are Alive at Month 6 and at Month 12</measure>
    <time_frame>Month 6, Month 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response, as Determined by Investigator According to RECIST v1.1</measure>
    <time_frame>From the date of first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 3-6 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Disease Control, as Determined by the Investigator per RECIST v1.1</measure>
    <time_frame>From randomization until disease progression or loss of clinical benefit (up to approximately 3-6 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Concentration of Atezolizumab</measure>
    <time_frame>Pre-infusion (0 hour [hr]), 30 minutes (min) post-infusion (infusion=60 min) on Day 1 of Cycle 1; pre-infusion (0 hr) on Day 1 of Cycles 2, 3, 4, 8, 12, 16 (each cycle=28 days); 30 days and 120 days after last dose (up to approximately 3-6 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Concentration of Cobimetinib</measure>
    <time_frame>Prior to cobimetinib dose, 2-4 hr after cobimetinib dose on Day 15 of Cycle 1 (cycle length=28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Concentration of PEGPH20</measure>
    <time_frame>Pre-infusion (0 hr) on Day 1 of Cycle 1 up to 30 days and 120 days after last dose (up to approximately 3-6 years) (Detailed timeframe is provided in outcome measure description)</time_frame>
    <description>Pre-infusion (0 hr), 5 min and 1-3 hrs post infusion (infusion duration=10-12 min) on Day 1 of Cycle 1; pre-infusion (0 hr) on Days 8 and 15 of Cycle 1, Day 1 of Cycles 3, 4, 8, 12, 16; pre-infusion (0 hr) and 5 min post-infusion on Day 1 of Cycle 2 (each cycle=21 days); 30 days and 120 days after last dose (up to approximately 3-6 years)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Concentration of BL-8040</measure>
    <time_frame>Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Day 1 of Cycle 1) up to 30 days after last dose (up to approximately 3-6 years) (Detailed timeframe is provided in outcome measure description)</time_frame>
    <description>Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Day 1 of Cycle 1); 1 hr post-dose on Days 1, 5 of priming period; pre-dose (0 hr), 1 hour post-dose on Day 15 of Cycle 1 and Day 1 of Cycles 2, 3, 4, 8, 12, 16; pre-dose (0 hr) on Day 1 of Cycle 20 and every 4 cycles thereafter (each cycle=21 days) (up to approximately 3-6 years); 30 days after last dose (up to approximately 3-6 years)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Concentration of Linagliptin</measure>
    <time_frame>2 hr postdose oral linagliptin on Day 1 of Cycle 1, prior to atezolizumab infusion and predose oral linagliptin on Day 15 of Cycle 1 as well as on Day 1 of Cycles 2, 3, and 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Anti-Drug Antibody (ADA) to Atezolizumab</measure>
    <time_frame>Pre-infusion (0 hr) on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 (each cycle=28 days); 30 days and 120 days after last dose (up to approximately 3-6 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With ADA to PEGPH20</measure>
    <time_frame>Pre-infusion (0 hr) on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 (each cycle=21 days); 30 days and 120 days after last dose (up to approximately 3-6 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With ADA to BL-8040</measure>
    <time_frame>Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Day 1 of Cycle 1) up to 30 days after last dose (up to approximately 3-6 years) (Detailed timeframe is provided in outcome measure description)</time_frame>
    <description>Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Cycle 1 Day 1), Day 15 of Cycle 1 and Day 1 of Cycles 2, 3, 4, 8, 12, 16, 20 and every 4 cycles thereafter (each cycle=21 days) (up to approximately 3-6 years); 30 days after last dose (up to approximately 3-6 years)</description>
  </secondary_outcome>
  <number_of_arms>12</number_of_arms>
  <enrollment type="Anticipated">410</enrollment>
  <condition>Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma or Esophageal Carcinoma</condition>
  <arm_group>
    <arm_group_label>1L-Control: mFOLFOX6 (Gastric Cancer)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants in the 1L Gastric Cancer Control arm will receive modified FOLFOX6 (mFOLFOX6) treatment consisting of 5-fluorouracil (5-FU), leucovorin (folinic acid), and oxaliplatin. Participants who progressed on treatment may have the option of receiving Atezolizumab + Cobimetinib treatment, provided they meet the eligibility criteria. No longer enrolling participants as of June 2018.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>1L-A: mFOLFOX6 + Atezo + Cobi (Gastric Cancer)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in the 1L-A Gastric Cancer arm will receive mFOLFOX6 treatment consisting of 5-FU, leucovorin and oxaliplatin in combination with atezolizumab plus cobimetinib. No longer enrolling participants as of June 2018.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>1L-A2: Atezo+mFOLFOX6 followed by Atezo+Cobi (Gastric Cancer)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in the 1L-A2 Gastric Cancer arm will receive mFOLFOX6 treatment consisting of 5-FU, leucovorin and oxaliplatin in combination with atezolizumab during cycles 1 and 2 followed by atezolizumab plus cobimetinib during cycles 3 and beyond. No longer enrolling participants as of June 2018.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2L-Control: Ramucirumab + Paclitaxel (Gastric Cancer)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants in the 2L Gastric Cancer Control arm received ramucirumab plus paclitaxel. Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2L-1: Atezo + Cobi (Gastric Cancer)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in the 2L-1 Gastric Cancer arm received atezolizumab in combination with cobimetinib. Enrollment completed as of October 2019.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2L-2: Atezo + PEGPH20 (Gastric Cancer)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in the 2L-2 Gastric Cancer arm received atezolizumab in combination with PEGylated recombinant human hyaluronidase (PEGPH20). Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2L-3: Atezo + BL-8040 (Gastric Cancer)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in the 2L-3 Gastric Cancer arm received atezolizumab in combination with BL-8040. Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2L-4: Atezo + Linagliptin (Gastric Cancer)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in the 2L-4 Gastric Cancer arm received atezolizumab in combination with linagliptin. Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>1L-1:Atezo+Tiragolumab+Cisplatin+5FU(Esophageal Cancer Cohort)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in the 1L-1 Esophageal Cancer arm will receive atezolizumab in combination with tiragolumab and chemotherapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>1L-2: Atezo+Cisplatin+5-FU (Esophageal Cancer Cohort)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in the 1L-2 Esophageal Cancer arm will receive atezolizumab in combination with chemotherapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>1L-Control: Cisplatin+5-FU (Esophageal Cancer Cohort)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants in the 1L-Control Eophageal Cancer arm will receive chemotherapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>1L-3: Atezo+Tiragolumab (Esophageal Cancer Cohort)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in the 1L-3 Esophageal Cancer arm will receive atezolizumab + tiragolumab treatment. Participants from the cisplatin + 5-FU esophageal cancer cohort arm may be permitted to enroll in this arm if they progress after receiving chemotherapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5-Fluorouracil (5-FU)</intervention_name>
    <description>5-FU 2400 milligrams per square meter (mg/m^2) by continuous intravenous (IV) infusion over 46 hours on Days 1 and 2 and Days 15 and 16 of every 28-day cycle.</description>
    <arm_group_label>1L-A2: Atezo+mFOLFOX6 followed by Atezo+Cobi (Gastric Cancer)</arm_group_label>
    <arm_group_label>1L-A: mFOLFOX6 + Atezo + Cobi (Gastric Cancer)</arm_group_label>
    <arm_group_label>1L-Control: mFOLFOX6 (Gastric Cancer)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Leucovorin</intervention_name>
    <description>Leucovorin: 100 mg/m^2 IV over 2 hours on Days 1 and 15 of every 28-day cycle.</description>
    <arm_group_label>1L-A2: Atezo+mFOLFOX6 followed by Atezo+Cobi (Gastric Cancer)</arm_group_label>
    <arm_group_label>1L-A: mFOLFOX6 + Atezo + Cobi (Gastric Cancer)</arm_group_label>
    <arm_group_label>1L-Control: mFOLFOX6 (Gastric Cancer)</arm_group_label>
    <other_name>Folinic acid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin</intervention_name>
    <description>Oxaliplatin: 100 mg/m^2 administered by IV infusion over 2 hours on Days 1 and 15 of every 28-day cycle.</description>
    <arm_group_label>1L-A2: Atezo+mFOLFOX6 followed by Atezo+Cobi (Gastric Cancer)</arm_group_label>
    <arm_group_label>1L-A: mFOLFOX6 + Atezo + Cobi (Gastric Cancer)</arm_group_label>
    <arm_group_label>1L-Control: mFOLFOX6 (Gastric Cancer)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atezolizumab</intervention_name>
    <description>Atezolizumab: 840 mg by IV infusion on Days 1 and 15 of every 28-day cycle.</description>
    <arm_group_label>1L-A2: Atezo+mFOLFOX6 followed by Atezo+Cobi (Gastric Cancer)</arm_group_label>
    <arm_group_label>1L-A: mFOLFOX6 + Atezo + Cobi (Gastric Cancer)</arm_group_label>
    <arm_group_label>2L-1: Atezo + Cobi (Gastric Cancer)</arm_group_label>
    <other_name>Tecentriq</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cobimetinib</intervention_name>
    <description>Cobimetinib: 60 mg by mouth once a day on Days 1-21 of every 28-day cycle</description>
    <arm_group_label>1L-A2: Atezo+mFOLFOX6 followed by Atezo+Cobi (Gastric Cancer)</arm_group_label>
    <arm_group_label>2L-1: Atezo + Cobi (Gastric Cancer)</arm_group_label>
    <other_name>Cotellic</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Ramucirumab</intervention_name>
    <description>Ramucirumab: 8 mg/kg administered by IV infusion over 60 minutes on Days 1 and 15 of every 28-day cycle.</description>
    <arm_group_label>2L-Control: Ramucirumab + Paclitaxel (Gastric Cancer)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>Paclitaxel: 80 mg/m^2 administered by IV infusion on Days 1, 8, and 15 of every 28-day cycle.</description>
    <arm_group_label>2L-Control: Ramucirumab + Paclitaxel (Gastric Cancer)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PEGylated recombinant human hyaluronidase (PEGPH20)</intervention_name>
    <description>PEGPH20: 3 micrograms per kilogram (mcg/kg) administered by IV infusion on Days 1, 8, and 15 of every 21-day cycle.</description>
    <arm_group_label>2L-2: Atezo + PEGPH20 (Gastric Cancer)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BL-8040</intervention_name>
    <description>BL-8040: 1.25 mg/kg administered by subcutaneous (SC) injection on Days 1-5 during the 5-day priming period prior to Cycle 1; 1.25 mg/kg administered by SC injection three times a week (Days 1, 3, 5, 8, 10, 12, 15, 17, and 19 of every 21-day cycle).</description>
    <arm_group_label>2L-3: Atezo + BL-8040 (Gastric Cancer)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Linagliptin</intervention_name>
    <description>Linagliptin: 5 mg orally once a day of every 21-day cycle.</description>
    <arm_group_label>2L-4: Atezo + Linagliptin (Gastric Cancer)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atezolizumab</intervention_name>
    <description>Atezolizumab: 1200 mg administered by IV infusion on Day 1 of every 21-day cycle</description>
    <arm_group_label>1L-1:Atezo+Tiragolumab+Cisplatin+5FU(Esophageal Cancer Cohort)</arm_group_label>
    <arm_group_label>1L-2: Atezo+Cisplatin+5-FU (Esophageal Cancer Cohort)</arm_group_label>
    <arm_group_label>1L-3: Atezo+Tiragolumab (Esophageal Cancer Cohort)</arm_group_label>
    <arm_group_label>2L-2: Atezo + PEGPH20 (Gastric Cancer)</arm_group_label>
    <arm_group_label>2L-3: Atezo + BL-8040 (Gastric Cancer)</arm_group_label>
    <arm_group_label>2L-4: Atezo + Linagliptin (Gastric Cancer)</arm_group_label>
    <other_name>Tecentriq</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cobimetinib</intervention_name>
    <description>Cobimetinib: 40 or 60 mg (depending on the recommended dose determined during the safety run-in phase) by mouth once a day on Days 1-21 of every 28-day cycle.</description>
    <arm_group_label>1L-A: mFOLFOX6 + Atezo + Cobi (Gastric Cancer)</arm_group_label>
    <other_name>Cotellic</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>Cisplatin: 80 mg/m^2 administered by IV infusion on Day 1 of each 21 day cycle. Treatment will be capped after 6 doses.</description>
    <arm_group_label>1L-1:Atezo+Tiragolumab+Cisplatin+5FU(Esophageal Cancer Cohort)</arm_group_label>
    <arm_group_label>1L-2: Atezo+Cisplatin+5-FU (Esophageal Cancer Cohort)</arm_group_label>
    <arm_group_label>1L-Control: Cisplatin+5-FU (Esophageal Cancer Cohort)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tiragolumab</intervention_name>
    <description>Tiragolumab: 600 mg administered by IV infusion on Day 1 of every 21 day cycle.</description>
    <arm_group_label>1L-1:Atezo+Tiragolumab+Cisplatin+5FU(Esophageal Cancer Cohort)</arm_group_label>
    <arm_group_label>1L-3: Atezo+Tiragolumab (Esophageal Cancer Cohort)</arm_group_label>
    <other_name>RO7092284</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5-Fluorouracil (5-FU)</intervention_name>
    <description>5-FU 800 mg/m^2 administerd by IV infusion on Days 1-5 of each 21 day cycle.</description>
    <arm_group_label>1L-1:Atezo+Tiragolumab+Cisplatin+5FU(Esophageal Cancer Cohort)</arm_group_label>
    <arm_group_label>1L-2: Atezo+Cisplatin+5-FU (Esophageal Cancer Cohort)</arm_group_label>
    <arm_group_label>1L-Control: Cisplatin+5-FU (Esophageal Cancer Cohort)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Gastric Cancer Cohorts Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt;/= 18 years;&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;&#xD;
&#xD;
          -  Life expectancy &gt;/= 3 months, as determined by the investigator;&#xD;
&#xD;
          -  Histologically or cytologically confirmed locally advanced unresectable or metastatic&#xD;
             adenocarcinoma of gastric or gastroesophageal junction; (for the 1L Gastric Cancer&#xD;
             Cohort: no prior systemic therapy for the locally advanced or metastatic disease; for&#xD;
             the 2L Gastric Cancer Cohort: disease progression during or following a first-line&#xD;
             platinum-containing or fluoropyrimidine-containing chemotherapy regimen);&#xD;
&#xD;
          -  Availability of a representative tumor specimen that is suitable for determination of&#xD;
             PD-L1 and TIGIT levels by IHC and/or additional biomarker status by means of&#xD;
             retrospective central testing;&#xD;
&#xD;
          -  Only for the 1L Gastric Cancer Cohort: human epidermal growth factor receptor 2&#xD;
             (HER2)-negative tumors;&#xD;
&#xD;
          -  Measurable disease (at least one target lesion) according to Response Evaluation&#xD;
             Criteria in Solid Tumors, Version 1.1 (RECIST v1.1);&#xD;
&#xD;
          -  Adequate hematologic and end organ function based on laboratory results obtained&#xD;
             within 14 days prior to initiation of study treatment;&#xD;
&#xD;
          -  For women of childbearing potential: agreement to remain abstinent (refrain from&#xD;
             heterosexual intercourse) or use contraceptive measures as outlined for each specific&#xD;
             treatment arm;&#xD;
&#xD;
          -  For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use&#xD;
             contraceptive measures, and agreement to refrain from donating sperm, as outlined for&#xD;
             each specific treatment arm.&#xD;
&#xD;
        Esophageal Cancer Cohort Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically confirmed diagnosis of squamous cell carcinoma or&#xD;
             adenocarcinoma of the esophagus in locally advanced or metastatic disease;&#xD;
&#xD;
          -  No prior systemic treatment for esophageal cancer, with the following exception:&#xD;
&#xD;
        For patients treated with chemotherapy in the locally advanced setting: occurrence of&#xD;
        metastasis after 6 months from the last dose of chemotherapy;&#xD;
&#xD;
          -  For patients with adenocarcinoma: absence of HER2 expression;&#xD;
&#xD;
          -  Life expectancy &gt;/=3 months as determined by the investigator;&#xD;
&#xD;
          -  Measurable disease per RECIST v1.1;&#xD;
&#xD;
          -  Adequate hematologic and end-organ function;&#xD;
&#xD;
          -  For women of childbearing potential: agreement to remain abstinent (refrain from&#xD;
             heterosexual intercourse) or use contraceptive measures, and agreement to refrain from&#xD;
             donating eggs;&#xD;
&#xD;
          -  For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use&#xD;
             contraceptive measures, and agreement to refrain from donating sperm;&#xD;
&#xD;
          -  ECOG Performance Status of 0, 1, or 2.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Exclusion criteria for the 2L Gastric Cancer Cohort:&#xD;
&#xD;
          -  Urinary protein is &gt; 1 + on dipstick and the required following 24-hour urine&#xD;
             collection shows urinary protein &gt; 2000 mg;&#xD;
&#xD;
          -  Serious or non-healing wound, peptic ulcer, or bone fracture within 28 days prior to&#xD;
             initiation of study treatment;&#xD;
&#xD;
          -  History of gastrointestinal perforation and/or fistulae within 6 months prior to&#xD;
             initiation of study treatment;&#xD;
&#xD;
          -  Presence of a bowel obstruction, history or presence of inflammatory enteropathy, or&#xD;
             extensive intestinal resection, Crohn disease, ulcerative colitis, or chronic&#xD;
             diarrhea;&#xD;
&#xD;
          -  Uncontrolled arterial hypertension &gt;/= 150/ &gt;/= 90 millimeter of mercury (mmHg)&#xD;
             despite standard medical management;&#xD;
&#xD;
          -  Chronic therapy with non-steroidal anti-inflammatory agents or other anti-platelet&#xD;
             agents.&#xD;
&#xD;
        Gastric Cancer Exclusion Criteria:&#xD;
&#xD;
          -  Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of&#xD;
             bisphosphonate therapy;&#xD;
&#xD;
          -  Symptomatic, untreated, or actively progressing central nervous system (CNS)&#xD;
             metastases;&#xD;
&#xD;
          -  History of leptomeningeal disease;&#xD;
&#xD;
          -  Active or history of autoimmune disease or immune deficiency;&#xD;
&#xD;
          -  History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis&#xD;
             obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of&#xD;
             active pneumonitis on screening chest computed tomography (CT) scan;&#xD;
&#xD;
          -  Positive test for human immunodeficiency virus (HIV) at screening;&#xD;
&#xD;
          -  Active hepatitis B virus (HBV) or hepatitis C (HCV) infection;&#xD;
&#xD;
          -  Severe infection within 4 weeks prior to initiation of study treatment;&#xD;
&#xD;
          -  Significant cardiovascular disease;&#xD;
&#xD;
          -  Significant bleeding disorder;&#xD;
&#xD;
          -  Prior allogeneic stem cell or solid organ transplantation;&#xD;
&#xD;
          -  Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation&#xD;
             of study treatment, or anticipation of need for a major surgical procedure during the&#xD;
             study;&#xD;
&#xD;
          -  Treatment with anticoagulation with warfarin, low-molecular-weight heparin, or similar&#xD;
             agents for therapeutic purposes;&#xD;
&#xD;
          -  History of malignancy other than gastric or gastroesophageal junction carcinoma within&#xD;
             2 years prior to screening, with the exception of those with a negligible risk of&#xD;
             metastasis or death;&#xD;
&#xD;
          -  Known allergy or hypersensitivity to any of the study drugs or their excipients.&#xD;
&#xD;
        Esophageal Cancer Cohort Exclusion Criteria:&#xD;
&#xD;
          -  High risk for developing esophageal fistula by clinical assessment or imaging;&#xD;
&#xD;
          -  Symptomatic, untreated, or actively progressing central nervous system (CNS)&#xD;
             Metastases;&#xD;
&#xD;
          -  Positive EBV viral capsid antigen IgM test at screening;&#xD;
&#xD;
          -  History of leptomeningeal disease;&#xD;
&#xD;
          -  Active or history of autoimmune disease or immune deficiency;&#xD;
&#xD;
          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced&#xD;
             pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening&#xD;
             chest computed tomography (CT) scan;&#xD;
&#xD;
          -  Active tuberculosis;&#xD;
&#xD;
          -  Significant cardiovascular disease within 3 months prior to initiation of study&#xD;
             treatment, unstable arrhythmia, or unstable angina;&#xD;
&#xD;
          -  History of malignancy other than esophageal cancer within 2 years prior to screening,&#xD;
             with the exception of malignancies with a negligible risk of metastasis or death;&#xD;
&#xD;
          -  Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment&#xD;
             or within 5 months after the final dose of atezolizumab or within 90 days after the&#xD;
             final dose of tiragolumab.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Reference Study ID Number: YO39609 https://forpatients.roche.com/</last_name>
    <phone>888-662-6728 (U.S. and Canada)</phone>
    <email>global-roche-genentech-trials@gene.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Mayo Clinic Cancer Center</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85259</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Uni of Southern California; Norris Comprehensive Cancer Ctr</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>UCLA Jonsson Comprehensive Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Robert H. Lurie Comprehensive Cancer Center of Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637-1447</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>University of Kentucky</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute - Gastrointestinal Cancer Treatment Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02111</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic - Rochester; Breast Cancer Center</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>The University of Texas MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030-4009</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Froedtert and The Medical College of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Blacktown Hospital</name>
      <address>
        <city>Blacktown</city>
        <state>New South Wales</state>
        <zip>2148</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Monash Medical Centre-Moorabbin Campus</name>
      <address>
        <city>Clayton</city>
        <state>Victoria</state>
        <zip>3168</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Peter MacCallum Cancer Centre; Medical Oncology</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3000</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Gustave Roussy Cancer Campus</name>
      <address>
        <city>Villejuif</city>
        <zip>94805</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Essen; Innere Klinik (Tumorforschung)</name>
      <address>
        <city>Essen</city>
        <zip>45147</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Krankenhaus Nordwest GmbH - Institut Fuer Klinisch-Onkologische Forschung (IKF)</name>
      <address>
        <city>Frankfurt am Main</city>
        <zip>60488</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Universitatsklinik Heidelberg; Universitätshautklinik und Nationales Centrum für Tumorerkrankungen</name>
      <address>
        <city>Heidelberg</city>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Ben-Gurion University of the Negev - Soroka University Medical Center</name>
      <address>
        <city>Beer Sheva</city>
        <zip>8410101</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Rambam Health Care Campus; Oncology</name>
      <address>
        <city>Haifa</city>
        <zip>3109601</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hadassah University Medical Center</name>
      <address>
        <city>Jerusalem</city>
        <country>Israel</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Rabin MC; Davidof Center - Oncology Institute</name>
      <address>
        <city>Petach Tikva</city>
        <zip>4941492</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Sourasky Medical Centre</name>
      <address>
        <city>Tel-Aviv</city>
        <zip>6423906</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Yonsei University College of Medicine (YUCM)-Yonsei Cancer Center; Cancer Metastasis Research Center</name>
      <address>
        <city>Seodaemun-Gu</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Seoul National University Bundang Hospital</name>
      <address>
        <city>Seongnam-si</city>
        <zip>463-707</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Korea University Anam Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>02841</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital (SNUH) - Medical Oncology Center</name>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>University of Ulsan College of Medicine - Asan Medical Center (AMC) - Asan Cancer Center (ACC)</name>
      <address>
        <city>Songpa-gu</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>The Catholic University of Korea St. Vincent's Hospital</name>
      <address>
        <city>Suwon-si</city>
        <zip>16247</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis</name>
      <address>
        <city>Amsterdam</city>
        <zip>1066 CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Universidad de Navarra - Clinica Universitaria de Navarra (CUN)</name>
      <address>
        <city>Pamplona</city>
        <state>Navarra</state>
        <zip>31008</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Vall dHebron; Oncology</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>National Cheng Kung University Hospital</name>
      <address>
        <city>Tainan</city>
        <zip>70457</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Taipei Veterans General Hospital</name>
      <address>
        <city>Taipei City</city>
        <zip>11217</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital (NTUH) - Cancer Research Center</name>
      <address>
        <city>Zhongzheng Dist.</city>
        <zip>10051</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Beatson West of Scotland Cancer Centre</name>
      <address>
        <city>Glasgow</city>
        <zip>G12 0YN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Barts and The London School of Medicine and Dentistry - Barts Cancer Institute (BCI)-CECM</name>
      <address>
        <city>London</city>
        <zip>0</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>The Royal Marsden</name>
      <address>
        <city>London</city>
        <zip>SW7 3RP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>The Christie NHS Foundation Trust</name>
      <address>
        <city>Manchester</city>
        <zip>M20 4BX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital (RMH) - Sutton</name>
      <address>
        <city>Sutton</city>
        <zip>SM2 5PT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>France</country>
    <country>Germany</country>
    <country>Israel</country>
    <country>Korea, Republic of</country>
    <country>Netherlands</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>September 11, 2017</study_first_submitted>
  <study_first_submitted_qc>September 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 13, 2017</study_first_posted>
  <last_update_submitted>August 31, 2023</last_update_submitted>
  <last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</mesh_term>
    <mesh_term>Esophageal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leucovorin</mesh_term>
    <mesh_term>Linagliptin</mesh_term>
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
    <mesh_term>Atezolizumab</mesh_term>
    <mesh_term>Ramucirumab</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03281369
org study id: YO39609
secondary id: 2016-004529-17
nct id: NCT03281369
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
A Phase Ib/II, open label, multi-center, randomized study designed to assess the safety,
      tolerability, pharmacokinetics and preliminary anti-tumor activity of immunotherapy-based
      treatment combinations in patients with locally advanced unresectable or metastatic G/GEJ
      cancer (hereafter referred to as gastric cancer) and esophageal cancer. Two cohorts of
      patients with gastric cancer have been enrolled in parallel in this study: the second-line
      (2L) Gastric Cancer Cohort consists of patients with gastric cancer who have progressed after
      receiving a platinum-containing or fluoropyrimide-containing chemotherapy regimen in the
      first-line setting, and the first-line (1L) Gastric Cancer Cohort consists of patients with
      gastric cancer who have not received prior chemotherapy in this setting. In each cohort,
      eligible patients will be assigned to one of several treatment arms. Additionally, a cohort
      of patients with esophageal cancer who have not received prior systemic treatment for their
      disease will be enrolled in this study. Eligible patients will be randomized to chemotherapy
      or the combination of chemotherapy with checkpoint inhibitor immunotherapy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants With Objective Response, as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1)
time frame: From Randomization until disease progression or loss of clinical benefit (up to approximately 3-6 years)
measure: Percentage of Participants with Adverse Events (AEs)
time frame: From first study treatment administration until 30 days after the last dose or until initiation of new systemic anti-cancer therapy, whichever occurs first (up to approximately 3-6 years)
measure: For Arm 1L-A : Percentage of Participants with Serious and Non-serious Treatment-related AEs
time frame: During the safety run-in phase up to 28 days
measure: Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1
time frame: From randomization up to the first occurrence of disease (up to approximately 3-6 years)
measure: Overall Survival (OS)
time frame: From randomization up to death from any cause (up to approximately 3-6 years)
measure: Percentage of Participants Who Are Alive at Month 6 and at Month 12
time frame: Month 6, Month 12
measure: Duration of Response, as Determined by Investigator According to RECIST v1.1
time frame: From the date of first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 3-6 years)
measure: Percentage of Participants With Disease Control, as Determined by the Investigator per RECIST v1.1
time frame: From randomization until disease progression or loss of clinical benefit (up to approximately 3-6 years)
measure: Serum Concentration of Atezolizumab
time frame: Pre-infusion (0 hour [hr]), 30 minutes (min) post-infusion (infusion=60 min) on Day 1 of Cycle 1; pre-infusion (0 hr) on Day 1 of Cycles 2, 3, 4, 8, 12, 16 (each cycle=28 days); 30 days and 120 days after last dose (up to approximately 3-6 years)
measure: Plasma Concentration of Cobimetinib
time frame: Prior to cobimetinib dose, 2-4 hr after cobimetinib dose on Day 15 of Cycle 1 (cycle length=28 days)
measure: Plasma Concentration of PEGPH20
time frame: Pre-infusion (0 hr) on Day 1 of Cycle 1 up to 30 days and 120 days after last dose (up to approximately 3-6 years) (Detailed timeframe is provided in outcome measure description)
description: Pre-infusion (0 hr), 5 min and 1-3 hrs post infusion (infusion duration=10-12 min) on Day 1 of Cycle 1; pre-infusion (0 hr) on Days 8 and 15 of Cycle 1, Day 1 of Cycles 3, 4, 8, 12, 16; pre-infusion (0 hr) and 5 min post-infusion on Day 1 of Cycle 2 (each cycle=21 days); 30 days and 120 days after last dose (up to approximately 3-6 years)
measure: Plasma Concentration of BL-8040
time frame: Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Day 1 of Cycle 1) up to 30 days after last dose (up to approximately 3-6 years) (Detailed timeframe is provided in outcome measure description)
description: Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Day 1 of Cycle 1); 1 hr post-dose on Days 1, 5 of priming period; pre-dose (0 hr), 1 hour post-dose on Day 15 of Cycle 1 and Day 1 of Cycles 2, 3, 4, 8, 12, 16; pre-dose (0 hr) on Day 1 of Cycle 20 and every 4 cycles thereafter (each cycle=21 days) (up to approximately 3-6 years); 30 days after last dose (up to approximately 3-6 years)
measure: Plasma Concentration of Linagliptin
time frame: 2 hr postdose oral linagliptin on Day 1 of Cycle 1, prior to atezolizumab infusion and predose oral linagliptin on Day 15 of Cycle 1 as well as on Day 1 of Cycles 2, 3, and 4
measure: Percentage of Participants With Anti-Drug Antibody (ADA) to Atezolizumab
time frame: Pre-infusion (0 hr) on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 (each cycle=28 days); 30 days and 120 days after last dose (up to approximately 3-6 years)
measure: Percentage of Participants With ADA to PEGPH20
time frame: Pre-infusion (0 hr) on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 (each cycle=21 days); 30 days and 120 days after last dose (up to approximately 3-6 years)
measure: Percentage of Participants With ADA to BL-8040
time frame: Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Day 1 of Cycle 1) up to 30 days after last dose (up to approximately 3-6 years) (Detailed timeframe is provided in outcome measure description)
description: Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Cycle 1 Day 1), Day 15 of Cycle 1 and Day 1 of Cycles 2, 3, 4, 8, 12, 16, 20 and every 4 cycles thereafter (each cycle=21 days) (up to approximately 3-6 years); 30 days after last dose (up to approximately 3-6 years)
arm group label: 1L-Control: mFOLFOX6 (Gastric Cancer)
arm group type: Active Comparator
description: Participants in the 1L Gastric Cancer Control arm will receive modified FOLFOX6 (mFOLFOX6) treatment consisting of 5-fluorouracil (5-FU), leucovorin (folinic acid), and oxaliplatin. Participants who progressed on treatment may have the option of receiving Atezolizumab + Cobimetinib treatment, provided they meet the eligibility criteria. No longer enrolling participants as of June 2018.
arm group label: 1L-A: mFOLFOX6 + Atezo + Cobi (Gastric Cancer)
arm group type: Experimental
description: Participants in the 1L-A Gastric Cancer arm will receive mFOLFOX6 treatment consisting of 5-FU, leucovorin and oxaliplatin in combination with atezolizumab plus cobimetinib. No longer enrolling participants as of June 2018.
arm group label: 1L-A2: Atezo+mFOLFOX6 followed by Atezo+Cobi (Gastric Cancer)
arm group type: Experimental
description: Participants in the 1L-A2 Gastric Cancer arm will receive mFOLFOX6 treatment consisting of 5-FU, leucovorin and oxaliplatin in combination with atezolizumab during cycles 1 and 2 followed by atezolizumab plus cobimetinib during cycles 3 and beyond. No longer enrolling participants as of June 2018.
arm group label: 2L-Control: Ramucirumab + Paclitaxel (Gastric Cancer)
arm group type: Active Comparator
description: Participants in the 2L Gastric Cancer Control arm received ramucirumab plus paclitaxel. Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019.
arm group label: 2L-1: Atezo + Cobi (Gastric Cancer)
arm group type: Experimental
description: Participants in the 2L-1 Gastric Cancer arm received atezolizumab in combination with cobimetinib. Enrollment completed as of October 2019.
arm group label: 2L-2: Atezo + PEGPH20 (Gastric Cancer)
arm group type: Experimental
description: Participants in the 2L-2 Gastric Cancer arm received atezolizumab in combination with PEGylated recombinant human hyaluronidase (PEGPH20). Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019.
arm group label: 2L-3: Atezo + BL-8040 (Gastric Cancer)
arm group type: Experimental
description: Participants in the 2L-3 Gastric Cancer arm received atezolizumab in combination with BL-8040. Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019.
arm group label: 2L-4: Atezo + Linagliptin (Gastric Cancer)
arm group type: Experimental
description: Participants in the 2L-4 Gastric Cancer arm received atezolizumab in combination with linagliptin. Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019.
arm group label: 1L-1:Atezo+Tiragolumab+Cisplatin+5FU(Esophageal Cancer Cohort)
arm group type: Experimental
description: Participants in the 1L-1 Esophageal Cancer arm will receive atezolizumab in combination with tiragolumab and chemotherapy.
arm group label: 1L-2: Atezo+Cisplatin+5-FU (Esophageal Cancer Cohort)
arm group type: Experimental
description: Participants in the 1L-2 Esophageal Cancer arm will receive atezolizumab in combination with chemotherapy.
arm group label: 1L-Control: Cisplatin+5-FU (Esophageal Cancer Cohort)
arm group type: Active Comparator
description: Participants in the 1L-Control Eophageal Cancer arm will receive chemotherapy.
arm group label: 1L-3: Atezo+Tiragolumab (Esophageal Cancer Cohort)
arm group type: Experimental
description: Participants in the 1L-3 Esophageal Cancer arm will receive atezolizumab + tiragolumab treatment. Participants from the cisplatin + 5-FU esophageal cancer cohort arm may be permitted to enroll in this arm if they progress after receiving chemotherapy.
intervention type: Drug
intervention name: 5-Fluorouracil (5-FU)
description: 5-FU 2400 milligrams per square meter (mg/m^2) by continuous intravenous (IV) infusion over 46 hours on Days 1 and 2 and Days 15 and 16 of every 28-day cycle.
arm group label: 1L-A2: Atezo+mFOLFOX6 followed by Atezo+Cobi (Gastric Cancer)
arm group label: 1L-A: mFOLFOX6 + Atezo + Cobi (Gastric Cancer)
arm group label: 1L-Control: mFOLFOX6 (Gastric Cancer)
intervention type: Drug
intervention name: Leucovorin
description: Leucovorin: 100 mg/m^2 IV over 2 hours on Days 1 and 15 of every 28-day cycle.
arm group label: 1L-A2: Atezo+mFOLFOX6 followed by Atezo+Cobi (Gastric Cancer)
arm group label: 1L-A: mFOLFOX6 + Atezo + Cobi (Gastric Cancer)
arm group label: 1L-Control: mFOLFOX6 (Gastric Cancer)
other name: Folinic acid
intervention type: Drug
intervention name: Oxaliplatin
description: Oxaliplatin: 100 mg/m^2 administered by IV infusion over 2 hours on Days 1 and 15 of every 28-day cycle.
arm group label: 1L-A2: Atezo+mFOLFOX6 followed by Atezo+Cobi (Gastric Cancer)
arm group label: 1L-A: mFOLFOX6 + Atezo + Cobi (Gastric Cancer)
arm group label: 1L-Control: mFOLFOX6 (Gastric Cancer)
intervention type: Drug
intervention name: Atezolizumab
description: Atezolizumab: 840 mg by IV infusion on Days 1 and 15 of every 28-day cycle.
arm group label: 1L-A2: Atezo+mFOLFOX6 followed by Atezo+Cobi (Gastric Cancer)
arm group label: 1L-A: mFOLFOX6 + Atezo + Cobi (Gastric Cancer)
arm group label: 2L-1: Atezo + Cobi (Gastric Cancer)
other name: Tecentriq
intervention type: Drug
intervention name: Cobimetinib
description: Cobimetinib: 60 mg by mouth once a day on Days 1-21 of every 28-day cycle
arm group label: 1L-A2: Atezo+mFOLFOX6 followed by Atezo+Cobi (Gastric Cancer)
arm group label: 2L-1: Atezo + Cobi (Gastric Cancer)
other name: Cotellic
intervention type: Biological
intervention name: Ramucirumab
description: Ramucirumab: 8 mg/kg administered by IV infusion over 60 minutes on Days 1 and 15 of every 28-day cycle.
arm group label: 2L-Control: Ramucirumab + Paclitaxel (Gastric Cancer)
intervention type: Drug
intervention name: Paclitaxel
description: Paclitaxel: 80 mg/m^2 administered by IV infusion on Days 1, 8, and 15 of every 28-day cycle.
arm group label: 2L-Control: Ramucirumab + Paclitaxel (Gastric Cancer)
intervention type: Biological
intervention name: PEGylated recombinant human hyaluronidase (PEGPH20)
description: PEGPH20: 3 micrograms per kilogram (mcg/kg) administered by IV infusion on Days 1, 8, and 15 of every 21-day cycle.
arm group label: 2L-2: Atezo + PEGPH20 (Gastric Cancer)
intervention type: Drug
intervention name: BL-8040
description: BL-8040: 1.25 mg/kg administered by subcutaneous (SC) injection on Days 1-5 during the 5-day priming period prior to Cycle 1; 1.25 mg/kg administered by SC injection three times a week (Days 1, 3, 5, 8, 10, 12, 15, 17, and 19 of every 21-day cycle).
arm group label: 2L-3: Atezo + BL-8040 (Gastric Cancer)
intervention type: Drug
intervention name: Linagliptin
description: Linagliptin: 5 mg orally once a day of every 21-day cycle.
arm group label: 2L-4: Atezo + Linagliptin (Gastric Cancer)
intervention type: Drug
intervention name: Atezolizumab
description: Atezolizumab: 1200 mg administered by IV infusion on Day 1 of every 21-day cycle
arm group label: 1L-1:Atezo+Tiragolumab+Cisplatin+5FU(Esophageal Cancer Cohort)
arm group label: 1L-2: Atezo+Cisplatin+5-FU (Esophageal Cancer Cohort)
arm group label: 1L-3: Atezo+Tiragolumab (Esophageal Cancer Cohort)
arm group label: 2L-2: Atezo + PEGPH20 (Gastric Cancer)
arm group label: 2L-3: Atezo + BL-8040 (Gastric Cancer)
arm group label: 2L-4: Atezo + Linagliptin (Gastric Cancer)
other name: Tecentriq
intervention type: Drug
intervention name: Cobimetinib
description: Cobimetinib: 40 or 60 mg (depending on the recommended dose determined during the safety run-in phase) by mouth once a day on Days 1-21 of every 28-day cycle.
arm group label: 1L-A: mFOLFOX6 + Atezo + Cobi (Gastric Cancer)
other name: Cotellic
intervention type: Drug
intervention name: Cisplatin
description: Cisplatin: 80 mg/m^2 administered by IV infusion on Day 1 of each 21 day cycle. Treatment will be capped after 6 doses.
arm group label: 1L-1:Atezo+Tiragolumab+Cisplatin+5FU(Esophageal Cancer Cohort)
arm group label: 1L-2: Atezo+Cisplatin+5-FU (Esophageal Cancer Cohort)
arm group label: 1L-Control: Cisplatin+5-FU (Esophageal Cancer Cohort)
intervention type: Drug
intervention name: Tiragolumab
description: Tiragolumab: 600 mg administered by IV infusion on Day 1 of every 21 day cycle.
arm group label: 1L-1:Atezo+Tiragolumab+Cisplatin+5FU(Esophageal Cancer Cohort)
arm group label: 1L-3: Atezo+Tiragolumab (Esophageal Cancer Cohort)
other name: RO7092284
intervention type: Drug
intervention name: 5-Fluorouracil (5-FU)
description: 5-FU 800 mg/m^2 administerd by IV infusion on Days 1-5 of each 21 day cycle.
arm group label: 1L-1:Atezo+Tiragolumab+Cisplatin+5FU(Esophageal Cancer Cohort)
arm group label: 1L-2: Atezo+Cisplatin+5-FU (Esophageal Cancer Cohort)
arm group label: 1L-Control: Cisplatin+5-FU (Esophageal Cancer Cohort)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
last name: Reference Study ID Number: YO39609 https://forpatients.roche.com/
phone: 888-662-6728 (U.S. and Canada)
email: global-roche-genentech-trials@gene.com
facility: 
status: Completed
facility: 
status: Completed
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Completed
facility: 
status: Withdrawn
facility: 
status: Completed
facility: 
status: Completed
facility: 
status: Completed
facility: 
status: Completed
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Completed
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
facility: 
status: Completed
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
facility: 
status: Withdrawn
facility: 
status: Completed
facility: 
status: Completed
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
country: Australia
country: France
country: Germany
country: Israel
country: Korea, Republic of
country: Netherlands
country: Spain
country: Taiwan
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Esophageal Neoplasms
mesh term: Leucovorin
mesh term: Linagliptin
mesh term: Paclitaxel
mesh term: Fluorouracil
mesh term: Oxaliplatin
mesh term: Atezolizumab
mesh term: Ramucirumab
mesh term: Antibodies, Monoclonal