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A Study of Multiple Immunotherapy-Based Treatment Combinations in Patients With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Cancer (G/GEJ) (Morpheus-Gastric Cancer)

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ClinicalTrials.gov Identifier: NCT03281369
Recruitment Status : Recruiting
First Posted : September 13, 2017
Last Update Posted : February 14, 2018
Sponsor:
Collaborator:
Halozyme and BiolineRx Ltd
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
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). Two cohorts will be enrolled in parallel in this study: the second-line (2L) Cohort will consist 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) Cohort will consist 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.

Condition or disease Intervention/treatment Phase
Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma Drug: 5-Fluorouracil (5-FU) Drug: Leucovorin Drug: Oxaliplatin Biological: Atezolizumab Drug: Cobimetinib Biological: Ramucirumab Drug: Paclitaxel Biological: PEGylated recombinant human hyaluronidase (PEGPH20) Drug: BL-8040 Drug: Linagliptin Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 357 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 (Morpheus-Gastric Cancer)
Actual Study Start Date : October 13, 2017
Estimated Primary Completion Date : November 13, 2021
Estimated Study Completion Date : November 13, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Stomach Cancer
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: 1L-Control: mFOLFOX6
Participants in the 1L 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.
Drug: 5-Fluorouracil (5-FU)
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.
Drug: Leucovorin
Leucovorin: 100 mg/m^2 IV over 2 hours on Days 1 and 15 of every 28-day cycle.
Other Name: Folinic acid
Drug: Oxaliplatin
Oxaliplatin: 100 mg/m^2 administered by IV infusion over 2 hours on Days 1 and 15 of every 28-day cycle.
Experimental: 1L-A: mFOLFOX6 + Atezo + Cobi
Participants in the 1L-A arm will receive mFOLFOX6 treatment consisting of 5-FU, leucovorin and oxaliplatin in combination with atezolizumab plus cobimetinib.
Drug: 5-Fluorouracil (5-FU)
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.
Drug: Leucovorin
Leucovorin: 100 mg/m^2 IV over 2 hours on Days 1 and 15 of every 28-day cycle.
Other Name: Folinic acid
Drug: Oxaliplatin
Oxaliplatin: 100 mg/m^2 administered by IV infusion over 2 hours on Days 1 and 15 of every 28-day cycle.
Biological: Atezolizumab
Atezolizumab: 840 mg by IV infusion on Days 1 and 15 of every 28-day cycle.
Other Name: Tecentriq
Drug: Cobimetinib
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.
Other Name: Cotellic
Experimental: 1L-A2: Atezo + mFOLFOX6 followed by Atezo + Cobi
Participants in the 1L-A2 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.
Drug: 5-Fluorouracil (5-FU)
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.
Drug: Leucovorin
Leucovorin: 100 mg/m^2 IV over 2 hours on Days 1 and 15 of every 28-day cycle.
Other Name: Folinic acid
Drug: Oxaliplatin
Oxaliplatin: 100 mg/m^2 administered by IV infusion over 2 hours on Days 1 and 15 of every 28-day cycle.
Biological: Atezolizumab
Atezolizumab: 840 mg by IV infusion on Days 1 and 15 of every 28-day cycle.
Other Name: Tecentriq
Drug: Cobimetinib
Cobimetinib: 60 mg by mouth once a day on Days 1−21 of every 28-day cycle
Other Name: Cotellic
Experimental: 1L-B: mFOLFOX6 + Atezo
Participants in the 1L-B arm will receive mFOLFOX6 treatment consisting of 5-FU, leucovorin and oxaliplatin in combination with atezolizumab. Participants who progressed on treatment may have the option of receiving Atezolizumab + Cobimetinib treatment, provided they meet the eligibility criteria.
Drug: 5-Fluorouracil (5-FU)
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.
Drug: Leucovorin
Leucovorin: 100 mg/m^2 IV over 2 hours on Days 1 and 15 of every 28-day cycle.
Other Name: Folinic acid
Drug: Oxaliplatin
Oxaliplatin: 100 mg/m^2 administered by IV infusion over 2 hours on Days 1 and 15 of every 28-day cycle.
Biological: Atezolizumab
Atezolizumab: 840 mg by IV infusion on Days 1 and 15 of every 28-day cycle.
Other Name: Tecentriq
Active Comparator: 2L-Control: Ramucirumab + Paclitaxel
Participants in the 2L Control arm will receive ramucirumab plus paclitaxel. Participants who progressed on treatment may have the option of receiving Atezolizumab + Cobimetinib treatment, provided they meet the eligibility criteria.
Biological: Ramucirumab
Ramucirumab: 8 mg/kg administered by IV infusion over 60 minutes on Days 1 and 15 of every 28-day cycle.
Drug: Paclitaxel
Paclitaxel: 80 mg/m^2 administered by IV infusion on Days 1, 8, and 15 of every 28-day cycle.
Experimental: 2L-1: Atezo + Cobi
Participants in the 2L-1 arm will receive atezolizumab in combination with cobimetinib.
Biological: Atezolizumab
Atezolizumab: 840 mg by IV infusion on Days 1 and 15 of every 28-day cycle.
Other Name: Tecentriq
Drug: Cobimetinib
Cobimetinib: 60 mg by mouth once a day on Days 1−21 of every 28-day cycle
Other Name: Cotellic
Experimental: 2L-2: Atezo + PEGPH20
Participants in the 2L-2 arm will receive atezolizumab in combination with PEGylated recombinant human hyaluronidase (PEGPH20). Participants who progressed on treatment may have the option of receiving Atezolizumab + Cobimetinib treatment, provided they meet the eligibility criteria.
Biological: PEGylated recombinant human hyaluronidase (PEGPH20)
PEGPH20: 3 micrograms per kilogram (mcg/kg) administered by IV infusion on Days 1, 8, and 15 of every 21-day cycle.
Biological: Atezolizumab
Atezolizumab: 1200 mg administered by IV infusion on Day 1 of every 21-day cycle
Other Name: Tecentriq
Experimental: 2L-3: Atezo + BL-8040
Participants in the 2L-3 arm will receive atezolizumab in combination with BL-8040. Participants who progressed on treatment may have the option of receiving Atezolizumab + Cobimetinib treatment, provided they meet the eligibility criteria.
Drug: BL-8040
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).
Biological: Atezolizumab
Atezolizumab: 1200 mg administered by IV infusion on Day 1 of every 21-day cycle
Other Name: Tecentriq
Experimental: 2L-4: Atezo + Linagliptin
Participants in the 2L-4 arm will receive atezolizumab in combination with linagliptin. Participants who progressed on treatment may have the option of receiving Atezolizumab + Cobimetinib treatment, provided they meet the eligibility criteria.
Drug: Linagliptin
Linagliptin: 5 mg orally once a day of every 21-day cycle.
Biological: Atezolizumab
Atezolizumab: 1200 mg administered by IV infusion on Day 1 of every 21-day cycle
Other Name: Tecentriq



Primary Outcome Measures :
  1. 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 3-5 years) ]
  2. 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 3-5 years) ]
  3. 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 ]

Secondary Outcome Measures :
  1. 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 3-5 years) ]
  2. Overall Survival (OS) [ Time Frame: From randomization up to death from any cause (up to approximately 3-5 years) ]
  3. Percentage of Participants Who Are Alive at Month 6 and at Month 12 [ Time Frame: Month 6, Month 12 ]
  4. 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 3-5 years) ]
  5. 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 3-5 years) ]
  6. 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 3-5 years) ]
  7. 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) ]
  8. 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 3-5 years) (Detailed timeframe is provided in outcome measure 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 3-5 years)

  9. 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 3-5 years) (Detailed timeframe is provided in outcome measure 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 3-5 years); 30 days after last dose (up to approximately 3-5 years)

  10. 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 ]
  11. 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 3-5 years) ]
  12. 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 3-5 years) ]
  13. 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 3-5 years) (Detailed timeframe is provided in outcome measure 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 3-5 years); 30 days after last dose (up to approximately 3-5 years)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age >/= 18 years;
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
  • Life expectancy >/= 3 months, as determined by the investigator;
  • Histologically or cytologically confirmed locally advanced unresectable or metastatic adenocarcinoma of gastric or gastroesophageal junction; (for the 1L Cohort: no prior systemic therapy for the locally advanced or metastatic disease; for the 2L Cohort: disease progression during or following a first-line platinum-containing or fluoropyrimidine-containing chemotherapy regimen);
  • Only for the 1L Cohort: human epidermal growth factor receptor 2 (HER2)-negative tumors;
  • Measurable disease (at least one target lesion) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1);
  • Adequate hematologic and end organ function based on laboratory results obtained within 14 days prior to initiation of study treatment;
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures as outlined for each specific treatment arm;
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm.

Exclusion Criteria:

Exclusion criteria for the 2L Cohort:

  • Urinary protein is > 1 + on dipstick and the required following 24-hour urine collection shows urinary protein > 2000 mg;
  • Serious or non-healing wound, peptic ulcer, or bone fracture within 28 days prior to initiation of study treatment;
  • History of gastrointestinal perforation and/or fistulae within 6 months prior to initiation of study treatment;
  • Presence of a bowel obstruction, history or presence of inflammatory enteropathy, or extensive intestinal resection, Crohn disease, ulcerative colitis, or chronic diarrhea;
  • Uncontrolled arterial hypertension >/= 150/ >/= 90 millimeter of mercury (mmHg) despite standard medical management;
  • Chronic therapy with non-steroidal anti-inflammatory agents or other anti-platelet agents.

Exclusion Criteria:

  • Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy;
  • Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases;
  • History of leptomeningeal disease;
  • Active or history of autoimmune disease or immune deficiency;
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan;
  • Positive test for human immunodeficiency virus (HIV) at screening;
  • Active hepatitis B virus (HBV) or hepatitis C (HCV) infection;
  • Severe infection within 4 weeks prior to initiation of study treatment;
  • Significant cardiovascular disease;
  • Significant bleeding disorder;
  • Prior allogeneic stem cell or solid organ transplantation;
  • Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study;
  • Treatment with anticoagulation with warfarin, low-molecular-weight heparin, or similar agents for therapeutic purposes;
  • History of malignancy other than gastric or gastroesophageal junction carcinoma within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death;
  • Known allergy or hypersensitivity to any of the study drugs or their excipients.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03281369


Contacts
Contact: Reference Study ID Number: YO39609 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
United States, Arizona
Mayo Clinic Cancer Center Not yet recruiting
Scottsdale, Arizona, United States, 85259
United States, California
Uni of Southern California; Norris Comprehensive Cancer Ctr Not yet recruiting
Los Angeles, California, United States, 90033
United States, Massachusetts
Dana-Farber Cancer Institute - Gastrointestinal Cancer Treatment Center Withdrawn
Boston, Massachusetts, United States, 02111
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Memorial Sloan Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
United States, Tennessee
Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
The University of Texas MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030-4009
France
Centre Leon Berard Not yet recruiting
Lyon, France, 69008
Institut Universitaire du Cancer de Toulouse-Oncopole; PHARMACIE Not yet recruiting
Toulouse, France, 31100
Gustave Roussy Cancer Campus Not yet recruiting
Villejuif, France, 94805
Germany
Universitaetsklinikum Essen; Westdeutsches Tumorzentrum; Innere Klinik (Tumorforschung) Not yet recruiting
Essen, Germany, 45122
Krankenhaus Nordwest GmbH - Institut Fuer Klinisch-Onkologische Forschung (IKF) Not yet recruiting
Frankfurt am Main, Germany, 60488
Universitatsklinik Heidelberg; Universitätshautklinik und Nationales Centrum für Tumorerkrankungen Not yet recruiting
Heidelberg, Germany, 69120
Korea, Republic of
Seoul National University Hospital (SNUH) - Medical Oncology Center Recruiting
Jongno -Gu, Korea, Republic of, 03080
Yonsei University College of Medicine (YUCM)-Yonsei Cancer Center; Cancer Metastasis Research Center Recruiting
Seodaemun-Gu, Korea, Republic of, 03722
Samsung Medical Center Recruiting
Seoul, Korea, Republic of, 06351
University of Ulsan College of Medicine - Asan Medical Center (AMC) - Asan Cancer Center (ACC) Recruiting
Songpa-gu, Korea, Republic of, 05505
Netherlands
Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis Withdrawn
Amsterdam, Netherlands, 1066 CX
Spain
Universidad de Navarra - Clinica Universitaria de Navarra (CUN) Not yet recruiting
Pamplona, Navarra, Spain, 31008
Hospital Universitari Vall dHebron - Vall dHebron Institut dOncologia (VHIO) Not yet recruiting
Barcelona, Spain
Taiwan
National Taiwan University Hospital (NTUH) - Cancer Research Center Not yet recruiting
Zhongzheng Dist., Taiwan, 10051
United Kingdom
Barts and The London School of Medicine and Dentistry - Barts Cancer Institute (BCI)-CECM Not yet recruiting
London, United Kingdom, 0
The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital (RMH) - Sutton Not yet recruiting
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
Hoffmann-La Roche
Halozyme and BiolineRx Ltd

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03281369     History of Changes
Other Study ID Numbers: YO39609
2016-004529-17 ( EudraCT Number )
First Posted: September 13, 2017    Key Record Dates
Last Update Posted: February 14, 2018
Last Verified: February 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Adenocarcinoma
Stomach Neoplasms
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Head and Neck Neoplasms
Esophageal Diseases
Paclitaxel
Oxaliplatin
Atezolizumab
Ramucirumab
Albumin-Bound Paclitaxel
Fluorouracil
Antibodies, Monoclonal
Linagliptin
Leucovorin
Levoleucovorin
Folic Acid
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents