A 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)
- Conditions
- ocally advanced unresectable or Metastatic gastric or gastroesophageal junction cancer or esophageal cancerMedDRA version: 20.1 Level: PT Classification code 10062878 Term: Gastrooesophageal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0 Level: LLT Classification code 10030151 Term: Oesophageal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-004529-17-GB
- Lead Sponsor
- F. Hoffman-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 262
Inclusion Criteria for Stages 1 and 2 (Gastric and Esophageal Cancer
Cohorts)
- Ability to comply with the study protocol, in the investigator's judgment
- Measurable disease (at least one target lesion) according to Response Evaluation Criteria in Solid Tumors, Version (RECIST) v1.1
- Adequate hematologic and end organ function
- Tumor accessible for biopsy
- Negative HIV test at screening
- Negative hepatitis B surface antigen test at screening
- Negative total hepatitis B core antibody test at screening, or positive total HBcAb test followed by quantitative hepatitis B virus DNA < 500 IU/mL at screening
- Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
- For women of childbearing potential: agreement to remain abstinent or use contraceptive measures as outlined for each specific treatment arm and to refrain from donating eggs
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm Inclusion Criteria for Stage 1 (Gastric and Esophageal Cancer Cohorts)
- Age >=18 years at the time of signing Informed Consent Form
- 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 according to 2018 National Comprehensive Cancer Network Gastric Cancer Guidelines or metastatic adenocarcinoma of gastric or gastroesophageal junction
- Availability of a representative tumor specimen that is suitable for determination of PD-L1 and TIGIT levels by IHC (Esophageal Cancer cohort only) and/or additional biomarker status by means of central testing
- Only for the 1L Gastric Cancer Cohort: patients whose tumors are without HER2 amplification documented by fluorescence in situ hybridization (FISH) or in situ hybridization (ISH) or are negative by immunohistochemistry (IHC) 0 or +1 on previously collected and assessed tumor tissue upon initial diagnosis of disease by local laboratory testing
Esophageal Cancer cohort only:
- No prior systemic treatment for esophageal cancer
- For patients with adenocarcinoma: absence of HER2 expression as documented as ISH-negative on previously collected and assessed tumor tissue upon initial diagnosis of disease
- Life expectancy >= 3 months as determined by the investigator
- Creatinine clearance (CrCl) >= 50 mL/min
Inclusion Criteria for Stage 2
- ECOG Performance Status of 0-2
- Participation in a 2L Cohort arm other than the Atezo+RO6874281 arm during Stage 1
- Patients in a control arm during Stage 1: ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity, provided that Medical Monitor approval for entry into Stage 2 is obtained, or disease progression per RECIST v1.1 while receiving treatment
- Patients in an experimental arm during Stage 1: ability to initiate Stage 2 treatment within 3 months after
Exclusion Criteria for 2L Gastric Cancer Cohort, Stage 1
- Urinary protein is > 1 + on dipstick and the required following 24-hour urine collection shows urinary protein > 2 g
- Serious or non-healing wound, peptic ulcer, or bone fracture within 28 days prior to initiation of treatment
- History of gastrointestinal (GI) perforation and/or fistulae within 6 months prior to initiation of 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, defined as systolic blood pressure of >= 140 mmHg and/or diastolic blood pressure of >= 95 mmHg
- Chronic therapy with non-steroidal anti-inflammatory agents (e.g., indomethacin, ibuprofen, naproxen or similar agents) or other antiplatelet agents (e.g., clopidogrel, ticlopidine, dipyridamole, anagrelide, or similar agents). Aspirin use at doses of up to 325 mg/day is permitted
Exclusion Criteria for Stage 1
- Systemic treatment for gastric cancer within 2 weeks or 5 half-lives of the drug prior to initiation of treatment
- Prior treatment with any of the protocol-specified study treatments, with the exception of chemotherapy
- Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
- Treatment with investigational therapy within 28 days prior to initiation of treatment
- Patients with Type 2 diabetes mellitus currently under treatment with dipeptidyl peptidase-4 inhibitors
- Known dihydropyrimidine dehydrogenase deficiency
- Eligible only for the control arm
For Esophageal cancer only:
- Patients with known hearing impairment
- Grade >= 2 peripheral neuropathy
Stages 1 and 2 (Gastric cancer cohort)
- Weight loss >5% within 4 weeks prior to screening
- Uncontrolled pleural effusion, pericardial effusion, or ascites, tumorrelated pain and hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
- Symptomatic, untreated, or actively progressing central nervous system metastases
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomographyscan
- Active hepatitis B, C virus infection
- Significant cardiovascular disease within 12 months prior to initiation of treatment, or unstable arrhythmia or unstable angina and bleeding
disorder, vasculitis, Grade >=3 hemorrhage, or significant bleeding episode from a gastrointestinal tract event within 3 months prior to initiation of treatment
- History of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism within 3 months prior to initiation of treatment and malignancy other than gastric or gastroesophageal junction carcinoma within 2 years prior to screening
- Treatment with anticoagulation with warfarin, low-molecular-weight heparin, or similar agents for therapeutic pu
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method