A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy- Based Treatments and Combinations in Patients with Urothelial Carcinoma Morpheus-UC
- Conditions
- rothelial carcinoma (UC)MedDRA version: 20.0Level: LLTClassification code 10064467Term: Urothelial carcinomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-004634-28-GR
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 345
For the metastatic urothelial carcinoma cohort
Stage 1
- Age >=18 years
- Life expectancy >= 3 months, as determined by the investigator
- Ineligible for cisplatin-based chemotherapy
- Histologically documented, locally advanced or metastatic UC (M1, Stage IV)
- No prior chemotherapy for inoperable, loally advanced or metastatic UC
- Availability of a representative tumor specimen that is suitable for determination of Programmed death-ligand 1 (PD-L1) and/or additional biomarker status by means of central testing
- Disease progression during or following treatment with no more than one platinum containing regimen for inoperable, locally advanced or metastatic UC or disease recurrence
Stage 1 and Stage 2
- Ability to comply with the study protocol, in the investigator’s judgment
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
- Measurable disease according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST) v1.1
- Adequate hematologic and end-organ function
- For patients receiving therapeutic anticoagulation: stable anticoagulant regimen during the 14 days before initiation of study treatment
- Negative HIV test at screening
- Negative total hepatitis B core antibody (HBcAb) test or positive total HBcAb test followed by quantitative hepatitis B virus (HBV) DNA < 500 IU/mL at screening and 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 and men of childbearing potential: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating eggs or donating sperm as outlined for each specific treatment arm
Stage 2
- Patients in the atezolizumab control arm: ability to initiate Stage 2 treatment within 3 months after loss of clinical benefit as determined by the investigator while receiving control treatment
- Patients in an experimental arm during Stage 1: ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity not related to atezolizumab or loss of clinical benefit as determined by the investigator while receiving Stage 1 treatment
- Availability of a tumor specimen from a biopsy performed upon discontinuation of Stage 1
For the Muscle Invasive Bladder Cancer Cohorts (MIBC)
- Age >= 18 years
- ECOG PS of 0 or 1
- Fit and planned-for cystectomy
- Histologically documented MIBC
- Availability of a TURBT specimen that is suitable for determination of PD-L1 and additional biomarker status by means of central testing
- N0 or M0 disease assessed by CT or magnetic resonance imaging (MRI) scan (within 4 weeks of registration)
- Adequate hematologic and end-organ function
- Negative HIV test at screening
- Negative total HBcAb test at screening, or positive total HBcAb test followed by quantitative HBV DNA < 500 IU/mL at screening
- Negative 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 and, if applicable, agreement to refrain from donating eggs as outlined for each specific treatment arm
- For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number
For the mUC cohort
Stage 1
-Prior treatment with a T-cell co-stimulating therapy or an immune checkpoint inhibitor, or investigational therapy within 28 days before C1D1 or any approved anti-cancer therapy within 3 weeks before study Stage 1 and Stage 2
-Prior systemic immunostimulatory treatments within 4 weeks or 5 half-lives of the drug before study, or with systemic immunosuppressants within 2 weeks before study or need such during study
-Uncontrolled pleural effusion, pericardial effusion, or ascites and tumor-related pain
-Uncontrolled or symptomatic hypercalcemia or untreated actively progressing CNS metastases or uncontrolled hypertension
-History of leptomeningeal disease, autoimmune disease, idiopathic pulmonary fibrosis (IPF) organizing pneumonia drug-induced pneumonitis or idiopathic pneumonitis or active pneumonitis at screening
-History of malignancy except UC within 2 years before screening
-Active tuberculosis (TB)
-Severe infection within 4 weeks before initiation of study treatment or major active infection
-Treatment with oral or IV antibiotics within 2 weeks before study
-Significant cardiovascular disease (CVD)
-Grade =3 hemorrhage within 28 days before study treatment
-Major surgery within 4 weeks before study treatment, or need such during study
-Adverse events from prior anti-cancer therapy that have not improved to Grade =1 or better, excluding alopecia of any grade and Grade =2 peripheral neuropathy
-Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug
-History of severe allergic reactions to chimeric or humanized antibodies or fusion proteins, or known hypersensitivity to any of the study drugs or excipients or any of the drugs required for premedication
-Patients entering Stage 2: inability to tolerate atezolizumab during Stage 1, or immunotherapy-related adverse events that have not resolved to Grade 1 or better or to baseline at the time of consent
-Pregnancy or breastfeeding, or intention of becoming pregnant during the study
For Atezo-EV Arm (Stage 1 and Stage 2)
-Ongoing sensory or motor neuropathy Grade= 2
-Active or evidence of active keratitis or corneal ulcerations
-Uncontrolled diabetes
-AST or ALT = 3.0 × ULN
For Atezo-Nira Arm (Stage 1)
-Inability to swallow medication or a malabsorption condition that would alter oral absorption of orally medications
-Patients with uncontrolled ventricular arrhythmia, uncontrolled major seizure disorder, unstable spinal cord compression, or superior vena cava syndrome
For Atezo-Hu5F9-G4 Arm (Stage 1)
-RBC transfusion dependence
-History of hemolytic anemia or Evans syndrome in the last 3 months For Atezo +TCZ Arm (Stage 1)
-Preexisting CNS demyelinating or seizure disorders
-History of diverticulitis, diverticulosis requiring antibiotics, or other symptomatic lower gastrointestinal conditions that might predispose to perforations
-Current liver disease unrelated to the underlying cancer diagnosis
-Active infection, or active TB requiring treatment within 3 years prior to study, or untreated latent TB
-Primary or secondary immunodeficiency
-ANC < 2 × 109/L
For Atezo+Tira Arm (Stage 1 and in the MIBC Cohorts)
-Active Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV infection at screening
For Atezo+RO7122290 Arm (Stage 1 and in the MIBC Cohorts)
-Clinically significant CVD or cerebrovascular disease within 6 months before study drug
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