A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Cisplatin-Ineligible Patients with Locally Advanced or Metastatic Urothelial Carcinoma After Failure with Platinum Containing Chemotherapy (Morpheus-mUC)
- Conditions
- rothelial carcinoma (UC)MedDRA version: 20.0 Level: LLT Classification code 10064467 Term: Urothelial carcinoma System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-004634-28-ES
- 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
- Not specified
- Target Recruitment
- 305
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 ncology Group Performance Status 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 prior to 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
- Tumor accessible for biopsy
- For women and men of childbearing potential: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating eggs 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
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 of subjects for this age range 92
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 213
Stage 1
- Prior treatment with a T-cell co-stimulating therapy or an immune checkpoint inhibitor including anti- CTLA-4 anti-PD-1, and anti-PD-L1 therapeutic antibodies
- Prior treatment with any of the protocol-specified study treatments including treatment with any poly polymerase inhibitor, nectin-4 targeting agents, signal regulatory protein a-targeting agents, or agents that block CD38
- Any approved anti-cancer therapy
- Eligible only for the control arm
Stage 1 and Stage 2
- Prior allogeneic stem cell or solid organ transplantation
- Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug prior to the initiation of study treatment
- Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressant medication during study treatment
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures and tumor-related pain
- Uncontrolled or symptomatic hypercalcemia and symptomatic, untreated or actively progressing central nervous system metastases
- History of leptomeningeal disease, autoimmune disease, idiopathic pulmonary fibrosis, organizing pneumonia drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
- History of malignancy other than UC within 2 years prior to screening
- Active tuberculosis (TB)
- Severe infection within 4 weeks prior to initiation of study treatment
- Treatment with therapeutic oral or intravenous (IV) antibiotics within 2 weeks prior to initiation of study treatment
- Significant cardiovascular disease
- Grade >=3 hemorrhage or bleeding event within 28 days prior to initiation of study treatment
- 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
- Adverse events from prior anti-cancer therapy that have not improved to Grade <=1 or better, with the exception of 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
- Known intolerance or hypersensitivity to any of the study drugs or their excipients and any of the drugs required for premedication
- Patients entering Stage 2: inability to tolerate atezolizumab during Stage 1
- Pregnancy or breastfeeding, or intention of becoming pregnant during the study
- Patients entering Stage 2: recovery from all immunotherapy-related adverse events to Grade 1 or better or to baseline at the time of consent
For Atezo-EV Arm during Stage 1 and Stage 2
- Ongoing sensory or motor neuropathy Grade >= 2
- Active keratitis or corneal ulcer
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