A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients with Locally Advanced or Metastatic Urothelial Carcinoma After Failure with Platinum Containing Chemotherapy (Morpheus-mUC)
- 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-GB
- 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
- 385
Stage 1
- Age >=18 years
- Life expectancy >= 3 months, as determined by the investigator
- Histologically documented, locally advanced or metastatic UC (M1, Stage IV)
- 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 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
- 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
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 115
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 270
Stage 1
- Prior treatment with a T-cell co-stimulating therapy or an immune checkpoint inhibitor
- 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, TIGIT-targeting agents, Trop-2 targeting agents, FAP-directed therapies, 4-1BB (CD137) directed therapies, or topoisomerase 1 inhibitors
- Treatment with investigational therapy within 28 days prior to C1D1
- Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment
- 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
- Uncontrolled hypertension
- 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 or known hypersensitivity to Chinese hamster ovary cell products or recombinant human antibodies
- 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
- Patients entering Stage 2: 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 during Stage 1 and Stage 2
- Ongoing sensory or motor neuropathy Grade >= 2
- Active keratitis or corneal ulcerations
- Uncontrolled diabetes
- AST or ALT >= 3.0 × ULN
- Evidence of active keratitis or corneal ulcerations during the Stage 1 and 2 ophthalmologic examination prior to Cycle 1, Day 1.
For Atezo-Nira Arm during Stage 1
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: • To evaluate the efficacy of immunotherapy-based treatment combinations during Stage 1 based on Objective response rate;Secondary Objective: • To evaluate the efficacy of immunotherapy-based treatment combinations during Stage 1 based on progression-free survival, overall survival after randomization, overall survival rate at specific time points (e.g., 12 months), duration of response, Disease control<br>• To evaluate the safety of immunotherapy-based treatment combinations during Stage 1 and Stage 2<br>;Primary end point(s): 1. Objective response rate;Timepoint(s) of evaluation of this end point: 1. Up to 5 years
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Progression-free survival<br>2. Overall survival after randomization<br>3. Overall survival rate at specific time points<br>4. Duration of response<br>5. Disease control<br>6. Incidence, nature, and severity of adverse events and laboratory abnormalities, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0<br>7. Change from baseline in vital signs<br>8. Change from baseline in targeted clinical laboratory test results;Timepoint(s) of evaluation of this end point: 1-2. Up to 5 years<br>3. 12 months<br>4-8. Up to 5 years