Advanced or Metastatic Urothelial Carcinoma MedDRA version: 19.0 Level: LLT Classification code 10064467 Term: Urothelial carcinoma System Organ Class: 100000004864
Conditions
Interventions
Product Name: MOXR0916
Product Code: anti-OX40, aOX40, PRO370916
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: N/A
Cur
Sponsors
Genentech, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age >= 18 years - Eastern Cooperative Oncology Group (ECOG) performance status of = 12 weeks - Histologically or cytologically confirmed locally advanced or metastatic urothelial carcinoma (UC) - Availability of a representative tumor specimen to enable central testing for determination of PD-L1 status and exploratory research on biomarkers - No prior systemic therapy for inoperable locally advanced or metastatic UC - Ineligible for cisplatin-based chemotherapy as defined by any one of the following criteria: Impaired renal function (glomerular filtration rate [GFR] > 30 but = 2 audiometric hearing loss (25 Decibel at two contiguous frequencies or more severe); NCI CTCAE v 4.0 Grade >= 2 peripheral neuropathy; ECOG Performance Status of 2 - Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1 - Adequate hematologic and end-organ function - For women of childbearing potential: agreement to remain abstinent or use a contraceptive method with a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 187
Exclusion criteria
Exclusion criteria: - Pregnant or lactating, or intending to become pregnant or breast feed during the study or 6 months afterward - Significant cardiovascular disease, such as New York Heart Association cardiac disease, myocardial infarction, or cerebrovascular accident within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina - Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, and inherited liver disease - Major surgical procedure within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during the course of the study - Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug - Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment except palliative radiotherapy for bone metastases or soft tissue lesions that is completed > 7 days prior to baseline imaging; radiotherapy for brain metastases; prior local intravesical chemotherapy or immunotherapy is allowed if completed at least 4 weeks prior to the initiation of study treatment; hormone-replacement therapy or oral contraceptives; patients should be recovered from any toxicities associated with permitted anti-cancer therapies - Prior treatment with CD137 or OX40 agonists, anti- cytotoxic T-lymphocyte-associated protein (CTLA4), anti-PD-1, anti-PD-L1, anti-CD-27, anti- Glucocorticoid-induced tumor necrosis factor receptor (GITR) therapeutic antibody or pathway-targeting agents - Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days prior to initiation of study treatment - Untreated central nervous system (CNS) metastases or active (progressing or requiring corticosteroids for symptomatic control) CNS metastases - Any history of leptomeningeal disease - Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures - Uncontrolled tumor-related pain - Malignancies other than UC within 5 years prior to Cycle 1, Day 1 - Uncontrolled or symptomatic hypercalcemia - History of autoimmune disease - Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study - Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug, whichever is longer, prior to initiation of study treatment - History of idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography scan - Active hepatitis B and C virus infection - Positive HIV test at screening - Active tuberculosis - Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia - Prior
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1-2. Up to approximately 45 months;Main Objective: To evaluate the efficacy of MOXR0916 plus atezolizumab compared with placebo plus atezolizumab in patients enrolled irrespective of tumor programmed death-Ligand 1 (PD-L1) score, as measured by progression-free survival (PFS) and overall survival (OS).; Primary end point(s): 1.PFS (in patients enrolled irrespective of tumor PD-L1 score) as determined by the investigator according to RECIST v1.1 2.OS (in patients enrolled irrespective of tumor PD-L1 score) ; Secondary Objective: •To evaluate the efficacy of MOXR0916 plus atezolizumab compared with placebo plus atezolizumab in patients enrolled irrespective of tumor PD-L1 score, as measured by objective response (OR) and duration of response (DOR). •To evaluate the efficacy of MOXR0916 plus atezolizumab compared with placebo plus atezolizumab in a subgroup of patients defined by tumor PD-L1 score. •To evaluate the safety of MOXR0916 plus atezolizumab compared with placebo plus atezolizumab •To characterize pharmacokinetics of MOXR0916 and atezolizumab when administered in combination •To evaluate the immune response to MOXR0916 and atezolizumab | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.PFS according to RECIST v1.1 and OS, in patients defined by tumor PD-L1 score 2.OR and DOR according to RECIST v1.1 3.Incidence of adverse events 4.Serum concentrations and presence of anti-therapeutic antibodies to MOXR0916 and atezolizumab ; Timepoint(s) of evaluation of this end point: 1-3. Up to approximately 45 months 4. At specified time points up to 120 days after last dose of study treatment | — |
Countries
Austria, Belgium, Canada, Denmark, France, Germany, Netherlands, Portugal, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd.
Outcome results
None listed