Urothelial carcinoma (UC) MedDRA version: 20.0 Level: LLT Classification code 10064467 Term: Urothelial carcinoma System Organ Class: 100000004864
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 =65 years) yes F.1.3.1 Number of subjects for this age range 213
Exclusion criteria
Exclusion criteria: 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 = 2 - Active keratitis or corneal ulcer
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 • To evaluate the safety of immunotherapy-based treatment combinations during Stage 1 and Stage 2 • To characterize the pharmacokinetic profile of drugs that are administered as part of an immunotherapy based treatment combination during Stage 1 and Stage 2 • To evaluate the immune response to drugs that are administered as part of an immunotherapy-based treatment combination during Stage 1 and Stage 2 ;Primary end point(s): 1. Objective response rate;Timepoint(s) of evaluation of this end point: 1. Up to 5 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Progression-free survival 2. Overall survival after randomization 3. Overall survival rate at specific time points 4. Duration of response 5. Disease control 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 7. Change from baseline in vital signs 8. Change from baseline in targeted clinical laboratory test results 9. Plasma or serum concentration of each drug at specified time points 10. For drugs for which anti-drug antibody (ADA) formation is measured: presence of ADAs during the study relative to the presence of ADAs at baseline ; Timepoint(s) of evaluation of this end point: 1-2. Up to 5 years 3. 12 months 4-8. Up to 5 years 9-10. Atezo Control Arm and Atezo-EV Arm (Preliminary Phase): Day (D) 1 of Cycle (C) 1, 2, 4, 8, 12, 16 and treatment discontinuation (TD) visit Atezo + Nira and Atezo + Isa Arm (Preliminary Phase): D1 of C1, 2, 4, 6, 8, 10, 12, 16; TD visit Atezo + Hu5F9-G4 Arm: D1, 8, 22 of C1; D1 of C2, 4, 8, 12, 16; TD visit Atezo + Isa Arm (Expansion Phase): D1, 8, 15 of C1; D1 of C2, 3, 4, 6, 8, 10, 12, 16; TD visit Atezo + Nira(Expansion Phase) and Atezo + Lina Arm: D1, 15 of C1; Day 1 of C2, 4, 8, 12, 16; TD visit Atezo + TCZ Arm: D1 of C1, 2, 4, 6, 8, 10, 12, 14, 16; every fourth cycle after cycle 16; TD visit Atezo-EV Arm (Expansion Phase): D1, 8 of C1, D1 of C2, 4, 8, 12, 16 TD visit | — |
Countries
France, Korea, Republic of, Spain, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed