Previously Untreated Locally Advanced or Metastatic Urothelial Bladder Cancer MedDRA version: 20.0 Level: LLT Classification code 10046714 Term: Urothelial carcinoma bladder System Organ Class: 100000004864
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age >= 18 years • Eastern Cooperative Oncology Group (ECOG) Performance Status of = 12 weeks • Adequate hematologic and end-organ function • Negative human immunodeficiency virus (HIV) test at screening • Negative hepatitis B surface antigen (HBsAg) test at screening • Positive hepatitis B surface antibody (HBsAb) test at screening, or a negative HBsAb at screening • Negative hepatitis C virus (HCV) antibody test at screening, or a positive HCV antibody test followed by a negative HCV ribonucleic acid (RNA) test at screening • Adequate cardiovascular function • Baseline-corrected QT (QTcF) interval = 50% assessed by either transthoracic echocardiogram (TTE) or multiple-gated acquisition (MUGA) scan (TTE preferred test) within 6 months prior to initiation of study treatment • Troponin T (TnT) or troponin I (TnI) 1 and 20% compared to the first reading. These participants should also undergo a cardiac evaluation and consider consulting a cardiologist to confirm no clinically significant findings before they receive study treatment • For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs during the treatment period and for 5 months after the final dose of atezolizumab, 4 months after the final dose of RO7247669, or 90 days after the final dose of tiragolumab • For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm 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 a
Exclusion criteria
Exclusion criteria: • Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of atezolizumab, 4 months after the final dose of RO7247669, or 90 days after the final dose of tiragolumab • Glomerular filtration rate (GFR) < 15 mL/min/1.73 m2 as calculated through use of the chronic kidney disease epidemiology collaboration (CKD-EPI) equation or receiving dialysis • Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases • History of leptomeningeal disease • Uncontrolled tumor-related pain • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures • Uncontrolled or symptomatic hypercalcemia • Active or history of autoimmune disease or immune deficiency • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan • Active tuberculosis (TB) • Active Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV infection at screening • Significant cardiovascular/cerebrovascular disease within 3 months 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 • History of another primary malignancy other than urothelial carcinoma within 5 years prior to Cycle 1, Day 1, with the exception of malignancies with a negligible risk of metastasis or death • Severe infection within 4 weeks prior to initiation of study treatment • Treatment with therapeutic oral or intravenous antibiotics within 2 weeks prior to initiation of study treatment • Prior allogeneic stem cell or solid organ transplantation • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications • Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during treatment or within 5 months after the final dose of atezolizumab, 4 months after the final dose of RO7247669, or 90 days after the final dose of tiragolumab • Current treatment with anti-viral therapy for HBV • Treatment with any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment • Treatment with investigational therapy within 28 days prior to initiation of study treatment • Prior treatment with CD137 agonists or immune checkpoint blockade therapies • Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives prior to initiation of study treatment • Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment • History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins • Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the efficacy of RO7247669 and RO7247669 in combination with tiragolumab compared to atezolizumab on the basis of confirmed objective response rate (ORR);Secondary Objective: • To evaluate the efficacy of RO7247669 and RO7247669 in combination with tiragolumab compared to atezolizumab on the basis of PFS, OS, DOR, PFS rate (6 and 12 months), OS rate (6, 12 and 18 months) and DCR • To evaluate the safety of RO7247669 and RO7247669 in combination with tiragolumab compared to atezolizumab • To evaluate the quality of life of participants treated with RO7247669 and RO7247669 in combination with tiragolumab compared to atezolizumab • To characterize the RO7247669 PK profile after administration of RO7247669 and RO7247669 in combination with tiragolumab • To characterize the PK profile of tiragolumab after administration of tiragolumab in combination with RO7247669 • To characterize the PK profile of atezolizumab after administration of atezolizumab • To evaluate the immune response to RO7247669;Primary end point(s): 1. Confirmed ORR, defined as the proportion of participants with a complete response (CR) or partial response (PR) on two consecutive occasions >= 4 weeks apart after randomization, as determined by the investigator according to RECIST v1.1;Timepoint(s) of evaluation of this end point: 1. Up to approximately 30 months for each individual | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Progression-free survival (PFS) after randomization defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1 2. Overall survival (OS) after randomization, defined as the time from randomization to death from any cause 3. Duration of response (DOR), defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1 4. PFS rate at 6 months and 12 months, defined as the proportion of participants who have not experienced disease progression or death from any cause as determined by the investigator according RECIST v1.1 5. OS rate at 6 months, 12 months, and 18 months, defined as the proportion of participants who have not experienced death from any cause at 6 months, 12 months, and 18 months 6. Disease control rate (DCR), defined as the proportion of participants with confirmed CR or PR as best response, or stable disease maintained for >= 12 weeks, per RECIST v1.1 7. Incidence and severity of adverse events, with severity determined according to national cancer institute common terminology criteria for adverse events, version 5.0 (NCI CTCAE v5) 8. Time to confirmed deterioration (TTCD) from randomization, in patient-reported pain, physical functioning, role functioning, and global health status (GHS)/ quality of life (QoL) scales as assessed through use of the european organisation for research and treatment of cancer (EORTC) item library (IL) 187; confirmed deterioration is defined as a decrease from baseline of >= 10 points (for the physical functioning, role functioning, and GHS/QoL scales) or an increase from baseline of >= 10 points (for the pain scale) that is either maintained for two consecutive assessments or followed by death from any cause within | — |
Countries
Australia, Brazil, China, Denmark, France, Germany, Greece, Italy, Korea, Republic of, Poland, Spain, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed