A Study of RO7247669 Alone or in Combination with Tiragolumab Versus Atezolizumab in Patients with Previously Untreated Locally Advanced or Metastatic Urothelial Bladder Cancer who are Ineligible for Platinum-Containing Chemotherapy

Phase 1

Conditions: Previously Untreated Locally Advanced or Metastatic Urothelial Bladder Cancer
MedDRA version: 20.0Level: LLTClassification code 10046714Term: Urothelial carcinoma bladderSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2022-002265-15-FR

Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 240

Inclusion Criteria

• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status of <= 2
• Histologically or cytologically documented locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium
• Considered to be ineligible (unfit) to receive platinum-based chemotherapy defined by one of the following criteria:
• ECOG Performance Status of 0 with baseline GFR = 15 mL/min/1.73 m2 and =30 mL/min/1.73 m2
• ECOG Performance Status of 1 or 2 with baseline GFR = 15 mL/min/1.73 m2 and = 45 mL/min/1.73 m2
• ECOG Performance Status of 0-2 with G=2 neuropathy
• Patients for whom chemotherapy is not deemed appropriate
• No prior chemotherapy for inoperable locally advanced or metastatic or recurrent urothelial carcinoma (UC)
• Measurable disease; at least one measurable lesion as defined by response evaluation criteria in solid tumors, version 1.1 (RECIST v1.1)
• Availability of a representative leftover tumor specimen that meet the criteria outlined prior to study enrollment, and that is suitable for determination of programmed death-ligand 1 (PD-L1) status, for stratification and for exploratory biomarker research as assessed by a central laboratory
• Life expectancy >= 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 <= 480 ms. If the QTcF interval is longer than 480 ms but shorter than 500 ms, the participant may undergo a cardiac evaluation and be considered for treatment in case of no clinically significant findings
• Resting systolic blood pressure <= 150 mmHg and diastolic blood pressure 100 mmHg
• Resting heart rate between 45-100 bpm
• Left ventricular ejection fraction (LVEF) >= 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) <= 3 x institutional upper limit of normal (ULN). Participants with TnT or TnI levels between >1 and <3 x ULN should have a further TnT or TnI reading within 3-6 hours and will be permitted to enter the study only if repeat levels remain = 3 x ULN and have not changed by > 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

• 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

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

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A Study of RO7247669 Alone or in Combination with Tiragolumab Versus Atezolizumab in Patients with Previously Untreated Locally Advanced or Metastatic Urothelial Bladder Cancer who are Ineligible for Platinum-Containing Chemotherapy

Recruitment & Eligibility

Study & Design

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