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

Phase 1

• Conditions: Previously Untreated Locally Advanced or Metastatic Urothelial Cancer; MedDRA version: 20.0Level: LLTClassification code 10046714Term: Urothelial carcinoma bladderSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2022-002265-15-DE
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-01-10
• Last Update Posted: 10 June 2024

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. Patients with squamous, sarcomatoid, micropapillary, and glandular variant histologies are eligible for inclusion in the study, provided that an urothelial component is present in the tumor specimen. Patients with other variant histologies or pure variant histologies are not eligible for inclusion in the study.
• 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 Grade =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
• For patients receiving therapeutic anticoagulation: stable anticoagulation regimen during the 14 days prior to initiation of study treatment
• 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 with the following criteria:
- New York Heart Association (NYHA) Heart Failure Class = 2
- 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 co

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 tobemstomig, 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)
• Acute 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 2 years prior initiation of study treatment, 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, with the exception of oral
antibiotics prescribed for urinary tract infections
• 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 tobemstomig, 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 4 weeks of 5 drugs elimination half-lives (whichever is longer) 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 comp

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified