A Study of Atezolizumab Versus Placebo as Adjuvant Therapy in Patients With High-Risk Muscle-Invasive Bladder Cancer Who Are ctDNA Positive Following Cystectomy

• Status: Recruiting
• Trial end date: 2027-11-22
• Target enrollment: 0
• Participant gender: All

Summary

This is a global Phase III, randomized, placebo-controlled, double-blind study designed to evaluate the efficacy and safety of adjuvant treatment with atezolizumab compared with placebo in participants with MIBC who are ctDNA positive and are at high risk for recurrence following cystectomy.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hoffmann-La Roche
• Treatments: Atezolizumab

Criteria

Inclusion Criteria for the Surveillance Phase:

• Histologically confirmed MIUC (also termed TCC) of the bladder

• TNM classification (based on AJCC Cancer Staging Manual, 7th Edition; Edge et al. 2010) at pathological examination of surgical resection specimen as follows: For patients treated with prior NAC: tumor stage of ypT2-4a or ypN+ and M0. For patients who have not received prior NAC: tumor stage of pT3-4a or pN+ and M0

• Surgical resection of MIUC of the bladder

• Patients who have not received prior platinum-based NAC, have refused, or are ineligible ("unfit") for cisplatin-based adjuvant chemotherapy

• ctDNA assay developed based on tumor tissue specimen and matched normal DNA from blood.

• Tumor PD-L1 expression per IHC and confirmed diagnosis of MIUC as documented through central testing of a representative tumor tissue specimen

• Absence of residual disease and absence of metastasis, as confirmed by a negative baseline computed tomography (CT) or magnetic resonance imaging (MRI) scan of the pelvis, abdomen, and chest no more than 4 weeks prior to enrollment.

• Full recovery from cystectomy and enrollment within 14 weeks following cystectomy. Minimum of 6 weeks must have elapsed from surgery.

Additional Inclusion Criteria for the Treatment Phase:

• Plasma sample evaluated to be ctDNA positive

• Absence of residual disease and absence of metastasis, as confirmed by a negative baseline CT or MRI scan of the pelvis, abdomen, and chest no more than 4 weeks prior to randomization.

• ECOG Performance Status of <= 2

• Life expectancy >=12 weeks

• Adequate hematologic and end-organ function

• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs

General Medical Exclusion Criteria:

• Pregnancy or breastfeeding

• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins

• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation

• History of autoimmune disease. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study. Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen may be eligible for this study.

• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.

• Positive test for HIV

• Patients with active hepatitis B virus or hepatitis C

• Active tuberculosis

• Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina

Cancer-Specific Exclusion Criteria:

• Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to study enrollment

• Adjuvant chemotherapy or radiation therapy for UC following cystectomy

• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or 5 half-lives of the drug, whichever is longer, prior to enrollment

• Malignancies other than UC within 5 years prior to study enrollment

Additional Exclusion Criteria for the Treatment Phase:

• Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to randomization to the treatment phase Hormone-replacement therapy or oral contraceptives are allowed.

• Adjuvant chemotherapy or radiation therapy for UC following cystectomy

• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or 5 half-lives of the drug, whichever is longer, prior to randomization to the treatment phase