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Histologically confirmed MIUC (also termed TCC) of the bladder |
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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 pT2-4a or pN+ and M0 |
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Surgical resection of MIUC of the bladder |
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Patients who have not received prior platinum-based NAC, have refused, or are ineligible ("unfit") for cisplatin-based adjuvant chemotherapy. pT2N0 patients who have not received prior platinum-based NAC regardless of cisplatin ineligibility are eligible |
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ctDNA assay developed based on tumor tissue specimen and matched normal DNA from blood |
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Tumor PD-L1 expression per IHC that is evaluable by central testing of a representative tumor tissue specimen |
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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 |
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Full recovery from cystectomy and enrollment within 14 weeks following cystectomy. Minimum of 6 weeks must have elapsed from surgery |
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Additional Inclusion Criteria for the Treatment Phase |
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Blood for plasma ctDNA sample evaluated to be ctDNA positive, defined as the presence of two or more mutations based on patient's WES evaluable (ctDNA assay designability) report |
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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 |
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ECOG Performance Status of <= 2 |
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Life expectancy >=12 weeks |
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Adequate hematologic and end-organ function |
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For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs |
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Pregnancy or breastfeeding
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History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
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Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
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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
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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
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Patients with active hepatitis B virus or hepatitis C
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Active tuberculosis
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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
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Cancer-Specific Exclusion Criteria
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Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to study enrollment
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Adjuvant chemotherapy or radiation therapy for UC following cystectomy
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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
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Malignancies other than UC within 5 years prior to study enrollment
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Additional Exclusion Criteria for the Treatment Phase
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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
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Positive test for HIV, with the following exception: Patients with a positive HIV test at screening are eligible provided they are stable on antiretroviral therapy, have a CD4 count >= 200/μL, and have an undetectable viral load
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Adjuvant chemotherapy or radiation therapy for UC following cystectomy
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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
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