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

Ведущий спонсор: Hoffmann-La Roche

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.

• Muscle-invasive Bladder Cancer

Тип вмешательства: Drug

Название вмешательства: Atezolizumab

Описание: Participants will receive 1680 mg intravenously every 4 weeks (Q4W) on Day 1 of each 28-day cycle.

Этикетка Arm Group: Arm A: Atezolizumab

Другое имя: Tecentriq

Тип вмешательства: Other

Название вмешательства: Placebo

Описание: Participants will receive placebo intravenously Q4W on Day 1 of each 28-day cycle

Этикетка Arm Group: Arm B: Placebo

Критерии:

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 pT2-4a 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. pT2N0 patients who have not received prior platinum-based NAC regardless of cisplatin ineligibility are eligible. - ctDNA assay developed based on tumor tissue specimen and matched normal DNA from blood. - Tumor PD-L1 expression per IHC that is evaluable by 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: - 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 - 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. - 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 - 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. - Patients with active hepatitis B virus or hepatitis C - Active tuberculosis

Пол:

All

Минимальный возраст:

18 Years

Максимальный возраст:

N/A

Здоровые волонтеры:

No

Фамилия: Reference Study ID Number: BO42843 https://forpatients.roche.com/

Телефон: 888-662-6728 (U.S. and Canada)

Argentina

Belgium

Brazil

Canada

China

Colombia

Czechia

France

Germany

Greece

Ireland

Israel

Italy

Japan

Korea, Republic of

Poland

Russian Federation

Spain

Turkey

Ukraine

United Kingdom

United States

2022-02-01

Тип: Sponsor

• Urinary Bladder Neoplasms

Метка: Arm A: Atezolizumab

Тип: Experimental

Описание: Atezolizumab will be administered intravenously at a dose of 1680 milligrams (mg) on Day 1 of each 28-day cycle for 12 cycles or up to 1 year (whichever occurs first). Atezolizumab will be discontinued in the event of IRF-assessed disease recurrence, unacceptable toxicity, withdrawal of consent, or study termination by the Sponsor.

Метка: Arm B: Placebo

Тип: Placebo Comparator

Описание: Placebo will be administered intravenously on Day 1 of each 28-day cycle. Placebo will be discontinued in the event of IRF-assessed disease recurrence, unacceptable toxicity, withdrawal of consent, or study termination by the Sponsor.

Распределение: Randomized

Модель вмешательства: Parallel Assignment

Первичное назначение: Treatment

Маскировка: Double (Participant, Investigator)