Phase II Evaluation of Atezolizumab Maintenance Post-Chemo-Radiotherapy in Muscle-Invasive Bladder Cancer Patients Ineligible for Radical Cystectomy

The primary objective of this study is to evaluate the **efficacy** of maintenance therapy with atezolizumab, an anti-PD-L1 agent, following chemo-radiotherapy in patients with muscle-invasive bladder cancer who are not eligible for radical cystectomy. The efficacy is assessed in terms of **disease-free survival (DFS)** at 2 years. This is clinically relevant as it aims to determine the potential of atezolizumab to prolong DFS, offering a therapeutic option for patients unable to undergo surgical intervention.

Secondary objectives include: - Evaluating local control at 2 and 5 years, which is crucial for understanding the long-term effectiveness of the treatment in preventing local recurrence. - Assessing DFS at 5 years to provide insights into the long-term benefits of the therapy. - Evaluating overall survival (OS) at 2 and 5 years, which is essential for determining the impact of the treatment on patient longevity. - Assessing the tolerance and safety of the treatment strategy, which is vital for ensuring patient safety and managing adverse effects. - Evaluating patients' quality of life, which is important for understanding the broader impact of the treatment on patients' well-being.

The clinical trial involves participants diagnosed with **muscle-invasive bladder cancer** who are not eligible for radical cystectomy. The study population includes both male and female subjects, aged 18 years and older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. Participants are required to have adequate haematological, renal, hepatic, and cardiac function, as well as a life expectancy of at least 12 months. The trial population was selected based on specific inclusion criteria, including the completion of standard chemo-radiotherapy and the ability to comply with study procedures. Participants must have no major pelvic involvement or distant metastasis and must be unfit for radical cystectomy due to age, comorbidities, or personal choice. The sponsor has not provided information regarding the total number of participants. The study considers lifestyle factors such as the use of medically acceptable contraception for participants of childbearing potential. The trial includes a vulnerable population, ensuring comprehensive ethical considerations are in place.

The clinical trial is designed to evaluate the efficacy of **atezolizumab**, an anti-PD-L1 therapy, as a maintenance treatment following chemo-radiotherapy in patients with muscle-invasive bladder cancer who are not eligible for radical cystectomy. This is a Phase II, randomized, double-blind, controlled trial with an estimated duration extending until May 31, 2028. The primary objective is to assess disease-free survival (DFS) at two years, with secondary endpoints including local control rate, overall survival, and quality of life assessments.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria such as histologically confirmed muscle-invasive bladder cancer, adequate hematological and biological parameters, and ECOG performance status ≤2. The first administration of atezolizumab must occur within 30 days following the last session of radiotherapy. Follow-up visits will be scheduled to monitor the participants' health status, treatment adherence, and any adverse events. These visits will include regular assessments through cystoscopy at two and five years to evaluate local control rates.

The end-of-study visit will mark the conclusion of the participant's involvement, which is expected to last up to five years, depending on individual response and disease progression. Participants may be withdrawn from the study early if they experience unacceptable toxicity, disease progression, or if they choose to withdraw consent. The trial will adhere to rigorous safety and efficacy monitoring protocols to ensure participant well-being throughout the study duration.

The clinical trial involves the administration of **atezolizumab**, marketed under the name Tecentriq, as the experimental medication. Tecentriq is provided as a concentrate for solution for infusion, with each vial containing 1,200 mg of the active substance. The pharmaceutical form is a solution for infusion, and the medication is administered intravenously. The dosing schedule involves a maximum daily dose of 1,200 mg, with a total maximum dose of 21,600 mg over the course of the treatment. The maximum treatment period is 12 months. Atezolizumab is a protein-based therapeutic agent classified under the ATC code L01FF05, and it functions as an anti-PD-L1 antibody. The medication is manufactured by Roche Registration GmbH and is authorized for use in the European Union under the marketing authorization number EU/1/17/1220/001.

In this study, atezolizumab is used as a maintenance therapy following chemo-radiotherapy in patients with muscle-invasive bladder cancer who are not eligible for radical cystectomy. The primary objective is to assess the efficacy of atezolizumab in terms of disease-free survival at two years. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial data. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment protocol.

The efficacy of the clinical trial will be assessed primarily through the evaluation of **disease-free survival (DFS)** at 2 years. DFS is defined as the time from the date of inclusion to the occurrence of tumor progression, whether local, regional, or distant, or death from any cause, whichever occurs first. Secondary endpoints include the local control rate, which will be evaluated by cystoscopy at 2 and 5 years. The presence of non-muscle-invasive or muscle-invasive bladder cancers will be considered a local failure, and the bladder must be completely free of tumors to be defined as locally controlled. The duration of local control will be calculated from the date of inclusion to the date of positive cystoscopy, with data censored at the time of regional or distant relapse if it occurs before local relapse.

Additionally, DFS will also be assessed at 5 years, using the same criteria as the primary endpoint. Overall survival (OS) will be measured at 2 and 5 years, defined as the time from the date of inclusion to the date of death from any cause. Tolerance and safety will be evaluated by assessing toxicity, both acute (less than 6 months after the start of treatment) and late (6 months or more after the start of treatment), using the NCI CTCAE v5.0. The evaluation of tolerance will continue up to 5 years. Quality of life is also included as a secondary endpoint, although specific methods for its assessment are not detailed in the provided data.