Evaluation of TAR-200 and Cetrelimab in Muscle-Invasive Urothelial Carcinoma of the Bladder Prior to Radical Cystectomy

The primary objective of this study is to determine the **anti-tumor effects** of TAR-200 in combination with cetrelimab (Cohort 1) and cetrelimab alone (Cohort 2) in participants with **muscle-invasive urothelial carcinoma of the bladder** who are scheduled for radical cystectomy and are ineligible for or refusing platinum-based neoadjuvant chemotherapy. This is clinically relevant as it explores potential therapeutic options for patients who cannot undergo standard chemotherapy, potentially improving treatment outcomes and expanding available interventions.

Secondary objectives include:

• Evaluating the safety and tolerability of up to four dosing cycles of TAR-200 combined with cetrelimab (Cohort 1) and cetrelimab alone (Cohort 2) prior to radical cystectomy.
• Determining the recurrence-free survival (RFS) in participants receiving TAR-200 with cetrelimab (Cohort 1) and cetrelimab alone (Cohort 2).

The clinical trial involves a total of **71 participants** diagnosed with **Muscle-Invasive Urothelial Carcinoma of the Bladder**. The study population includes both male and female subjects, aged 18 years and older, with a focus on individuals who are considered vulnerable. Participants were selected based on specific inclusion criteria, such as having a histologically proven cT2-T4a N0, M0 infiltrating urothelial carcinoma of the bladder, and an Eastern Cooperative Oncology Group (ECOG) performance status of Grade 0 or 1. The trial population is required to have adequate bone marrow, liver, and renal function, and must either refuse or be ineligible for cisplatin-based chemotherapy. Lifestyle considerations include adherence to contraceptive guidelines to prevent pregnancy during and after the study period. Participants must not have any residual tumor larger than 3 cm following transurethral resection of bladder tumor (TURBT) and must be willing to undergo radical cystectomy (RC) as deemed eligible by the attending urologist. The trial does not specify any particular dietary or physical activity requirements for participants.

The clinical trial is a Phase 2, open-label, multi-center, randomized study designed to evaluate the **anti-tumor effects** of TAR-200 in combination with **cetrelimab** and cetrelimab alone in participants with **muscle-invasive urothelial carcinoma of the bladder**. The trial involves two cohorts: Cohort 1 will receive TAR-200 combined with cetrelimab, while Cohort 2 will receive cetrelimab alone. The study is structured to assess the primary endpoint of pathological complete response (pCR) rate at radical cystectomy, with secondary endpoints including the frequency and grade of adverse events, laboratory abnormalities, and recurrence-free survival.

The trial is expected to run from December 2021 to March 2027, with participant involvement lasting up to 36 months. The study visits are sequenced as follows: an initial screening visit to confirm eligibility, followed by regular follow-up visits to monitor treatment response and safety, and an end-of-study visit to assess final outcomes. Participants will be required to attend these visits as per the study schedule, and adherence to the protocol is crucial for the integrity of the trial data.

Inclusion criteria for the study require participants to be at least 18 years old, with histologically proven cT2-T4a N0, M0 infiltrating urothelial carcinoma of the bladder. Participants must be eligible for and willing to undergo radical cystectomy and must refuse or be ineligible for cisplatin-based chemotherapy. Exclusion criteria include unresolved adverse events from prior surgeries or treatments, and any condition that may interfere with the study protocol. Participants may be terminated early from the study if they experience significant adverse events, fail to comply with study procedures, or withdraw consent.

The clinical trial involves the administration of **Cetrelimab**, an experimental medication, which is a monoclonal antibody of biological/biotechnological origin. Cetrelimab is provided in two pharmaceutical forms: a **solution for infusion** and a **powder for solution for infusion**. Both forms are administered via the **intravenous route**. The maximum treatment period for Cetrelimab is 18 months. The dosing schedule and specific dosage amounts are not specified in the provided data. Participant compliance with the administration schedule will be monitored throughout the trial.

Another experimental treatment used in the study is **Gemcitabine Hydrochloride**, which is provided in the form of a **tablet**. This chemical entity is part of a combination product that includes a device but does not involve advanced therapy. The administration route for Gemcitabine Hydrochloride is **intravesical use**, facilitated by a urinary placement catheter (inserter) that serves as an accessory device to insert the single integral drug-device combination product (TAR-200) into the bladder through the urethra. The maximum treatment period for Gemcitabine Hydrochloride is 36 months. As with Cetrelimab, the specific dosage and administration frequency are not detailed in the available data, and participant adherence to the treatment regimen will be closely monitored.

The efficacy of the clinical trial will be assessed using specific endpoints to evaluate the therapeutic effects of the investigational treatments. The primary endpoint is the **pCR rate at radical cystectomy (RC)**, which will measure the pathological complete response rate in participants undergoing the procedure. Secondary endpoints include the frequency and grade of adverse events (AEs), laboratory abnormalities, and recurrence-free survival (RFS). These parameters will provide a comprehensive evaluation of the treatment's impact on participants with muscle-invasive urothelial carcinoma of the bladder.