SunRISe-4: TAR-200 plus cetrelimab or cetrelimab alone as neoadjuvant therapy in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for or refuse neoadjuvant platinum-based chemotherapy.

TPS584 Background: Standard of care for patients (pts) with MIBC is radical cystectomy (RC) with neoadjuvant systemic platinum-based chemotherapy (PBC); however, systemic chemotherapy is associated with significant toxicity. TAR-200 is an intravesical drug delivery system that provides local continuous gemcitabine release within the bladder. SunRISe-4 (NCT04919512) is an open-label, multicenter, randomized phase 2 study designed to assess the efficacy and safety of neoadjuvant TAR-200 + systemic cetrelimab (CET [anti–programmed death-1 antibody]) vs neoadjuvant CET alone in pts with MIBC scheduled for RC who are ineligible for or refuse neoadjuvant PBC. Methods: Eligibility criteria: age ≥18 years, Eastern Cooperative Oncology Group performance status of 0 or 1, histologically confirmed cT2-T4a MIBC with absence of nodal or metastatic disease at screening, and residual intravesical tumor volume of ≤3 cm prior to randomization. Pts will be stratified by completeness of transurethral resection of bladder tumor (TURBT; visibly complete vs incomplete and ≤3 cm) and tumor stage (cT2 vs cT3-4a) at initial diagnosis. Pts (N≈160) will be randomized 5:3 to receive TAR-200 + CET (Cohort 1, n≈100) or CET alone (Cohort 2, n≈60). In Cohort 1, TAR-200 (225 mg gemcitabine) will be placed intravesically at the initial treatment visit; TAR-200 will be removed and replaced over a 12-week period. In both cohorts, CET will be serially dosed intravenously over the same timeframe. Primary disease assessments include axial imaging (at screening and Week 6), centralized review of TURBT (initial diagnostic TURBT or debulking TURBT for pts with lesions >3 cm after initial TURBT) as well as RC and nodal tissue specimens. After RC, all pts will have follow-up visits from Weeks 4 to 108 post RC (end of study). The primary outcome measure is the pathologic complete response rate at time of RC. Secondary outcome measures include safety, tolerability, and recurrence-free survival (per Response Evaluation Criteria in Solid Tumors 1.1 or histologic evidence). Exploratory outcome measures include patient-reported cancer-related quality of life (Functional Assessment of Cancer Therapy–Bladder questionnaire) and pathologic overall response rate at RC. Overall survival and time to symptomatic progression, pharmacokinetics, biomarker analysis, and immunogenicity will also be evaluated. As of September 12, 2022, 2 of 160 planned pts have been enrolled and randomized, and recruitment is ongoing at ≈95 sites. Clinical trial information: NCT04919512 .