(UroToday.com) On the second day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2023 focussing on urothelial cancer, the Trials in Progress Poster Session B included a presentation from Dr. Sarah Psutka highlighting the rationale and design of the SunRISe-4 trial, assessing TAR-200 plus cetrelimab or cetrelimab alone as neoadjuvant therapy in patients with muscle-invasive bladder cancer (MIBC) who are unable or unwilling to receive neoadjuvant platinum-based chemotherapy.
Among the standard of care options for patients with MIBC is radical cystectomy (RC) with neoadjuvant systemic platinum-based chemotherapy (PBC). Unfortunately, many patients are ineligible for cisplatin-based chemotherapy and systemic chemotherapy is associated with significant toxicity. Thus, there is a need to develop alternative treatment approaches. On such approach is TAR-200, an intravesical drug delivery system that provides local continuous gemcitabine release within the bladder.
Dr. Psutuka described the design of SunRISe-4 (NCT04919512), 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 patients with MIBC scheduled for RC who are ineligible for or refuse neoadjuvant PBC.
This phase 2 trial is enrolling adult patients (age ≥18 years) with good performance status (Eastern Cooperative Oncology Group performance status of 0 or 1) who have 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. Following enrollment, patients 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.
Among the target sample of approximately 160 patients, included individuals will be randomized 5:3 to receive TAR-200 + CET (Cohort 1, approximately 100 patients) or CET alone (Cohort 2, approximately 60 patients). In Cohort 1, patients will be treated with a TAR-200 (225 mg gemcitabine) device, placed intravesically at the initial treatment visit. This TAR-200 device will be removed and replaced over a 12-week period. In both cohorts, CET will be serially dosed intravenously over the same timeframe.
In terms of primary disease assessments, patients will receive axial imaging (at screening and Week 6), centralized review of TURBT (initial diagnostic TURBT or debulking TURBT for patients with lesions >3 cm after initial TURBT) as well as RC and nodal tissue specimens.
Following radical cystectomy, all patients 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 with a number of secondary outcomes including safety, tolerability, and recurrence-free survival (per Response Evaluation Criteria in Solid Tumors 1.1 or histologic evidence). There are additional exploratory outcomes including patient-reported cancer-related quality of life (Functional Assessment of Cancer Therapy–Bladder questionnaire) and pathologic overall response rate at RC in addition to overall survival and time to symptomatic progression, pharmacokinetics, biomarker analysis, and immunogenicity.
As of a data cut off of September 12, 2022, 2 of 160 planned patients had been enrolled and randomized, and recruitment is ongoing at approximately 95 sites.
Presented by: Sarah P. Psutka, MD, MS | University of Washington, Fred Hutchinson Cancer Center