ASCO 2021: A Phase 3, Multicenter, Randomized Study Evaluating the Efficacy of TAR-200 in Combination with Cetrelimab Versus Concurrent Chemoradiotherapy in Participants with Muscle-Invasive Urothelial Carcinoma of the Bladder

( The standard of care for patients with muscle-invasive bladder cancer consists of neoadjuvant chemotherapy and radical cystectomy or chemoradiotherapy. However, radical cystectomy is associated with potential morbidity or mortality from the procedure. TAR-200 is an intravesical drug-delivery system designed for the local continuous release of gemcitabine within the bladder:



Cetrelimab is an investigational immunoglobulin G4 anti-programmed cell death protein-1 antibody. In patients with muscle-invasive bladder cancer, this clinical trial will evaluate whether combination treatment with intravesical TAR-200 and systemic cetrelimab will result in enhanced local and systemic antitumor activity versus concurrent chemoradiotherapy. At the American Society of Clinical Oncology (ASCO) 2021 Annual Meeting, Dr. Stephen Williams and colleagues presented the trial design for this phase 3 trial.

SunRISe-2 is a prospective, multicenter, open-label, randomized phase 3 study evaluating the efficacy and safety of intravesical TAR-200 plus systemic cetrelimab versus chemoradiotherapy in participants with muscle-invasive bladder cancer. Eligible participants are aged 18 years or older with an ECOG performance status of 0, 1, or 2, and histologically proven, cT2-T4a, N0, M0 urothelial carcinoma of the bladder diagnosed within 90 days of the randomization date, and who refuse or are ineligible for radical cystectomy. Approximately 550 participants will be randomized in a 1:1 ratio and with stratification by 2 factors: transurethral resection of bladder tumor screening results (visibly complete vs incomplete) and screening tumor stage (T0 vs Ta/T1/Tis vs T2-T4a). Participants in Arm 1 will receive intravesical TAR-200 every 3 weeks for the first 18 weeks on study; and, beginning at week 24, every 12 weeks through study year 3. Cetrelimab will be dosed every 3 weeks until month 18. Participants in Arm 2 will receive standard of care chemoradiotherapy (with either cisplatin or gemcitabine, for up to 6 weeks).

The trial schema for SunRISe-2 is as follows:


A primary disease assessment will be performed at week 18 to evaluate treatment response in both arms. Subsequent assessments (axial imaging and cystoscopy) will occur at week 24 and every 12 weeks thereafter through study year 2, and then every 24 weeks through study year 5. The primary endpoint is bladder intact event-free survival, defined as the time from randomization to first bladder intact event-free survival event, including histologically proven muscle-invasive bladder cancer, clinical evidence of nodal or metastatic disease (per RECIST 1.1), radical cystectomy, or death. Key secondary endpoints include metastasis-free survival, overall survival, overall response rate (at week 18: complete response + partial response), safety, and tolerability. Other/exploratory endpoints include assessments of cancer-specific survival, time to symptomatic progression, pharmacokinetics, immunogenicity, health-related quality of life, healthcare resource utilization, and biomarkers. Participants are being enrolled at approximately 272 study sites worldwide and the study opened for enrollment on December 7, 2020. It is expected to reach primary completion on December 30, 2026.


Clinical trial information: NCT04658862

Presented by: Stephen B. Williams, MD, MS, FACS, University of Texas Medical Branch (UTMB), Galveston, TX

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Annual Meeting #ASCO21, June, 4-8, 2021