Updated results from the SunRISe-1 study reveal that TAR-200 monotherapy achieved a high complete response (CR) rate of 84% in patients with Bacillus Calmette-Guérin (BCG)-unresponsive, high-risk non-muscle-invasive bladder cancer (NMIBC) carcinoma in situ (CIS). The findings, presented at the 2024 European Society for Medical Oncology (ESMO) Congress in Barcelona, Spain, highlight the potential of TAR-200 as a bladder-sparing treatment option for patients who have failed BCG therapy and are not candidates for radical cystectomy.
The study's principal investigator, Dr. Michiel van der Heijden, a medical oncologist at the Netherlands Cancer Institute, emphasized the significance of these results, noting that TAR-200 offers a novel approach for patients facing life-altering decisions like radical cystectomy. "The safety and efficacy profile observed across multiple patient cohorts in the SunRISe-1 study further support the potential of TAR-200 for patients with high-risk non-muscle invasive bladder cancer as an innovative targeted releasing system," said Dr. van der Heijden.
SunRISe-1 Study Design and Results
SunRISe-1 is an open-label phase 2b study evaluating TAR-200 plus cetrelimab (cohort 1), TAR-200 monotherapy (cohort 2), and cetrelimab monotherapy (cohort 3), along with a TAR-200 monotherapy cohort consisting only of patients with papillary disease (cohort 4). Patients in cohorts 1-3 were at least 18 years of age with histologically confirmed high-risk NMIBC CIS (with or without papillary disease), ECOG performance status of 0 to 2, persistent or recurrent disease within 12 months of completion of BCG, were unresponsive to BCG and not undergoing radical cystectomy.
The primary endpoint for cohorts 1-3 was overall CR rate at any time; key secondary end points included duration of response, overall survival, safety, and tolerability. Cohort 4’s primary end point was disease-free survival rate at 12 months.
The centrally assessed CR rates were 67.9% (95% CI, 53.7-80.1) for the TAR-200 plus cetrelimab cohort, 84% (95% CI, 73.9-90.7) for the TAR-200 monotherapy cohort, and 46.4% (95% CI, 27.5-66.1) for the cetrelimab monotherapy cohort. Estimated 12-month CR rates were 56.7% (95% CI, 41.2-69.6), 57.4% (40.6-71.0), and 22.8% (8.6-41.1), respectively.
Safety and Tolerability
TAR-200 was found to be well-tolerated, with most adverse events (AEs) being grade 1 or 2. The rate of serious treatment-related AEs was 13.2%, 5.9%, and 3.6% in cohorts 1-3, respectively. The rate of discontinuation due to treatment-related AEs was 5.9% in cohort 2. No treatment-related deaths were reported.
Mechanism of Action and Clinical Context
TAR-200 is a novel gemcitabine intravesical releasing system designed for sustained, local delivery of chemotherapy in the bladder. It is placed in an office procedure, offering a less invasive alternative to radical cystectomy. Cetrelimab is an anti-PD1 agent with an efficacy and safety profile consistent with other checkpoint inhibitors.
Addressing Unmet Needs in NMIBC
High-risk NMIBC is characterized by a high-grade, large tumor size, presence of multiple tumors, and CIS. Radical cystectomy is currently recommended for HR-NMIBC patients who fail BCG therapy, with over 90 percent cancer-specific survival if performed before muscle-invasive progression. Given that NMIBC typically affects older patients, many may be unwilling or unfit to undergo radical cystectomy. The high rates of recurrence and progression can pose significant morbidity and distress for these patients.
The results from the SunRISe-1 study support the prioritized development of TAR-200 monotherapy in patients with BCG-unresponsive high-risk non–muscle-invasive bladder cancer.
