(UroToday.com) The 2025 SESAUA annual meeting featured a bladder cancer session and a presentation by Dr. Peter Clark discussing results of the SunRISe-1 study assessing TAR-200 in patients with BCG-unresponsive high-risk non-muscle invasive bladder cancer.
Unfortunately, patients with BCG unresponsive, high-risk, non-muscle invasive bladder cancer have limited treatment options. Standard of care for these patients is radical cystectomy, which is a life-changing operation associated with considerable morbidity and impact on quality of life, and a 90 day mortality risk of up to 8%. Limited US FDA approved treatment options are available to treat BCG-unresponsive high-risk non-muscle invasive bladder cancer CIS, with 12 month complete response rates of:
- 19% with pembrolizumab1
- 23% with nadofaragene firadenovec2
- 45% with nogapendekin alfa inbakicept + BCG3
Cetrelimab is an anti-PD-1 agent with an efficacy and safe profile consistent with approved anti-PD-1 agents. TAR-200 is an intravesical targeted releasing system designed to provide sustained delivery of gemcitabine in the bladder over 3 weeks. SunRISe-1 (NCT04640623) is an ongoing, randomized, phase 2b study assessing efficacy and safety of TAR-200 + cetrelimab (anti-PD1) (cohort 1), TAR-200 alone (cohort 2), or cetrelimab alone (cohort 3) in patients with BCG-unresponsive high risk non-muscle invasive bladder cancer non-muscle invasive bladder cancer with CIS ± papillary disease, ineligible for/refusing radical cystectomy. TAR-200 alone is also being assessed only in patients with papillary disease (cohort 4). At the SESAUA annual meeting, Dr. Clark and colleagues reported results from Cohort 1-3.
Eligible patients aged ≥18 years had histologically confirmed CIS ± papillary disease (high-grade Ta, any T1) after adequate BCG and ECOG performance status 0-2. TAR-200 was dosed every 3 weeks through Week 24, then every 12 weeks until Week 96. Response was assessed by cystoscopy and centrally-assessed urine cytology, CT/MRI, and bladder biopsy (Weeks 24, 48, and as clinically indicated). The primary end point was overall complete response rate, and secondary end points included duration of response and safety. The SunRISe-1 trial design is as follows:
Assessments included local cystoscopy, centrally assessed urine cytology every 12 weeks, and centrally assessed biopsy at weeks 24 and 48.
At a May 13, 2024, data cutoff, 53 patients in Cohort 1, 85 in Cohort 2, and 28 in Cohort 3 were treated (median age 71.5 years, 80% male, 31% papillary disease). The baseline characteristics across the cohorts are as follows: 
Centrally confirmed complete response rates in Cohort 1, Cohort 2, and Cohort 3 were 67.9%, 83.5%, and 46.4%, respectively:
In Cohort 2, the estimated 12-month complete response rate was 57.4%, estimated 12-month duration of response rate was 65.7%, median follow-up in responders was 9.2 months (range: 3.7-36.6), and patients remaining in response was 81.6%:
Sixty-one patients (72%) had treatment-related adverse events, of which the most common (≥10%) were pollakiuria (35%), dysuria (29%), micturition urgency (15%), and urinary tract infection (15%). Seven patients (8%) had grade ≥3 treatment-related adverse events, 4 (5%) had serious treatment-related adverse events, and 4 (5%) had treatment-related adverse events leading to discontinuation. There were no treatment-related deaths reported.
Dr. Clark concluded his presentation discussing results of the SunRISe-1 study with the following take-home points:
- TAR-200 monotherapy provides the highest single agent complete response rate of 84% in patients with BCG-unresponsive high-risk non-muscle invasive bladder cancer, based on published data, without the need for re-induction
- Responses to TAR-200 monotherapy are highly durable; 82% of patients remain in response after a median follow-up of 9.2 months
- TAR-200 monotherapy was well tolerated, with few grade >= 3 treatment related adverse events or treatment related adverse events leading to discontinuation
- Cetrelimab monotherapy provided a complete response rate comparable to other anti-PD-(L)1 agents
- SunRISe-1 results indicate a more favorable risk benefit profile for TAR-200 monotherapy compared with TAR-200 + cetrelimab or cetrelimab monotherapy in BCG-unresponsive high risk non-muscle invasive bladder cancer
- Results from SunRISe-1 Cohorts 1-3 support the prioritized development of TAR-200 monotherapy in patients with BCG-unresponsive high-risk non-muscle invasive bladder cancer
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the Southeastern Section of the American Urological Association (SESAUA) 2025 Annual Meeting, Nashville, TN, Wed, Mar 12 – Sat, Mar 15, 2025.
- Balar AV, Kamat AM, Kulkarni GS, et al. Pembrolizumab monotherapy for the treatment of high-risk non-muscle-invasive bladder cancer unresponsive to BCG (KEYNOTE-057): An open-label, single-arm, multicenter, phase 2 study. Lancet Oncol. 2021 Jul;22(7):919-930.
- Boorjian SA, Alemozaffar M, Konety BR, et al. Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: A single-arm, open-label, repeat-dose clinical trial. Lancet Oncol. 2021 Jan;22(1):107-117.
- Chamie K, Chang SS, Kramolowsky E, et al. IL-15 Superagonist NAI in BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer. NEJM Evid 2022; 2(1)