SunRISe-1 data point to safety, tolerability of TAR-200 in NMIBC

TAR-200 monotherapy treatment of BCG-unresponsive, high-risk non–muscle invasive bladder cancer (NMIBC) was found to be well tolerated in patients, according to data presented at the Society of Urologic Oncology 25th Annual Meeting in Dallas, Texas.¹

A total of 71 (83.5%) patients reported treatment-related adverse events, most of which were grade 1-2 lower urinary tract symptoms.

TAR-200 is an intravesical delivery system that works by providing sustained low doses of localized gemcitabine via insertion into the bladder. “SunRISe-1 (NCT04640623) is an ongoing phase 2b study assessing the efficacy and safety of TAR-200 + cetrelimab (anti-PD1)^2,3 (cohort 1), TAR-200 monotherapy (cohort 2), or cetrelimab monotherapy (cohort 3) in patients with BCG-unresponsive [high-risk] NMIBC ineligible for or refusing radical cystectomy,” wrote the authors in their poster. Additionally, TAR-200 monotherapy is being evaluated in patients with papillary disease only (cohort 4).

At the SUO Annual Meeting, the authors, led by Siamak Daneshmand, MD, a professor of urology and director of Clinical Research at the Keck School of Medicine of the University of Southern California, Los Angeles, reported additional data on the safety and tolerability of TAR-200 monotherapy from cohort 2.

Patients were included in cohorts 1-3 if they were at least 18 years of age and had histologically confirmed carcinoma in situ (CIS) +/- papillary disease (high-grade Ta, any T1), an ECOG Performance Status of 0-2, and persistent or recurrent high-risk NMIBC with the last dose of BCG 12 months or earlier prior to CIS diagnosis, according to the authors.

“TAR-200 was dosed every 3 weeks through week 24, then every 12 weeks until week 96,” the authors wrote.

The primary end point was complete response (CR) rate at any time, with the secondary end points including duration of response, safety, and tolerability.

The investigators reported that as of May 13, 2024, a total of 85 patients with CIS had received TAR-200 monotherapy. Median age was 71 years (range, 40-88 years). Most of the patients were male (80%) and White (72.9%). Seventy-eight (91.8%) had an ECOG Performance Status of 0. Fifty-seven (67.1%) patients had CIS only, whereas 28 (32.9%) had CIS + papillary disease. Median total doses of prior BCG was 12 (range, 7-42), and median time from last BCG to CIS diagnosis was 3.4 months (range, 0-22 months). Eighty-two (96.5%) patients declined radical cystectomy and 3 (3.5%) were ineligible for the procedure.

As centrally assessed, the CR rate was 83.5% (95% CI, 73.9-90.7); the CR rate was 85.9% (95% CI, 76.6-92.5) per investigator assessment.

“The TAR-200 insertion success rate was 98.8%, and the median indwelling duration was 22 days (range, 5-26),” the authors wrote.

A total of 71 (83.5%) patients reported treatment-related adverse events (TRAEs), most of which were grade 1-2 lower urinary tract symptoms.

“The most common TRAEs (≥10%) were pollakiuria (38.8%), dysuria (35.3%), urinary tract infection (20.0%), micturition urgency (17.6%), and hematuria (14.1%),” wrote the authors.

The median duration all TRAEs that recovered/resolved was 22 days (interquartile range, 8-112). Eight (9.4%) patients had grade 3-4 TRAEs, and 5 (5.9%) patients had serious TRAEs. There were no treatment-related deaths. Five (6%) patients had TRAEs that resulted in discontinuation of TAR-200 treatment. These TRAEs included noninfective cystitis, pollakiuria, and urinary retention.

“The TAR-200 treatment experience is well tolerated in patients with BCG-unresponsive HR NMIBC, with favorable insertion rates, indwelling times, and safety profile,” the authors wrote.

REFERENCES

1. Daneshmand S, Zainfeld D, Pieczonka C, et al. Safety and tolerability of TAR-200 monotherapy in patients with bacillus Calmette–Guérin (BCG)-unresponsive high-risk non–muscle-invasive bladder cancer (HR NMIBC) in SunRISe-1. Presented at: Society of Urologic Oncology 25th Annual Meeting. December 4-6, 2024. Dallas, Texas. Abstract 135. Accessed December 5, 2024. https://suo-abstracts.secure-platform.com/a/gallery/rounds/21/details/3800

2. DeAngelis N, Ferrante C, Powers G, et al. Discovery and pharmacological characterization of cetrelimab (JNJ-63723283), an anti-programmed cell death protein-1 (PD-1) antibody, in human cancer models. Cancer Chemother Pharmacol. 2022;89(4):515-527. doi:10.1007/s00280-022-04415-5

3. Felip E, Moreno V, Morgensztern D, et al. First-in-human, open-label, phase 1/2 study of the monoclonal antibody programmed cell death protein-1 (PD-1) inhibitor cetrelimab (JNJ-63723283) in patients with advanced cancers. Cancer Chemother Pharmacol. 2022;89(4):499-514. doi:10.1007/s00280-022-04414-6