TAR-200 Produces High CR Rates, Tolerability in BCG-unresponsive NMIBC

Treatment with TAR-200 (GemRIS), a novel intravesical chemotherapy delivery system, produced complete responses (CRs) and was well tolerated in patients with Bacillus Calmette-Guérin–unresponsive, high-risk non–muscle-invasive bladder cancer (NMIBC), according to preliminary data from the phase 2b SunRISe-1 trial (NCT04640623) presented at the 2023 American Urological Association Annual Meeting.¹

TAR-200 works by providing continuous low-doses of localized gemcitabine via insertion into the bladder. The SunRISe-1 data, which were shared at the 2023 AUA Annual Meeting, showed that TAR-200 achieved a CR rate of 72.7% (95% CI, 49.8-89.3), consisting of 16 CRs in 22 evaluable patients.

Further, at a median follow-up of 10.6 months, 15 of the 16 CRs remained ongoing and the median duration of response was not reached. Of the complete responders, 6 maintained their response for more than 12 months, and none of the complete responders had disease recurrence or progression.

SunRISe-1 is also assessing the PD-1 inhibitor cetrelimab in this setting, and the initial data showed that the CR rate with single-agent cetrelimab was 38.1% (95% CI, 18.1-61.6), consisting of 8 CRs among 21 evaluable patients.

“The first efficacy and safety data from SunRISe-1 support ongoing investigation of TAR-200 with or without cetrelimab in patients with BCG-unresponsive as well BCG-naive (SunRISe-3) high-risk NMIBC,” said Siamak Daneshmand, MD, professor of Urology, director of Clinical Research, Keck Medicine of USC.

Overall, the SunRISe-1 trial is enrolling patients with BCG-unresponsive, histologically confirmed high-risk NMIBC (CIS with or without papillary disease) who decline to receive or are ineligible for radical cystectomy.

Patients in SunRISe-1 are being randomized to 3 treatment arms: cohort 1 is TAR-200 dosed every 3 weeks for up to 24 weeks, then every 12 weeks until week 96 (year 2) plus cetrelimab dosed every 3 weeks through week 78; cohort 2 is TAR-200 alone at the same dose as cohort 1; and cohort 3 is cetrelimab alone dosed at the same dose as cohort 1.

The data shared at AUA were for the TAR-200 alone and the cetrelimab alone cohorts. The data for the combination cohort were immature at the time of the study analysis.

Overall, there were 23 patients in the TAR-200 cohort with a median age of 72.0 years (range, 40-81). The majority were male (82.6%), White (69.6%), and had an ECOG performance status of 0 (95.7%). The cetrelimab cohort included 24 patients with a median age of 70.0 years (range, 51-88). As in the TAR-200cohort,The majority were male (79.2%), White (83.3%), and had an ECOG performance status of 0 (95.8%).

In the TAR-200 cohort, the tumor stage was CIS only for 69.6% of patients and CIS + papillary disease for 30.4% of patients. The rates were 65.2% and 34.7%, respectively, for the cetrelimab cohort. The median number of prior doses of BCG was 12 in both cohorts.

The primary end point was CR, with secondary end points including duration of response, overall survival, quality of life, safety, and tolerability.

Regarding safety, most adverse events (AEs) in the TAR-200 arm were grade ≤2. The AEs reported in the cetrelimab arm were comparable to those observed in studies of other PD-1/PD-L1 inhibitors. Treatment-related AEs led to discontinuations in 8.7% and 4.2% of the TAR-200and cetrelimab arms, respectively. Two patients in each arm had treatment-related grade ≥3 AEs and 1 patient in each arm had a treatment-related serious AE. There were no patients deaths on study.

Beyond SunRISe-1, TAR-200 is being investigated in several other ongoing clinical trials including SunRISe-2 (NCT04658862) in patients with muscle-invasive bladder cancer (MIBC) who are radical cystectomy–ineligible or refuse to receive the surgery; SunRISe-3 (NCT05714202) in patients with BCG-naive high-risk NMIBC; and SunRISe-4 in the neoadjuvant MIBC setting (NCT04919512).

Reference

1. Daneshmand S, van der Heijden MS, Jacob JM, et al. First results from sunrise-1 in patients with BCG unresponsive high-risk non–muscle-invasive bladder cancer receiving TAR-200 in combination with cetrelimab, TAR-200, or cetrelimab alone. Presented at 2023 AUA Annual Meeting. April 27-May 1, 2023; Chicago, IL. Abstract LBA02-03. doi.org:10.1097/JU.0000000000003361.03