TAR-200 Appears Highly Efficacious, Safe in BCG-Unresponsive NMIBC

TAR-200 monotherapy elicited deep and durable responses with a tolerable safety profile in patients with Bacillus Calmette-Guérin (BCG)–unresponsive high-risk non-muscle invasive bladder cancer (NMIBC), as shown in results from the parallel-cohort phase 2b SunRISe-1 trial (NCT04640623) published in the Journal of Clinical Oncology.¹

Patients in the trial were assigned to 4 cohorts: in cohort 1, patients received TAR-200 plus cetrelimab; in cohort 2, patients received TAR-200 monotherapy; in cohort 3, patients received cetrelimab monotherapy; and in cohort 4, patients with only high-risk papillary disease received TAR-200 monotherapy.

In all cohorts, TAR-200 was administered in a brief office procedure every 3 weeks through month 6, then every 12 weeks through month 24; cetrelimab was administered intravenously at 360 mg every 3 weeks through month 18. Treatment with TAR-200 and cetrelimab, respectively, was continued for up to 2 years and 18 months, or until confirmed high-risk disease persistence, recurrence, or progressive disease.

“Traditionally, these patients have had very limited treatment options. This new therapy is the most effective one reported to date for the most common form of bladder cancer,” stated lead study author Siamak Daneshmand, MD, director of Urologic Oncology with Keck Medicine of USC in a press release.² “The findings of the clinical trial are a breakthrough in how certain types of bladder cancer might be treated, leading to improved outcomes and saved lives.”

In July 2025, the FDA granted priority review to TAR-200 in patients with BCG-unresponsive high-risk NMIBC.³

Cohort 2

In cohort 2, 85 patients with BCG-unresponsive carcinoma in situ (CIS) with or without papillary disease received TAR-200 monotherapy. The median patient age was 71 years, and the majority were male (80.0%) and White (87.1%). Additionally, 32.9% had concurrent papillary disease, 96.5% refused radical cystectomy, and 91.8% had a consistent modality of cystoscopy at baseline and post-baseline.

At the data cut-off of March 31, 2025, in cohort 2, the centrally-confirmed complete response (CR) rate was 82.4% (n = 70/85; 95% CI, 72.6%-89.8%); the investigator-assessed CR rate was 83.5% (95% CI, 73.9%-90.7%). The overall concordance between the centrally- and investigator-assessed CR rate was 95.0%. Notably, 96% of responses were achieved at first disease evaluation, with a median time to response of 2.8 months.

At 3, 6, and 12 months following treatment, the CR rates were 78.8% (95% CI, 68.6%-86.9%), 58.8% (95% CI, 47.6%-69.4%), and 45.9% (95% CI, 35.0%-57.0%). Subgroup analyses showed consistently high CR rates across all clinically relevant subgroups.

With a median follow-up of 20.2 months (range, 5.0-48.0) in responders, the median duration of response (DOR) was 25.8 months (95% CI, 8.3-not estimable); 52.9% of responders had a DOR of 12 months or more. The median time to cystectomy was NE, with 12- and 24-month radical cystectomy-free rates of 86.6% (95% CI, 76.6%-92.6%) and 75.5% (95% CI, 63.4%-84.1%).

The overall survival (OS) rates at 6 and 12 months were 98.7% (95% CI, 91.2%-99.8%) and 94.7% (95% CI, 86.5%-98.0%), respectively.

Regarding safety, treatment-related adverse events (TRAEs) occurred in 83.5% of patients; the most common were low-grade urinary tract events such as pollakiuria (43.5%), dysuria (40.0%), micturition urgency (24.7%), and urinary tract infection (UTI; 21.2%). Grade 3 or higher TRAEs occurred in 12.9% of patients, with the most common being urinary tract pain (4.7%). TRAEs led to dose interruption in 31.8% and treatment discontinuation in 3.5%.

Cohort 4

In cohort 4, 52 patients with BCG-unresponsive high-risk papillary disease-only NMIBC received TAR-200 monotherapy; 71.2% were male, 86.5% were White, and 69.2% were former or current users of nicotine.

With a median follow-up of 12.8 months (range, 4-17), the median disease-free survival (DFS) was NE; the 6-, 9-, and 12-month DFS rates were 85.3% (95% CI, 71.6%-92.7%), 81.1% (95% CI, 66.7%-89.7%), and 70.2% (95% CI, 51.6%-82.8%), respectively. The 12-month DFS rates were consistent in patients with high-grade Ta (70.0%) and T1 disease (72.2%).

TRAEs were reported in 80.8% of patients, most being lower urinary tract symptoms; grade 3 or higher TRAEs occurred in 13.5%, with the most common being bladder pain (3.8%). Serious TRAEs were sepsis, spinal fracture, and UTI occurring in one patient each. TAR-200 was discontinued due to TRAEs in 7.7%.

Cohort 1

In cohort 1, 53 patients with CIS with or without papillary disease received TAR-200 plus cetrelimab.

The centrally-confirmed CR rate was 67.9% (95% CI, 53.7%-80.1%), and the investigator-assessed CR rate was 83.0% (95% CI, 70.2%-91.9%). After a median follow-up of 33.4 months (range, 10.0-47.0), the median DOR was NE, the 12-month DOR rate was 76.3% (95% CI, 58.1%-87.4%), and 55.6% of patients remained in a CR. The 12-month OS rate was 98.0% (95% CI, 86.6%-99.7%).

TRAEs occurred in 92.5% of patients, with dysuria (30.2%) and pollakiuria (28.3%) being the most common. Grade 3 or higher TRAEs occurred in 37.7%, serious TRAEs occurred in 15.1%, and immune-related AEs occurred in 64.2%. TRAEs led to TAR-200 treatment discontinuation in 26.4% and cetrelimab discontinuation in 24.5%.

Cohort 3

In cohort 3, 28 patients with CIS with or without papillary disease received cetrelimab monotherapy.

The CR rate was 46.4% (95% CI, 27.5%-66.1%) via central assessment and 50.0% (95% CI, 30.6%-69.4%) via investigator assessment. With a median follow-up of 29.2 months (range, 11.0-45.0), the median DOR was 8.6 months (95% CI, 2.8-NE), the 12-month DOR rate was 38.5% (95% CI, 14.1%-62.8%), and the 12-month OS rate was 100% (95% CI, 100%-100%).

TRAEs occurred in 53.6% of patients, with the most common being pruritus (10.7%); grade 3 or higher TRAEs occurred in 7.1%. Serious TRAEs occurred in 3.6%, which was myopericarditis. Cetrelimab was discontinued due to TRAEs in 7.1%.

References

1. Daneshmand S, Van der Heijden M, Jacob JM, et al. TAR-200 for bacillus Calmette-Guérin–unresponsive high-risk non–muscle-invasive bladder cancer: results from the phase IIb SunRISe-1 study. J Clin Oncol. Published online July 20, 2025. doi:10.1200/JCO-25-01651
2. New treatment eliminates bladder cancer in 82% of patients. News release. Keck Medicine of USC. August 13, 2025. Accessed August 14, 2025. https://tinyurl.com/yeypdbzy
3. Johnson & Johnson receives U.S. FDA Priority Review for TAR-200 NDA in high-risk non-muscle invasive bladder cancer. News release. Johnson & Johnson. July 17, 2025. Accessed August 14, 2025. https://tinyurl.com/4v6c4swz