News

Article

TAR-200 Leads to Durable Responses in Bacillus Calmette–Guérin-Unresponsive NMIBC

Author(s):

TAR-200 displayed a high complete response rate in Bacillus Calmette–Guérin-unresponsive high-risk non–muscle-invasive bladder cancer.

Joseph Jacob, MD, MCR

Joseph Jacob, MD, MCR

TAR-200, a novel targeted delivery system of gemcitabine, demonstrated rapid, durable responses in patients with Bacillus Calmette–Guérin-unresponsive high-risk non–muscle-invasive bladder cancer (NMIBC), according to findings from the phase 2 SunRISe-1 trial (NCT04640623) presented at the 2024 AUA Annual Meeting.1

At the January 2, 2024, data cutoff, 82.8% (95% CI, 70.6%-91.4%) of response-evaluable patients who were treated with TAR-200 monotherapy (n = 58) achieved a centrally assessed complete response (CR) and 86.2% (95% CI, 74.6%-93.9%) achieved an investigator-assessed CR. Additionally, the Kaplan-Meier estimates for CR rate at 6 and 12 months were 75.7% (95% CI, 59.1%-86.3%) and 61.9% (95% CI, 41.1%-77.1%), respectively. Nearly all (98%) CRs were achieved at the first disease assessment at week 12.

Additionally, most responses (85%) were ongoing at the clinical cutoff, with 4 of 5 patients who completed 2 years of treatment remaining in response. Notably, no responders (n = 48) progressed to muscle-invasive bladder cancer or metastatic disease and only 1 responder underwent radical cystectomy. The Kaplan-Meier estimates for the 6-, 12-, and 18-month duration of response (DOR) rates were 87.0% (95% CI, 69.0%-94.9%), 74.6% (95% CI, 49.8%-88.4%), and 74.6% (95% CI, 49.8%-88.4%), respectively.

“Radical cystectomy is a life-changing operation with considerable morbidity and quality of life considerations. Moreover, there is a 90-day mortality risk of up to 8%. As such, there is a high unmet need for bladder-sparing therapies in this population,” Joseph Jacob, MD, MCR, an associate professor of urology at SUNY Upstate Medical University Hospital in Syracuse, New York, said during a presentation of the data. “TAR-200 is a novel targeted releasing system designed for sustained local release of gemcitabine into the bladder. It is placed in the clinic with a urinary placement catheter and it takes approximately 2 to 3 minutes. Removal is with a cystoscope and is very similar to how you would remove a ureteral stent. In my practice, my nurse practitioner places the TAR-200 devices and removes them.”

SunRISe-1 enrolled patients with histologically confirmed high-risk NMIBC carcinoma in situ (CIS) with or without papillary disease. Eligible patients also needed to have an ECOG performance status of 2 or less, persistent or recurrent disease within 12 months of the completion of Bacillus Calmette–Guérin, and were unresponsive to Bacillus Calmette–Guérin and not receiving radical cystectomy.

Patients were randomly assigned 2:1:1 to receive TAR-200 plus cetrelimab (cohort 1; n = 55), TAR-200 monotherapy (cohort 2; n = 85), or cetrelimab monotherapy (cohort 3; n = 28). There was also a fourth cohort of approximately 50 patients with papillary-only high-risk NMIBC who were treated with TAR-200 monotherapy. TAR-200 was administered every 3 weeks for the first 24 weeks, then every 12 weeks through week 96. Findings from cohort 2 were presented during the 2024 AUA Annual Meeting.

The primary end point in cohorts 1 through 3 was overall CR rate. Key secondary end points included DOR, overall survival, safety, and tolerability. The primary end point in cohort 4 was 12-month disease-free survival rate.

At baseline, patients in cohort 2 had a median age of 71 years (range, 40-88). Most patients were male (80.0%), White (72.9%), and former nicotine users (57.6%), and had an ECOG performance status of 0 (91.8%), declined radical cystectomy (96.5%), and CIS only (67.1%). The median number of total doses of prior Bacillus Calmette–Guérin was 12 (range, 7-42) and the median time from last Bacillus Calmette–Guérin to CIS diagnosis was 3.4 months (range, 0-22).

Additional findings from a subgroup analysis showed that the high CR rate with TAR-200 monotherapy was consistent across patient subgroups. Notably, patients from the Asia Pacific region (n = 7), females (n = 13), and those with CIS with papillary disease (n = 20) achieved CR rates of 100% (95% CI, 59.0%-100.0%), 92.3% (95% CI, 64.0%-99.8%), and 90.0% (95% CI, 68.3%-98.8%), respectively.

In terms of safety, most adverse effects (AEs) were grade 1 or 2 in severity and occurred within 12 weeks of treatment initiation. Most patients experienced an any-grade AE (85.9%) and 22.4% experienced a grade 3 or higher AE. Common any-grade treatment-related AEs (TRAEs) included pollakiuria (35.3%), dysuria (29.4%), micturition urgency (15.3%), and urinary tract infection (15.3%). Grade 3 or higher TRAEs included urinary tract pain (2.4%), as well as bladder pain, renal impairment, urinary retention, urosepsis, urinary tract infection, and dysuria which occurred in 1 patient each. Four patients discontinued treatment due to AEs and there were no treatment-related deaths.

In December 2023, the FDA granted breakthrough therapy designation to TAR-200 for use in the treatment of patients with Bacillus Calmette-Guérin­–unresponsive, high-risk NMIBC who are not candidates for or opted not to receive radical cystectomy. The regulatory decision was supported by findings from SunRISe-1.2

“In conclusion, TAR-200 monotherapy provides a rapid and high CR rate [for patients with] Bacillus Calmette-Guérin­–unresponsive high-risk NMIBC,” Jacob said.

References

  1. Necchi A, Daneshmand S, Simone G, et al. TAR-200 in patients with Bacillus Calmette–Guérin-unresponsive high-risk non–muscle-invasive bladder cancer: results from SunRISe-1 study. J Urol. Published online May 1, 2024. doi:10.1097/01.JU.0001015816.87470.c9.01
  2. Johnson & Johnson’s investigational TAR-200 granted US FDA breakthrough therapy designation for the treatment of high-risk non-muscle-invasive bladder cancer. News release. Johnson & Johnson. December 4, 2023. Accessed May 3, 2024. https://www.jnj.com/media-center/press-releases/johnson-johnsons-investigational-tar-200-granted-u-s-fda-breakthrough-therapy-designation-for-the-treatment-of-high-risk-non-muscle-invasive-bladder-cancer
Related Videos
Sujith Samarasinghe, MD
Suzanne Trudel, MSc, MD
Consuelo Bertossi, MD
Michael R. Grunwald, MD, FACP
Manali Kamdar, MD
Ibrahim Aldoss, MD
Laurence Albigès, MD, PhD
Joaquim Bellmunt, MD, PhD
Timothy Hughes, MD, MBBS, FRACP, FRCPA
 Bernard H. Bochner, MD, FACS