TAR-200 Phase 2b SunRISe-1 study shows 84% complete response in high-risk non-muscle-invasive bladder cancer

Investigational TAR-200 therapy has shown a significant complete response (CR) rate in patients with Bacillus Calmette-Guérin (BCG)-unresponsive, high-risk non-muscle-invasive bladder cancer (HR-NMIBC), according to new data presented by Johnson & Johnson. The findings were part of the Phase 2b SunRISe-1 study and were revealed during a late-breaking oral presentation at the European Society of Medical Oncology (ESMO) 2024 Congress in Barcelona, Spain.

Dr. Michiel S. van der Heijden, a medical oncologist at the Netherlands Cancer Institute, highlighted the importance of the new data. He stated that the safety and efficacy observed across various patient cohorts solidify TAR-200's potential as an innovative treatment option for patients who do not respond to BCG immunotherapy and are faced with drastic treatment choices like radical cystectomy.

The pivotal cohort of the study, which involved 85 patients, showed a high single-agent complete response (CR) rate of 83.5%, with a 95% confidence interval (CI) between 74 and 91. The durability of these responses was noteworthy, as 82% of the patients maintained their response after a median follow-up of nine months, with an estimated 12-month CR rate of 57.4% based on the Kaplan-Meier curve. These results suggest that TAR-200 monotherapy could be highly effective without the need for reinduction.

Earlier results from this cohort were presented at the 2024 American Urological Association Annual Meeting. The other cohorts studied included TAR-200 plus cetrelimab (CET) and CET monotherapy, respectively. Cohort 1 showed a centrally-confirmed CR rate of 67.9%, while Cohort 3 had a CR rate of 46.4%. The overall risk-benefit profile favored TAR-200 monotherapy.

Christopher Cutie, M.D., Vice President, Disease Area Leader, Bladder Cancer, Innovative Medicine at Johnson & Johnson, emphasized the company's commitment to innovating cancer treatments. He stated that the data from the SunRISe clinical program could redefine the treatment landscape for bladder cancer, potentially improving patient well-being and treatment experience.

Adverse events leading to treatment discontinuation were low, with TAR-200 (Cohort 2) showing a discontinuation rate of 6%, CET (Cohort 3) at 7%, and a combination of TAR-200 and CET (Cohort 1) showing higher rates of 26% and 23%, respectively. Common adverse events, occurring in more than 20% of cases across Cohorts 1 and 2, included pollakiuria, dysuria, hematuria, and urinary tract infections. Importantly, there were no treatment-related deaths reported.

Bladder cancer ranks as the ninth most common cancer globally. Despite BCG immunotherapy being a standard treatment for decades, 30-40% of patients do not respond and experience recurrence or progression of the disease. For these patients, a radical cystectomy, which involves removing the bladder and surrounding organs, is often the primary treatment. This major surgery requires creating a urinary diversion to collect and store urine, posing significant challenges for patients.

TAR-200 is an investigational targeted releasing system that locally delivers gemcitabine into the bladder over an extended period. The drug is administered in a physician's office within a 2-3 minute procedure without anesthesia. In December 2023, the FDA granted TAR-200 Breakthrough Therapy Designation for BCG-unresponsive HR-NMIBC patients who are ineligible or unwilling to undergo radical cystectomy.

The SunRISe-1 study is an open-label, Phase 2 clinical trial evaluating TAR-200 alone or in combination with cetrelimab for BCG-unresponsive HR-NMIBC carcinoma in situ patients who are not suitable for radical cystectomy. Participants were randomized into four cohorts: TAR-200 with cetrelimab, TAR-200 alone, cetrelimab alone, and TAR-200 alone for papillary disease. The primary endpoint for the first three cohorts was CR rate, with secondary endpoints including duration of response, overall survival, pharmacokinetics, quality of life, safety, and tolerability. Enrollment for Cohorts 1 and 3 was closed as of June 1, 2023.

In summary, the investigational TAR-200 shows promise as a highly effective treatment for BCG-unresponsive HR-NMIBC, potentially offering a less invasive alternative to radical cystectomy. The ongoing evaluation in various clinical studies will further elucidate its safety and efficacy.