New data from Phase 2b SunRISe-1 study show rapid achievement of complete response (CR) with 98% achieving a CR within 12 weeks

TAR-200 provides durable CRs in patients with Bacillus Calmette-Guérin (BCG)–unresponsive high-risk non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ – a disease area with limited treatment options for patients

SAN ANTONIO, May 3, 2024 /PRNewswire/ -- Johnson & Johnson announced today updated results from Cohort 2 of the Phase 2b SunRISe-1 study evaluating the efficacy and safety of investigational TAR-200 monotherapy in patients with BCG-unresponsive high-risk non–muscle-invasive bladder cancer (HR-NMIBC) with carcinoma in situ, who are ineligible for, or decline, radical cystectomy. These data were featured today in a plenary session (Abstract #P2-01) at the 2024 American Urological Association Annual Meeting (AUA) taking place May 3-6, 2024, in San Antonio, Texas.

"The high complete response rate and durability of these responses observed in patients treated with TAR-200 underscores the potential of this treatment approach for patients with BCG-unresponsive HR-NMIBC," said Joseph Jacob,* M.D., M.S., Department of Urology, Upstate Medical University, presenting author. "These results address an area of high unmet need for bladder sparing therapies in this patient population."

Results included an evaluation of 85 patients (median age of 71 years old: range 40-88; 32.9% with concurrent papillary disease) who received TAR-200 monotherapy. The centrally confirmed complete response (CR) rate was 82.8% by urine cytology and/or biopsy (95% confidence interval [CI], 70.6-91.4). The study protocol did not allow retreatment for nonresponders, consistent with U.S. Food and Drug Administration (FDA) guidance. The estimated 1-year duration of response (DOR) rate is 74.6% (95% CI, 49.8-88.4), with median follow-up in responders of 29.9 weeks (range, 14-140); 41 of 48 responders (85%) remain in CR at data cutoff as of January 2, 2024, and none of the responders progressed to muscle-invasive bladder cancer or metastasis. Ninety-eight percent (47 of 48) of CRs were achieved at first disease assessment at week 12, and four of five patients who have completed two years of treatment remain in CR. The investigator-assessed confirmed CR rate correlated strongly with central results.¹ 

Interim results from the SunRISe-1 study were featured at the European Society for Medical Oncology 2023 Congress and shared at AUA 2023. These results were also presented at the European Association of Urology 2024 Congress.

Treatment-related adverse events (TRAEs) occurred in 61 patients (71.8%). The most common (≥10%) were pollakiuria (35.3%), dysuria (29.4%), micturition urgency (15.3%), and urinary tract infections (15.3%). Seven patients (8.2%) had Grade 3 or higher TRAEs and four patients (4.7%) had one or more serious TRAEs. Four patients (4.7%) had TRAEs leading to discontinuation and no deaths were reported.

"These study results mark a significant step in our mission to bring new treatment options to patients that focus on bladder preservation and long-term survival," said Christopher Cutie, M.D., Vice President, Disease Area Leader, Bladder Cancer, Johnson & Johnson Innovative Medicine. "These results reinforce the potential of TAR-200 to transform the treatment landscape and our ongoing dedication to address unmet needs for patients facing this challenging disease."

TAR-200 is an investigational targeted releasing system designed to provide extended local release of gemcitabine into the bladder. It is installed in a physician's office setting during a 3- to 5-minute procedure with no anesthesia. In December 2023, the FDA granted TAR-200 Breakthrough Therapy Designation (BTD) for the potential future treatment of patients with  BCG-unresponsive HR-NMIBC, who are ineligible for or elected not to undergo radical cystectomy (surgical removal of the bladder).

Bladder cancer is the sixth most common cancer in the U.S., with more than 83,000 patients diagnosed each year, with NMIBC accounting for about 75-85% of all newly diagnosed bladder cancers.^2,3 Although BCG immunotherapy has been accepted as the standard of care for nearly five decades, 30-40% of patients do not respond to BCG and experience disease recurrence or progression.⁴ In such scenarios, radical cystectomy (removal of the bladder and neighboring structures and organs) emerges as the primary treatment option. This major abdominal procedure requires a urinary diversion to be created to collect and store urine.⁵

About SunRISe-1
SunRISe-1 (NCT04640623) is a randomized, parallel-assignment, open-label Phase 2 clinical study evaluating the safety and efficacy of TAR-200 in combination with cetrelimab, TAR-200 alone, or cetrelimab alone for BCG-unresponsive HR-NMIBC carcinoma in situ (CIS) patients who are ineligible for, or elected not to undergo, radical cystectomy. Participants are randomized to 1 of 4 cohorts: treatment with TAR-200 in combination with cetrelimab (Cohort 1), TAR-200 alone (Cohort 2), cetrelimab alone (Cohort 3), or TAR-200 alone with papillary disease only (Cohort 4). The primary endpoint is CR rate at any time point. Secondary endpoints include DOR, overall survival, pharmacokinetics, quality of life, safety and tolerability. Cohorts 1 and 3 were closed to further enrollment effective June 1, 2023. 

About TAR-200
TAR-200 is an investigational targeted releasing system, enabling controlled release of gemcitabine into the bladder, increasing the amount of time the drug delivery system spends in the bladder and sustaining local drug exposure. The safety and efficacy of TAR-200 are being evaluated in Phase 2 and Phase 3 studies in patients with muscle-invasive bladder cancer in SunRISe-2 and SunRISe-4, NMIBC in SunRISe-1, SunRISe-3 and SunRISe-5.

About Cetrelimab
Administered intravenously, cetrelimab is an investigational programmed cell death receptor-1 (PD-1) monoclonal antibody being studied for the treatment of bladder cancer, prostate cancer, melanoma, and multiple myeloma as part of a combination treatment. Cetrelimab is also being evaluated in multiple other combination regimens across the Janssen Oncology portfolio.

About High-Risk Non–Muscle-Invasive Bladder Cancer
High-risk non–muscle-invasive bladder cancer (HR-NMIBC) is a type of non-invasive bladder cancer that is more likely to recur or spread beyond the lining of the bladder, called the urothelium, and progress to invasive bladder cancer compared to low-risk NMIBC.^6,7 HR-NMIBC makes up 15-44% of patients with NMIBC and is characterized by a high-grade, large tumor size, presence of multiple tumors, and CIS. Radical cystectomy is currently recommended for NMIBC patients who fail BCG therapy, with over 90% cancer-specific survival if performed before muscle-invasive progression.^8,9 Given that NMIBC typically affects older patients, many may be unwilling or unfit to undergo radical cystectomy.¹⁰ The high rates of recurrence and progression can pose significant morbidity and distress for these patients.^6,10

About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at https://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine. Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC and Janssen Biotech, Inc., are both Johnson & Johnson companies.

Cautions Concerning Forward-Looking Statements
This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of TAR-200 or cetrelimab. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, Janssen Biotech, Inc., and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of Janssen Research & Development, LLC, Janssen Biotech, Inc., nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

*Dr. Jacob has not been paid for any media work.

¹ Necchi A, Daneshmand S, Simone G, Xylinas E, Morris DS, Zainfeld D, et al. P2-01 TAR-200 in patients with Bacillus Calmette-Guérin-unresponsive high-risk non–muscle-invasive bladder cancer: results from SunRISe-1 study. Journal of Urology. 2024;211.
² Key statistics for bladder cancer. American Cancer Society. Accessed April 1, 2024. https://www.cancer.org/cancer/types/bladder-cancer/about/key-statistics.html#:~:text=time%20of%20diagnosis-,How%20common%20is%20bladder%20cancer?,men%20and%204%2C550%20in%20women)
³ Deng S, Meng F, Wang L, et al. Global research trends in non–muscle invasive bladder cancer: bibliometric and visualized analysis. Front Oncol. 2022;12:1044830. Published 2022 Nov 17. doi:10.3389/fonc.2022.1044830
⁴ Zlotta AR, Fleshner NE, Jewett MA. The management of BCG failure in non-muscle-invasive bladder cancer: an update. Can Urol Assoc J. 2013;3(6-S4):199.
⁵ Bladder removal surgery: What is a radical cystectomy? Bladder Cancer Advocacy Network. Accessed April 1, 2024. https://bcan.org/bladder-removal-surgery/. 
⁶ Grab-Heyne K, Henne C, Mariappan P, et al. Intermediate and high-risk non–muscle-invasive bladder cancer: an overview of epidemiology, burden, and unmet needs. Front Oncol. 2023;13:1170124.
⁷ Lieblich A, Henne C, Mariappan P, Geiges G, Pöhlmann J, Pollock RF. The management of non–muscle-invasive bladder cancer: A comparison of European and UK guidelines. J Clin Urol. 2018;11(2):144-148.
⁸ Brooks NA, O'Donnell MA. Treatment options in non–muscle-invasive bladder cancer after BCG failure. Indian J Urol. 2015;31(4):312-319. doi:10.4103/0970-1591.166475
⁹ Guancial EA, Roussel B, Bergsma DP, et al. Bladder cancer in the elderly patient: challenges and solutions. Clin Interv Aging. 2015;10:939-949.
¹⁰ Chamie K, Litwin MS, Bassett JC, et al. Recurrence of high-risk bladder cancer: A population-based analysis. Cancer. 2013;119(17):3219-3227.

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