TAR-210 results show 90 percent recurrence-free survival and 90 percent complete response in patients with high-risk and intermediate-risk non-muscle-invasive bladder cancer, respectively

Updated results reinforce the potential of TAR-210 to transform treatment of non-muscle-invasive bladder cancer with fibroblast growth factor receptor (FGFR) alterations^1

BEERSE, BELGIUM, May 05, 2024 (GLOBE NEWSWIRE) -- Janssen-Cilag International NV, a Johnson & Johnson company, announced today updated results from an open-label, multicentre, multi-cohort Phase 1 study of the safety and efficacy of TAR-210, an intravesical targeted releasing system designed to provide sustained, local release of erdafitinib into the bladder, in patients with non-muscle-invasive bladder cancer (NMIBC) with select FGFR alterations.^1 These data were featured today in an Oral Presentation Session (Abstract #PD48-02)^1 at the 2024 American Urological Association (AUA) Annual Meeting taking place 3-6 May, 2024, in San Antonio, Texas.

Results featured updated data from Cohort 1 (C1); patients with recurrent, Bacillus Calmette-Guérin (BCG)-unresponsive high-risk (HR) NMIBC (high-grade Ta/T1; papillary only) who refused or were ineligible for radical cystectomy and Cohort 3 (C3); patients with recurrent, intermediate-risk (IR) NMIBC (Ta/T1) low-grade papillary disease left in situ as tumour marker lesions.^1 First results were featured at the European Society for Medical Oncology 2023 Congress, with interim results presented at the European Association of Urology (EAU) 2024 Annual Congress.^2^,3

“Advancement in the treatment landscape of high or intermediate-risk non-muscle-invasive bladder cancer has remained stagnant for more than 50 years,” said Antoni Vilaseca*, M.D., Ph.D., of the Hospital Clínic de Barcelona, presenting author of the Phase 1 TAR-210 study. “Results presented today further underscore that TAR-210 for the localised treatment of bladder cancer may offer a promising alternative for patients with limited treatment options.”

At the data cutoff of 22 March, 2024, 64 patients had been treated with TAR-210 across the two cohorts.^1 Of the 21 patients in C1 with HR-NMIBC, the 12-month recurrence free (RF) survival rate was 90 percent (95 percent confidence interval (CI), 66-97).^1 In C3, 31 patients were efficacy evaluable with 28/31 achieving a complete response (CR) rate of 90 percent (95 percent CI, 74-98).^1

The most common treatment-related emergent adverse events (TEAEs) were Grade 1/2 lower urinary tract events.^1 There were no dose-limiting toxicities and no deaths.^1 Two patients (3 percent) discontinued the study due to TEAEs of low-grade urinary symptoms and two patients had serious TEAEs with pyelonephritis and sepsis or UTI (urinary tract infection) and sepsis, respectively.^1

“FGFR genetic alterations are most common in NMIBC,” said Sabine Brookman-May, M.D., Vice President, Late Development Oncology, Johnson & Johnson Innovative Medicine. “These results further support the potential of TAR-210 with quarterly administration as a bladder-sparing and BCG-free treatment option, underscoring our deep commitment to pioneering novel therapies for patients who face limited treatment avenues.” 

“At Johnson & Johnson, we are committed to transforming bladder cancer treatment with novel drug delivery technology and precision-based therapies,” said Henar Hevia, Senior Director, EMEA Therapeutic Area Lead, Oncology at Johnson and Johnson Innovative Medicine. “As the data continue to mature, it is encouraging to see sustained positive responses to treatment. We look forward to investigating the full potential of TAR-210 in patients with FGFR-altered non-muscle invasive bladder cancer through an ongoing and comprehensive clinical development programme.”

Europe has one of the highest rates of bladder cancer in the world^4 with nearly 225,000 patients diagnosed in 2022,^5 a 10 percent increase from 2020.^6 NMIBC constitutes approximately 75 percent of all newly diagnosed bladder cancers.^7 Currently, adjuvant intravesical immunotherapy with BCG or intravesical chemotherapy is the standard of care for patients with intermediate- and high-risk NMIBC.^8 Between 30 to 40 percent of patients do not respond to BCG, facing disease recurrence or progression.^9 In such scenarios of HR-NMIBC, radical cystectomy (removal of the bladder) emerges as the primary treatment option.^9 This major abdominal procedure requires a urinary diversion to be created to collect and store urine.^10

#ENDS#

*About TAR-210*
TAR-210 is an investigational erdafitinib intravesical targeted releasing system.^11 The safety and efficacy of TAR-210 is being evaluated in a Phase 1 study (NCT05316155)^12 in patients with muscle-invasive bladder cancer (MIBC) and NMIBC. The study categorises patients into four cohorts based on their disease presentation.^13 Cohort 1 (C1) includes patients with recurrent, BCG-unresponsive HR-NMIBC with concomitant high-grade papillary disease who have refused or are ineligible for radical cystectomy (RC).^13 Cohort 2 (C2) includes patients with the same presentation, but who are scheduled for RC.^13 Cohort 3 (C3) includes patients with recurrent, intermediate-risk NMIBC with a history of low-grade papillary disease.^13 To be eligible for C3, the presence of visible tumour(s) is required. Cohort 4 (C4) includes patients with MIBC.^1^3 The primary endpoint of the study is safety (adverse events, including dose-limiting toxicity).^13 Secondary endpoints include pharmacokinetics (PK), RF survival in patients in C1 and C2, CR rate and duration of CR in patients in C3 and pathologic CR rate in C4.^13

*About Erdafitinib*
Erdafitinib is a once-daily, oral pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor being evaluated by Johnson & Johnson Innovative Medicine in Phase 2 and 3 clinical trials in patients with advanced urothelial cancer.^14 In addition to the Phase 1 study (NCT05316155)^12 in patients with MIBC and NMIBC, erdafitinib is also being studied in the Phase 3 THOR study (NCT03390504),^15 a study assessing whether erdafitinib provided a survival advantage versus chemotherapy in patients with advanced or metastatic urothelial cancer (mUC) with select FGFR alterations; the Phase 2 THOR-2/BLC2003 (NCT04172675)^16 study examining erdafitinib versus investigator choice of intravesical chemotherapy in participants who received BCG and recurred with HR-NMIBC; the Phase 1b/2 NORSE (NCT03473743)^17 study of erdafitinib in combination with cetrelimab in patients with locally advanced or mUC and FGFR3 or FGFR2 gene alterations; the Phase 2 RAGNAR (NCT04083976)^18 study evaluating the safety and efficacy of erdafitinib in patients with advanced solid tumours, regardless of cancer type or tumour location (tumour-agnostic), driven by FGFR1–4 alterations.

In addition to the marketing authorisation application submitted to the European Medicines Agency (EMA) in September 2023, Johnson & Johnson also submitted a Supplemental New Drug Application to the U.S. Food and Drug Administration (FDA), in August 2023, based upon the Phase 3 THOR study.^19^,^20

In 2008, Janssen Pharmaceuticals entered into an exclusive worldwide licence and collaboration agreement with Astex Pharmaceuticals to develop and commercialise erdafitinib.^21

*About Urothelial Carcinoma *
Urothelial carcinoma (UC), also known as transitional cell carcinoma, starts in the innermost lining of the bladder.^22 Almost all bladder cancers – more than 90 percent – are UCs.^23 Up to one in five patients (20 percent) diagnosed with mUC have a FGFR genetic alteration.^24 FGFRs are a family of receptor tyrosine kinases that can be activated by genetic alterations in a variety of tumour types, and these alterations may lead to increased tumour cell growth and survival.^25 FGFRs play a key role in several biological processes including tissue repair, inflammatory response and metabolism.^26 Fusions or mutations in the genes that control FGFR (known as FGFR1–4 alterations) may lead to the development and progression of certain cancers by increasing tumour cell growth and survival.^27 Patients with advanced UC, including FGFR-driven tumours, face a poor prognosis and the need for innovative therapies remains high.^28 The five-year survival rate for patients with metastatic bladder cancer that has spread to distant parts of the body is currently eight percent.^29

*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.^30 HR-NMIBC is characterised by a combination of high-grade, large tumour size, presence of multiple tumours, and carcinoma in situ (CIS).^30 Radical cystectomy is currently recommended for HR-NMIBC patients who fail BCG therapy, with over 90 percent cancer-specific survival if performed before muscle-invasive progression.^30 Given that NMIBC typically affects older patients, many may be unwilling or unfit to undergo radical cystectomy.^30 The high rates of recurrence and progression can pose significant morbidity and distress for these patients.^30

*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/emea. Follow us at https://twitter.com/JNJInnovMedEMEA and https://www.linkedin.com/company/jnj-innovative-medicine-emea/ for our latest news. Janssen-Cilag International NV, Janssen Pharmaceutica NV, and Janssen Research & Development, LLC are 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-210 or erdafitinib. 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-Cilag International NV, Janssen Pharmaceutica NV, and Janssen Research & Development, LLC and 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-Cilag International NV, Janssen Pharmaceutica NV, and Janssen Research & Development, LLC nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

© Janssen-Cilag International NV, Inc. 2024. All rights reserved. 

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

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^1 Vilaseca A, et al. First-in-Human Study of TAR-210 Erdafitinib Intravesical Delivery System in Patient With Non-Muscle-Invasive Bladder Cancer With Select FGFR Alterations. 2024 Annual Urological Association. Oral presentation, 2024 American Urological Association Annual Meeting. May 2024.
^2 Vilaseca A, et al. First Safety and Efficacy Results of the TAR-210 Erdafitinib Intravesical Delivery System in Patients with Non–Muscle-Invasive Bladder Cancer (NMIBC) With Select FGFR Alterations. 2023 European Society for Medical Oncology. Oral presentation, 2023 ESMO Annual Meeting. October 22, 2023. Available at: https://www.jnj.com/media-center/press-releases/first-results-with-erdafitinib-releasing-intravesical-delivery-system-tar-210-show-early-evidence-of-positive-clinical-activity-in-patients-with-non-muscle-invasive-bladder-cancer-with-select-fibroblast-growth-factor-receptor-alterations. Last accessed May 2024.
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