Carcinoma of urinary bladder, invasive

Merck & Co.'s Keytruda (pembrolizumab) closed out on a high note towards the end of last year, with two positive readouts in bladder cancer and the FDA signing off on full approval for a combination with Padcev (enfortumab vedotin-ejfv). However, efforts to expand Keytruda's position in this treatment space could face some challenges, according to new Phase III results unveiled Friday at the American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium.While Merck confirmed that its PD-1 inhibitor improved disease-free survival (DFS) by a significant 31% when used as adjuvant therapy, it fell short on the trial's other co-primary endpoint of overall survival (OS). Marjorie Green, head of oncology, global clinical development, at Merck Research Laboratories, was nevertheless pleased with the pivotal KEYNOTE-123 results, saying they "demonstrate the expanding role of Keytruda into earlier stages of resectable muscle-invasive bladder cancer (MIUC)."KEYNOTE-123 trial, also known as AMBASSADOR, enrolled 702 patients with localised MIUC and locally advanced urothelial carcinoma who were randomised to receive Keytruda or undergo observation. Merck in October reported that the trial had achieved the dual primary endpoint of DFS.Observation cohort edge in survivalMedian DFS was 29 months with Keytruda, or 15 months longer than what was reported in the observation arm, according to Friday's late-breaking presentation at ASCO GU. This first interim analysis of the study also showed that the DFS results were consistent regardless of a patient's PD-L1 expression status.However, the other survival endpoint did not achieve statistical significance, with the analysis suggesting OS favoured the observation arm. Specifically, after a median follow up of roughly 3 years, median OS with Keytruda was 50.9 months, compared to 55.8 months for the comparator group. Merck said the OS endpoint would continue to be monitored as the data mature.The noted that 17.4% of patients receiving Keytruda withdrew from the trial without experiencing a DFS event, while the rate was 27.2% in the observation arm. It said that 22% of those in the observation group received an immune checkpoint inhibitor following a DFS event. Bristol Myers Squibb rival immunotherapy Opdivo (nivolumab) in 2021 became the first adjuvant treatment to be approved in the US for high-risk bladder cancer patients.The KEYNOTE-123 results amount to a partial victory for Keytruda, particularly in light of results Merck reported last year at the European Society of Medical Oncology (ESMO) congress. When paired with Astellas and Pfizer's antibody-drug conjugate Padcev, Keytruda reduced the risk of death by 53% versus chemotherapy in the Phase III KEYNOTE-A39 trial of patients with previously untreated locally advanced or metastatic urothelial carcinoma. The results led to the FDA in December converting an earlier accelerated approval of the combo to a full approval.Aside from the Padcev combination, Keytruda's current label also includes use as monotherapy for previouslybtreated patients with locally advanced or metastatic urothelial carcinoma, and certain patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ, with or without papillary tumours.

[04-December-2023] Breakthrough Therapy Designation for Novel Targeted Releasing System Based on Results from Ongoing Phase 2b SunRISe-1 Study RARITAN, N.J., Dec. 4, 2023 /PRNewswire/ -- Johnson & Johnson announced today that the U.S. Food and Drug Administration (FDA) has granted TAR-200 Breakthrough Therapy Designation (BTD) for the potential future treatment of patients with Bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (HR-NMIBC), who are ineligible for or elected not to undergo radical cystectomy (surgical removal of the bladder). TAR-200 is a novel investigational targeted releasing system designed to provide sustained local release of gemcitabine into the bladder. Today's BTD marks Johnson & Johnson's 13th such designation in oncology. "TAR-200 represents a novel interventional approach for the treatment of localized bladder cancer where today, unfortunately, options are limited and include antiquated BCG therapy or radical cystectomy," said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Johnson & Johnson Innovative Medicine. "This Breakthrough Therapy Designation recognizes TAR-200 as a promising advancement and marks an important step forward in our innovative focus to transform the treatment of bladder cancer." The BTD is supported by data from SunRISe-1 (NCT04640623), an open-label Phase 2b 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.1 Data from the SunRISe-1 study were featured during the 2023 European Society for Medical Oncology Annual Congress as a late-breaking mini-oral presentation (Abstract #LBA105) and interim results were presented at the 2023 American Urological Association Annual Meeting (Abstract #LBA02-03). A U.S. FDA BTD is granted to expedite the development and regulatory review of a medicine that is intended to treat a serious or life-threatening condition and is based on preliminary clinical evidence that demonstrates the drug may have substantial improvement over available therapies on a clinically significant endpoint(s).2 About SunRISe-1 SunRISe-1 (NCT04640623) is an open-label Phase 2b 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 were randomized to one of three cohorts: treatment with TAR-200 in combination with cetrelimab (Cohort 1), TAR-200 alone (Cohort 2), or cetrelimab alone (Cohort 3). The primary endpoint is Complete Response rate at any time point. Secondary endpoints include duration of response, 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, sustaining local drug exposure for weeks at a time. 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 and NMIBC in SunRISe-1 and SunRISe-3. 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 regimen. 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- and intermediate risk NMIBC.3,4 HR-NMIBC makes up 15–44 percent 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 are unresponsive to BCG therapy, with over 90 percent cancer-specific survival if performed before muscle-invasive progression.5,6 Given that NMIBC typically affects older patients, many may be unwilling or unable to undergo radical cystectomy.7 The high rates of recurrence and progression can pose significant morbidity and distress for patients with NMIBC.8 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 or at . 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 January 1, 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 , or on request from Johnson & Johnson. None of Janssen Research & Development, Janssen Biotech, Inc., nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. Media contacts: Suzanne Frost +1 416 317-0304 Brian Kenney +1 215 620-0111 Investor contact: Raychel Kruper investor-relations@its.jnj.com U.S. Medical Inquiries +1 800 526-7736

Phase 2b SunRISe-1 study results showed sustained, durable complete responses beyond one year with intravesical gemcitabine delivery system MADRID, Oct. 22, 2023 /PRNewswire/ -- The Janssen Pharmaceutical Companies of Johnson & Johnson today announced that data from the Phase 2b SunRISe-1 study evaluating the efficacy and safety of TAR-200 monotherapy in patients with Bacillus Calmette-Guérin (BCG)-unresponsive, high-risk non-muscle-invasive bladder cancer (HR-NMIBC), who are ineligible for, or decline, radical cystectomy, showed that 77 percent of patients (23 out of 30 [95 percent Confidence Interval (CI), 58-90]) achieved a complete response (CR). These data were featured today in a Late-Breaking Mini-Oral Presentation Session (Abstract #LBA105) at the European Society for Medical Oncology (ESMO) 2023 Congress taking place October 20-24 in Madrid, Spain.1 TAR-200 is an investigational intravesical drug delivery system designed to provide sustained local release of gemcitabine into the bladder. Interim results from the SunRISe-1 study were featured earlier this year at the American Urological Association Annual Meeting. Results presented today included an evaluation of 54 patients (median age of 71; range 40-85; 33 percent with concurrent papillary disease) who received TAR-200 monotherapy. Centrally confirmed CR by urine cytology and/or biopsy was achieved in 23 of 30 patients (CR 77 percent; 95 percent CI, 58-90) and investigator-confirmed CR was achieved in 24 out of 30 patients (CR 80 percent; 95 percent CI, 61-92). Twenty-one out of 23 responders had ongoing CR with 11 patients maintaining their CR for six months or more, and six patients had ongoing CR for 12 months or more. Median duration of response (DOR) was not reached. Treatment-related adverse events (TRAEs) occurred in 29 patients (54 percent). The most common (≥10 percent) were pollakiuria, dysuria, micturition urgency, and hematuria. Four patients (seven percent) had Grade 3 or higher TRAEs and one patient (two percent) had serious TRAEs. Two patients (four percent) had TRAEs leading to discontinuation and no deaths were reported. "Patients with NMIBC, who are unresponsive to BCG treatments, are at high risk for disease progression, and unfortunately, available treatment options remain limited," said Andrea Necchi,* M.D., of Italy's Vita-Salute San Raffaele University and the IRCCS San Raffaele Hospital and Scientific Institute and a presenting author of the study. "The results of TAR-200 observed in this study present a potential less-invasive option for patients in the future." "The current treatment options for patients with HR-NMIBC, who are unresponsive to BCG, remain limited and typically include repeated BCG therapy or radical cystectomy," said Christopher Cutie, M.D., Vice President, Disease Area Leader, Bladder Cancer, Janssen Research & Development, LLC. "Our goal is to transform the treatment landscape for patients with bladder cancer through innovative approaches that focus on bladder preservation and long-term survival." Bladder cancer is the tenth most common cancer worldwide, with more than 600,000 patients diagnosed each year, and more than 200,000 new cases every year across Europe alone.2 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 decline, radical cystectomy. Participants are randomized to one of three cohorts: treatment with TAR-200 in combination with cetrelimab (Cohort 1), TAR-200 alone (Cohort 2), or cetrelimab alone (Cohort 3). 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 drug delivery 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 and NMIBC in SunRISe-1 and SunRISe-3. 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. 3, 4 HR-NMIBC makes up 15–44 percent 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 percent cancer-specific survival if performed before muscle-invasive progression.5,6 Given that NMIBC typically affects older patients, many may be unwilling or unfit to undergo radical cystectomy.7 The high rates of recurrence and progression can pose significant morbidity and distress for these patients.6,8 About the Janssen Pharmaceutical Companies of Johnson & Johnson At Janssen, we're creating a future where disease is a thing of the past. We're the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Oncology, Immunology, Neuroscience, Cardiovascular, Pulmonary Hypertension, and Retina. Learn more at . Follow us at @JNJInnovMed and @JanssenUS. Janssen Research & Development, LLC and Janssen Biotech, Inc. belong to the Janssen Pharmaceutical Companies of Johnson & Johnson. 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 January 1, 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 , or on request from Johnson & Johnson. None of Janssen Research & Development, Janssen Biotech, Inc., the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. *Dr. Necchi has not been paid for any media work. 1 Necchi A, et al. Results From SunRISe-1 in Patients (Pts) With Bacillus Calmette–Guérin (BCG)-Unresponsive High-Risk Non–Muscle-Invasive Bladder Cancer (HR NMIBC) Receiving TAR-200 Monotherapy. ESMO 2023. Abstract. 2 Saginala K, Barsouk A, Aluru JS, Rawla P, Padala SA, Barsouk A. Epidemiology of bladder cancer. Med Sci (Basel). 2020;8(1):15. Published 2020 Mar 13. doi:10.3390/medsci8010015 3 Grab-Heyne K, et al. Intermediate and high-risk non-muscle-invasive bladder cancer: an overview of epidemiology, burden, and unmet needs. Front Oncol. 2023;13:1170124. 4 Lieblich A, et al. The management of non-muscle-invasive bladder cancer: A comparison of European and UK guidelines. J Clin Urol. 2018;11(2):144-148. 5 Claps F, et al. BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer: Current Treatment Landscape and Novel Emerging Molecular Targets. Int J Mol Sci. 2023;24(16):12596. 6 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. 7 Guancial EA, et al. Bladder cancer in the elderly patient: challenges and solutions. Clin Interv Aging. 2015; 10: 939–949. 8 Chamie K, et al. Recurrence of high-risk bladder cancer: A population-based analysis. Cancer. 2013. 119(17): 3219–3227. Media Contacts: Suzanne Frost +1 416-317-0304 Brian Kenney +1 215-620-0111 Investor Relations: Raychel Kruper [email protected] U.S. Medical Inquiries: +1 800-526-7736 SOURCE Janssen Pharmaceutical Companies of Johnson & Johnson