Johnson & Johnson announced results from the primary analysis of its ongoing Phase 2b SunRISe-4 study, which evaluated the combination of INLEXZO (gemcitabine intravesical system) and intravenous cetrelimab in patients with muscle invasive bladder cancer (MIBC) who are ineligible for or refuse neoadjuvant platinum-based chemotherapy and are scheduled for radical cystectomy. The findings were presented as a late-breaking oral presentation at the European Society of Medical Oncology (ESMO) 2025 Congress.
According to Andrea Necchi, M.D., of Vita-Salute San Raffaele University and IRCCS San Raffaele Hospital and Scientific Institute, "The SunRISe-4 data show that the ability of INLEXZO to provide extended local delivery of a cancer medication in the bladder, together with the systemic PD-1 inhibitor cetrelimab, may lead to a significant rate of complete pathological responses while remaining manageable and safe for patients. These early results support the potential role of neoadjuvant combination therapy in future muscle invasive trials."
In the study, cohort 1 (101 patients) received four cycles of INLEXZO plus IV cetrelimab every 21 days, while cohort 2 (58 patients) received four cycles of IV cetrelimab monotherapy on the same schedule. The centrally confirmed pathologic complete response rate was 38% for the combination group and 28% for monotherapy. Pathological overall response rates were 53% and 44%, respectively. One-year recurrence-free survival was observed at 77% in the combination group and 64% in the monotherapy group.
No new safety concerns were identified. In cohort 1, 81.2% experienced treatment-related adverse events, with 15.8% at Grade ≥3 severity; in cohort 2, these rates were 51.7% and 10.3%. Common side effects included dysuria, pollakiuria, and fatigue. Serious treatment-related adverse events occurred in 13.9% of patients receiving both drugs, compared to 5.2% receiving only cetrelimab. No treatment-related deaths were reported, and immune-related adverse events were generally manageable.
Exploratory results from urine tumor DNA and circulating tumor DNA analyses suggest these biomarkers may help predict residual disease after neoadjuvant therapy in this patient population.
Christopher Cutie, M.D., Vice President, Disease Area Leader, Bladder Cancer at Johnson & Johnson Innovative Medicine, commented, "The current treatment landscape offers few alternatives to cisplatin-based chemotherapy prior to radical cystectomy for patients with muscle-invasive bladder cancer. With no signs of detectable cancer in more than a third of patients prior to surgery, we are looking forward to following up on recurrence-free survival endpoints in these patients post-cystectomy."
Bladder cancer is one of the most common cancers worldwide, ranking ninth globally according to Globocan’s latest statistics (https://gco.iarc.who.int/media/globocan/factsheets/populations/900-world-fact-sheet.pdf). Muscle invasive bladder cancer is an aggressive form that accounts for about one-fifth of new cases globally and typically requires surgical removal of the bladder and surrounding organs, often followed by urinary diversion procedures (https://bcan.org/bladder-removal-surgery/). Standard pre-surgical treatment involves cisplatin-based chemotherapy, but approximately half of all patients are unable to receive it due to factors such as kidney function or other health issues.
INLEXZO is currently approved by the U.S. Food and Drug Administration for treating adult patients with Bacillus Calmette-Guérin-unresponsive, non-muscle invasive bladder cancer with carcinoma in situ, with or without papillary tumors.
The SunRISe-4 trial is not intended as a registrational trial for either INLEXZO or cetrelimab.
For more information about INLEXZO, visit https://www.INLEXZO.com.
Johnson & Johnson stated that forward-looking statements regarding product development are subject to risks including research challenges, regulatory approvals, manufacturing difficulties, competition, product safety concerns, changes in healthcare regulations, among others. More information can be found at http://www.jnj.com or through filings with the Securities and Exchange Commission at http://www.sec.gov.