September 17, 2025
5 min read
Key takeaways:
- Most patients with non-muscle-invasive bladder cancer who received TAR-200 with gemcitabine achieved complete response.
- Multiple patients have had responses persist for more than 2 years.
A novel drug-releasing system for bladder cancer that allows for sustained delivery of medicine for several weeks recently received FDA approval after producing superior and longer-lasting response results than historical standards.
Data from a phase 2b study showed more than 80% of patients with bacillus Calmette-Guérin (BCG)-unresponsive, high-risk non-muscle-invasive bladder cancer who received TAR-200, a small drug releasing system placed in the bladder that delivered gemcitabine over a 3-week period, had a complete response to treatment.
Data derived from Daneshmand S, et al. J Clin Oncol. 2025;doi:10.1200/JCO-25-01651.
The FDA on Sept. 9 approved TAR-200, since renamed Inlexzo (gemcitabine intravesical system, Johnson & Johnson), for treatment of adult patients with BCG-unresponsive, non-muscle-invasive bladder cancer with carcinoma in situ, with or without papillary tumors. “Absolutely remarkable results,” Siamak Daneshmand, MD, professor of urology and director of clinical research at Keck School of Medicine at USC, told Healio.
Siamak Daneshmand
“Not only is it working in most of the patients, but the results are durable,” he added. “Some patients are responding beyond 2 years. Not all the patients are out that far, but approximately half of the patients maintained a complete responses at 1 year . This was the highest complete-response rate we had seen in non-muscle-invasive bladder cancer in a novel delivery mechanism. Obviously, we’re super excited about this.”
‘Love to have other options’
Standard of care for high-risk non-muscle-invasive bladder cancer includes transurethral resection of bladder tumor and intravesical BCG therapy, according to study background.
However, between 12% and 60% of patients who receive this care have disease recurrence within a year, and 2% to 15% experience progression.
These individuals often develop BCG-unresponsive cancer.
Standard of care for BCG-unresponsive disease is radical cystectomy, but less than 20% of patients undergo this procedure due to its high morbidity and negative impact on quality of life.
“Most patients want to retain their bladder,” Daneshmand said. “They want their bladder cancer treated, but they don’t want to lose their bladder because the surgery results in changes in lifestyle. Not to mention, there’s a mortality rate associated with the operation [about 2% to 5% die within 90 days]. It is a complex surgery, and we do it when necessary. It’s very effective, but we’d love to have additional options available to treat patients.”
Other FDA-approved treatments for BCG-unresponsive disease include intravesical nadofaragene firadenovec-vncg (Adstiladrin, Ferring Pharmaceuticals) and intravesical nogapendekin alfa inbakicept-pmln (Anktiva, ImmunityBio) with BCG. Systemic therapies, such as pembrolizumab (Keytruda, Merck), are not used much due to limited long-term response rates and adverse events.
“We’re used to seeing complete response rates at 3 months in the 50% to 60% range,” Daneshmand said. “The other half of patients have persistent, recurrent or progressive disease.”
Intravesical gemcitabine has demonstrated effectiveness in previous research, but its short dwell time in the bladder likely limited its efficacy and durability.
Researchers sought to change that with TAR-200.
TAR-200
Inlexzo is a porous, pretzel-shaped device approximately the size of a quarter. It can be uncoiled and placed in a catheter, then it returns to shape in the bladder.
Removal is like taking out a ureteral stent.
“There’s nothing new to learn here. It’s very, very easy,” Daneshmand said.
It was originally developed to treat interstitial cystitis with lidocaine.
“It was not a big leap to think we can put a chemotherapy drug in this and treat bladder cancer, as well,” Daneshmand said.
An early phase 1 trial with gemcitabine demonstrated promise in patients with bladder cancer who were scheduled to undergo radical cystectomy. The device was inserted and remained in the bladder for a couple weeks and then removed for two cycles.
“Some patients actually had their disease eradicated prior to the bladder removal,” Daneshmand said.
That led to the SunRISe trials.
SunRISe-1 included patients with BCG-unresponsive carcinoma in situ with or without papillary disease. The phase 2b parallel cohort study included an Inlexzo monotherapy arm, one with Inlexzo plus PD-1 inhibitor cetrelimab (JNJ-63723283, Janssen) and another with cetrelimab alone.
The Inlexzo monotherapy cohort consisted of 85 patients (median age, 71 years; range, 40-88; 80% men; 87.1% white).
Patients received TAR-200 once every 3 weeks for the first 6 months, then once every 12 weeks through 2 years.
Complete response served as the primary endpoint. Duration of response and OS served as secondary endpoints.
‘People are excited’
The Inlexzo monotherapy cohort had a complete response rate of 82.4% (95% CI, 72.6%-89.8%).
The cohort had a 3-month complete-response rate of 78.8%, a 6-month rate of 58.8% and a 1-year rate of 45.9%.
“Seeing something work 80% of the time was pretty remarkable,” Daneshmand said.
At median follow-up of 20.2 months, median duration of response was 25.8 months (95% CI, 8.3-not estimated).
Among responders, 52.9% had a response for at least 1 year and 15.7% completed 2 years of treatment.
The Inlexzo plus cetrelimab cohort had a complete response rate of 67.9% and the cetrelimab monotherapy cohort had a complete response rate of 46.4%.
“We thought combining TAR-200 with a PD-1 inhibitor might work better, but it turned out the response rates were so high with the monotherapy that they ended up closing the other cohorts and concentrating on rapid accrual to the TAR200 monotherapy,” Daneshmand said.
The Inlexzo monotherapy cohort had an OS of 98.7% at 6 months and 94.7% at 1 year. In all, 8.2% of the cohort died, but no deaths occurred due to treatment.
Treatment-related adverse events occurred in 83.5% of patients. The most frequent events included pollakiuria (43.5%), dysuria (40%), micturition urgency (24.7%) and urinary tract infection (21.2%).
Grade 3 or worse adverse events occurred in 12.9% of participants, the most common being urinary tract infection (4.7%). Treatment-related serious adverse events occurred in 5.9% of the cohort.
“The other part [to this study was], how is this placed? How is this removed? And how do patients tolerate this? The answer is very well,” Daneshmand said. “Patients are doing quite well for the most part. It’s an easy insertion and removal process. The insertion of the drug and the device is through a special catheter that’s placed in the bladder. Practitioners are extremely familiar with that process, but also patients are very familiar with it. These are patients who’ve had at least two cycles of BCG, and all the BCG is placed via a catheter, so this is not novel to them.”
Researchers acknowledged study limitations, including the noncomparative design, but they wrote that such a study would be unethical.
“This is one more chance to treat resistant tumors so that patients can maintain and keep their bladder,” Daneshmand said.
“People are excited about it,” he added. “I’m hoping that it’ll be in our hands very soon so that we can deliver this into patients.”
‘Just the beginning’
Inlexzo is currently being investigated in other trials, too.
SunRISe-3 is evaluating Inlexzo vs. BCG in patients who have not received BCG treatment. That includes more than 1,100 patients worldwide, Daneshmand said.
“There’s a shortage of BCG around the globe, mostly in the U.S.,” he explained. “We’d love to have some alternatives.”
Sequencing medications will be a key part of future investigations. So will the evaluation of other drugs.
The Moonrise trials are investigating the drug-delivery system with erdafitinib (Balversa, Janssen) in patients with intermediate-risk non-muscle-invasive bladder cancer and an FGFR3 mutation.
“This is just the beginning,” Daneshmand said. “It’s just a matter of imagination and technology in terms of what can be delivered through a sustained release within the bladder.
“We’re quite excited about the future.”
References:
For more information:
Siamak Daneshmand, MD, can be reached at daneshma@med.usc.edu.
Sources/Disclosures
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Disclosures:
Johnson & Johnson supported this study. Daneshmand reports stock and other ownership interests in Taris; honoraria from Allergan, AstraZeneca, Bausch + Lomb, Bristol Myers Squibb, CG Oncology, enGene, Eli Lilly & Co., Ferring, ImmunityBio, Johnson & Johnson, Pacific Edge, Pfizer, Photocure, Protara Therapeutics, Sesen Bio, Storz and UroGen Pharma; consulting or advisory roles with AstraZeneca, Bristol Myers Squibb/Pfizer, CG Oncology, enGene, Ferring, ImmunityBio, Johnson & Johnson/Janssen, Pacific Edge, Pfizer, Photocure, Taris, UroGen Pharma and UroToday; research funding from Photocure; and travel, accommodations and expenses from Janssen Oncology and Photocure. Please see the study for all other authors’ relevant financial disclosures.
