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Benjamin P. Saylor is associate editor of Urology Times, an Advanstar Communications publication.

The SOPHIA2 trial will assess the safety and efficacy of the UroActive implant in  men with SUI.

FDA, French ANSM greenlight pivotal trial of UroActive smart implant for male SUI

The new drug application for TAR-200 is supported by data from cohort 2 of the phase 2b SunRISe-1 trial.

FDA grants priority review to NDA for TAR-200 in BCG-unresponsive NMIBC

The Continuity Grant will support projects in bladder cancer and/or upper tract urothelial carcinoma that were previously scientifically reviewed, approved, and funded.

BCAN launches $1 million grant for bladder cancer research impacted by federal funding cuts

Alpha1H was granted a fast track designation in November 2023.

Meeting with FDA paves way for phase 3 trial of Alpha1H in NMIBC

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In these videos, expert surgeons demonstrate robot-assisted penile inversion vaginoplasty, single-stage metoidioplasty, and simple orchiectomy for transgender patients.

Transgender surgery: Videos demonstrate cutting-edge techniques

The FDA has accepted a new drug application (NDA) for zoliflodacin, an investigational first-in-class, single-dose, spiropyrimidinetrione oral antibiotic for the treatment of adult and pediatric patients 12 years and older with uncomplicated gonorrhea, Innoviva Specialty Therapeutics announced in a news release.

The Prescription Drug User Fee Act (PDUFA) target action date for the application is December 15, 2025.

Zoliflodacin is an oral antibiotic that inhibits type II topoisomerase, a bacterial enzyme that plays a key role in bacterial function and reproduction. According to the company, “If approved, zoliflodacin would be the first new antibiotic for treating gonorrhea in decades.”

The FDA has also granted a Qualified Infectious Disease Product designation to zoliflodacin, which enables the agent to benefit from priority review and market exclusivity.

“Today’s acceptance of the zoliflodacin NDA marks significant progress toward delivering health care providers with a potential new oral treatment option for uncomplicated gonorrhea, including infections caused by drug-resistant strains,” said David Altarac, MD, Chief Medical Officer of Innoviva Specialty Therapeutics, in the news release.

 “We look forward to working closely with the FDA during its review and, if approved, we are committed to expediting the availability of zoliflodacin to patients in the U.S.”

The NDA for zoliflodacin is supported by data from several clinical trials conducted through a collaboration with the Global Antibiotic Research & Development Partnership (GARDP). This portfolio of studies includes a pivotal phase 3 trial (NCT03959527) that evaluated zoliflodacin vs a standard of care (SOC) regimen (500 mg ceftriaxone intramuscular plus 1g oral azithromycin) in patients with uncomplicated gonorrhea.

Overall, the trial met its primary end point by demonstrating that zoliflodacin was non-inferior to the SOC regimen regarding microbiological response at the urogenital site at the test of cure visit (6 +/- 2 days following treatment). Specifically, the microbiological cure rate was 90.9% in the zoliflodacin arm vs 96.2% in the ceftriaxone/azithromycin arm, representing a difference of 5.3% (95% CI, 1.4% to 8.7%) across patients in the micro-intent-to-treat (ITT) population.

The 2 cohorts also demonstrated comparable results on the trial’s secondary end point of microbiological response at extragenital (rectal or pharyngeal) sites. Specifically, at pharyngeal sites, the cure rate was 79.2% in the zoliflodacin arm vs 78.6% in the ceftriaxone/azithromycin arm (difference, -0.67%; 95% CI, -20.8 to 16.3). At rectal sites, the cure rate was 87.3% and 88.6%, respectively (difference, 1.23%; 95% CI, -14.4 to 12.6).

Zoliflodacin was generally well-tolerated in the trial. Treatment-emergent adverse events (TEAEs) occurred in 46.2% of patients in the zoliflodacin arm vs 46.4% of patients in the ceftriaxone/azithromycin arm. The most common TEAEs in the zoliflodacin arm included headache (9.9%), neutropenia (6.8%), and leukopenia (3.9%).

There were no deaths or serious adverse events reported in either arm.

In total, the phase 3 trial included 930 patients with uncomplicated gonorrhea, including patients living with HIV. The study enrolled participants across 16 clinical trial sites in the US, Belgium, the Netherlands, South Africa, and Thailand.

According to Innoviva, the phase 3 study was “the largest clinical trial ever conducted for a new treatment against gonorrhea infection.”

Those enrolled in the study were randomly assigned 2:1 to receive 3 g single-dose, oral zoliflodacin (n = 621) or to 500 mg ceftriaxone intramuscular plus 1g oral azithromycin (n = 309). The primary end point was microbiological cure by culture at urogenital sites in the micro-ITT populations, with a non-inferiority margin of 12%. The trial’s secondary end point was microbiological cure at extragenital sites.

“This important milestone demonstrates the crucial role that public-private partnerships can play in tackling the escalating global antimicrobial resistance crisis,” said Manica Balasegaram, Executive Director of GARDP, in the news release.

 “If zoliflodacin is approved, this collaboration paves the way for millions of people across the world to get access to a potentially powerful new drug to treat multidrug-resistant gonorrhea.”

1. Innoviva Specialty Therapeutics receives FDA New Drug Application acceptance for zoliflodacin, a first-in-class oral antibiotic for uncomplicated gonorrhea in adults. News release. Innoviva Specialty Therapeutics. Published online and accessed June 10, 2025. https://innovivaspecialtytherapeutics.com/innoviva-specialty-therapeutics-receives-fda-new-drug-application-acceptance-for-zoliflodacin-a-first-in-class-oral-antibiotic-for-uncomplicated-gonorrhea-in-adults/

2. FDA Grants Priority Review for Zoliflodacin New Drug Application for the Treatment of Uncomplicated Gonorrhea and Assigns Target PDUFA Date of December 15, 2025. News release. Innovia Specialty Therapeutics, Inc. Published online and accessed June 12, 2025. https://www.businesswire.com/news/home/20250612432209/en/FDA-Grants-Priority-Review-for-Zoliflodacin-New-Drug-Application-for-the-Treatment-of-Uncomplicated-Gonorrhea-and-Assigns-Target-PDUFA-Date-of-December-15-2025 

3. Luckey A, Broadhurst H, Daram P, et al. Oral zoliflodacin is non-inferior to a combination of ceftriaxone and azithromycin for treatment of uncomplicated urogenital gonorrhoea: results of a large global Phase 3 randomised controlled trial. Presented at: European Society of Clinical Microbiology and Infectious Disease Global Congress. April 27-30, 2024. Barcelona, Spain. https://gardp.org/wp-content/uploads/2024/04/Zoli001-Topline-ECCMID2024_final_V1.0_23Apr2024_.pdf

The FDA has accepted the NDA for zoliflodacin, a novel oral antibiotic for treating uncomplicated gonorrhea in patients aged 12 and older. Zoliflodacin, which inhibits type II topoisomerase, has been granted a Qualified Infectious Disease Product designation, allowing for priority review. Clinical trials, including a pivotal phase 3 study, demonstrated that zoliflodacin is non-inferior to the standard regimen of ceftriaxone and azithromycin. The trials showed comparable microbiological cure rates at urogenital and extragenital sites, with zoliflodacin being generally well-tolerated and no serious adverse events reported.

The NDA is supported by a pivotal phase 3 trial of zoliflodacin vs ceftriaxone plus azithromycin in patients with uncomplicated gonorrhea. 

News

FDA accepts new drug application for zoliflodacin for uncomplicated gonorrhea

Dr. De La Cerda provides an overview of a patient case involving a 68 year-old male presenting with severe back pain, with an analysis of the clinical presentation, workup, and medical history.

Bone Predominant mCRPC Patient Case

Video content above is prompted by the following:

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The FDA has accepted a Biologics License Application (BLA) seeking approval of nivolumab (Opdivo) co-formulated with Halozyme’s proprietary recombinant human hyaluronidase (rHuPH20), or subcutaneous nivolumab, for the treatment of patients with all previously approved solid tumor indications for nivolumab as a monotherapy, monotherapy maintenance following completion of combination therapy with nivolumab plus ipilimumab (Yervoy), or in combination with chemotherapy or cabozantinib (Cabometyx).

Nivolumab is currently approved under several indications, including in combination with ipilimumab for the first-line treatment of patients with intermediate- or poor-risk advanced renal cell carcinoma (RCC), in combination with cabozantinib for the first-line treatment of patients with advanced RCC, for the treatment of patients with advanced RCC who have received prior anti-angiogenic therapy, and in combination with cisplatin and gemcitabine for the first-line treatment of patients with unresectable or metastatic urothelial carcinoma.

The FDA is set to have a decision regarding the subcutaneous nivolumab formulation on or by December 29, 2024.

 According to a news release from Bristol Myers Squibb,

 approval of the formulation would make it the first and only subcutaneously administered PD-1 inhibitor.

“We believe subcutaneous nivolumab has the potential to make a significant difference in the lives of patients, which is reinforced by the FDA’s acceptance of our application,” said Gina Fusaro, PhD, vice president, global program lead, Bristol Myers Squibb, in the news release.

 “Opdivo is a foundational PD-1 inhibitor approved for many different types of cancer, and our continued investment in research that puts patients first remains a priority. If approved by the FDA, the subcutaneous administration of nivolumab would provide patients and their physicians with a new option that delivers the same well-known benefits as IV Opdivo but with the improved convenience of an injection administered in 3 to 5 minutes rather than a 30-to-60-minute infusion.”

The BLA submission is supported by findings from the phase 3 CheckMate-67T trial (NCT04810078), in which subcutaneous nivolumab met the study’s co-primary end points by demonstrating noninferiority to intravenous (IV) nivolumab regarding time average nivolumab serum concentration over 28 days (C

; geometric mean ratio [GMR}, 2.098; 90% CI, 2.001-2.200) and minimum serum concentration at a steady state (C

Data from the study, which were presented at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium in San Francisco, California,

 also showed that subcutaneous nivolumab demonstrated noninferiority to IV nivolumab in the key powered secondary end point of objective response rate (ORR). Specifically, the subcutaneous arm demonstrated an ORR of 24.2% (95% CI, 19.0-30.0) per blinded independent central review (BICR), compared with 18.2% (95% CI, 13.6-23.6) in the IV arm.

The safety profile for subcutaneous nivolumab was consistent with that of the IV formulation. Among patients who received the subcutaneous formulation, 8.1% experienced injection-site reactions, with all being low-grade and transient. Deaths due to study drug toxicity occurred in 3 patients in the subcutaneous arm and 1 patient in the IV arm. Most deaths that occurred during the study were due to disease progression.

In total, the phase 3, open-label CheckMate-67T trial enrolled 495 patients with advanced or metastatic ccRCC who had received prior systemic therapy. Patients were randomly assigned 1:1 to receive 1200 mg subcutaneous nivolumab plus rHuPH20 every 4 weeks (n = 248) or to 3 mg/kg IV nivolumab every 2 weeks (n = 247) for up to 2 years of treatment or until disease progression, unacceptable toxicity, withdrawal, or death.

The co-primary pharmacokinetic end points for noninferiority testing were C

 of subcutaneous nivolumab vs IV nivolumab. The key secondary end point was ORR per BICR.

Final completion of the CheckMate-67T study is expected in January 2026.

1. U.S. Food and Drug Administration accepts Bristol Myers Squibb’s application for subcutaneous nivolumab (nivolumab and hyaluronidase). News release. Bristol Myers Squibb. May 6, 2024. Accessed May 7, 2024. https://news.bms.com/news/corporate-financial/2024/U.S.-Food-and-Drug-Administration-Accepts-Bristol-Myers-Squibbs-Application-for-Subcutaneous-Nivolumab-nivolumab-and-hyaluronidase/default.aspx

2. Bristol Myers Squibb announces updated action date by the U.S. Food and Drug Administration for subcutaneous nivolumab (nivolumab and hyaluronidase). News release. Published online and accessed May 21, 2024. https://investors.bms.com/iframes/press-releases/press-release-details/2024/Bristol-Myers-Squibb-Announces-Updated-Action-Date-by-the-U.S.-Food-and-Drug-Administration-for-Subcutaneous-Nivolumab-nivolumab-and-hyaluronidase/default.aspx

3. George S, Bourlon TB, Chacon MR, et al. Subcutaneous nivolumab (NIVO SC) vs intravenous nivolumab (NIVO IV) in patients with previously treated advanced or metastatic clear cell renal cell carcinoma (ccRCC): Pharmacokinetics (PK), efficacy, and safety results from CheckMate 67T. 

4. A study of subcutaneous nivolumab versus intravenous nivolumab in participants with previously treated clear cell renal cell carcinoma that is advanced or has spread (CheckMate-67T). ClinicalTrials.gov. Last updated March 1, 2024. Accessed May 7, 2024. https://clinicaltrials.gov/study/NCT04810078

The FDA is set to have a decision regarding the subcutaneous nivolumab formulation on or by December 29, 2024. 

FDA accepts BLA for subcutaneous nivolumab in solid tumors

Treatment with BCG plus mitomycin demonstrated comparable efficacy and safety to BCG alone while leading to fewer treatment discontinuations and fewer BCG doses in patients with non–muscle invasive bladder cancer (NMIBC), according to data from the phase 3 ANZUP 1301 trial (NCT02948543) presented at the 

2025 American Society of Clinical Oncology (ASCO) Annual Meeting

According to presenting author Professor Dickon Hayne, these findings have important implications in the context of the ongoing BCG shortage.

“BCG has been the mainline treatment for high-risk NMIBC cancer for more than half a century, usually given with 6-week induction and then maintenance to at least a year. According to guidelines, the ideal regimen and indeed, strain, of BCG is unknown,” Hayne explained during the presentation. “There's also a global BCG shortage, and BCG supply, by best estimates, falls 30% to 50% short of demand. Some evidence already exists of a benefit of adding mitomycin to BCG.”

In total, the ANZUP 1301 trial enrolled 501 patients who were randomly assigned to receive intravesical BCG plus mitomycin (n = 249) or intravesical BCG alone (n = 252). Female patients comprised 22% and 16% of each study arm, respectively. Treatment was not blinded due to the different dosing schedules in each arm.

The primary end point was disease-free survival (DFS). Secondary end points included complete response rate, time to recurrence, time to progression, overall survival, and safety. The trial also assessed quality of life outcomes, which Hayne noted will be presented at a later date.

At the current analysis, data showed a 24-month DFS of 75% (95% CI, 70 to 81) in the mitomycin plus BCG arm vs 71% (95% CI, 65 to 77) in the BCG alone arm (HR, 0.87; 95% CI, 0.65 to 1.16; 

 = .34). Further, 90% (95% CI, 85 to 93) of patients who received mitomycin plus BCG vs 86% (95% CI, 81 to 90) of patients who received BCG alone achieved a complete response on cystoscopy at the 3-month timepoint (RR, 1.05; 95% CI, 0.98 to 1.12; 

Data also showed that 80% (95% CI, 75 to 85) of patients in the mitomycin plus BCG arm vs 75% (95% CI, 70 to 81) in the BCG alone arm remained recurrence-free at 24 months (HR, 0.85; 95% CI, 0.61 to 1.19; 

 = .35). Further, 92% (95% CI, 89 to 96) of patients in the combination arm remained free from progression at 24 months compared with 90% of patients in the monotherapy arm (HR, 0.68; 95% CI, 0.41 to 1.11; 

At 5 years, overall survival was 88% in the combination arm compared with 87% in the monotherapy arm (HR, 1.06; 95% CI, 0.60 to 1.86; 

 = .85). Death due to bladder cancer occurred in 7 patients in the mitomycin plus BCG arm and 5 patients in the BCG alone arm.

Hayne added, “As stated already, the primary outcome measure for the study was disease-free survival, stratified by T stage and the presence or absence of CIS. However, when the study was conceived, high-grade Ta disease was considered high-risk NMIBC in its own right. However, more recent EAU risk stratifications would put a lot of these patients into an intermediate risk group. So, we decided to perform an exploratory post-hoc subgroup analysis, analyzing the patients by the pre-specified stratification criteria, as in T1 or the presence or absence of CIS, but also to look at the risk group of higher-risk, as in any T1 disease or those with CIS, vs the lower-risk group, high-grade Ta with no CIS.”

In this analysis looking at DFS, the HR was 0.69 in the high-risk group and 1.28 in the low-risk group (

“You can see that the addition of mitomycin to the subgroup at higher risk deserves further investigation,” Hayne noted.

Regarding safety, the proportion of adverse events (AEs) between both arms was similar. The incidence of grade 3 or higher AEs was low across both cohorts.

In total, there were 3 deaths on treatment: 1 due to myocardial infarction (BCG only), 1 due to sepsis (BCG only), and 1 due to BCG-related mycotic aortic aneurysm (mitomycin plus BCG). There was another instance of mycotic aortic aneurysm in the BCG only cohort, as well as 1 report of myasthenia gravis in the combination arm.

Data also showed that although the total number of treatment instillations was greater in the combination arm (4033 vs 3383), there was a 40% reduction in the number of BCG doses required with the mitomycin plus BCG regimen (2056 vs 3383). The median number of BCG doses per patient was 9 in the combination arm and 16 in the monotherapy arm.

Overall, 78% of patients in the mitomycin plus BCG arm complete more than 75% of planned treatment doses vs 68% of patients in the BCG alone arm. Additionally, 75% of patients in the combination arm completed all doses (100%) of planned treatment compared with 64% of patients in the monotherapy arm.

Based on these data, Hayne concluded, “[In] ANZUP 1301, which is one of the largest non–muscle invasive bladder cancer studies to be reported in recent times, BCG plus mitomycin shows similar efficacy and safety to BCG alone with fewer treatment discontinuations, 40% fewer BCG doses required, and we've seen that high-risk patients may do better with the addition of the mitomycin. BCG plus mitomycin is a good alternative to BCG alone. Wide adoption of this regimen could go some way to alleviate the global BCG shortage.”

1. Hayne D, Zhang A, Thomas H, et al. Mitomycin plus BCG as adjuvant intravesical therapy for high-risk, non–muscle-invasive bladder cancer: A randomized phase 3 trial (ANZUP 1301). 

. 2025;43 (suppl 17; abstr LBA4504). doi:10.1200/JCO.2025.43.17_suppl.LBA4504

The phase 3 ANZUP 1301 trial evaluated the efficacy and safety of BCG plus mitomycin compared to BCG alone in patients with non–muscle invasive bladder cancer (NMIBC). Results showed comparable efficacy and safety between the two regimens, with the combination therapy leading to fewer treatment discontinuations and a 40% reduction in BCG doses. The study highlighted the potential of BCG plus mitomycin as an alternative treatment, especially in the context of a global BCG shortage. High-risk patients may benefit more from the addition of mitomycin.

According to the authors, the mitomycin/BCG regimen could alleviate some of the burden of the global BCG shortage.  

Data supports mitomycin plus BCG as alternative to BCG alone in NMIBC

First-line nivolumab (Opdivo) plus ipilimumab (Yervoy) continued to show improved survival and durable response benefits vs sunitinib (Sutent) in patients with previously untreated advanced renal cell carcinoma (aRCC), according to final results from the phase 3 CheckMate-214 trial (NCT02231749) presented at the 

2025 American Society of Clinical Oncology Annual Meeting

In total, the CheckMate-214 trial enrolled 1096 patients with aRCC who were randomly assigned 1:1 to receive nivolumab plus ipilimumab or sunitinib. Initial data from the trial, which led to FDA approval of the combination in April 2018, showed that nivolumab plus ipilimumab significantly improved overall survival (OS) and objective response rate (ORR) vs sunitinib in this population.

Robert J. Motzer, MD, of Memorial Sloan Kettering Cancer Center, presented data on the final analysis of the trial, which is the longest follow-up (median follow-up, 9.3 years) of a first-line checkpoint inhibitor combination in aRCC.

In patients with IMDC intermediate or poor-risk, data showed sustained benefits OS, progression-free survival, and duration of response (DOR) with the nivo/ipi combination.

In these patients, the median OS was 46.7 months (95% CI, 35.0 to 55.7) in the nivo/ipi arm vs 26.0 months (95% CI, 21.8 to 32.6) in the sunitinib arm (HR, 0.69; 95% CI, 0.59 to 0.81). Median PFS was 12.4 months (95% CI, 8.7 to 16.8) in the treatment arm vs 8.5 months (95% CI, 7.0 to 11.1) in the sunitinib arm (HR, 0.73; 95% CI, 0.61 to 0.87). Additionally, the median DOR was 82.8 months (95% CI, 54.1 to NE) in the nivo/ipi arm vs 19.8 months (95% CI, 16.4 to 26.4) in the sunitinib arm (HR, 0.48; 95% CI, 0.33 to 0.69).

In the IMDC favorable-risk population, nivo/ipi was associated with a 13% improvement in OS at 9 years (HR, 0.80).

Motzer added, “Sunitinib still is the winner in progression-free survival compared to nivo/ipi. When responses do occur with nivo/ipi, they're considerably more durable.”

There was also an OS advantage with nivo/ipi observed in the intent to treat (ITT) population. At a median follow-up of 9 years, the median OS was 52.7 months (95% CI, 45.8 to 64.4) in the nivo/ipi arm vs 37.8 months (95% CI, 31.9 to 43.8) in the sunitinib arm (HR, 0.71; 95% CI, 0.62 to 0.82). The OS benefit was consistent across subgroups within the ITT population, including in the intermediate-risk group and those with sarcomatoid features.

The advantage in PFS with nivo/ipi in the ITT population was also maintained from 24 months onward. At a median of 9 years of follow-up, the median PFS was 12.4 months (95% CI, 9.9 to 16.6) in the nivo/ipi arm vs 12.3 months (95% CI, 9.8 to 15.2) in the sunitinib arm (HR, 0.88; 95% CI, 0.76 to 1.04).

The combination of nivo/ipi also demonstrated improvements in ORR vs sunitinib in both the ITT population and in patients with IMDC intermediate/poor risk. In the ITT population, the ORR was 39.5% with nivo/ipi vs 33.0% with sunitinib. Likewise, in the intermediate/poor risk population, the ORR was 42.4% in the nivo/ipi arm vs 27.5% in the sunitinib arm.

At the time of data report, 58% of patients in the ITT population and 59% of patients in the IMDC intermediate/poor risk population who received nivo/ipi remain in response. Further, 80% of patients in the ITT population and 84% of patients in the IMDC intermediate/poor risk population had an ongoing complete response.

Data also showed a DOR benefit with nivo/ipi vs sunitinib. Specifically, the median DOR was 76.2 months (95% CI, 59.0 to NE) in the nivo/ipi arm vs 25.1 months (95% CI, 19.8 to 33.2) in the sunitinib arm (HR, 0.53; 95% CI, 0.38 to 0.73).

Nearly all patients on trial had discontinued study therapy at the time of this analysis. Discontinuation due to disease progression was reported in 49% of patients in the nivo/ipi arm and 68% of patients in the sunitinib arm.

Treatment-related adverse events (AEs) were observed in 94% of patients in the nivo/ipi arm and 98% of patients in the sunitinib arm. Grade 3 or higher events were reported in 49% of patients in the nivo/ipi arm and 64% of patients in the sunitinib arm.

Immune-mediated AEs (imAEs) were as expected, according to Motzer, with the most common being related to GI, skin, thyroid, and liver. Most imAEs occurred early in the course of treatment. Overall, 31% of patients in the nivo/ipi arm received corticosteroids to manage imAEs.

“In summary, CheckMate-214 provides the longest reported follow-up to date of any immune-oncology combination therapy for first-line clear cell RCC,” Motzer concluded during the presentation. “This final analysis of this study continues to support nivo+ipi as a standard of care for patients with untreated RCC. In addition, subcutaneous nivolumab has been reported to show clinical equipoise to standard IV dosing and can be considered as an alternative for maintenance nivolumab, following nivo+ipi doublet in patients with advanced RCC.”

1. Choueiri T, Escudier B, McDermott D, et al. Nivolumab plus ipilimumab vs sunitinib for first-line treatment of advanced renal cell carcinoma: Final analysis from the phase 3 CheckMate 214 trial. 

. 2025;43 (suppl 17; abstr 4505). doi:10.1200/JCO.2025.43.16_suppl.4505

The CheckMate-214 trial demonstrated that nivolumab plus ipilimumab significantly improved survival and response rates compared to sunitinib in patients with advanced renal cell carcinoma. With a median follow-up of 9.3 years, the combination showed sustained benefits in overall survival, progression-free survival, and duration of response, particularly in intermediate and poor-risk patients. The trial confirmed nivolumab plus ipilimumab as a standard of care, with durable responses and manageable adverse events. Subcutaneous nivolumab may offer an alternative to intravenous dosing for maintenance therapy in advanced RCC.

"This final analysis of this study continues to support nivo+ipi as a standard of care for patients with untreated RCC," says Robert J. Motzer, MD. 

Nivolumab/ipilimumab continues to show improved survival, durable response in aRCC

Findings of an exploratory analysis of the phase 3 NIAGARA trial (NCT03732677) evaluating perioperative durvalumab (Imfinzi) plus neoadjuvant chemotherapy (NAC) with radical cystectomy vs NAC with radical cystectomy alone appear to support the utility of circulating tumor DNA (ctDNA) as a biomarker in the neoadjuvant setting.

The findings also lend further credence to this muscle-invasive bladder cancer treatment regimen, investigators reported at the 

“Essentially, what we showed was, at all points, ctDNA was really strongly prognostic. We also showed quite high levels of ctDNA clearance, and these levels of ctDNA clearance were higher when you added durvalumab to neoadjuvant chemotherapy,” said Thomas B. Powles, MBBS, MRCP, MD, director of the Barts Cancer Centre at St. Bartholomew’s Hospital in London, United Kingdom.

During his ASCO 2025 presentation, Powles provided a summary of NIAGARA, the results of which were published in 

 The investigators reported that perioperative durvalumab plus NAC with radical cystectomy vs NAC with radical cystectomy alone was associated with improved event-free survival (EFS) (HR=0.68; 95% CI: 0.56-0.82, 

<. 0001) and overall survival (HR=0.75; 95% CI: 0.59-0.93, 

= .0106), a pathological complete response rate of 37.3% vs 27.5%, radical cystectomy rates of 88% vs 83%, and a tolerable and manageable safety profile.

 The FDA approved neoadjuvant durvalumab in combination with gemcitabine and cisplatin, followed by adjuvant durvalumab monotherapy following radical cystectomy, for adult patients with muscle-invasive bladder cancer on March 28, 2025.

“There's been increased attention to circulating tumor DNA recently,” said Powles, although he noted that much of the data reported to date have been in the adjuvant setting as opposed to the neoadjuvant setting.

Powles explained that ctDNA was assessed with the Signatera assay, and it was measured at baseline (prior to therapy), after NAC/prior to cystectomy, and following cystectomy. Of 1063 patients in NIAGARA’s intent-to-treat (ITT) population, the total biomarker evaluable population (BEP) was 462, and then 460 at baseline, 422 pre-cystectomy, and 345 post cystectomy. Compared to the ITT population, the baseline characteristics of the BEP were found to be generally similar. More patients (95) in the BEP underwent cystectomy compared with the ITT population (86).

Powles reported a decrease of ctDNA-positivity through the course of the study. At baseline, 57% of the BEP was ctDNA-positive; after NAC, 22% was ctDNA-positive; and 9% was ctDNA-positive following cystectomy. For the durvalumab arm, these figures were 58%, 19%, and 10%, respectively, whereas in the comparator arm the rates were 55%, 26%, and 8%, respectively.

According to Powles, at baseline, ctDNA detection was prognostic for EFS (HR=0.42; 95% CI: 0.30-0.60). Treatment with durvalumab appeared to confer EFS benefit to patients regardless of ctDNA status, with an HR of 0.45 (95% CI: 0.24-0.84) for ctDNA-negative patients and 0.73 (95% CI: 0.51-1.05) for ctDNA-positive patients.

The exploratory analysis of the phase 3 NIAGARA trial supports the use of circulating tumor DNA (ctDNA) as a prognostic biomarker in the neoadjuvant setting for muscle-invasive bladder cancer. The study demonstrated that perioperative durvalumab combined with neoadjuvant chemotherapy and radical cystectomy improved event-free and overall survival compared to chemotherapy and cystectomy alone. The trial also highlighted the significant ctDNA clearance rates with durvalumab addition. The FDA approved durvalumab for muscle-invasive bladder cancer, reinforcing its role in combination with chemotherapy in this context.

The findings also lend further credence to the muscle-invasive bladder cancer treatment regimen, investigators reported.

Aaron Grotas, MD

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