AUA 2025 recap: Urologic oncology trials in progress

The 2025 American Urological Association (AUA) Annual Meeting in Las Vegas, Nevada featured several sessions on ongoing clinical trials in urologic oncology. These spanned several up-and-coming agents in the non–muscle invasive bladder cancer (NMIBC) space, as well as potential practice-informing studies in both prostate and kidney cancer.

Take a look through some of the notable studies that were spotlighted during this year’s meeting.

These trials are set to provide insights on treatment options in bladder, prostate, and kidney cancer.

Bladder

MoonRISe-1

The phase 3 MoonRISe-1 trial (NCT06319820) is assessing the safety and efficacy of TAR-210 vs intravesical chemotherapy in patients who have intermediate-risk NMIBC with susceptible FGFR alterations.¹ TAR-210 is intravesical erdafitinib releasing system.

In total, the study plans to enroll 540 patients. Patients will be randomly assigned to receive TAR-210 or to chemotherapy with either intravesical mitomycin C or gemcitabine. The primary end point is disease-free survival (DFS). Study completion is expected in June 2028.

ADVANCED-2

The safety and anti-tumor activity of TARA-002 in patients with high-grade NMIBC with carcinoma in situ (CIS) is being explored in the phase 2 ADVANCED-2 trial (NCT05951179).² The trial is broken up into 2 cohorts: patients with CIS who are BCG-naïve or BCG-exposed but have not received BCG for at least 24 months prior to most recent CIS diagnosis (cohort A) and patients with persistent or recurrent CIS who are unresponsive to BCG within 12 months following adequate therapy completion (Cohort B).

In total, the trial is expected to enroll 127 patients. The primary end point for both cohorts A and B is the incidence of high-grade complete response (CR) at any time point. CRs in cohort A will also be assessed by patient subgroup (BCG-naïve and BCG-exposed).

Interim data from the ADVANCED-2 trial were presented at AUA, showing that TARA-002 was well-tolerated and demonstrated encouraging clinical activity in both the BCG-naïve and BCG-unresponsive cohorts.

SunRISe-5

The phase 3 SunRISe-5 trial (NCT06211764) adds onto the extensive SunRISe trial platform. Overall, the study is assessing TAR-200, a gemcitabine releasing system, vs chemotherapy following BCG in patients with recurrent papillary-only high-risk NMIBC.³ The open-label trial plans to enroll approximately 250 patients, and the primary end point is DFS.

PIVOT-006

The phase 3 PIVOT-006 trial (NCT06111235) is exploring adjuvant cretostimogene grenadenorepvec following transurethral resection of bladder tumor (TURBT) vs TURBT alone in patients with intermediate-risk NMIBC. The primary end point in recurrence-free survival.⁴

In addition to PIVOT-006, the therapy is also being explored in the phase 3 BOND-003 trial (NCT04452591), which enrolled patients with BCG-unresponsive NMIBC. Initial data from BOND-003 led the FDA to grant both fast track and breakthrough designations to cretostimogene for BCG-unresponsive NMIBC in December 2023.

Trial of NDV-01

The background and design of a phase 2 study (NCT06663137) evaluating the safety and efficacy of the intravesical sustained release formulation of gemcitabine/docetaxel, NDV-01, were also presented. According to Relmada Therapeutics, NDV-01 is “designed for intravesical dosing and intended to be an in-office ready-to-use therapy that is administered rapidly and requires no anesthesia or new or dedicated equipment to employ.”⁵

In total, the prospective, open-label study plans to enroll 70 patients with high-risk NMIBC. The primary end points for the study include the number of patients achieving a CR at 48 weeks as well as the frequency and severity of adverse events.⁶

Prostate

ProstACT GLOBAL

In the prostate cancer space, the phase 3 ProstACT GLOBAL trial (NCT06520345) is assessing the safety and efficacy of ¹⁷⁷Lu-TLX591 plus standard of care (SOC) vs SOC alone in patients with metastatic castration-resistant prostate cancer.⁷ The study will consist of 3 parts: a safety and dosimetry lead-in, a randomized treatment expansion portion, and long-term follow-up.

The trial plans to enroll 430 patients who will be randomly assigned 2:1 to receive ¹⁷⁷Lu-TLX591 plus SOC or to SOC alone, with SOC including either an androgen receptor pathway inhibitor (enzalutamide [Xtandi] or abiraterone [Zytiga]) or docetaxel.The primary end point is radiographic progression-free survival (rPFS). Secondary end points include overall survival (OS), objective response rate, and time to first symptomatic skeletal event.

WATER IV

The WATER IV prostate cancer trial (NCT06651632) is comparing the safety and efficacy of first-line Aquablation therapy with radical prostatectomy in the treatment of patients with localized prostate cancer.⁸ The FDA approved the investigational device exemption study in October 2024,⁹ following a previous decision to grant a breakthrough device designation to Aquablation for use in patients with prostate cancer.

In total, the global, multicenter, prospective, randomized WATER IV PCa trial plans to enroll up to 280 patients with grade group 1 to 3 localized prostate cancer. The primary end point for the trial are rates of pad use for urinary incontinence and rates of erectile dysfunction, which will be assessed at 6-month follow-up. Patients enrolled in the trial will be followed for up to 10 years.

CAPTAIN

The TULSA procedure is being compared against radical prostatectomy for localized, intermediate-risk prostate cancer in the CAPTAIN trial (NCT05027477).¹⁰ The trial plans to enroll 201 patients, with 134 patients randomly assigned to TULSA and 67 patients randomly assigned to radical prostatectomy. The trial will assess quality of life and freedom from treatment failure across both cohorts. Participants in the study will be followed for up to 10 years.

ARASTEP

The phase 3 ARASTEP trial (NCT05794906) is exploring the combination of darolutamide (Nubeqa) plus androgen deprivation therapy (ADT) in patients with high-risk biochemical recurrence of prostate cancer.¹¹ The study is aiming to enroll a total of 970 patients who will be randomly assigned to receive darolutamide plus ADT vs placebo plus ADT. The primary end point is rPFS.

The combination of darolutamide plus ADT is currently under review by the FDA for potential approval in metastatic hormone-sensitive prostate cancer, with a decision expected later this year.

Kidney

PROBE (SWOG S1931)

The phase 3 PROBE trial (NCT04510597) is assessing whether the addition of cytoreductive nephrectomy to a standard of care immunotherapy-based drug combination will improve overall survival vs the drug combination alone in patients with treatment-naïve metastatic renal cell carcinoma (RCC).¹²

Participants will be assigned to 1 of 3 treatment regimens: nivolumab (Opdivo) plus ipilimumab (Yervoy), pembrolizumab (Keytruda) and axitinib (Inlyta), or avelumab (Bavencio) and axitinib. Participants will then be randomly assigned to continuation of treatment with or without the addition of radical or partial nephrectomy.

NORDIC SUN

The NORDIC SUN trial (NCT03977571) is seeking to determine whether there is a survival benefit to using a deferred cytoreductive nephrectomy approach following treatment with initial nivolumab plus ipilimumab or an IO/TKI-combination in patients with metastatic RCC.¹³ Approximately 400 patients will be enrolled in the study through clinical trial sites in Denmark. The primary end point of OS will be assessed through a minimum of 3 years follow-up.

REFERENCES

1. A study to evaluate TAR-210 versus single agent intravesical cancer treatment in participants with bladder cancer (MoonRISe-1). ClinicalTrials.gov. Last updated April 27, 2025. Accessed May 5, 2025. https://clinicaltrials.gov/study/NCT06319820

2. Safety and efficacy study of intravesical instillation of TARA-002 in adults with high-grade non-muscle invasive bladder cancer (ADVANCED-2). ClinicalTrials.gov. Last updated April 29, 2025. https://clinicaltrials.gov/study/NCT05951179

3. A study of TAR-200 versus intravesical chemotherapy in participants with recurrent high-risk non-muscle-invasive bladder cancer (HR-NMIBC) after Bacillus Calmette-Guérin (BCG) (SunRISe-5). ClinicalTrials.gov. Last updated April 27, 2025. Accessed May 5, 2025. https://clinicaltrials.gov/study/NCT06211764

4. A study of adjuvant cretostimogene grenadenorepvec for treatment of intermediate risk NMIBC following TURBT. ClinicalTrials.gov. April 17, 2025. Accessed May 5, 2025. https://clinicaltrials.gov/study/NCT06111235

5. UPDATE -- Relmada Therapeutics to present NDV-01 data at AUA2025. News release. Relmada Therapeutics. April 14, 2025. Accessed May 5, 2025. https://www.relmada.com/for-investors/news/detail/313/update----relmada-therapeutics-to-present-ndv-01-data-at

6. Open label study to evaluate the safety and efficacy of NDV01 KIT in high grade NMIBC (HGNMIBC). ClinicalTrials.gov. Last updated October 29, 2024. Accessed May 5, 2025. https://clinicaltrials.gov/study/NCT06663137

7. The study of 177Lu-TLX591 plus SOC versus SOC alone in patients with mCRPC (ProstACT Global). ClinicalTrials.gov. Last updated February 28, 2025. Accessed May 5, 2025. https://clinicaltrials.gov/study/NCT06520345

8. WATER IV Prostate Cancer (WATER IV PCa). ClinicalTrials.gov. Last updated April 3, 2025. Accessed May 5, 2025. https://clinicaltrials.gov/study/NCT06651632

9. PROCEPT BioRobotics received U.S. FDA approval to initiate pivotal randomized clinical study for prostate cancer. News release. PROCEPT BioRobotics. October 7, 2024. Accessed October 8, 2024. https://ir.procept-biorobotics.com/news-releases/news-release-details/procept-biorobotics-received-us-fda-approval-initiate-pivotal

10. A comparison of TULSA procedure vs. radical prostatectomy in participants with localized prostate cancer (CAPTAIN). ClinicalTrials.gov. Last updated February 21, 2025. Accessed May 5, 2025. https://clinicaltrials.gov/study/NCT05027477

11. A study to compare darolutamide given with androgen deprivation therapy (ADT) with ADT in men with hormone sensitive prostate cancer and raise of prostate specific antigen (PSA) levels after local therapies (ARASTEP). ClinicalTrials.gov. Last updated April 6, 2025. Accessed May 5, 2025. https://clinicaltrials.gov/study/NCT05794906

12. Comparing the outcome of immunotherapy-based drug combination therapy with or without surgery to remove the kidney in metastatic kidney cancer, the PROBE trial (PROBE). ClinicalTrials.gov. Last updated August 16, 2024. Accessed May 5, 2025. https://clinicaltrials.gov/study/NCT04510597

13. Deferred cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma: The NORDIC-SUN-Trial (NORDIC-SUN). ClinicalTrials.gov. Last updated February 26, 2025. Accessed May 5, 2025. https://clinicaltrials.gov/study/NCT03977571