Benign Conditions

Benign Prostatic Hyperplasia

Bladder Cancer

Female Urology

Genitourinary Cancers

Genomic Testing

Hormone Therapy

Kidney Cancer

Challenging Anatomy

Innovative Techniques

Laser Lithotripsy

PCNL Tech & Devices

Ureteroscopy Tech & Devices

Kidney Stones

Men's Health

Next-Generation Imaging

Voiding Dysfunction

OAB and Incontinence

Pediatrics

Controveries in Urologic Cancer

Drug Therapy

Prostate Cancer

Sexual Dysfunction

UTUC

Cosmetic Surgery

Urologic Surgery

Business

Practice Management

Malpractice Consult

Health Law & Policy

Media

Case-Based Peer Perspectives

Investigator Perspectives 

Medical World News

Podcasts

Urology Medical Perspectives

UTv Videos

Peer Exchange

Special Report

Virtual Tumor Board

Insights

Medcast

Peers & Perspectives

Conferences

Conference Listing

Conference Previews 

Conference Recaps

Publications

Urology Times Journal

Editorial Advisory Board

Urologists in Cancer Care

Supplements and Featured Publications

Clinical Forums Recaps

CME/CE

Resources

Begin Your Journey: Tackling Burnout

Live Events

Interactive Tools

Job Board

Partners

Treatment Landscape Evolutions

Subscribe

Articles

Overall, 71% of patients had no fragment greater than 2 mm following treatment.

BWL plus ultrasonic propulsion shows safety, efficacy for small renal stones

“We are witnessing the dawn of teletreatment,” says Jihad Kaouk, MD, FACS. 

Urologists perform first remote robot-assisted HIFU for prostate cancer

Two recent Clinical Forum discussions sought to examine how emerging therapeutic options and evolving treatment standards in non–muscle invasive bladder cancer affect clinical practices and patient outcomes.

NMIBC Clinical Forums highlight novel therapies and treatment strategies

Three recent expert-led Clinical Forums explored current challenges and advancements in the management of non–muscle invasive bladder cancer.

Exploring new avenues in non–muscle invasive bladder cancer treatment

Urology Times is the leading resource for urologists & allied health professionals offering clinical analysis, policy perspectives, & practical advice.

About Us

Advertise

Editorial

Contact Us

Terms and Conditions

Privacy

Do not sell my Personnal Information

Urology Times | News & Insights for Urologists & Health Professionals

Facebook

LinkedIn

Spotlight

Peers and Perspectives

Clinical

1rem

Authors

A panelist discusses how benign prostatic hyperplasia (BPH) treatment has evolved to include a spectrum of minimally invasive and surgical interventions, ranging from emerging technologies like prostatic urethral lift (PUL) and water vapor thermal therapy (WVTT) to more established resective surgical techniques such as transurethral resection of the prostate (TURP), holmium laser enucleation (HoLEP), Aquablation, and Greenlight XPS, providing urologists with a diverse array of options tailored to individual patient characteristics, prostate size, and specific clinical needs.

Resective Surgery and Minimally Invasive Procedures For BPH

A panelist discusses how benign prostatic hyperplasia (BPH) management involves a comprehensive patient journey that encompasses initial diagnostic evaluation, tailored pharmacological interventions including α-blockers and 5-α reductase inhibitors, and a progressive treatment approach ranging from conservative drug therapy to potential surgical options based on symptom severity and patient response.

BPH: The Patient Journey

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:

What are your initial impressions of the case?

Video Series

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. 

News

FDA accepts BLA for subcutaneous nivolumab in solid tumors

hosted Clinical Forum events in San Francisco, California; Houston, Texas; and Baltimore, Maryland. These discussions focused on current challenges and advancements in the management of non–muscle invasive bladder cancer (NMIBC), touching on approved therapies such as nadaofaragene firadenovec (Adstiladrin), nogapendekin alfa inbakicept (Anktiva), and pembrolizumab (Keytruda), along with investigational treatments such as sasanlimab. What follows is a summary of these discussions.

This summary was AI generated and edited by human editors for clarity.

medical director of the Bladder Cancer Program for Chesapeake Urology in Maryland, served as moderator for this forum. At the beginning of the discussion, various techniques used in the assessment of NMIBC were reviewed, highlighting the preference for bipolar resection over monopolar techniques among attendees. The use of enhanced imaging modalities, such as narrow band imaging, was also a topic of consensus, demonstrating a growing trend toward utilizing advanced diagnostic tools in the evaluation and management of bladder cancer.

Central to the discussion were various therapeutic strategies, particularly for patients who have not responded adequately to BCG treatments. One prominent therapy discussed was pembrolizumab. Though its 1-year response rates were considered lower compared to those of BCG, it was acknowledged that pembrolizumab offers a different safety profile, making it an important option to consider especially for patients with limited treatment alternatives.

A pivotal moment in the conversation was the overview of clinical trials that are currently influencing treatment paradigms. The CREST trial (NCT04165317), investigating the use of sasanlimab, was highlighted. Sasanlimab, a subcutaneously administered PD-1 inhibitor, potentially eliminates the need for intravenous infusions, streamlining the treatment process. The appeal of this trial lies not only in its innovative approach but also in the notion that it could allow urologists to manage therapy independently, crafting a more direct line of care for patients. With its recent completion, the anticipation surrounding the trial’s results reflects the significant interest in therapies that offer convenience and efficacy.

Another clinical trial presented during the discussion was the POTOMAC study (NCT03528694), which focused on the combination of durvalumab (Imfinzi) with BCG. Positive results from European counterparts of this trial set a strong precedent, instigating further investigation within the US. Although still in the early phases, initial findings from the US segment create an encouraging backdrop for adapting treatment strategies that integrate immunotherapeutic approaches alongside existing protocols like BCG.

Furthermore, there was substantial interest in new developments in bladder cancer treatment technologies. Nadofaragene firadenovec was mentioned as part of a growing array of innovative treatments. Trials involving nadofaragene are exploring its potential to elicit robust immune responses, representing a novel avenue in immunotherapy for patients who exhibit resistance to standard treatments.

The discussion also broached the subject of nogapendekin alfa inbakicept (Anktiva), an intravesical treatment based on interleukin-2 intended to augment the immune response within the bladder. Encouraging observances regarding its efficacy have fueled interest in conducting head-to-head trials against BCG to better define its role within treatment algorithms.

The roundtable also reflected concerns about the therapeutic landscape’s evolving nature. The shift from categorizing patients purely as BCG unresponsive to a more nuanced understanding of treatment unresponsiveness indicates ongoing deliberations about how to best approach therapy selection in bladder cancer. The necessity for rigorous clinical studies—especially those employing placebo-controlled or double-arm designs—was emphasized, as many recent approvals were achieved through single-arm trials, which may not provide sufficiently robust evidence for long-term treatment efficacy.

Amid these advances, participants expressed a shared concern regarding the logistical challenges that arise in deploying newer treatment modalities and ensuring they fit seamlessly into existing clinical workflows. Discussions regarding patient management also highlighted the importance of considering patient preferences and risk profiles when deciding on treatment pathways. An effective patient-centered approach is crucial to navigating the complexities of treatment, particularly when dealing with the uncertainties surrounding responses to various immunotherapies and chemotherapies.

Overall, the forum offered a comprehensive overview of the current state of bladder cancer treatment strategies, emphasizing the importance of collaboration, innovation, and patient-centered care in refining therapy protocols. The clinical trials discussed, including CREST and POTOMAC, along with emerging therapies like sasanlimab, pembrolizumab, nadofaragene, and Anktiva, reflect the dynamic landscape of bladder cancer management and the ongoing quest for improved patient outcomes. The dialogue reinforced the need for continued research and open communication among providers to ensure that advancements are effectively translated into clinical practice.

 an associate professor and urologic oncologist with Houston Methodist, served as moderator for this forum. One focal point of the discussion was the definition and identification of patients deemed BCG-unresponsive. A critical component involves ensuring that these patients have undergone adequate treatment with BCG, which can be quantified using the "5 plus 2 rule." This guideline specifies that patients must receive 5 of 6 induction doses and 2 of 3 maintenance doses of BCG, alongside certain recurrence patterns—CIS (carcinoma in situ) recurrence within 12 months or TA (transitional cell carcinoma) recurrence within 6 months—to consider them as unresponsive. The need for proper identification of this patient group was seen as pivotal in attracting pharmaceutical interest to develop novel therapies.

The group noted ongoing trials aimed at this demographic, such as the EA8212 BRIDGE trial, which compares gemcitabine and docetaxel vs BCG in BCG-naive patients. This trial holds significance as it seeks to reserve BCG for patients who require it, maintaining its availability. The conversation also addressed the sourcing of BCG, especially the challenges associated with trials relying on different strains of BCG.

The discussion touched on new immunotherapeutic approaches, including the use of sasanlimab in the CREST clinical trial. Sasanlimab targets immune checkpoints, with the trial focusing on evaluating its efficacy. Another topic of interest was the TAR-200 platform, which is being studied in the SunRISe-3 trial and involves the delivery of erdafitinib, an FGFR receptor inhibitor, directly to the bladder in conjunction with BCG, or as monotherapy. This trial seeks to explore alternative administration routes and their potential benefits over systemic delivery methods, which have been associated with greater toxicity and require extensive monitoring.

The conversation shifted to practical challenges faced by oncology offices and urologists regarding the administration of these treatments. Participants acknowledged the difficulty in accommodating chemotherapy administration in various clinical settings, emphasizing the need for seamless operation between urology and oncology practices to facilitate the delivery of gemcitabine and docetaxel. Cost considerations, such as the affordability of certain therapies like gemcitabine and docetaxel, highlight a positive aspect of treatment access, but logistical hurdles persist.

Discussion participants emphasized the importance of keeping abreast of ongoing trials and data reporting from various studies like POTOMAC, which are expected to redefine treatment options in clinical practice. Notably, there was a strong consensus on the necessity for more effective trial designs that adequately address the needs of specific patient populations and adequately prove the efficacy and safety of new treatments.

 a urologic oncologist and director of the Advanced Therapeutics Center in Nashville, Tennessee, served as moderator for this forum. At the forefront of the discussion was sasanlimab. The CREST trial was noted for its aim to establish how this therapy performs in combination with BCG remains the standard care for NMIBC, and the results from CREST are anticipated to provide insights into whether sasanlimab can improve outcomes for patients who are BCG unresponsive or naïve. Given that BCG treatment has become complicated by shortages and variations in patient adherence, finding effective complements to this therapy is a priority for urologists.

The experts also discussed the application of pembrolizumab, which may provide an effective treatment option for patients who cannot undergo surgery or those who have progressed after initial therapies. However, the conversation highlighted the importance of patient selection, as the effectiveness of pembrolizumab can vary based on tumor characteristics and patient health status. Clinical trial data continues to refine the understanding of pembrolizumab’s role in bladder cancer, suggesting it may serve best in a personalized treatment approach.

Another novel therapy discussed was Anktiva. The participants noted that incorporating various immunotherapies such as Anktiva alongside traditional treatments could improve patient outcomes. The group expressed the necessity of continuing to investigate combination therapies, particularly as evolving data emerges from ongoing clinical trials.

Throughout the discussion, the challenges of treating NMIBC were emphasized, particularly in the post-BCG setting. One of the difficulties noted was the issue of incomplete treatment courses for patients, which can occur due to adverse events or limitations in treatment availability. The speakers agreed that the lack of standardized adherence to recommended BCG protocols has led to variations in patient outcomes. As bladder cancer management continues to evolve with new pharmacological options, strategies must also be developed to ensure complete and consistent access to therapies, especially for patients at risk of recurrence after BCG treatment.

The experts acknowledged that although advances in treatment options through trials like CREST provide hope, they must also consider practical implications within clinical practice. Understanding how newly approved or experimental therapies could integrate with existing standards of care is crucial, as is assessing the long-term outcomes associated with these combinations. Complications arising from both systemic and local treatments—particularly with agents that can have significant adverse events—were emphasized as an important consideration.

The Clinical Forum events in 2025 focused on advancements in non-muscle invasive bladder cancer (NMIBC) management, emphasizing the role of therapies like pembrolizumab, sasanlimab, and Anktiva. Discussions highlighted the importance of advanced diagnostic tools and the need for innovative treatment strategies, especially for BCG-unresponsive patients. Clinical trials such as CREST and POTOMAC were pivotal, exploring new therapeutic combinations and administration methods. The forums underscored the necessity of patient-centered care, effective trial designs, and seamless integration of new treatments into clinical practice to improve patient outcomes.

Urologists from Cleveland Clinic have collaborated across borders to perform the world’s first remotely conducted robot-assisted high-intensity focused ultrasound (HIFU) focal therapy procedure for prostate cancer.

Remote operation for the HIFU procedure was conducted by Ruben Olivares, MD, of Cleveland Clinic’s main campus, who was more than 7000 miles away from the procedure that was performed at Cleveland Clinic Abu Dhabi.

Olivares was able to connect remotely to the Focal One System to lead treatment planning from Cleveland Clinic’s main campus in Ohio, United States. On-site procedural execution—including positioning the patient, preparing the HIFU system, and starting the procedure—was led by Waleed A. Hassen, MD, MBA, at Cleveland Clinic Abu Dhabi, United Arab Emirates.

“We are thrilled to have successfully performed the first-ever transcontinental robotic assisted focal therapy procedure for prostate cancer by working in tandem with our partners at Cleveland Clinic Abu Dhabi,” said Olivares, a urologist in the Glickman Urological Institute at Cleveland Clinic, in a news release on the procedure.

 “Here at Cleveland Clinic, we use cutting-edge technology, but unfortunately, it's not available in many places throughout the US and in the world. We look forward to expanding the adoption of the latest alternative minimally invasive options and increasing access for patients throughout the world with this first step."

Overall, the HIFU procedure lasted approximately 1 hour, and no complications were reported. Olivares and Hassen collaborated in real-time during the procedure using shared Focal One system displays and an audio connection.

“There are many ways to treat prostate cancer, and one of the options is HIFU focal therapy. This is proof of principle that we can contour the prostate and design the plan remotely. This milestone is a testament to the power of collaboration and innovation,” said Hassen, who is the department chair of urology at the Surgical Subspecialties Institute at Cleveland Clinic Abu Dhabi. “By leveraging the expertise of our global network, we are not only providing patients with world-class care but also shaping the future of medical education and surgical innovation.”

The remote procedure was the product of nearly 2 years of planning. According to the news release from Cleveland Clinic, this planning included, “testing various connectivity networks, working with cybersecurity teams, and navigating legal and ethical frameworks to ensure a secure and reliable process, with patient safety and quality being the primary goals.”

This marks the first time that a procedure like this has been conducted in the world, opening the door for expanded access to urologic care.

“We are witnessing the dawn of teletreatment,” said Jihad Kaouk, MD, FACS, enterprise chair of urology at Cleveland Clinic.

 “This innovative approach not only allows us to share expertise across Cleveland Clinic’s locations but also expands access to specialized care for patients, no matter where they are. Teletreatment offers a unique opportunity to improve health care delivery, enhance clinical training, and reduce global health disparities, bringing quality care to patients worldwide.”


1. Cleveland Clinic Abu Dhabi performs world’s first robotic-assisted, transcontinental ultrasound focal therapy procedure for prostate cancer. News release. Cleveland Clinic Abu Dhabi. April 16, 2025. Accessed April 17, 2025. https://www.mediaoffice.abudhabi/en/health/cleveland-clinic-abu-dhabi-performs-worlds-first-robotic-assisted-transcontinental-ultrasound-focal-therapy-procedure-for-prostate-cancer/

2. Cleveland Clinic performs first transcontinental robotic-assisted HIFU focal therapy procedure for prostate cancer. News release. Cleveland Clinic. Published online and accessed April 18, 2025. https://consultqd.clevelandclinic.org/cleveland-clinic-leads-first-transcontinental-hifu-procedure-to-treat-prostate-cancer

Cleveland Clinic urologists have achieved a groundbreaking milestone by performing the first-ever remotely conducted robot-assisted high-intensity focused ultrasound (HIFU) focal therapy for prostate cancer. The procedure was executed transcontinentally, with Dr. Ruben Olivares operating from Ohio, USA, and Dr. Waleed A. Hassen managing on-site execution in Abu Dhabi, UAE. This innovative approach, a result of two years of meticulous planning, demonstrates the potential of teletreatment to enhance global healthcare access, improve medical education, and reduce health disparities by leveraging advanced technology and international collaboration.

ImmunityBio announced that it has submitted a supplemental biologics license application (sBLA) to the FDA seeking an expanded approval for nogapendekin alfa inbakicept-pmln (Anktiva) in combination with BCG for BCG-unresponsive non–muscle invasive 

 in April 2024 for use in combination with BCG for patients with BCG-unresponsive NMIBC with carcinoma in situ (CIS) with or without papillary disease.

According to the company, “This combination immunotherapy wherein ANKTIVA rescues BCG efficacy, currently approved in the BCG-unresponsive CIS indication, may provide an effective therapeutic option for papillary patients who did not respond to BCG alone and face the prospect of a radical cystectomy.”

The sBLA is supported by data from cohort B of the pivotal QUILT-3.032 trial (NCT03022825), which assessed Anktiva in combination with BCG in patients with histologically confirmed BCG-unresponsive high-grade Ta/T1 papillary NMIBC.

The median age of patients in this cohort was 72 years (range, 46 to 93 years). The primary end point was disease-free survival (DFS). 

Overall, the study found a DFS of 55.4% (95% CI, 42.0% to 66.8%) at 12 months, 51.1% (95% CI, 37.6% to 63.1%) at 18 months, and 48.3% (95% CI, 34.5% to 60.7%) at 24 months, per Kaplan-Meier estimates. The median DFS was 19.3 months (95% CI, 7.4 to NR).

Progression-free survival (PFS) was 97.1% (95% CI, 88.8% to 99.3%) at 12 months, 94.8% (95% CI, 84.3% to 98.3%) at 18 months, and 88.8% (95% CI, 74.1% to 95.4%) at 24 months. Overall survival was 98.6% (95% CI, 90.2% to 99.8%) at 12 months, 94.3% (95% CI, 82.9% to 98.1%) at 18 months, and 91.7% (95% CI, 79.0% to 96.9%) at 24 months. Disease-specific survival was 100% (95% CI, 100% to 100%) and 97.7% (95% CI, 84.6% to 99.7%) at 12 and 24 months, respectively.

At a median follow-up of 20.7 months (range, 2.9 to 37.1), the cystectomy rate was 7% (5 of 72).

According to ImmunityBio, “In 88% and 82% of subjects, the probability of avoiding surgical removal of the bladder was achieved for as long as 2 and 3 years, respectively, following treatment with ANKTIVA plus BCG.”

The majority (86%) of treatment-emergent adverse events (TEAEs) were grade 1 to 2. According to the authors, “The most frequently reported TEAEs for patients who received BCG plus NAI (cohorts A and B, n=161) were those expected for intravesical instillation of BCG and included dysuria, pollakiuria, and hematuria.”

The most common grade 3 TEAEs included hematuria (2%) and urinary tract infection (2%).

Overall, the QUILT-3.032 trial enrolled patients across 3 study cohorts. Cohorts A and C in the trial included patients with BCG-unresponsive bladder CIS with or without Ta/T1 papillary tumors who received Anktiva plus BCG (cohort A) or Anktiva alone (cohort C). The trial also enrolled patients with BCG-unresponsive high-grade Ta/T1 papillary NMIBC who received Anktiva plus BCG (cohort B).

The QUILT-3.032 trial is ongoing, with final completion expected in March 2029.


1. ImmunityBio announces FDA submissions of supplemental BLA for NMIBC papillary disease and for expanded access of ANKTIVA to treat lymphopenia. News release. ImmunityBio. April 15, 2025. Accessed April 15, 2025. https://immunitybio.com/immunitybio-announces-fda-submissions-of-supplemental-bla-for-nmibc-papillary-disease-and-for-expanded-access-of-anktiva-to-treat-lymphopenia/

2. Chamie K, Chang SS, Kramolowky E, et al. IL-15 superagonist NAI in BCG-unresponsive non–muscle-invasive bladder cancer. 

. 2023;2(1):EVIDoa2200167. doi:10.1056/EVIDoa2200167

3. QUILT-3.032: A multicenter clinical trial of intravesical Bacillus Calmette-Guerin (BCG) in combination with ALT-803 (N-803) in patients with BCG unresponsive high grade non-muscle invasive bladder cancer. ClinicalTrials.gov. Last updated April 13, 2025. Accessed April 15, 2025. https://clinicaltrials.gov/study/NCT03022825

ImmunityBio has submitted a supplemental biologics license application to the FDA for expanded approval of Anktiva in combination with BCG for BCG-unresponsive non–muscle invasive bladder cancer (NMIBC) in the papillary indication. The application is supported by data from the QUILT-3.032 trial, which demonstrated promising disease-free survival rates and a low cystectomy rate. The trial also reported manageable treatment-emergent adverse events. Anktiva, previously approved for BCG-unresponsive NMIBC with carcinoma in situ, may offer an effective therapeutic option for papillary patients.

The sBLA is supported by data from cohort B of the pivotal QUILT-3.032 trial.

FDA approval sought for Anktiva in papillary NMIBC

investigated the impact of conservative management, specifically an app-based therapeutic, on lower urinary tract symptoms (LUTS) in men.

 The 12-week randomized controlled trial involved more than 200 men with LUTS, who were randomly assigned to an intervention group using the app in addition to their usual medication, or a control group maintaining their regular medication.

The app incorporates various modules focusing on physiotherapy, lifestyle adjustments, and other resources aimed at enhancing patient motivation and adherence. It also includes a game that can be played to defer the urge to void. The primary outcome, the International Prostate Symptom Score (IPSS), showed a significant 8-point reduction in the intervention group, whereas no change was observed in the control group. The study also reported significant improvements in overactive bladder symptoms and overall quality of life in the group using the app. Although the individual contribution of each app 

component wasn't specifically measured, study author 

said he believes physiotherapy to be a particularly strong element. “We concluded that by using this app, in addition to the patient's usual medication, it is possible to improve [LUTS] by only looking at conservative measurements,” Gratzke said. In the following interview, Gratzke discusses the study and highlights the app’s utility. Gratzke is professor and chair of urology at the Albert-Ludwigs-University in Freiburg, Germany.

Please provide an overview of this study and its notable findings.

The idea was to look at the improvement of conservative measurements that we do in men with [LUTS]. As you know, we have conservative options, we have medical options, and invasive options. In this trial, we were particularly interested in doing the less invasive treatment options that are all recommended by all the guidelines—by the AUA [American Urological Association], by the EAU [European Association of Urology]. We constructed a randomized controlled trial for 12 weeks where we looked at the improvement of [LUTS] as measured by the IPSS and also overactive bladder as measured by the OAB-q. We did this by using an app. We had more than 200 patients [who were randomly assigned into] 2 groups: an intervention group and a control group. Patients [in the intervention group] were asked to follow the instructions of the app, in addition to the treatment they were already given, and [those in] the control group were just kept on their usual medication.

The app is made up of various modules, which consist of physiotherapy, lifestyle modification, and other modules that reinforced the patient’s motivation to carry on with the app, so it adapted to the individual needs of those patients. We showed in the trial that in the intervention group, the improvement of LUTS was significant as measured by the IPSS. There was a reduction of 8 points, whereas there was no change in the control group, which was an important validation of this study. There was also a significant improvement in overactive bladder symptoms and quality of life. We concluded that by using this app, in addition to the patient's usual medication, it is possible to improve [LUTS] by only looking at conservative measurements.

The study demonstrated a statistically significant improvement in IPSS with app-based therapeutics. Could you elaborate on the specific components of the app-based therapy that you believe contributed most to this improvement? What specific exercises or educational components were included?

We don't know which module was the most important one, because we didn't measure that. We just looked at the whole program, but we will do step analysis and look at individual modules and how much each of them contributed to the improvement of the symptoms. I personally believe that the physiotherapy component is a very strong [part], because, as we know, female patients use physiotherapy all the time, and it improves the pelvic floor, whereas in male patients, we neglect this. I think this study might be a good basis to recommend more physiotherapy. It is a conservative measurement. You have very few [adverse events], if any, and this is a very strong component that contributes to the improvement of LUTS. There's also a knowledge section that provides information on reducing fluid intake at night. It elucidates what [LUTS] actually are. It looks at the anatomy of the prostate. It explains what incontinence actually is, and you get pieces of information every day and every week for those 12 weeks. There is also a 

 button, which, if you experience a significant urge, you press this button, and then you play a little game, which should defer the desire to void.

The minimal clinically important difference for IPSS is 3 points. The intervention group demonstrated a LSM of -7.0 points. How does this translate to clinically meaningful improvement in your opinion, and how does this compare to other standard LUTS treatments?

For anyone working in the BPH [benign prostatic hyperplasia]/LUTS space, you would expect for anything to work to be in the 3-, 4-point difference when you look at the IPSS. If you have less than that, it's usually not clinically meaningful. By having a 7- or 8-point improvement, that would actually show a clinically substantial improvement in LUTS. If you compare this to gold standard medication—tamsulosin [Flomax], alpha blockers—if you look at what you get by doing a minimally invasive treatment option such as UroLift or iTind, by using this app for 12 weeks, you do achieve a significant improvement. So, compared to what you usually use as a first step, we believe that it is really worthwhile performing that intervention, because it's only the first step, and we don't do it in the very severely obstructed patients. This is really important. This is in mild and moderately [obstructed] patients where this is the first step. If this works, this is great. It’s also good because the patient really thinks about how to behave. It explores the body. Usually, the patient has very little knowledge about what the prostate is and what those symptoms are, and it might help to actually inform the patient better.

You mentioned that physiotherapeutic approaches are often neglected in LUTS management. How does this app-based therapy aim to bridge the gap between traditional medical care and these conservative treatments, and what are the barriers you see to wider adoption?

Physiotherapy might not be used by a patient simply because it’s not reinforced by the doctor or the nurse. Nurses play a major role here. If physiotherapy is instructed by somebody who's really knowledgeable, then that might work by itself, without using the app. But the app, of course, uses various components. It gives you haptic feedback. It's adaptive to the individual patient's needs, and you can do it wherever you are and wherever you work. Many patients, as you know, travel a lot. [You can use this] app no matter where you are. It's very easy to use, so I think the barriers to using any of those conservative measurements might be overcome by [it]. It highlights why you should be actually using the individual components, because physiotherapy is also divided into various components, [such as] the strength component and the endurance component. It highlights why each of those components is important.

Given the app-based nature of the intervention, what are your recommendations for health care professionals in terms of integrating this type of therapy into their clinical practice, and what are the training requirements for patients to use it effectively?

I believe that if you look at a certain algorithm that a urologist would hand out to a patient, this might provide the first step in this algorithm. So, before going into any interventions, whether they are medical or surgical interventions, you might be able to use this app in a meaningful fashion. The training requirements are really minimal. It is very easy to use. It is self-explanatory, so I would give it a go. If I were the urologist, there's nothing to lose. Worst-case scenario, it doesn't help, but the threshold to use it is very low.

1. Gratzke C, Schönburg S, Eger S, et al. A randomized trial of an app-based therapeutic for lower urinary tract symptoms. 

2025;4(4):EVIDoa2400290. doi:10.1056/EVIDoa2400290

A recent study explored the efficacy of an app-based therapeutic in managing lower urinary tract symptoms (LUTS) in men. Conducted over 12 weeks with more than 200 participants, the trial revealed a significant 8-point reduction in the International Prostate Symptom Score (IPSS) for the intervention group using the app, compared to no change in the control group. The app, which includes physiotherapy and lifestyle modules, also improved overactive bladder symptoms and quality of life. The study suggests that conservative management can effectively enhance LUTS outcomes.

Christian Gratzke, MD, explains why an app shows promise for patients with lower urinary tract symptoms.

Christopher E. Kelly, MD

Articles

Latest Updated Articles