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Panelists discuss how BCG-unresponsive bladder cancer is defined by disease persistence/recurrence within 6 to 12 months of adequate BCG therapy. Treatment options include cystectomy, intravesical chemotherapy, immunotherapy, or clinical trials.

BCG-Unresponsive NMIBC and Treatments

Panelists discuss how low-risk non–muscle-invasive bladder cancer (NMIBC) requires transurethral resection of bladder tumor (TURBT) with surveillance. Intermediate-risk disease needs adjuvant intravesical chemotherapy. High-risk cases receive BCG induction/maintenance therapy after TURBT, with close monitoring.

Standard of Care in NMIBC

“There are a lot of other ways to look at bel-sar with other immunotherapy agents, other combinations, to truly help prevent patients needing to go to the operating room,” says Gary D. Steinberg, MD. 

Gary Steinberg, MD, on exploring novel combinations with bel-sar in NMIBC

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

, highlights a study characterizing the diversity and composition of the urinary and intestinal microbiomes in patients with spina bifida, which was presented at the Society for Pediatric Urology (SPU) and the International Children’s Continence Society (ICCS) Annual Fall Congress in Louisville, Kentucky.

 Frainey is a pediatric urology fellow at Monroe Carell Jr. Children's Hospital at Vanderbilt University Medical Center in Nashville, Tennessee.

Could you describe the background/rationale for this study?

This study is one that our group has been thinking about for a while. [It's] something I'm passionate about because what we see is that individuals with spina bifida come into the emergency [department] or the clinic frequently for what is presumed to be a urinary tract infection (UTI). It is challenging to diagnose a “true” or “symptomatic UTI” and distinguish that from what's called asymptomatic bacteriuria. It’s challenging for a variety of reasons, but the primary reason is that individuals with spina bifida don't often present with typical symptoms [such as] dysuria, urgency, or frequency because they have altered sensation in their lower abdomen and pelvis. So, we often have to go off limited information and utilize both a positive urine culture and hopefully some clinical symptoms, such as fever, flank pain, nausea, or vomiting, but that doesn't always happen.

My worry as a pediatric urologist who takes care of young adults with spina bifida is that [as] they get older, they present to the hospital with multidrug-resistant bacteria because they either have had many true UTIs over the course of their lifetime or have been overtreated with antibiotics. The goal of this study was to understand, over the lifetime in individuals with spina bifida, what bacteria are present in their urine normally, what bacteria are present when they have a [UTI], and what are some important clinical differences we can tease out to help understand which patients should really be treated.

What were the key findings from this study?

This study had several key findings and a lot of things that we're excited to continue pursuing. The 3 big things that we took away from this thus far are [first] that bacteria are present in the urinary microbiomes of almost all individuals with spina bifida. In the next-generation sequencing, or the 16S sequencing we did, 97% of people had some bacterial growth in their urine, and 100% had it in their stool. In the specialized urine cultures that we did—these are patients [who] weren't having any symptoms at the time—82% of patients had bacteria growing in their urine. The notion that urine is sterile should be hopefully abolished by now, especially in this group where we know that these individuals do have a lot of bacteria growing in their bladders. We are hoping to understand how that contributes to their overall health.

The second big thing is that in their microbiomes,

 was a major player. That's a common bug that leads to [UTIs]. It was the most common organism we found and the most abundant. We looked at all the organisms in their microbiomes or the things that grew on urine culture, and we found that 

 was the dominant organism. In addition to that, we realized that there wasn't a ton of diversity in the microbiomes. These individuals often only had 1 or 2 bacteria that were dominating the whole microbiome, which is very different from a typical individual who has a lot of other what we call commensal bacteria that may be contributing to their health. We don't necessarily know what that means yet, but we know that there's not much diversity in the microbiomes of these individuals, which [may] play a [role] in why they get recurrent UTIs.

Then the final thing, which isn't that surprising, but we proved for the first time, was that patients who catheterize their bladder—a lot of individuals with spina bifida catheterize to empty their bladder—have higher proportions of skin flora growing and living in their bladder. 

 is one of the common bacteria that live on our skin and our hands. We took hand swaps and showed that was more common in individuals [who] catheterize than those [who] didn't. It's something that we've presumed because they're using their hands to catheterize themselves, but we've now shown [it to be true]. Hopefully, down the line, we can say, if these bacteria might be growing and [the patients] don't have symptoms, that's expected. We shouldn't be treating individuals with spina bifida [who] have some of these common skin flora in their bladder if they're not having symptoms of a UTI or fever. I think that'll be helpful to show and to prove down the line.

What gaps do these findings help to address in the current literature?

One of the things that is unique about this study is that we took stool samples, so we looked at the intestinal microbiome as well. There is some suggestion that a lot of the UTIs that patients experience can come from the gut flora. What we showed in our study was that patients [who] had recurrent UTIs had higher rates of 

 in their gut. While this is just a preliminary piece of information, it's allowing us to drive our hypothesis that the gut may be a reservoir for UTIs for a lot of these patients. Having specimens and doing data analysis on both of these niches within the body will help us understand where these UTIs are coming from and how the gut and bladder are interrelated. That's another unique aspect of our study, which no other study ever has really done before.

[Overall,] there are a lot of gaps in this care, and there are a lot of unknowns. I think our study is hopefully going to be a springboard for future studies, both at our institution and others across the country down the line. I think the interplay of how the microbiome affects our health is something that's gaining a lot of interest, but the urinary microbiome is still very new and understudied. I hope this specific study focusing on a specific group of patients can help give us some information that will lead to future studies within the microbiome, specifically the urobiome, and demonstrate how it can contribute to our health and potentially how some of the interventions that we are asking patients to do can alter their microbiome, such as giving antibiotics or starting someone on a catheter program. We do surgeries [such as] bladder augmentations, where we're taking a piece of intestine and putting it in the bladder. How does that alter someone's microbiome and predispose them to future [UTIs] down the line? This is an early study helping to characterize some of the key findings, but we have a lot of exciting work that we’re going to continue working on and hopefully get the field to join as well.

What are the implications of these findings for clinical practice?

This is still very preliminary work. We are drawing some associations, but there are no hard conclusions yet. We haven't demonstrated causation. I think some of the things that excite me are understanding that there are bacteria that are living in the bladders of these individuals all the time and understanding which are the bad players and which are the ones that we can observe and not overtreat our patients with spina bifida. It's a double-edged sword because this is a common source of morbidity and mortality for these patients, but also something where, in the era of antibiotic stewardship, we need to be doing better for these individuals and not overtreating. I think these data will show us what pathogens are in the bladders of individuals with this condition, but also what bacteria are there that maybe don't need to be treated. We're just getting into how we can decipher that.

I think some of the really interesting things are—once we start getting longitudinal samples in these individuals—understanding how the things that we're doing to these patients change and alter their microbiomes. When they come in with a [UTI], when we get urine, how is that different from when they're healthy? That's the next phase of this, which we're already doing now, but we haven't published data on yet, that I think will start to give us some more conclusive evidence as to which bacteria are the good ones and the bad ones.

Could you expand on some of the ongoing research on this topic?

We have some grant funding and a lot of collaborations ongoing for this project. As I alluded to, I think the first and most exciting step is getting longitudinal data. The data I presented at SPU and the ICCS was a characterization of 1 point in time of 60 individuals with spina bifida, giving us both urine, stool, and hand samples. But we've been collecting data prospectively over the course of the past year and a half to get repeated samples from these individuals. So, when they come in, either hospitalized for a UTI or back to our clinic for repeated urodynamics, we're getting additional samples. In the interval, what exposures to antibiotics have they had? What interventions have we done to them? What things could alter their microbiome? That's going to give us this evolution of the microbiome that we are really excited about.

I'm [also] working with some talented people in our lab [who] know how to do some of the bioinformatics and some of the microbiology behind this to look at the next generation sequencing, the 16S, as I talked about. [We’re also looking at] more detailed next-generation sequencing—metagenomics, whole genome sequencing—to understand the interplay of these bacteria and how they're surviving within the bladder and coming up with altered mechanisms to thrive and avoid our antibiotics or become resistant. That's the next phase of all this that we're already starting and have some preliminary data. [This will help show] the mechanisms of why this is happening, and not just a point-in-time characterization, which is where the field is at right now, unfortunately. We want to push this further to understand some causation and to understand at a molecular and microbiology level how this is happening.

It'll be a multi-institutional undertaking, with hopefully additional institutions joining on as we get more grant funding and get more of our data out. We've already expanded to working with Duke University, which has a very large spina bifida cohort and a really successful clinic there. They've been sending us data as well, and they’re going to be very big contributors to our coming data and the findings.

1. Frainey BT, Reasoner SA, Hadjifrangiskou M, Clayton DB. Characterization of the urinary and intestinal microbiomes in individuals with spina bifida. Presented at: Pediatric Urology Fall Congress; September 12-15, 2024; Louisville, Kentucky. Abstract 67. https://fallcongress.spuonline.org/program/2024/67.cgi

The study investigates the urinary and intestinal microbiomes in spina bifida patients, focusing on the prevalence of bacteria and their implications for urinary tract infections (UTIs). It highlights the presence of bacteria in the urinary microbiomes of nearly all patients, with E. coli being a dominant organism. The study also notes the lack of diversity in these microbiomes and the presence of skin flora in patients who catheterize. The research aims to inform better treatment strategies and reduce antibiotic overuse, with ongoing efforts to gather longitudinal data and explore microbiome evolution.

"The goal for this study was to understand, over the lifetime in individuals with spina bifida, what bacteria are present in their urine normally, what bacteria are present when they have a UTI, and what are some important clinical differences we can tease out to help understand which patients should really be treated," says Brendan T. Frainey, MD. 

In-depth study of microbiomes may lead to better UTI care for patients with spina bifida 

Ferring Pharmaceuticals has announced the opening of the first clinical trial sites for 2 studies within the ABLE clinical trial program of nadofaragene firadenovec-vncg (Adstiladrin) in non–muscle invasive bladder cancer (NMIBC), the company announced in a news release.

The company also reported the launch of the phase 1/2 LUNAR trial (NCT06668493) to explore the safety, tolerability, and efficacy of nadofaragene instilled to the renal pelvis in patients with low-grade upper tract urothelial cancer (LG-UTUC).

Nadofaragene was approved by the FDA in December 2022 for the treatment of patients with high-risk BCG-unresponsive NMIBC with carcinoma in situ with or without papillary tumors.

“The availability of an innovative locally delivered gene therapy has the potential to be organ sparing for appropriate NMIBC and UTUC patients,” said Joern Jakobsen, MD, PhD, vice president and head of global research and medical for Uro-Oncology and Urology at Ferring Pharmaceuticals, in the news release.

 “The extension of the ADSTILADRIN clinical trial program—with a focus on IR [intermediate risk] NMIBC and LG UTUC where there is a desperate need for new treatments, and generation of mono and combination therapy data, including re-induction, for high-risk BCG-unresponsive NMIBC—is key to understanding how ADSTILADRIN may be able to help even more patients.”

The first study opening enrollment within the ABLE platform includes the phase 2 ABLE-22 trial (NCT06545955), which is exploring nadofaragene as a monotherapy or in combination with chemotherapy (gemcitabine and docetaxel) or an immune checkpoint inhibitor (pembrolizumab [Keytruda]) in patients with high-risk BCG-unresponsive NMIBC. In total, the trial plans to enroll 150 patients across sites in the US.

The primary end point is the complete response rate, assessed for up to 12 months. Secondary end points include the durability of complete response, cystectomy-free survival, overall survival, and the incidence of adverse events. Primary completion of the study is anticipated for July 2026.

Additionally, the first clinical trial sites were activated in the phase 3B ABLE-32 trial (NCT06510374), which is evaluating the safety and efficacy of nadofaragene vs observation in patients with IR NMIBC. The randomized controlled study will enroll approximately 454 patients across study sites in the US.

The primary outcome measure is recurrence-free survival at 24 months. The frequency of adverse events is a secondary end point. Primary completion of the trial is expected for August 2028.

Ferring has also initiated the phase 1/2 LUNAR trial (NCT06668493), which is seeking to enroll 20 adult patients with LG-UTUC.

 The study will begin with a safety lead-in period, instilling only the first 6 patients in the study. All patients will receive instillations of nadofaragene into the renal pelvis.

The primary outcome measures include the number of treatment-emergent adverse events as well as the complete response rate at 3- and 6-month time points. Completion of the study is anticipated for November 2029.

In addition to these 3 studies, nadofaragene is also being assessed in the ongoing ABLE-41 trial (NCT06026332), a real-world evidence study to assess the early utilization, experiences, and outcomes of the agent in the routine care setting. Patients are eligible for inclusion in the observational study if they have NMIBC and have not previously received nadofaragene in a clinical trial.

The first patient was enrolled in the study in September 2023. The target enrollment is approximately 400 patients. Final completion of the trial is anticipated for December 2025.

1. Ferring advances three studies in ADSTILADRIN (nadofaragene firadenovec-vncg) clinical trial program. News release. Ferring Pharmaceuticals. December 3, 2024. Accessed December 3, 2024. https://www.businesswire.com/news/home/20241203511070/en/Ferring-Advances-Three-Studies-in-ADSTILADRIN%C2%AE-nadofaragene-firadenovec-vncg-Clinical-Trial-Program

2. A trial to evaluate intravesical nadofaragene firadenovec alone or in combination with chemotherapy or immunotherapy in participants with high-grade BCG unresponsive non-muscle invasive bladder cancer (ABLE-22). ClinicalTrials.gov. Updated November 14, 2024. Accessed December 3, 2024. https://www.clinicaltrials.gov/study/NCT06545955

3. Trial of nadofaragene firadenovec vs observation in participants with intermediate risk non-muscle invasive bladder cancer (ABLE-32). ClinicalTrials.gov. Updated November 26, 2024. Accessed December 3, 2024. https://www.clinicaltrials.gov/study/NCT06510374

4. Low-grade UTUC treated with nadofaragene firadenovec administered to renal pelvis (LUNAR). ClinicalTrials.gov. Updated October 31, 2024. Accessed December 3, 2024. https://www.clinicaltrials.gov/study/NCT06668493

5. ADSTILADRIN early utilization and outcomes in the real world setting (ABLE-41). ClinicalTrials.gov. Updated November 13, 2024. Accessed December 3, 2024. https://clinicaltrials.gov/study/NCT06026332

Ferring Pharmaceuticals has initiated clinical trials for nadofaragene firadenovec-vncg (Adstiladrin) in non–muscle invasive bladder cancer (NMIBC) and low-grade upper tract urothelial cancer (LG-UTUC). The ABLE-22 trial explores nadofaragene as monotherapy or combined with chemotherapy or immunotherapy in high-risk BCG-unresponsive NMIBC. The ABLE-32 trial compares nadofaragene to observation in intermediate-risk NMIBC. The LUNAR trial assesses safety and efficacy in LG-UTUC. Additionally, the ABLE-41 trial evaluates real-world outcomes. These studies aim to expand treatment options and improve patient outcomes.

Ferring has announced the opening of the first clinical trial sites for 2 studies within the ABLE clinical trial program as well as the launch of the phase 1/2 LUNAR trial. 

Trials launch of nadofaragene firadenovec in bladder cancer

Nogapendekin alfa inbakicept-pmln (Anktiva; N-803) plus BCG demonstrated a high rate of complete response in patients with BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), according to updated data from the ongoing QUILT 3.023 trial (NCT03022825).

The preliminary findings, shared in a news release by ImmunityBio, encompass the first 100 patients enrolled and treated in the phase 2/3 study. At the time of data cutoff (November 2024), 71% of patients achieved a complete response following treatment. Among the responders, the duration of response ranged as long as 54 months.

According to ImmunityBio, “This data update will be submitted to the European Medicines Agency (EMA) in a Marketing Authorization Application (MAA) for ANKTIVA in the European Union (EU), which is anticipated during Q4 2024.”

The agent was approved by the FDA in April 2024.

“We are encouraged by the consistent complete response rates observed in our expanded patient cohort,” said Patrick Soon-Shiong, MD, executive chairman and global chief scientific and medical officer of ImmunityBio, in the news release.

 “These results highlight the potential of ANKTIVA to transform the treatment landscape for patients with BCG-unresponsive NMIBC CIS, offering hope for improved outcomes and cystectomy avoidance, especially with the prolonged duration of response now ranging as much as 54 months in this 100-patient analysis. Duration of complete response is the key efficacy element in driving cystectomy avoidance in this BCG-unresponsive population. I am pleased that this updated ANKTIVA data confirms that one of the highest durable responses is achieved when compared to other approved products in this indication.”

Overall, the phase 2/3, open-label, multicenter study is assessing the use of Anktiva across 3 patient cohorts. Cohorts A and C in the trial include patients with BCG-unresponsive bladder CIS with or without Ta/T1 papillary tumors who received Anktiva plus BCG (cohort A; n = 84) or Anktiva alone (cohort C; n = 10). The trial also enrolled patients with BCG-unresponsive high-grade Ta/T1 papillary NMIBC who received Anktiva plus BCG in cohort B (n = 77).

Findings from cohort A of the study were the basis of the approval for the agent earlier this year.

The primary end point for the trial is the incidence of complete response at 3 and 6-month timepoints for cohorts A and C, and disease-free survival at 12 months for cohort B. Secondary end points for cohort A are durability, cystectomy avoidance, progression-free survival, disease-specific survival, and overall survival.

Previous data on the QUILT-3.032 trial were published in 

In cohort A, 71% (95% CI, 59.6% – 80.3%) of patients achieved a CR with a median follow-up of 23.9 months. The median duration of CR was 26.6 months (95 CI, 9.9 months – not reached). Among those with a CR at 24 months, the probability of avoiding a cystectomy was 89.2%, and the probability of disease-specific survival was 100%, per Kaplan-Meier estimates.

In cohort B (n = 72), the disease-free survival (DFS) rate was 55.4% (95% CI, 42% - 66.8%) at 12 months, with a median DFS of 19.3 months (95% CI, 7.4 months – not reached). At the time of the FDA approval, the complete response rate was 62% to 73% among the 77 evaluable patients included in the analysis. The duration of complete response was longer than 47 months at the time of data cutoff, which exceeded the threshold for meaningful clinical results per a panel of experts at the International Bladder Cancer Group. Among patients with a complete response, 58% demonstrated a duration of response (DOR) of 12 months or longer, and 40% demonstrated a DOR of 24 months or longer.

In cohort C, data from the published study in 2022 showed that 20% of patients achieved a complete response at 3-month follow-up. Only 1 patient maintained a CR at 6 months. Six patients underwent reinduction. The median follow-up for all patients was 7.9 months at the time of data cutoff.

Regarding safety, 86% of treatment-emergent adverse events (TEAEs) from the combination therapy were grade 1 to 2, with 3 grade 3 immune-related TEAEs.

The QUILT 3.023 study remains ongoing to assess the durability of response and overall survival. Final study completion is expected in October 2028.

1. ImmunityBio completes ANKTIVA’s post-approval enrollment of the 100th patient in BCG unresponsive NMIBC CIS trial and reports a complete response rate of 71% with a durable duration of response ranging up to 54 months. News release. ImmunityBio. Published online and accessed November 19, 2024. https://www.businesswire.com/news/home/20241119975432/en/ImmunityBio-Completes-ANKTIVA%E2%80%99s-Post-Approval-Enrollment-of-the-100th-Patient-in-BCG-Unresponsive-NMIBC-CIS-Trial-and-Reports-a-Complete-Response-Rate-of-71-with-a-Durable-Duration-of-Response-Ranging-Up-to-54-Months

2. 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 8, 2024. Accessed November 19, 2024. https://clinicaltrials.gov/study/NCT03022825

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

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

Nogapendekin alfa inbakicept-pmln (Anktiva; N-803) combined with BCG shows promising results in treating BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS). The QUILT 3.023 trial reports a 71% complete response rate among the first 100 patients, with some responses lasting up to 54 months. The trial's findings support the potential of ANKTIVA to improve outcomes and avoid cystectomy. The study, which includes three patient cohorts, continues to evaluate response durability and overall survival, with completion expected in October 2028.

At the time of data cutoff, 71% of patients achieved a complete response following treatment. 

Gary D. Steinberg, MD

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