Long-Term Results of N-803 Plus BCG for BCG-Unresponsive Bladder Cancer - Sam Chang
May 5, 2025
Zachary Klaassen interviews Sam Chang about updates on N-803 (ANKTIVA®/nogapendekin alfa-inbakicept-pmln) plus BCG for BCG-unresponsive bladder cancer. Dr. Chang explains that this IL-15 superagonist combined with BCG was FDA-approved for BCG-unresponsive CIS with or without papillary disease. He presents long-term data with median follow-up now exceeding 2.5 years, showing a complete response rate of 71% in the CIS population. 51% of patients maintined complete response beyond 45 months, cancer-specific survival at 99%, and cystectomy-free rates in the mid-80% range at three years. For papillary disease, one- and two-year disease-free rates were 58% and 52% respectively. Dr. Chang highlights the medication's advantages including refrigerator storage and a familiar dosing schedule similar to BCG.
Biographies:
Sam S. Chang, MD, MBA, Urologist, Patricia and Rodes Hart Professor of Urologic Surgery, Vanderbilt University Medical Center, Chief Surgical Officer, Vanderbilt-Ingram Cancer Center, Nashville, TN
Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Wellstar MCG, Georgia Cancer Center, Augusta, GA
Biographies:
Sam S. Chang, MD, MBA, Urologist, Patricia and Rodes Hart Professor of Urologic Surgery, Vanderbilt University Medical Center, Chief Surgical Officer, Vanderbilt-Ingram Cancer Center, Nashville, TN
Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Wellstar MCG, Georgia Cancer Center, Augusta, GA
Related Content:
AUA 2025: An Update on QUILT-3.032: Complete Responses to N-803 plus BCG Therapy in BCG-Unresponsive Bladder Carcinoma In Situ (CIS) with or without Ta/T1 Papillary Disease
Advances in Treatment Options for BCG Unresponsive CIS and Papillary Non-Muscle Invasive Bladder Cancer - QUILT 3.032 - Sam Chang
Unmatched Long-Term Bladder Preservation for 36 Months in over 80 percent of Responders with ANKTIVA® Plus BCG in BCG-Unresponsive NMIBC CIS and Papillary Disease Alone – Best in Disease and Best in Class with 5 Year Follow-Up
Novel Bladder Cancer Treatment: Mechanisms, Clinical Findings, and Implications - Patrick Soon-Shiong
The Triangle Offense: Harnessing NK Cells, T-Cells, and Memory Cells in Bladder Cancer - Patrick Soon-Shiong
AUA 2025: An Update on QUILT-3.032: Complete Responses to N-803 plus BCG Therapy in BCG-Unresponsive Bladder Carcinoma In Situ (CIS) with or without Ta/T1 Papillary Disease
Advances in Treatment Options for BCG Unresponsive CIS and Papillary Non-Muscle Invasive Bladder Cancer - QUILT 3.032 - Sam Chang
Unmatched Long-Term Bladder Preservation for 36 Months in over 80 percent of Responders with ANKTIVA® Plus BCG in BCG-Unresponsive NMIBC CIS and Papillary Disease Alone – Best in Disease and Best in Class with 5 Year Follow-Up
Novel Bladder Cancer Treatment: Mechanisms, Clinical Findings, and Implications - Patrick Soon-Shiong
The Triangle Offense: Harnessing NK Cells, T-Cells, and Memory Cells in Bladder Cancer - Patrick Soon-Shiong
Read the Full Video Transcript
Zachary Klaassen: Hi, and welcome to the Las Vegas AUA 2025. My name is Zach Klaassen. I'm a urologic oncologist in Augusta, Georgia. Delighted to be joined on UroToday, as always, by Dr. Sam Chang, urologic oncologist at Vanderbilt University. Sam, thanks so much for joining us.
Sam Chang: Zach, thank you. It's always an honor and privilege. And to be under the lights in Las Vegas, I think I can tell my parents I've made it. So really a pleasure and honor to be here with you today.
Zachary Klaassen: So as much as we normally would talk about hockey, we're going to talk a little bit about bladder cancer. So I know you've been really involved with the N‑803 plus BCG that really has been around for a few years now. So just briefly highlight for our listeners what the combination and what the rationale was to combine these two agents.
Sam Chang: Yeah, so like many of these medications for bladder cancer, there's been a name change, name revolution, et cetera. So the trade name for the medication is ANKTIVA, A‑N‑K‑T‑I‑V‑A. I've known it as N‑803. And now it goes by NAI, nogapendekin alfa‑inbakicept et cetera, et cetera, dot dot dot. NAI is how I actually now describe it, or ANKTIVA.
So this is actually a combination therapy utilizing an IL‑15 superagonist combined with BCG, and was FDA‑approved for patients with BCG‑unresponsive CIS with or without papillary disease. And so the presentation that I was a part of and that was fortunate enough to present on behalf of multiple co‑authors looked at basically long‑term results with that combination therapy for patients with BCG‑unresponsive disease.
Zachary Klaassen: Awesome. And so before we get into the updates you presented at AUA, just tell us about the data leading up to it, specifically the big publication—New England Journal of Medicine—evidence in 2022 that really would put this on the map and got FDA approval.
Sam Chang: Right. Exactly. I think that was the key point was that FDA approval, obviously, for any of our therapies is to achieve that kind of level of here's evidence‑based therapeutic intervention that is beneficial. Benefits outweigh harms. And so this is a medication that's been, obviously, years in development looking initially at utilizing this IL‑15 superagonist. So interleukin‑15, along with the other interleukins, are obviously an important part of our immune system and our immune defense system.
And this is actually a modified version of IL‑15 that actually lasts longer in the bloodstream. Usually, IL‑15 only lasts seconds, minutes in the bloodstream. So it lasts longer, has actually improved membrane binding with the receptor with an IL‑2 alpha receptor. So all that being said, what does it do?
In combination with BCG, by working concurrently and symbiotically, we are actually, with this medication, really improving the ability to recruit natural killer cells to actually improve CD4 and CD8 actual killing with monocytes and macrophages, dendritic cells, and yet, not inducing response with T‑cell regulation. So this combination has been shown in combination to really show a benefit in patients with CIS, as well as with papillary disease.
Zachary Klaassen: Awesome. And so we're now 2 and 1/2‑year median follow‑up removed from that initial publication. What's the durability? And what data did you present at AUA this year?
Sam Chang: Yeah, so we looked at both cohort A and cohort B. Cohort A was the CIS population that led to FDA approval. And what we found in looking at long‑term data, average follow‑up now more than 2 and 1/2 years, is that complete response rate was still quite high at 71%.
Zachary Klaassen: Excellent.
Sam Chang: But then you start looking at, OK, what are the key figures after that? What really matters to patients? So how did we do in terms of overall cancer‑specific survival? You're talking about 99%. You're talking about high 90s at more than 2 and 1/2 years, three‑year, longer than anything that we currently have. Secondly, we looked at that cystectomy‑free rate.
So that's the terminology that's been developed as companies and pharmaceutical industry look at, what are we doing to try to help these patients? And the majority want to avoid cystectomy. So cystectomy‑free rate at three years, 85%, 84%, all right? And then you're looking for durability of response. I've struggled with this complete response. Patients want to know if they have gotten any benefit.
Zachary Klaassen: If it worked.
Sam Chang: Exactly, but they want to know how long. And so now, looking at it, more than half the patients, so 51%, had a duration of complete response of more than 45 months.
Zachary Klaassen: Wow.
Sam Chang: So basically, more than half actually had almost four years CR. So it's that durability of response. If you look at the papillary cohort, cohort B, similarly, you had at one‑ and two‑years disease‑free rates of 58%, 52%. But again, the safety. 96% cancer‑specific survival at greater than three years. And if you look at cystectomy‑free rate, again, in the mid‑80s free of requiring that operation. And so it's the longest‑term data that I know of in terms of duration of follow‑up, and then the duration of response.
Zachary Klaassen: When we're getting into territory that we've wanted to get to for five years now, like we said, six‑month complete response, fantastic. But how long is it going to last for? We're starting to see that. Not just CR rates in the 50s, but 70s. And then now, as you mentioned, these numbers of cystectomy‑free rate. These are the things as surgeons that we worry about. Are we missing a window? Are we missing an opportunity to save their life from bladder cancer to not miss the window for cystectomy? But this data is very encouraging.
Sam Chang: Yeah, I think it's that tale at the end of the curves, of the survival curves, where we have tended to see that with other immunotherapies and other advanced disease. But this is not advanced disease. It's localized disease and, in fact, non‑invasive disease that these agents—but this agent in particular has shown this tale of, hey, if you have response, and the majority do, then that response can be withheld for a curve that tends to be flat, which I think when you can tell patients, look, we have a great chance of response. And then if you respond, we can't guarantee, but there's really a chance for a long‑term response. With this follow‑up of so long and this duration that's held up, maybe it means a cure.
And so I think that combination for CIS and papillary disease really is exciting for patients. It's an exciting time for bladder cancer with so many agents being studied. And I applaud all the different trials that are going on that we're part of as well to help determine, OK, for each patient population, what is the best therapeutic intervention going to be? Is it going to be intravesical? Is it going to be combination? Is it going to be systemic with intravesical? And that's the exciting part of being involved in the research is, all right, where do we go next? How can we improve options? What do we do next?
Zachary Klaassen: I just want to take a quick step back before we wrap up. FDA‑approved, people are using this in the clinics. Just quickly highlight the dosing schedule so people have an idea of what that is.
Sam Chang: So that's the nice thing about this medication. In terms of storage, this can be in a regular refrigerator. It's combined with BCG. We know how we give BCG. It's a very protocol schedule that we're familiar with, once a week for six weeks, that we follow. Then after that, if we have a response, we have that once a week for a three‑week type of regimen that's then spaced out to twice a year. We do and we have done repeat induction. Just like BCG, if we haven't had the response that we thought that we would have, or not the complete response, we do a repeat induction. But it is very similar to giving BCG, and it's given with BCG.
Zachary Klaassen: That's great. Great updates on QUILT‑3.032. Any quick take‑home messages for UroToday listeners?
Sam Chang: I think an exciting time for all patients with bladder cancer in terms of I've got options, we've got treatment choices. Secondly, I think we need to, obviously, improve the educational information out there for all clinicians regarding, here, we've got options. And importantly, clinical trials are out there. In terms of durability of response, I think those are the key points that we gained from this data that was presented at the AUA.
Zachary Klaassen: Super exciting time. As you mentioned, this has been just revolutionary the last five years. And this data is certainly helpful as we look at those 3‑, 4‑, 5‑year outcomes. So thanks for joining us on UroToday.
Sam Chang: Zach, always a pleasure and truly an honor. And it gives me a chance to thank you for all the efforts that you've made with UroToday and getting it out there. I cannot tell you how many people have come up and said Zach had this great—Zach? What? No, they say exactly. Zach has given this information on this and this. And the updates that you provide and the summaries have been fantastic.
Zachary Klaassen: That's very kind. It's the best platform out there, so I'm delighted to be a part of it. Thanks, Sam.
Zachary Klaassen: Hi, and welcome to the Las Vegas AUA 2025. My name is Zach Klaassen. I'm a urologic oncologist in Augusta, Georgia. Delighted to be joined on UroToday, as always, by Dr. Sam Chang, urologic oncologist at Vanderbilt University. Sam, thanks so much for joining us.
Sam Chang: Zach, thank you. It's always an honor and privilege. And to be under the lights in Las Vegas, I think I can tell my parents I've made it. So really a pleasure and honor to be here with you today.
Zachary Klaassen: So as much as we normally would talk about hockey, we're going to talk a little bit about bladder cancer. So I know you've been really involved with the N‑803 plus BCG that really has been around for a few years now. So just briefly highlight for our listeners what the combination and what the rationale was to combine these two agents.
Sam Chang: Yeah, so like many of these medications for bladder cancer, there's been a name change, name revolution, et cetera. So the trade name for the medication is ANKTIVA, A‑N‑K‑T‑I‑V‑A. I've known it as N‑803. And now it goes by NAI, nogapendekin alfa‑inbakicept et cetera, et cetera, dot dot dot. NAI is how I actually now describe it, or ANKTIVA.
So this is actually a combination therapy utilizing an IL‑15 superagonist combined with BCG, and was FDA‑approved for patients with BCG‑unresponsive CIS with or without papillary disease. And so the presentation that I was a part of and that was fortunate enough to present on behalf of multiple co‑authors looked at basically long‑term results with that combination therapy for patients with BCG‑unresponsive disease.
Zachary Klaassen: Awesome. And so before we get into the updates you presented at AUA, just tell us about the data leading up to it, specifically the big publication—New England Journal of Medicine—evidence in 2022 that really would put this on the map and got FDA approval.
Sam Chang: Right. Exactly. I think that was the key point was that FDA approval, obviously, for any of our therapies is to achieve that kind of level of here's evidence‑based therapeutic intervention that is beneficial. Benefits outweigh harms. And so this is a medication that's been, obviously, years in development looking initially at utilizing this IL‑15 superagonist. So interleukin‑15, along with the other interleukins, are obviously an important part of our immune system and our immune defense system.
And this is actually a modified version of IL‑15 that actually lasts longer in the bloodstream. Usually, IL‑15 only lasts seconds, minutes in the bloodstream. So it lasts longer, has actually improved membrane binding with the receptor with an IL‑2 alpha receptor. So all that being said, what does it do?
In combination with BCG, by working concurrently and symbiotically, we are actually, with this medication, really improving the ability to recruit natural killer cells to actually improve CD4 and CD8 actual killing with monocytes and macrophages, dendritic cells, and yet, not inducing response with T‑cell regulation. So this combination has been shown in combination to really show a benefit in patients with CIS, as well as with papillary disease.
Zachary Klaassen: Awesome. And so we're now 2 and 1/2‑year median follow‑up removed from that initial publication. What's the durability? And what data did you present at AUA this year?
Sam Chang: Yeah, so we looked at both cohort A and cohort B. Cohort A was the CIS population that led to FDA approval. And what we found in looking at long‑term data, average follow‑up now more than 2 and 1/2 years, is that complete response rate was still quite high at 71%.
Zachary Klaassen: Excellent.
Sam Chang: But then you start looking at, OK, what are the key figures after that? What really matters to patients? So how did we do in terms of overall cancer‑specific survival? You're talking about 99%. You're talking about high 90s at more than 2 and 1/2 years, three‑year, longer than anything that we currently have. Secondly, we looked at that cystectomy‑free rate.
So that's the terminology that's been developed as companies and pharmaceutical industry look at, what are we doing to try to help these patients? And the majority want to avoid cystectomy. So cystectomy‑free rate at three years, 85%, 84%, all right? And then you're looking for durability of response. I've struggled with this complete response. Patients want to know if they have gotten any benefit.
Zachary Klaassen: If it worked.
Sam Chang: Exactly, but they want to know how long. And so now, looking at it, more than half the patients, so 51%, had a duration of complete response of more than 45 months.
Zachary Klaassen: Wow.
Sam Chang: So basically, more than half actually had almost four years CR. So it's that durability of response. If you look at the papillary cohort, cohort B, similarly, you had at one‑ and two‑years disease‑free rates of 58%, 52%. But again, the safety. 96% cancer‑specific survival at greater than three years. And if you look at cystectomy‑free rate, again, in the mid‑80s free of requiring that operation. And so it's the longest‑term data that I know of in terms of duration of follow‑up, and then the duration of response.
Zachary Klaassen: When we're getting into territory that we've wanted to get to for five years now, like we said, six‑month complete response, fantastic. But how long is it going to last for? We're starting to see that. Not just CR rates in the 50s, but 70s. And then now, as you mentioned, these numbers of cystectomy‑free rate. These are the things as surgeons that we worry about. Are we missing a window? Are we missing an opportunity to save their life from bladder cancer to not miss the window for cystectomy? But this data is very encouraging.
Sam Chang: Yeah, I think it's that tale at the end of the curves, of the survival curves, where we have tended to see that with other immunotherapies and other advanced disease. But this is not advanced disease. It's localized disease and, in fact, non‑invasive disease that these agents—but this agent in particular has shown this tale of, hey, if you have response, and the majority do, then that response can be withheld for a curve that tends to be flat, which I think when you can tell patients, look, we have a great chance of response. And then if you respond, we can't guarantee, but there's really a chance for a long‑term response. With this follow‑up of so long and this duration that's held up, maybe it means a cure.
And so I think that combination for CIS and papillary disease really is exciting for patients. It's an exciting time for bladder cancer with so many agents being studied. And I applaud all the different trials that are going on that we're part of as well to help determine, OK, for each patient population, what is the best therapeutic intervention going to be? Is it going to be intravesical? Is it going to be combination? Is it going to be systemic with intravesical? And that's the exciting part of being involved in the research is, all right, where do we go next? How can we improve options? What do we do next?
Zachary Klaassen: I just want to take a quick step back before we wrap up. FDA‑approved, people are using this in the clinics. Just quickly highlight the dosing schedule so people have an idea of what that is.
Sam Chang: So that's the nice thing about this medication. In terms of storage, this can be in a regular refrigerator. It's combined with BCG. We know how we give BCG. It's a very protocol schedule that we're familiar with, once a week for six weeks, that we follow. Then after that, if we have a response, we have that once a week for a three‑week type of regimen that's then spaced out to twice a year. We do and we have done repeat induction. Just like BCG, if we haven't had the response that we thought that we would have, or not the complete response, we do a repeat induction. But it is very similar to giving BCG, and it's given with BCG.
Zachary Klaassen: That's great. Great updates on QUILT‑3.032. Any quick take‑home messages for UroToday listeners?
Sam Chang: I think an exciting time for all patients with bladder cancer in terms of I've got options, we've got treatment choices. Secondly, I think we need to, obviously, improve the educational information out there for all clinicians regarding, here, we've got options. And importantly, clinical trials are out there. In terms of durability of response, I think those are the key points that we gained from this data that was presented at the AUA.
Zachary Klaassen: Super exciting time. As you mentioned, this has been just revolutionary the last five years. And this data is certainly helpful as we look at those 3‑, 4‑, 5‑year outcomes. So thanks for joining us on UroToday.
Sam Chang: Zach, always a pleasure and truly an honor. And it gives me a chance to thank you for all the efforts that you've made with UroToday and getting it out there. I cannot tell you how many people have come up and said Zach had this great—Zach? What? No, they say exactly. Zach has given this information on this and this. And the updates that you provide and the summaries have been fantastic.
Zachary Klaassen: That's very kind. It's the best platform out there, so I'm delighted to be a part of it. Thanks, Sam.