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24-Month Follow-Up Data from Phase 3 BOND-003 Cohort C Trial - Mark Tyson

December 4, 2025

Zachary Klaassen speaks with Mark Tyson about 24-month follow-up data from BOND-003 Cohort C evaluating cretostimogene grenadenorepvec in BCG-unresponsive CIS patients. Dr. Tyson reports that 42% of patients maintained complete response at 24 months in the intention-to-treat population, representing clinically meaningful durability for this heavily pretreated cohort with median 12 prior BCG instillations. The overall complete response rate at any time reached 75.5% with median duration of response of 27.9 months. The treatment demonstrated no grade three treatment-related adverse events, no treatment-related discontinuations, and no deaths. Dr. Tyson emphasizes that the 42% landmark complete response number provides more practical patient counseling value than duration of response curves, allowing clinicians to tell patients their likelihood of maintaining response two years after starting therapy. 

Biographies:

Mark Tyson II, MD, MPH, Urologic Oncologist, Mayo Clinic, Scottsdale, AZ

Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor of Surgery/Urology at the Medical College of Georgia at Augusta University, Wellstar MCG, Georgia Cancer Center, Augusta, GA



Related Content:

 SUO 2025: Durable 24 Month Outcomes from BOND-003 Cohort C: Phase 3 Study of Intravesical Cretostimogene Grenadenorepvec for High-Risk BCG-Unresponsive Non-Muscle Invasive Bladder Cancer with CIS

Cretostimogene Grenadenorepvec Complete Response in BOND-003 Cohort C - Trinity Bivalacqua

BOND-003 Cohort C Trial Results for Cretostimogene Grenadenorepvec in BCG-Unresponsive Bladder Cancer - Mark Tyson

WSAUA 2025: Final Results from BOND-003 Cohort C: A Phase 3, Single-Arm Study of Intravesical Cretostimogene Grenadenorepvec for High Risk BCG Unresponsive NMIBC with CIS
Read the Full Video Transcript

Zachary Klaassen: Hi, welcome to UroToday. My name is Zach Klaassen, urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. Delighted to be joined, as always, by Dr. Mark Tyson, who is a urologic oncologist at Mayo Clinic in Phoenix, Arizona. Today we're going to be discussing his SUO 2025 presentation looking at BOND-003 Cohort C and really interesting data looking at the 24-month follow-up. So Mark, thank you so much for joining us as always.

Mark Tyson: Yes, thanks for having me, Zach. I'm delighted to be here and happy to present on behalf of my co-investigators for BOND-003 Cohort C. Just as a reminder to your viewers, Cohort C was a single-arm, open-label, phase 3, registrational trial evaluating cretostimogene in patients with BCG-unresponsive CIS. So these are patients that conform to the standard FDA definition of a CIS recurrence within 12 months of the last dose of adequate BCG. And as expected, these are heavily pretreated, very difficult to treat populations. The median number of instillations for prior BCG for these patients was 12, and so they're obviously quite treatment refractory. And on this trial, they get weekly cretostimogene once a week for six weeks followed by maintenance every quarter. So weekly times three, every quarter for a year, and then every six months in years two and three. And these patients do undergo a mandatory biopsy at a year with bladder mapping. So rigorous prospective trial data from Cohort C. And now we have long-term follow-up, which is what we presented at the SUO.

At the top line number, 75.5% of patients have a complete response at any time point. So this includes those who have a complete response after the first induction, as well as those who convert to a CR after repeat induction. And we've known that number for a while. That number hasn't changed. And the median duration of response hasn't changed at 27.9 months. What's changed is the 24-month intention-to-treat population for those in complete response. And we previously reported the 12-month of 46%, but now we're reporting that 24-month number of 42%. So it's basically what we've observed from the DOR curves in the past, and those in whom this works, it works quite well and is durable. For a monotherapy to have 42% of patients in complete response at two years is quite incredible. And to do so with no grade three treatment-related AEs and no treatment-related discontinuations and no deaths is I think a pretty promising risk-benefit ratio. And so I guess that kind of highlights mainly what we presented, Zach. And I'll stop there and take questions.

Zachary Klaassen: Yeah, no, that's great. That's an awesome summary. I think a couple things I want to get into. It seems like yesterday we were talking about... You and I were talking SUO '23 when you presented the first results from Cohort C, and now we're two years later. Maybe just off the cuff, just speak to your experience with this drug tolerability, how easy it is for your nurses and your team to use it.

Mark Tyson: Yeah, I think that's one of the main pieces of this whole logistical puzzle is I think you and I are busy and most of us are busy, so I'm not actually administering it myself. Nurses are doing it, and it's very similar to BCG. There is a few additional components like the DDM wash, which adds about 15 minutes to the instillation. That breaks down the GAG layer and allows transduction of the virus. But yeah, aside from that kind of two-step modification, it's very similar to BCG. Just at a very high level, I have a lot of confidence in this drug. I've treated now probably 65 or so patients across the whole portfolio of trials at Mayo. And I put patients on these trials quite readily. And I mean, we've all seen the numbers, and so I don't hesitate. I don't hesitate on any of the trials. But this one, the numbers have looked so good and it's so well tolerated, I've been pretty confident and pretty happy with the results so far.

Zachary Klaassen: Yeah, no, and this 24-month data I think is super important. When we sit there and we talk to patients about risks and how this is going to work, I mean, think about this, this is CIS, BCG-unresponsive, 24-month, 42%. So one in two of our patients are going to have a complete response at two years. Just maybe put that into, I guess, more poetic words of how we would say this to a patient. What's a conversation like now?

Mark Tyson: Well, that's the really tricky piece. And I think that's maybe it would be helpful to clarify for your viewers the difference between intention-to-treat landmark CR and DOR curve. So what the FDA has asked for is complete response and duration of response, and that's what the field is providing. And that's what you find in the FDA inserts. And that's the 75% number with a 27-month median DOR, but patients don't really know how to make sense of that. And candidly, sometimes I don't know how to make sense of that.

Zachary Klaassen: Sure.

Mark Tyson: And so I much prefer the what proportion of patients at one year, at two years, at three years is still in complete response after starting the trial. And so that denominator includes everybody, not just those who responded. And I don't want KM estimated [inaudible 00:05:31] either. I want the actual number because we have the follow-up with these patients. And so in this trial, that number is 42% at two years. That means you can look your patient in the eye and say, "Your chances of being in complete response two years from now is 42%." And that's just a much easier number to digest.

Zachary Klaassen: Well, I think it's important too, because that's what they're going to ask us. They're not going to ask us if it works initially. They want to ask us, "If this works, how long is it going to work for?" So I think this is really important data for us to be able to talk to our patients. Mark, always great having you on. I appreciate all your valuable time talking about cretostimogene and certainly these 24-month follow-up data you presented at SUO. Any take-home messages, any final thoughts for our listeners?

Mark Tyson: No, I appreciate this opportunity to be here. I am very excited about the Cohort C data. The only thing I would add is that Cohort C data should be available in manuscript form for your viewers and others I would expect some time in the first quarter of 2026.

Zachary Klaassen: Wonderful.

Mark Tyson: Fingers crossed.

Zachary Klaassen: We'll look forward and we'll probably have you back on to discuss it in more detail with the manuscript. Thanks so much, Mark.

Mark Tyson: Thanks for having me, Zach.

Zachary Klaassen: Always.