Jonathan Anker: Yes. Well, first off, thank you very much for having me here. So the data we presented is a phase two investigator-initiated study, GU 20-444, which was looking at TURBT followed by pembrolizumab, a clinical re-staging assessment, in an attempt to do a risk-adapted bladder-sparing approach.
Elizabeth Plimack: In MIBC.
Jonathan Anker: Yes, muscle-invasive bladder cancer. And so briefly, some of the rationale for this is that we know when we ask patients what they want, the answer that very often comes back is, "We want to retain our bladders." And so cystectomy is obviously with its risk. It has significant morbidities, permanent urinary diversion, mortality rate, especially in patients of older age, which is the patients we see.
And we know from historical data, patients with muscle-invasive bladder cancer who get systemic therapy, and then traditionally they get radical cystectomy. In the past, we weren't giving much adjuvant therapy. And we have long-term data that a subset of those patients, typically the ones that achieve a pathologic complete response, are the ones that often can have very long-term five-plus-year survival without evidence of recurrence. So it's suggestive that many of those patients are cured prior to even having gone for the surgery. And so this was a follow-up study from a phase two study, GU 16257, both were out of the HCRN. There were some differences in eligibility, but that was with chemotherapy, cisplatin chemotherapy, and PD-1 blockade. The main difference is that this is with TURBT and then only pembrolizumab, no chemotherapy.
Elizabeth Plimack: Okay, great. So what was your clinical complete response rate in this study?
Jonathan Anker: Yes. I should also mention that it was two cycles of pembrolizumab, specifically dosed at Q6 week with 400 milligrams.
Elizabeth Plimack: Good.
Jonathan Anker: The clinical restaging was a stringent and uniform assessment. So it was comprised of cystoscopy for everybody at the clinical restaging. They had either resection of visible tumor or biopsies of where the initial tumor site was, or a predefined template of the bladder, cytology, MRI of the bladder. If all three of those were without evidence of disease, they were considered to have achieved a clinical complete response and they had seven additional cycles of maintenance pembrolizumab. For patients where any one of those were positive, did not achieve a clinical complete response, then they had immediate upfront definitive local therapy, either radical cystectomy or chemoradiation, and then were offered seven additional cycles of what would be adjuvant pembrolizumab. And then also the co-primary endpoints were clinical complete response and the ability of clinical CR to predict benefit from treatment, which was two-year MFS in those patients.
Elizabeth Plimack: Right, right.
Jonathan Anker: And so when we did that, we did the stringent clinical restaging. We enrolled 46 patients. We saw 20 of those 46, so 43% achieved a clinical complete response.
Elizabeth Plimack: That's excellent. And I think that's more than we might expect from a single-agent checkpoint, given that it's higher than we saw with chemo plus checkpoints.
Jonathan Anker: Yes, yes. Actually, we were very pleased to see that number. I mean, kind of coincidentally, but also quite profoundly. It was exactly the same. 43% was the clinical CR rate we saw in the initial study, which was neoadjuvant cisplatin chemo plus IO. So I think it's very promising.
Elizabeth Plimack: Yeah, that's great.
Jonathan Anker: Yes. And all of those patients omitted upfront cystectomy.
Elizabeth Plimack: Right, right. And I'm sure many of them are still happy today with their bladders intact, which is great.
Jonathan Anker: Yes.
Elizabeth Plimack: So you collected ctDNA and I think other correlates, what did you learn from those?
Jonathan Anker: Yes. So that is ongoing. The data is still maturing, but we're looking at ctDNA. We are assessing it at different time points, baseline, and then multiple on-treatment time points. And so we see as patients who have undetectable ctDNA at baseline versus those who have detectable ctDNA, were a lot more likely to go on to achieve a clinical complete response. And then patients who, if we only look at patients then who achieve a clinical complete response and we look at the on-treatment ctDNA, so that's cycle two day one, 100% of those patients achieved a clinical complete response, which is what we saw in the prior study as well. So all patients who achieve a clinical complete response have undetectable ctDNA on treatment after... this was in fact after only one dose of treatment, and that included two patients that cleared their initially detectable ctDNA.
Elizabeth Plimack: Interesting.
Jonathan Anker: And then of the patients, if we go back of the undetectable baseline ctDNA patients, a much lower risk of metastatic recurrence.
Elizabeth Plimack: Right, right. Excellent. That's really interesting because we saw data earlier this morning that ctDNA really doesn't describe what's in the bladder as well as it describes what's outside the bladder. And we saw that with NIAGARA. So it's really compelling and I think interesting to see how well it correlated here, which is great.
Jonathan Anker: Yes.
Elizabeth Plimack: Good. So where does this study take us and sort of as we look at what the future brings?
Jonathan Anker: Well, I think our study, the RETAIN studies, I think they're very, very important for this field. I think as our therapeutics advance, as our systemic therapy advances, our diagnostic advances, our understanding of restaging and making this a more uniform and stringent assessment advances, I think we could make this a much more individualized patient-focused pathway. Of those 20 patients that we had that achieved a clinical CR, our follow-up is still ongoing. It's about 12 months median follow-up to date, but none of those patients have had a metastatic recurrence.
Elizabeth Plimack: None. Wow.
Jonathan Anker: No. And only one of them had a local non-muscle-invasive recurrence, still has the bladder at the latest data lock. One patient had a cystectomy that was actually for a diagnosis of prostate cancer and had a path CR in the bladder. So follow-up's ongoing, but I think very promising.
Elizabeth Plimack: So great results.
Jonathan Anker: Yes, yes. And I think it'll be a challenge to make these studies larger and randomized, but I think this is eventually going to be where this field goes.
Elizabeth Plimack: Yeah. Well, I'm with you on that. Congratulations on completing an investigator-initiated study with a really important patient-centric endpoint and delivering the results today. Great work. Thank you.
Jonathan Anker: Thank you for having me.