Matthew Galsky: Thank you. Thanks for having me.
Tian Zhang: We wanted to catch up on the TROPION-03 trial. Can you tell us a little bit about the trial and where it's at?
Matthew Galsky: Yes, so this is a phase 2, 3 study. It's evaluating Dato-DXd, which is an antibody drug conjugate directed against TROP-2 with the topoisomerase payload. This has been evaluated as monotherapy in patients with metastatic urothelial cancer as part of a larger basket study. And in that study, in heavily pretreated patients, there was a response rate of 25% and so an active drug.
And so, this study is really trying to identify whether or not the post enfortumab vedotin plus pembrolizumab setting is the right setting for this drug. And it's asking a pretty interesting question from the standpoint of phase 3s in this setting. And that question is, should we give an ADC plus platinum-based chemotherapy or should we give platinum-based chemotherapy with gemcitabine?
Tian Zhang: And that's your current practice, Matt, and I think it's been mine to sequence platinum-based chemos after EV pembrolizumab. What percentage of the population do you think are progressing past EV pembrolizumab and is eligible for this type of trial?
Matthew Galsky: So I think there are two populations of patients who get EV pembrolizumab, of course, who would be considered for a trial like this. And based on the approval of EV pembrolizumab in the metastatic setting, I think early on we were seeing more of one group of patients and now unfortunately we're seeing more of another group. That is that there are a small subset of patients, as you well know, who have primary refractory disease to EV pembrolizumab. It's a small subset, but of course those patients need a subsequent treatment pretty quickly.
And then there's the group of patients who have responses to EV pembrolizumab, maybe response to one drug or another, maybe response to both. Of course, hard to know when you give a doublet, but ultimately have disease progression and that's quite variable. And we know from the EV pembrolizumab long-term follow-up data that we saw at ASCO that if you have a response to that regimen, that response can be very long-lasting. But of course there are patients who ultimately develop disease progression need subsequent treatment.
Platinum-based chemotherapy has been my default regimen in that setting, recognizing that there's really a paucity of data to support that. But we've just moved platinum-based chemotherapy from the first-line setting to the second-line setting because of EV pembrolizumab.
A couple of data sets with EV pembrolizumab, including single institutional data in addition to data that was presented at ASCO 2026 that included an analysis of patients on EV-302 who received platinum-based chemotherapy after progressing on EV pembrolizumab. That's one of the more interesting data sets because it was part of a clinical trial of course, but it's not really prospective data assessing platinum-based chemotherapy. That said, with all of the caveats, a pretty low response rate with platinum-based chemotherapy in that data set.
Tian Zhang: Matt, we've followed the other TROP-2 ADC a bit, sacituzumab govitecan in this space. Any differences of Datopotamab deruxtecan and this development in this particular refractory trial?
Matthew Galsky: So there are a few differences both in terms of the drug and then in terms of the trial design in the context. The differences in the drug, of course, are that sacituzumab govitecan, the payload is SN-38. SN-38 is a topoisomerase inhibitor, but as you well know, SN-38 can be administered even without antibody conjugation. One of the main benefits of giving an ADC is to give a drug that's so potent that you otherwise couldn't give it when it's not targeted for delivery with an antibody. And DXd of course, is a high potency payload.
So there are differences in the potency of the payload. And then there are differences of course in the trial designs. As mentioned, this is Dato-DXd plus platinum versus platinum-based chemotherapy. Of course, the phase 3 with sacituzumab was in a different time, and therefore it was sacituzumab monotherapy versus non-platinum-based chemotherapy because patients had already received platinum-based chemotherapy at that time.
Tian Zhang: Got it. No, I think it's a really important trial in this refractory space. Is it open globally? What's the enrollment been like?
Matthew Galsky: So this is open globally. It's a phase 2/3 design. The phase 3 endpoint is objective response rate. This is a 60 patient study, which is really seeking to define the optimal dosing of Dato-DXd plus platinum. And then based on that data, the phase 3 will open, which will randomize patients between Dato-DXd plus either cis or carbo, it's dealer's choice versus gem plus sis or carbo, dealer's choice based on what the patient's most suitable for. And that is a larger phase 3 portion with a dual endpoint of PFS and overall survival.
Tian Zhang: Awesome. Well, I hope the trial goes really well. I know we're both participating centers, and hopefully we'll find our patients and be able to treat them on trial. Any last thoughts for the UroToday audience?
Matthew Galsky: I would say that a number of ADC trials in this space, each asking a slightly nuanced question. So we have ADC monotherapy versus chemotherapy monotherapy. Here, we have ADC plus platinum versus platinum-based chemotherapy. And in another phase 3, we have immune checkpoint blockade re-treatment plus an antibody drug conjugate versus an antibody drug conjugate alone. And so, a number of important questions which will be addressed by these phase 3 studies, and together, we'll really have a good understanding of the best path forward.
Tian Zhang: Absolutely. Thank you so much for joining us, Matt.
Matthew Galsky: Thank you.