Elizabeth Plimack: Hi, I'm Betsy Plimack. I'm a GU Medical Oncologist at Fox Chase Cancer Center in Philadelphia. I am here at ASCO 2025, and I'm so happy to be here with my colleague and longtime friend Jeannie Hoffman-Censits, who is an associate professor of medical Oncology and Neurology at the Sidney Kimmel Comprehensive Cancer Center in Baltimore. Jeannie, thank you so much for joining us.

Jeannie Hoffman-Censits: Thanks for having me.

Elizabeth Plimack: I loved your presentation this morning.

Jeannie Hoffman-Censits: Oh, thank you.

Elizabeth Plimack: Expertly done. Really an interesting study. So you were looking at Avelumab in the maintenance setting using sort of even within the study data from JAVELIN Bladder 100.

Jeannie Hoffman-Censits: Right.

Elizabeth Plimack: And then looking at this beautifully designed Medley study, looking at ways to help boost the efficacy of Avelumab in this setting. So tell me a little bit about the study, the design, how it came about, and then we can dive into the arm that you presented today.

Jeannie Hoffman-Censits: Sure. Well, thanks so much for inviting me to talk about the study. So this was a study looking at Avelumab maintenance and then Avelumab maintenance plus other anti-cancer therapies. And this part of the study was really focusing on Avelumab plus Sacituzumab. As you mentioned, it was an interesting study design, and that interesting part of the design came in the form of the control arm.

So instead of a traditional kind of one-to-one randomization, we had this contemporary dataset of the JAVELIN Bladder 100 randomized phase three study. So because this was not built as a registry study, it was more of a hypothesis-generating study, the idea was pulling some patients from the JAVELIN Bladder 100 study and using that dataset to fill in so that we can do a more efficient study moving forward. And that when you know when you're having a conversation with a patient in clinic, talking to them about being on a randomized study, patients are usually very interested if they want to be a part of a study of generally not being a part of the control arm.

Elizabeth Plimack: Right.

Jeannie Hoffman-Censits: So I think both for efficiency and also kind of listening to what patients have to say in the clinic, it was, I think, a unique way to do a study like this. And so thanks for pointing that out.

Elizabeth Plimack: Yeah. By the way, it's brilliant. I hope we see more of them. I think we need to innovate how we do these trials and move quickly to investigate agents. So yes, kudos to the design.

Jeannie Hoffman-Censits: Thank you. It's team effort as usual. Yeah. So Sacituzumab is a drug that has efficacy as we know in patients with urothelial cancer. It's of course approved in a very different population of patients with breast cancer. But we know based on a few prior studies that Sacituzumab definitely has efficacy and we know it can be safely combined with checkpoint inhibitor therapies. So I think to improve upon what we already know about the maintenance setting, taking patients who are already doing quite well, and then switching therapies including Avelumab maintenance, and then trying to really increase the bar of efficacy and long-term outcomes by adding additional active anti-cancer therapies is the idea behind the trial.

Elizabeth Plimack: Great. Yeah, we're always looking, once you have a good answer, you're always looking to do better.

Jeannie Hoffman-Censits: Right. Right.

Elizabeth Plimack: That's great.

Jeannie Hoffman-Censits: It's what we do.

Elizabeth Plimack: So what did you find with the Sacituzumab govitecan plus Avelumab arm in this maintenance setting?

Jeannie Hoffman-Censits: Well, I think one thing we found just in general is that thinking about the maintenance setting, knowing what we know about the JAVELIN Bladder 100 study and then this study, which was a positive study in terms of the outcomes that we were looking for, this is actually a space that we can think about future studies.

So just like the maintenance space wasn't really a space before Avelumab was proved, now thinking about this space as one where you can do additional therapies in the future or additional studies in the future, I think is important. So what we found was first of all, no new safety concerns with the combination, which is important. And there was a significant improvement in progression-free survival, adding Sacituzumab to Avelumab versus Avelumab maintenance alone.

Elizabeth Plimack: Yeah. No, that's great. I know you presented also, these weren't primary endpoints of the study, but overall survival.

Jeannie Hoffman-Censits: Yeah. Overall survival is immature at this point. So this was the interim analysis based on events expected in the progression-free survival endpoint. So overall survival would be looking for as well as some other endpoints coming sometime early next year.

Elizabeth Plimack: Right. So let's talk about Sacituzumab govitecan for a minute. I think Jackie Brown said we have a complicated relationship with SG. We were super excited to have something else approved for bladder cancer. Then the indication was withdrawn in the US. But it's certainly something we think about.

It still has its place in the guidelines. How do you think about Sacituzumab govitecan for your patients. Two-part question. Is this maintenance space where it's investigated sort of its place to shine, or is there another setting where you use it? And then I'll ask you a little bit more about the art of giving SG, because you're very good at it.

Jeannie Hoffman-Censits: Yeah. No. Well, thank you. Well, even though the data are really compelling, I don't think in clinic today, if we go back to practice next week, that you can use Sacituzumab in combination with checkpoint inhibitors right now outside of a clinical trial. So even though the data are interesting, we really can't do that. But in terms of thinking about how we use that tool and all tools in our patients with bladder cancer, we're living in this brand new era. Right? We have this very kind of powerful new combination of EV and Pembro, and then the question is X, Y, and Z, kind of what happens after that.

Elizabeth Plimack: Right. Right.

Jeannie Hoffman-Censits: I think one of the very interesting things about Sacituzumab is one of the tools that we may be using in the later-line setting is, although we kind of focus on some of the cytopenias in terms of toxicity, it does not have the same side-effect profile in terms of peripheral neuropathy that we're dealing with in patients that may be getting EV and Pembro and then subsequent platinum-based chemotherapy. I think we kind of somewhat dogmatically think about that, but when patients are really suffering with neuropathy, maybe had to stop Enfortumab when they're having a great response because of neuropathy, that's sometimes when I think about grabbing Sacituzumab as an earlier-line agent.

Elizabeth Plimack: That's a really good point.

Jeannie Hoffman-Censits: Yeah.

Elizabeth Plimack: Right. The side-effect profile is different enough. It offers a break.

Jeannie Hoffman-Censits: Right. Right.

Elizabeth Plimack: From what they had before.

Jeannie Hoffman-Censits: And then the other thing is we're now living in an era too where we have these biomarker-directed therapies. And I don't know about you, but my heart sinks a little bit when I see those sequencing reports that come back that really don't have any compelling targets for a patient and I know that some of the tools that I would use in my expanded toolkit based on those targets, if they don't have it, then I'm grateful that Sacituzumab is still a part of the NCCN guidelines that we can use it under certain circumstances. And I think that really falls into that category.

Elizabeth Plimack: Yeah, that's a really good point. I feel like not enough of my patients get those hits on the sequencing reports. I always wish we were seeing more, and I share that. Yes. So tell me how you give SG. I know you have a really long experience with it from the trials and this trial and beyond. What are some pearls for our listeners who might be reaching for that in exactly these situations that you mentioned?

Jeannie Hoffman-Censits: Yeah. Well, I think, again, Jackie Brown's presentation was so amazing, jaw-droppingly good. So plug for her for people to go back and watch it. As she said, patients with urothelial cancer are not the same patients as the young women with breast cancer. They have a lot of medical comorbidities, they're older, and potentially that's maybe why the drug is behaving somewhat differently.

So because of some early experiences, I just in my own practice start with a dose reduction at 20% with upfront growth-factor support. If a patient does exceedingly well, we have a conversation about escalating that dose in cycle two. If not, we stay with a 20% dose reduction and go from there. In that setting, I feel like I've been able to shepherd patients through multiple cycles of treatment where I'm then looking at scans and not holding and making dose adjustments with that strategy.

Elizabeth Plimack: Right. I think that's great. Again, we get good at using these, we know how the trial was done. We know how we're supposed to dose it and what we're supposed to do, but in the real world in practice, I think we develop an art around those. And I think those suggestions—starting with the dose reduction, cautioning patients of course about what to watch for, and then using growth factor in everybody from the get-go—that's what I've heard most people support. So yeah.

Jeannie Hoffman-Censits: Yes. And I think that word that you just used is great, is those suggestions.

Elizabeth Plimack: Right.

Jeannie Hoffman-Censits: I had lunch with a few colleagues today and found out that we all have kind of a different tweaking pattern in terms of how we utilize Sacituzumab.

Elizabeth Plimack: Right. Right. And that's why I think it's just as important as sharing clinical-trial data to share our real-world art of oncology.

Jeannie Hoffman-Censits: Exactly.

Elizabeth Plimack: How we can use these. And as you said, our toolbox is always more limited than we would like. It's nice to still have that in there.

Jeannie Hoffman-Censits: Absolutely. Yeah.

Elizabeth Plimack: Good. Great. Well, Jeannie, thank you so much for presenting that data so clearly, so well. I love, again, the adaptive trial design that really lets us focus on the questions we want to answer and not repopulating a control arm that we already had. So I hope this will go down in sort of the teaching mantle for how to design these sort of signal-finding trials in the future. Just one last question. There were a couple of other arms of that study. Did those proceed to accrual and might we be seeing those in the future?

Jeannie Hoffman-Censits: Yeah. We hope to present the final analysis and those arms will be there hopefully in 2026.

Elizabeth Plimack: Okay.

Jeannie Hoffman-Censits: So keep a lookout.

Elizabeth Plimack: Great. We will.

Jeannie Hoffman-Censits: Thank you.

Elizabeth Plimack: Thank you so much.