Zachary Klaassen: Hi, my name is Zach Klaassen, urologic oncologist at the Georgia Cancer Center. We're in Chicago for ASCO 2025, and I'm delighted to be joined by Dr. Joaquim Bellmunt, who is a medical oncologist at the Dana-Farber Cancer Institute. Professor Bellmunt, thanks for joining us on here today.

Joaquim Bellmunt: It's a pleasure to be here.

Zachary Klaassen: Wonderful. And we're going to talk today about some of the early results that we're seeing from the SSANTROP study. So this is another study we're seeing in this BCG-unresponsive high-risk non-muscle invasive bladder cancer space. There's been a lot of activity in this space. Maybe just give us a little bit of rationale for what you guys looked at in the SSANTROP study.

Joaquim Bellmunt: Yeah. The SSANTROP stands for-- the first two "S"s are sasanlimab. "AN" is an anti-PD-1. And "TROP" is a TROP2 inhibitor combined. So this is an investigator-initiated trial. And this was designed when the first results that came back from the metastatic setting, meaning combining a PD-L1 inhibitor plus an ADC were so successful. And then we try to move this earlier and earlier in that space of a BCG-refractory that nowadays is a really crowded space.

At the time this trial was designed, we were trying to beat the results of obtaining pembrolizumab. That was at least 41% of pathologic complete responses at three months. And based on that, we designed a trial, based on 116 patients, with the aim to increase the complete responses to 53.

Zachary Klaassen: I see.

Joaquim Bellmunt: So during the time of recruitment and evolving, so obviously the landscape, as you mentioned, became very crowded. And we needed to consider that the benefits of the SSANTROP tropic, sasanlimab is an anti-PD-L1 that can be given subcutaneously. And this is really attractive.

Zachary Klaassen: Sure.

Joaquim Bellmunt: sacituzumab govitecan, that is an ADC, that has a payload, is the TROP2 inhibitor, targeting TROP2, this needs to be given intravenously. So the trial was designed to give, let's say, an induction phase for five months where SG and sasanlimab were given together and patients getting the complete response were kept on maintenance, sasanlimab, so that the PD-L1 inhibitor--

Zachary Klaassen: Just the subcu treatment.

Joaquim Bellmunt: --as maintenance for two years. So, as mentioned, during the accrual evolution, the landscape changed. So this trial was designed in 2022. So we had Adstiladrin, FDA-approved. We had the super-agonist IL-15, Anktiva. And then also the chemotherapy, docetaxel gemcitabine became a new star. That is even now compared with the BCG.

Also, the sasanlimab was also used together with the BCG. We have heard just 10 minutes ago about the results, some of the analysis that already was presented at AUA, subset analysis on patients with CIS, meaning the landscape is quickly changing. And based on that, then the accrual went a bit down. And then we redefined the endpoint. And we were looking to look for 42 patients in this trial.

And in fact, what is presented here is for the first time, results on 25 patients that have been well evaluated. We have the toxicity results of the 41. In terms of toxicity, we see that 58% can have some side effects. Mainly, it's fatigue. Some patients have some mild diarrhea.

The grade 3 adverse events are only seen in around 22% of patients, meaning that was neutropenia and febrile neutropenia. That is a concern of sacituzumab because we know that sacituzumab is something that also changes what was withdrawn because the TROPiCS-04 in metastatic third-line was negative.

And there were concerns about the toxicity. We didn't see any grade 5 toxicities in this trial. We implemented the G-CSF. And the rate of febrile neutropenia was seen in 12%. That is still a bit high, so likely some nuances need to be applied to SG.

But in the end, the results, based on these 25 patients that have been evaluated at three months, we see 68% of pathologic complete responses, meaning 17 out of 25 patients having at three months. The trial, as mentioned, is immature.

Zachary Klaassen: Sure.

Joaquim Bellmunt: Follow-up is needed. Likely, we need to look-- well, there are additional endpoints in the study at 6 and 9 and at 12 and 18 months that obviously-- when this became mature, we are going to see if this is going to be a potential useful combination.

But as you have mentioned, the landscape has been changing. And this trial was done jointly, and there were two PIs, a urologist and a medical oncologist, was mainly done in Europe. And obviously, urologists like to give up on patients. They prefer to receive things in intravesically than systemically. And this is what all these intravesical therapies have been taken over versus the intravenous therapy.

Zachary Klaassen: Yeah, great background, great overview of the results. When we look at the sasanlimab story, it's really taken off the last couple of months. You mentioned way more data presented here. PRO is presented here as well.

When we look at-- let's just fast forward. Let's say the CR rate holds at 68%. We're balancing toxicity in a non-muscle invasive bladder cancer population with other options that are available. Cretostimogene coming along. The pretzel's coming along. So how do you potentially see this fitting in? What patient would this potentially be a good option for?

Joaquim Bellmunt: What I envision, based on the attractive intravesical therapies, the pretzel that you have mentioned, and all these new retroviral strategies, maybe this is going to be a rescue therapy.

Zachary Klaassen: Sure.

Joaquim Bellmunt: Because more and more patients don't like to have their bladder removed. And despite pembrolizumab being approved in the US, so urologists have jumped to use the combination of docetaxel gemcitabine. And then all these intravenous therapies are moving later.

So it might happen that the patients will be receiving BCG, then they will change to gemcitabine docetaxel. And then Adstiladrin, then Anktiva, and then if there is nothing available, maybe pembrolizumab, or maybe you could use these types of therapies. So because, as mentioned, more and more these patients are receiving several lines of therapy.

Zachary Klaassen: That's right.

Joaquim Bellmunt: Because no one wants the bladder to be removed.

Zachary Klaassen: That's right.

Joaquim Bellmunt: And despite-- these patients included in this trial, they declined cystectomy. Obviously, we recommended that the standard of care is cystectomy. But obviously, as mentioned, some patients want to keep their bladders.

Zachary Klaassen: Absolutely. Great summary. And really more options in this disease space are going to be good. So we appreciate you taking time out of your busy meeting to chat with us about your trial.

Joaquim Bellmunt: It has been a great pleasure. Thank you very much for your time.