Zachary Klaassen: Hi, my name is Zach Klaassen, urologic oncologist in Augusta, Georgia. We are at ASCO 2025 in Chicago. I'm delighted to be joined on UroToday by Elena Sevillano, who is a medical oncologist in Madrid, Spain. Elena, thanks so much for joining us on UroToday.

Elena Sevillano: Thank you.

Zachary Klaassen: We're going to talk today about your trial in progress, looking at the SASAN-SPARING trial, basically looking at neoadjuvant chemotherapy plus sasanlimab and neoadjuvant treatment for muscle-invasive bladder cancer. So just by way of a background, just to bring our listeners up to speed on that disease space, why is it important to have safe oncological efficacious treatment options that are bladder sparing for these patients?

Elena Sevillano: Well, thank you very much. Yes, muscle-invasive is a highly aggressive disease. And treatment is neoadjuvant chemotherapy followed by radical cystectomy. But this impacts very much the quality of life of our patients, not only their urinary function, but also their bowel and sexual function.

So moreover, not all patients need a radical cystectomy, because some of them, we are overtreating some of the patients who clinically respond to neoadjuvant chemotherapy. So nowadays, there is a growing interest in trials that are exploring the bladder-sparing options, especially in clinically responding patients to neoadjuvant chemotherapy.

Zachary Klaassen: Yeah. Great answer. As a surgeon, when we see a T0, we're excited because the five-year survival is excellent for these patients. But we also say, it's a big operation. The 90-day readmission rate's 40%.

So I'm with you. If we can safely spare some of those bladders with aggressive treatment, I think that's awesome. So what was the rationale for combining sasanlimab with neoadjuvant chemotherapy?

Elena Sevillano: Well, we are trying to explore if we can de-escalate the radical cystectomy for those patients who clinically respond to neoadjuvant chemotherapy. And then we try to make an approach of maintaining with immunotherapy to those patients with clinical response, because we think that immunotherapy maintenance not only can treat the molecular residual disease, but also maintain the long remission responses. So this trial is trying to make this.

We are also incorporating a comprehensive molecular approach that we are going to monitor to track the ctDNA not only in blood, but also in urine, in these patients to make a correlation with the clinical and molecular response, to see the mechanisms of resistance, and also to see if there is a correlation between clinical response and ctDNA.

Zachary Klaassen: Absolutely. And I want to get into that a little bit too, because I think that's a very exciting part of this trial. Just tell us a little bit about the eligibility criteria and the intervention schedule that you guys have set up.

Elena Sevillano: Yes. We are going to perform the trial with 70 patients. It's a single-arm, multicenter trial that is open in 10 centers in Spain. So these patients are going to receive four cycles of GemCis in the neoadjuvant setting. And then we are going to reevaluate the clinical response.

So we are going to evaluate by cytology, by TURBT, and by imaging. And those patients who achieve a clinical T1 or less response, we are going to maintain their bladder, and we are going to start with a maintenance treatment with immunotherapy with sasanlimab. That is very important. It's very special because it's a subcutaneous treatment that we administer once a month for up to 12 months.

So then those patients who don't achieve clinical response, who still have muscle-invasive residual disease, those patients are going to proceed with a radical cystectomy.

Zachary Klaassen: Excellent. I know sasanlimab has made a big splash in the last month, with the CREST trial presented at AUA with BCG and BCG-naive patients. So we're seeing it now in a different setting. I think it's exciting to see it in that neoadjuvant space. You guys have a really interesting primary outcome. Tell us about the primary outcome for this trial.

Elena Sevillano: Yes. The primary outcome is a bladder-intact overall survival of 12 months. We are going to see if these patients can preserve their bladder at 12 months. And we are going to define this primary endpoint from the time sasanlimab starts to cystectomy or death.

Zachary Klaassen: Excellent. And I know you mentioned the Biomarker Program is awesome for this trial. That's one thing that jumped out when I was looking at it—looking at blood, urine, ctDNA.

When I look at this from a surgical standpoint, there was an interesting study a few years ago at Fox Chase called the Bladder SEE trial, where they had clinical complete response, MRI negative, imaging negative, cysto negative, but still 20% of patients had underlying muscle-invasive disease at the time of cystectomy. So this is a great opportunity, with this combination, to try to put together something that says, we think they're pathological complete response. Here's our likelihood of predicting that. Just tell us about how this may change how we think about these patients once they've had all this treatment.

Elena Sevillano: Well, yes. I think it's one of the major strengths of this trial, because we are going to perform a WES (Whole Exome Sequencing) on the TURBT tumor samples at the beginning, and then we are going to make a personalized ctDNA monitoring, not only with blood, but also with urine.

So we are going to monitor how these patients respond, if there is a correlation with clinical response and ctDNA status. And we are also going to perform microbiome profiling to see if there is a relation, as well, between the response and the microbiome.

Zachary Klaassen: That's very exciting work. I'm excited for that part of it.

Elena Sevillano: Thank you.

Zachary Klaassen: Tell us about the status of the trial. I know it just opened recently, correct?

Elena Sevillano: Yes. We started the accrual this January, January 2025, and we have been enrolling these patients. We plan to finish the enrollment by the first quarter of 2026.

Zachary Klaassen: Excellent. Maybe results in a couple years, once we get the primary outcome?

Elena Sevillano: Yes, I hope so.

Zachary Klaassen: We'll have you back on to discuss it. It'll be excellent.

Elena Sevillano: Yes. It will be.

Zachary Klaassen: Excellent discussion. Really enjoyed it. Any take-home messages or anything you want to hit on before we finish up our conversation?

Elena Sevillano: Yeah. I think this trial is maybe going to lead the foundation of how adaptive trials or biomarker trial designs could be incorporated in the next couple of years or in the near future. So I hope this biomarker design could answer some of the questions we have now around.

Zachary Klaassen: Absolutely. Great discussion. Congratulations to you and your collaborators in Spain. We look forward to the results.

Elena Sevillano: Thank you. Thank you very much.