SSANTROP Trial: Evaluating Sacituzumab Govitecan and Sasanlimab for BCG-Unresponsive Bladder Cancer - Oscar Rodriguez-Faba
May 20, 2024
Sam Chang interviews Oscar Rodriguez-Faba about the SSANTROP trial. This phase II trial assesses the efficacy of combining sacituzumab govitecan, a monoclonal antibody targeting the Trop-2 receptor, with the PD-1 inhibitor sasanlimab in BCG-unresponsive non-muscle-invasive bladder cancer. The trial aims to provide a systemic therapy alternative to radical cystectomy, with a sample size goal of 120 patients across 26 centers in Spain. Early results show promising tolerability. The primary endpoint is a complete response at three months, with secondary endpoints including disease-free survival and overall survival. Dr. Rodriguez-Faba discusses the trial’s timeline, side effects, and the potential for combining systemic and intravesical therapies.
Biographies:
Oscar Rodriguez-Faba, MD, PhD, Urologist, Fundació Puigvert, The Universitat Autònoma de Barcelona, Barcelona, Spain
Sam S. Chang, MD, MBA, Urologist, Patricia and Rodes Hart Professor of Urologic Surgery, Vanderbilt University Medical Center, Chief Surgical Officer, Vanderbilt-Ingram Cancer Center Nashville, TN
Biographies:
Oscar Rodriguez-Faba, MD, PhD, Urologist, Fundació Puigvert, The Universitat Autònoma de Barcelona, Barcelona, Spain
Sam S. Chang, MD, MBA, Urologist, Patricia and Rodes Hart Professor of Urologic Surgery, Vanderbilt University Medical Center, Chief Surgical Officer, Vanderbilt-Ingram Cancer Center Nashville, TN
Read the Full Video Transcript
Sam Chang: Hi, my name is Sam Chang, a urologist at Vanderbilt University in Nashville, Tennessee. And we're quite fortunate to have Dr. Oscar Rodriguez, who is a urologist in Barcelona. And your institution in Barcelona?
Oscar Rodriguez-Faba: It's Fundació Puigvert in Barcelona.
Sam Chang: Fantastic. And you'll be actually presenting at AUA 2024 a trial in progress looking at a combination of therapies. So why don't you go ahead and tell us about the trial that you'll be presenting in that trial in progress?
Oscar Rodriguez-Faba: Yeah. Thank you very much for the opportunity to present our trial here. So, we are conducting the SSANTROP trial. The SSANTROP trial is a phase II trial that tries to assess the efficacy of a combination of a monoclonal antibody, sacituzumab govitecan, that binds to the Trop-2 receptor and binds to the tumor cells with chemotherapy, in combination with a PD-1 inhibitor, sasanlimab. So the aim of this study is to try to know if in the setting of BCG-unresponsive non-muscle-invasive bladder cancer, this combination is going to be really useful in terms of efficacy. I mean, similar combinations have been very useful, and results have been very promising in other settings of bladder cancer.
Sam Chang: In more advanced disease. Advanced disease.
Oscar Rodriguez-Faba: Exactly.
Sam Chang: So this combination of an antibody-drug conjugate focused on Trop-2, that's the target, as well as combining it with an immunotherapy, seeing if that's actually tolerated. So tell me about, you're looking at BCG-unresponsive patients. What are you looking for in terms of enrollment and how are things going?
Oscar Rodriguez-Faba: Yeah. This trial tries to find a gap for the BCG-unresponsive bladder cancer patients that, as you know, the first option for them is radical cystectomy. Now we have results for other trials, and we have previous results of immunotherapy in this setting, because recently pembrolizumab has been approved in BCG-unresponsive. And sacituzumab govitecan has been tested in other tumors, and also in muscle-invasive bladder cancer.
Now, in Spain, we have started this study with 26 centers. And the sample size that we want to reach is 120 patients.
Sam Chang: All right.
Oscar Rodriguez-Faba: For this, we have enrolled 25 patients so far. And the initial view of the results or the tolerability is positive. I mean, the study consists of a first setting of induction with the combination of sacituzumab govitecan plus sasanlimab, and then a maintenance period only with sasanlimab. So, this is a systemic therapy that the patient has to be on for one hour, one hour and a half with the...
Sam Chang: Intravenous treatment.
Oscar Rodriguez-Faba: Intravenous treatment. Sasanlimab is an intramuscular treatment. There are two possibilities. It's a three-vial injection or a single injection. Until now, we're using the three-vial injection, but in the future, we'll have the only one injection. And until now, we have to say that the expectations are quite good. We expect to have more equipment because the sample size is 120 patients, but we expect to have more centers open and increased enrollment in the next month.
Sam Chang: And then, are these looking at CIS patients, TA patients, combination, basically all BCG-unresponsive patients? Is that correct?
Oscar Rodriguez-Faba: Yeah. It's BCG-unresponsive patients according to the definition of the FDA. I mean, those patients have to have received previously a BCG-adequate regime of treatment.
Sam Chang: Of induction, and at least two out of three of maintenance.
Oscar Rodriguez-Faba: And we can include all patients in the high-risk group, T1, TA, high-grade with or without CIS.
Sam Chang: Great. And so the primary endpoint is disease-free, complete response...
Oscar Rodriguez-Faba: Complete response at three months.
Sam Chang: Exactly.
Oscar Rodriguez-Faba: So at three months, we have to assess the response with a cystoscopy and cytology. And in case of CIS, or if the results of the cytology are not positive, or if the cytology is positive, we go for random biopsies. Got it. But it's complete response at three months.
Sam Chang: First three months. Understood.
Oscar Rodriguez-Faba: Secondary endpoints are disease-free survival, overall survival. And we also have another endpoint, which is to identify the ctDNA in the samples.
Sam Chang: And the ctDNA that you use, that is serum, I'm assuming.
Oscar Rodriguez-Faba: Yeah.
Sam Chang: And so you're getting that pre-treatment and post-treatment, I'm assuming.
Oscar Rodriguez-Faba: Exactly.
Sam Chang: Absolutely. Oh, fantastic. Tell us, I know it's early in the trial enrollment, what are the common side effects with either one of these systemic therapies? I am assuming they're not too dissimilar from IO and the ADCs, depending upon which ADC has a different side effect profile. Tell me a little bit about that.
Oscar Rodriguez-Faba: Yeah, for sure. The most common side effects with sacituzumab govitecan are neutropenia and gastrointestinal side effects. In the case of sasanlimab, it's mainly gastrointestinal side effects. Sometimes it's difficult to know which is responsible for the combination. In the case of dermatological side effects, we really know that they come mainly from sacituzumab govitecan, but sometimes it's difficult to really assess which of the two drugs is responsible for the side effects.
Sam Chang: So then, if you get the complete response at three months, then you get on maintenance sasanlimab in terms of the maintenance therapy. How long? Six months, one year? What's the plan?
Oscar Rodriguez-Faba: One year maintenance.
Sam Chang: One year maintenance after that. Well, Dr. Rodriguez, thank you so much for spending some time with us. We're very excited about all the different treatment options that are being developed for non-muscle invasive bladder cancer. And to have an idea of a broad group of patients that get some other therapy, those that will not actually get intravascular, but a systemic therapy and see how they respond will be fantastic. And you could also see at some point, perhaps a combination of systemic and intravascular, as all these agents are being studied.
Oscar Rodriguez-Faba: This is a very good point because now we are getting the results from intravascular treatment. These are very good results. But we have to wait for the systemic therapy's oncological outcomes. And then, once we have the results of the oncological outcomes, we have to put in balance oncological outcomes with toxicity, and then we have to really assess if we can assume toxicity. If we have very good oncological outcomes, we have to really decide which toxicity we can assume.
Sam Chang: Absolutely. Good point. And patient tolerability, all those things that you say, I think, really make a difference. So, when do you have an estimate of when you'll finish your accrual and then read out of outcomes? Any idea?
Oscar Rodriguez-Faba: Yeah. Initially, the final date of recruitment was December 2nd, 2025. But we are going a little bit slow with recruitment. That's why we encourage all the centers to include patients. And we have a longer time, and it will be in 2027, the final recruitment.
Sam Chang: Fantastic. Well, thank you so much for spending some time with us. We're really excited to see your presentation for trials in progress at AUA 2024, and enjoy some time in San Antonio.
Oscar Rodriguez-Faba: Thank you very much for the opportunity.
Sam Chang: Hi, my name is Sam Chang, a urologist at Vanderbilt University in Nashville, Tennessee. And we're quite fortunate to have Dr. Oscar Rodriguez, who is a urologist in Barcelona. And your institution in Barcelona?
Oscar Rodriguez-Faba: It's Fundació Puigvert in Barcelona.
Sam Chang: Fantastic. And you'll be actually presenting at AUA 2024 a trial in progress looking at a combination of therapies. So why don't you go ahead and tell us about the trial that you'll be presenting in that trial in progress?
Oscar Rodriguez-Faba: Yeah. Thank you very much for the opportunity to present our trial here. So, we are conducting the SSANTROP trial. The SSANTROP trial is a phase II trial that tries to assess the efficacy of a combination of a monoclonal antibody, sacituzumab govitecan, that binds to the Trop-2 receptor and binds to the tumor cells with chemotherapy, in combination with a PD-1 inhibitor, sasanlimab. So the aim of this study is to try to know if in the setting of BCG-unresponsive non-muscle-invasive bladder cancer, this combination is going to be really useful in terms of efficacy. I mean, similar combinations have been very useful, and results have been very promising in other settings of bladder cancer.
Sam Chang: In more advanced disease. Advanced disease.
Oscar Rodriguez-Faba: Exactly.
Sam Chang: So this combination of an antibody-drug conjugate focused on Trop-2, that's the target, as well as combining it with an immunotherapy, seeing if that's actually tolerated. So tell me about, you're looking at BCG-unresponsive patients. What are you looking for in terms of enrollment and how are things going?
Oscar Rodriguez-Faba: Yeah. This trial tries to find a gap for the BCG-unresponsive bladder cancer patients that, as you know, the first option for them is radical cystectomy. Now we have results for other trials, and we have previous results of immunotherapy in this setting, because recently pembrolizumab has been approved in BCG-unresponsive. And sacituzumab govitecan has been tested in other tumors, and also in muscle-invasive bladder cancer.
Now, in Spain, we have started this study with 26 centers. And the sample size that we want to reach is 120 patients.
Sam Chang: All right.
Oscar Rodriguez-Faba: For this, we have enrolled 25 patients so far. And the initial view of the results or the tolerability is positive. I mean, the study consists of a first setting of induction with the combination of sacituzumab govitecan plus sasanlimab, and then a maintenance period only with sasanlimab. So, this is a systemic therapy that the patient has to be on for one hour, one hour and a half with the...
Sam Chang: Intravenous treatment.
Oscar Rodriguez-Faba: Intravenous treatment. Sasanlimab is an intramuscular treatment. There are two possibilities. It's a three-vial injection or a single injection. Until now, we're using the three-vial injection, but in the future, we'll have the only one injection. And until now, we have to say that the expectations are quite good. We expect to have more equipment because the sample size is 120 patients, but we expect to have more centers open and increased enrollment in the next month.
Sam Chang: And then, are these looking at CIS patients, TA patients, combination, basically all BCG-unresponsive patients? Is that correct?
Oscar Rodriguez-Faba: Yeah. It's BCG-unresponsive patients according to the definition of the FDA. I mean, those patients have to have received previously a BCG-adequate regime of treatment.
Sam Chang: Of induction, and at least two out of three of maintenance.
Oscar Rodriguez-Faba: And we can include all patients in the high-risk group, T1, TA, high-grade with or without CIS.
Sam Chang: Great. And so the primary endpoint is disease-free, complete response...
Oscar Rodriguez-Faba: Complete response at three months.
Sam Chang: Exactly.
Oscar Rodriguez-Faba: So at three months, we have to assess the response with a cystoscopy and cytology. And in case of CIS, or if the results of the cytology are not positive, or if the cytology is positive, we go for random biopsies. Got it. But it's complete response at three months.
Sam Chang: First three months. Understood.
Oscar Rodriguez-Faba: Secondary endpoints are disease-free survival, overall survival. And we also have another endpoint, which is to identify the ctDNA in the samples.
Sam Chang: And the ctDNA that you use, that is serum, I'm assuming.
Oscar Rodriguez-Faba: Yeah.
Sam Chang: And so you're getting that pre-treatment and post-treatment, I'm assuming.
Oscar Rodriguez-Faba: Exactly.
Sam Chang: Absolutely. Oh, fantastic. Tell us, I know it's early in the trial enrollment, what are the common side effects with either one of these systemic therapies? I am assuming they're not too dissimilar from IO and the ADCs, depending upon which ADC has a different side effect profile. Tell me a little bit about that.
Oscar Rodriguez-Faba: Yeah, for sure. The most common side effects with sacituzumab govitecan are neutropenia and gastrointestinal side effects. In the case of sasanlimab, it's mainly gastrointestinal side effects. Sometimes it's difficult to know which is responsible for the combination. In the case of dermatological side effects, we really know that they come mainly from sacituzumab govitecan, but sometimes it's difficult to really assess which of the two drugs is responsible for the side effects.
Sam Chang: So then, if you get the complete response at three months, then you get on maintenance sasanlimab in terms of the maintenance therapy. How long? Six months, one year? What's the plan?
Oscar Rodriguez-Faba: One year maintenance.
Sam Chang: One year maintenance after that. Well, Dr. Rodriguez, thank you so much for spending some time with us. We're very excited about all the different treatment options that are being developed for non-muscle invasive bladder cancer. And to have an idea of a broad group of patients that get some other therapy, those that will not actually get intravascular, but a systemic therapy and see how they respond will be fantastic. And you could also see at some point, perhaps a combination of systemic and intravascular, as all these agents are being studied.
Oscar Rodriguez-Faba: This is a very good point because now we are getting the results from intravascular treatment. These are very good results. But we have to wait for the systemic therapy's oncological outcomes. And then, once we have the results of the oncological outcomes, we have to put in balance oncological outcomes with toxicity, and then we have to really assess if we can assume toxicity. If we have very good oncological outcomes, we have to really decide which toxicity we can assume.
Sam Chang: Absolutely. Good point. And patient tolerability, all those things that you say, I think, really make a difference. So, when do you have an estimate of when you'll finish your accrual and then read out of outcomes? Any idea?
Oscar Rodriguez-Faba: Yeah. Initially, the final date of recruitment was December 2nd, 2025. But we are going a little bit slow with recruitment. That's why we encourage all the centers to include patients. And we have a longer time, and it will be in 2027, the final recruitment.
Sam Chang: Fantastic. Well, thank you so much for spending some time with us. We're really excited to see your presentation for trials in progress at AUA 2024, and enjoy some time in San Antonio.
Oscar Rodriguez-Faba: Thank you very much for the opportunity.