Brigida Maiorano: Yes.
Elizabeth Plimack: So talk us through the study and tell us what you found.
Brigida Maiorano: Thank you, Elizabeth. The study is a Phase 2 trial of neoadjuvant, sacituzumab govitecan in patients with muscle-invasive bladder cancer. This is a trial which was designed for a bigger met need in this setting because as you know, patient with muscle-invasive bladder cancer were treated with cisplatin-based neoadjuvant chemotherapy, but only in case of cisplatin eligibility and we know that around 50% of our patient are cisplatin-ineligible. So we started to treat this patient with an alternative option. In the SURE-02 trial, this is a Phase 2 single arm trial. We treated the patient with the CT2 to T4, N0, M0 muscle-invasive bladder cancer who were ineligible for all refusing cisplatin with four cycles of neoadjuvant sacituzumab govitecan followed by radical cystectomy. The trial we used at the beginning, the standard dose of sacituzumab at 10 milligrams per kilogram. But in the first eight patients, we had important adverse events, especially 75% of patients reporting Grade 3 or over neutropenia and in 50% of cases, severe diarrhea.
So we amended the protocol. We reduced the dose of sacituzumab to 7.5 mg/kg. Then we introduced the prophylaxis with the GCSF and excluded patients with more than three risk factors for severe neutropenia according to ASCO guidelines. And we continued the protocol like this. The primary endpoint was the rate of pathologic complete response, of course. And among secondary endpoint, there were the event-free survival and the overall survival. Over a three-year period, we enrolled 44 patients in this trial. Around 31% of them, they refused the radical cystectomy, but we used Re-TURBT for these patients. And we found that the rate of ypT0 and 02X responses was around 29.5%. And with a median follow-up of 22 months, we found a two-year seventh free survival of around 71% and a two-year overall survival of around 80%. We also showed a good safety profile with the reduced dose of sacituzumab to 7.5 mg/kg.
Most adverse events, they were up grade one or two with no severe adverse events or relevant severe adverse events after this first amendment. In the poster which we presented at ASCO, we also did some genomic and transcriptomic analysis. And for example, we found that there was an enrichment in ypT-0210 responses among non-luminal compared to luminal tumors. No particular genomic alteration were associated with the response rate, but we found that the lower top one gene expression was associated with longer event-free survival.
So basically with this trial, we showed a good efficacy and also a good manageable safety profile with sacituzumab as a neoadjuvant option for cisplatin in eligible patients, which we think it's very useful to think about different option. We know that after EV pembrolizumab scenario is changing, but of course there are option in the neoadjuvant setting also for patients ineligible for cisplatin. This is a big unmet need we know.
Elizabeth Plimack: Right. Now that we saw (KEYNOTE) 905 with EV+P in cisplatin in ineligible patients who have these much better responses obviously than the control arm, for what patient would you reach for sacituzumab govitecan instead of EV+P in the neoadjuvant space?
Brigida Maiorano: Well, I think that the two trials are not comparable, of course we're in a basically a single arm Phase 2 trial-
Elizabeth Plimack: But your path CR rate was-
Brigida Maiorano: Yeah, very interesting.
Elizabeth Plimack: ... inferior to the EV+P-
Brigida Maiorano: Yes.
Elizabeth Plimack: ... if you compare, right? Yeah.
Brigida Maiorano: Yes. Of course, the ideal situation is that in such cases we could run a bigger Phase 3 trial or at least a comparative trial between the different options. But for example, this could be an option for patients who cannot do the pembro combination because they are ineligible for immunotherapy, for example.
Elizabeth Plimack: That's true.
Brigida Maiorano: Still, for patients for this kind of population, there is space for alternative options. And I think that in this case is ADC could be a feasible option in terms of both efficacy and the safety profile. But in this case, we amended the protocol. We know that the dose of sacituzumab is different, but still with a different dose, we had an efficacy signal.
Elizabeth Plimack: So it sounds like you learned a lot about how to give SG in this population, how to protect them from the neutropenia that you saw before you added the prophylaxis and maybe we'll see. I know there are a lot of Topo ADCs out there with different targets, different linkers, different designs. So I think it's not the end of the topoisomerase story for sure.
Brigida Maiorano: Yeah, I think. I agree with you, but we see in the future, of course, we hope in bigger trials and also for the metastatic setting for the sequencing strategies in which we introduce different ADC maybe.
Elizabeth Plimack: Yeah. Great. Well, thank you. Congratulations on completing the study. I heard it's going to be published in JCO.
Brigida Maiorano: Yes.
Elizabeth Plimack: So congratulations on that and we'll all get to read about it and look at the results more detail.
Brigida Maiorano: We're very happy. Thank you.
Elizabeth Plimack: Yeah, thank you.
Brigida Maiorano: Thank you very much.