Yijun Shen: Yeah.
Elizabeth Plimack: So tell us a little bit about the study and what you found.
Yijun Shen: Thank you, Dr. Plimack. So our study, the phase two to three study, this time we report the phase two study and this study was an open label and one arm and we just enrolled the MIBC patients and we use four cycles of an nectin-4 ADC, just called SHR-A2102 plus adebrelimab PD-L1 inhibitor as a new adjuvant therapy. Within six weeks we will have radical cystectomy for patients and after that the patients will be given the adjuvant phase with five cycles for the SHR-A2102 and 13 cycles for the patients to give them the PD-L1 inhibitor, adebrelimab. And we have enrolled 37 patients and in the new adjuvant phases that 36 patients have the new adjuvant therapy and about 27 patients they have accept the radical cystectomy.
Elizabeth Plimack: Cystectomy, okay.
Yijun Shen: Yes. And we found that the path CR for these 27 evaluable patients, the rate was 48% and the pathological down-staging is almost 60%. Most of all, also we have enrolled some patients with renal impairment patients, just CCR from 30 to 60.
Elizabeth Plimack: Okay.
Yijun Shen: Yes. And we also find that these patients have just the same pathological responses about path CR within the normal renal function patients.
About the safety profile, we found that this 194 top per on ADC with the PD-L1 inhibitor, over three grade toxicity is only 27. We also call these GIAs and most of them experience the hematological toxicity, just like the anemia, neutropenia and something else like the nausea and something else. And most of them I think have a very nice tolerability.
Elizabeth Plimack: Right.
Yijun Shen: Yes.
Elizabeth Plimack: That's great. So fascinating that we're looking at the combination of a nectin-4 targeted ADC with a different payload. So the natural thing that we sort of draw comparisons to is EV+P, right?
Yijun Shen: Yeah.
Elizabeth Plimack: Enfortumab vedotin being also targeting the same target with a different payload. We did see higher pathologic complete response rates with that. What do you attribute that to in terms of the differences between this obviously small pilot trial and the EV+P data that we know about from 905?
Yijun Shen: Yes. The EV+P have showed very good responses and the EFS positive results about the renal cisplatin tolerable and also the untolerable patients about in our study you have told us that this normal 194 ADC, the payload is not like the EV-
Elizabeth Plimack: Right. Different payload.
Yijun Shen: It's a topo I. Yeah, different payload. So different payload have the different toxicity, I think that. So most of the patients just have not the toxicity like the MMAE toxicity like neuropathy.
Elizabeth Plimack: Or rash, right?
Yijun Shen: Yes. Rash and something else. In China we have another ADC just targeted the HER2, but the payload is also the MMAE, like the EV. So we have some experience to treat these patients with the neuropathy. And we think the median duration patients for the latest stage patient is just about the median cycles, maybe seven to nine six.
Elizabeth Plimack: Right. And then they have to stop.
Yijun Shen: But, it's very, very hard for these patients to have more cycles for the patient-
Elizabeth Plimack: You raise a really good point, which is that EV is really dose limiting at some point for everybody. We saw that in one of the other presentations at the session. This offers a different approach. Where are you going next with this study? You said it's a phase two, three.
Yijun Shen: Yeah. So first we have another dose exploration for such MIBC patients and we have some results of another dose for these patients. And this study we reported here just for the nectin-4 ADC SHR-A2102 it's eight milligram per kilogram. And we have another dose exploration of the six. And we found that six milligram per kilogram just have the same effects with the age and the toxicity is just a lower than age.
Elizabeth Plimack: Okay. So you're still dose finding with this drug?
Yijun Shen: Yes. Yes.
Elizabeth Plimack: Got it. Got it.
Yijun Shen: And we also will plan another, we call it the phase-three study, just the RCT with the cisplatin GC.
Elizabeth Plimack: Oh, okay.
Yijun Shen: And have some high risk patients just after the radical cystectomy we have give them the PD-1, just the nivolumab as a control.
Elizabeth Plimack: Got it.
Yijun Shen: Yeah.
Elizabeth Plimack: Okay. Fascinating. Well, thank you so much for sharing your data with us, for really pushing the boundaries of ADCs here with different targets, different payloads, all of that. I'm really eager to see what the rest of the studies around this combination and the other ones you spoke about, where they go.
Yijun Shen: Thank you.
Elizabeth Plimack: Thank you.
Yijun Shen: Thank you.