Jeannie Hoffman-Censits: Yeah, a long time.
Tian Zhang: ... in ECOG-ACRIN. And you lead it with Vitaly Margulis, who is one of our surgeons at UT Southwestern, as well as Petros Grivas, one of our good colleagues at Fred Hutch in Seattle. But tell us a bit about that inception, and the design of the trial, and what you're presenting here.
Jeannie Hoffman-Censits: Sure. So ECOG 8192 is a prospective trial looking at preoperative chemo and immunotherapy for patients with high-grade upper tract urothelial cancer. There are two parts to it. We're actually presenting Arm C, which is for patients who are ineligible to receive cisplatin-based chemotherapy. Arms A and B, which is MVAC versus MVAC plus durvalumab, are continuing to enroll for patients who are cisplatin-eligible. So this is building on the original trial that presented a couple of years ago and published ECOG 8141, looking at similar populations. So we learned some things from that trial. So one was our definition of cisplatin ineligibility was pretty tight, including the reason why most patients are cisplatin-ineligible is because of kidney function, renal function. So we expanded the creatinine clearance eligibility criteria in this trial. And what we're looking at is four cycles of preoperative gemcitabine plus durvalumab ahead of a radical nephroureterectomy.
Tian Zhang: Very good. And so this cohort, though, focuses more on the cisplatin-ineligible patients. And did you find a benefit in adding immunotherapy there?
Jeannie Hoffman-Censits: Yeah. So I think the first thing that we were pretty excited about compared to 8141, where we had to stop enrollment, because we really were having a very hard time enrolling patients, is that this was a feasible design. That we enrolled 31 patients, 30 eligible patients are going to be presented here at GU ASCO. So we were actually able to kind of complete a prospective upper tract preoperative trial, which I think is a feat in and of itself, and continues to show that this is an important population of patients with a high unmet need, who can tell us information that we need to really understand in this setting.
Tian Zhang: Yeah. It's certainly a necessary component for upper tract care, and thinking about the high-grade patients. So anything special about those patients? And I notice a pretty high pathologic CR rate for those patients treated in cohort C. Anything special about those patients that had a good pathologic response?
Jeannie Hoffman-Censits: Yeah, I think as we are continuing to analyze the data, hopefully we'll be able to understand those patients a little bit better. The path CR rate that we found in the intention-to-treat population was 10%, which seems pretty low when you're looking at some of the higher and exciting path CR rates that we're seeing here at GU ASCO in the bladder cancer space, but in the upper tract setting, we're really not seeing those kinds of numbers to neoadjuvant chemotherapy. So 10% is, I think, on par of what we expect for an upper tract trial. And importantly, the majority of patients were able to tolerate the planned four cycles of therapy prior to surgery.
Tian Zhang: Yeah. Those patients who had these upper tract disease, do you think anything special about them may or may not have contributed to their response for gemcitabine and durvalumab?
Jeannie Hoffman-Censits: Yeah. I think at this point, it's not really quite clear. What is clear is that these are patients, again, with high unmet need because they're relatively frail. We looked at creatinine clearance, issues with hearing, peripheral neuropathy, not the easiest group of patients to think about getting chemotherapy in. So in a small study, I'm not sure whether we'll be able to really understand those endpoints to that extent, but the fact that they were able to participate in a trial and kind of meet the eligibility criteria is quite important.
Tian Zhang: Yeah, that's wonderful. Kudos for completing the study, and this particular cohort that's a more frail population. I'm really also looking forward to you doing more biomarker work on them and looking at some genomic changes too. So I think they'll add a lot to our understanding of upper tract disease.
Jeannie Hoffman-Censits: Yeah. It's interesting that you mention that, because I think one of the challenges that we have in patients with upper tract urothelial cancer, that we have both from a research perspective and a day-to-day clinical perspective, is that they're difficult to diagnose, they're difficult to stage clinically because of where these tumors are located, either trying to access them endoscopically or percutaneously. Oftentimes patients have to go back more than once in order to get that diagnosis. And then the amount of tissue that we get is really pretty scant. So the vision and the goal would be biomarker work, understanding whether or not that's going to be feasible is a different challenge, but we're looking forward to trying to meet that.
Tian Zhang: Yeah. Anything else you want to add about 8192?
Jeannie Hoffman-Censits: I think one of the other interesting things in 8192 is that there were six patients who actually did not have a lymph node dissection. And I think it's compelling, even in the setting of a prospective trial, that there continues to be heterogeneity in terms of surgical management of these patients, and reflective, I think, of the general population, that there remains heterogeneity in the management of patients with upper tract urothelial cancer. So again, I think more clinical trials, more data, more agreement in terms of best oncologic management, both from a chemo or chemoimmunotherapy perspective, as well as a surgical perspective, will help improve outcomes for patients in the future.
Tian Zhang: Perfect. Thanks so much for telling me all about 8192. I'm looking forward to seeing your data.
Jeannie Hoffman-Censits: Yeah. And this study remains open, and again, in the cisplatin-eligible arms, and we're hopeful that we will be able to complete enrollment in the coming months.
Tian Zhang: Right. I hope those of us who have 8192 open, continue to look for those cisplatin-eligible, and the more data we have about this patient population, the better.
Jeannie Hoffman-Censits: Yep, absolutely. Thank you so much.