Jiwei Huang: Yeah. Nice to meet you. Nice to meet you, everyone.
Pedro Barata: Absolutely. Thank you for joining us, and great job presenting this combination for patients with non-clear cell renal cell carcinoma. This is data from a trial that you conducted there. Maybe for context, it would be great if you could just share with us some of the highlights of the data you just presented, and then we'll have a chitchat about it. Is that okay?
Jiwei Huang: Thank you. So I will introduce our study very shortly. So our study is using fruquintinib plus serplulimab as a first-line treatment in metastatic non-clear cell RCC. So it's a multicenter single-arm phase II trial. So our key point is that with a median follow-up time of 10 months, the median PFS was not reached. At nine months, I think PFS rate was 87.3%, and ORR was 52.8%, and DCR was 97.2% in 36 available patients. And the rapid progression of non-clear-cell RCC patients may be associated with sarcomatoid features. So the trial is still ongoing. That's the background and that's our study design.
So we included the patients with pathologically confirmed metastatic non-clear cell RCC, which has not received any anti-cancer therapy before. And at last, one measurable lesion has been showed in CT or MRI scan. And we used fruquintinib three-week cycle, and we also use an PD-L1 inhibitor as a three-week cycle. And the primary outcome is PFS. And this is the baseline characteristics. Let's see the efficiency. So we can see with median follow-up time of 10 months, the median PFS was not reached, and we can see the waterfall of the best response. The ORR is about 52.8%, and one patient achieved CR, and 18 patients achieved PR in the trial. I think the DOR is 97.2%. That's very interesting.
And three patients finally experienced rapid progression or was with sarcomatoid features, so I think this is maybe associated with rapid progression. Maybe we need to do some future work to have maybe some research in it and tell what will happen with sarcomatoid features. And for the safety profile, the most common treatment-related AE is rash, proteinuria, and hypertension, and also ALT increase and AST increase, all manageable. And no SAE and AEs lead to permanent discontinuation of the medicine were observed during the study period. So take all this in. I think if we combine the anti-VEGFR and PD-1, we can have maybe promising antitumor activity with acceptable tolerability as a first-line treatment for advanced non-clear cell RCC.
Pedro Barata: Thank you so much, Dr. Huang. This is very interesting data. Congratulations on conducting this study. It shows data almost 40 patients. So I guess one question that I have for you, and it has to do with... When we look at this combination of VEGFR, TKI, along with a PD-1 inhibitor, fruquintinib with serplulimab, it does seem to be aligned with data we've seen in the past with other IO-TKI combinations for non-clear cell. I'm thinking of lenvatinib-pembrolizumab, which gave an extended approval for non-clear cell RCC in this side of the world, I guess. And we also seen that with cabozantinib-nivolumab. So here, you're showing responses around 50%, 52%, progression-free survival better than nine months.
And so, my question is, do you think there's anything unique about these two compounds, fruquintinib, serplulimab? And why use those two specifically? Maybe that's the availability. But tell me a little bit about why did you pick specifically this VEGF-TKI along with this PD-1 inhibitor when you were putting this trial together? And do you agree with that, or did you see something different compared to the other data out there?
Jiwei Huang: Yeah, thank you. So I think we choose these two drugs because maybe as the VEGFR of fruquintinib, it's an inhibitor of VEGFR-1 and 2 and 3. I think it's maybe a little like axitinib, I think, maybe. And we choose this two combination together, I think maybe we can just get this two together in this trial, but not... I think maybe if we choose another one, it may be better, I think. But I think we choose this two together because in the design of our study, that there's no study just focused on this PD-1 inhibitor and VEGFR, so we choose these two drugs, I think. But as the study going on, some of the data has been shown the result of two of this combination.
Pedro Barata: Okay. So just to see if I understand correctly, is that because the sponsor... I mean, I know there's a partnership, if you will, for HUTCHMED developing fruquintinib. Outside China, I think there was a partnership with Takeda, I believe. Is that why? Is that what's available in China? Or are you using this combination IO-TKI in other histologies? I'm just curious how you manage patients with RCC. Do you use any of the combos that we use on the Western side, like cabozantinib-nivolumab, lenvatinib-pembrolizumab, axitinib-pembrolizumab, or you use different IO-TKI combinations?
Jiwei Huang: Because I think this drug is more available, because I think in China, several TKI has been approved by CFDA, and one of this... We choose this VEGFR drug is maybe just it will approved by CFDA maybe several months later, I think, for metastatic RCC, so it's much more available for the patients in China.
Pedro Barata: Okay, gotcha. It has to do availability, understood. I mean, of course, as we look at the breakdown of the patient population, you have about half of them with papillary RCC, but then you have basically a representation of different subtypes, unclassified, translocation. You even included one collecting duct and two chromophobe patients, I believe. I didn't see any RMC. But my question is, oftentimes, we do see exclusion of renal medullary carcinoma, as well as collecting duct, sometimes chromophobe can be excluded. What are your thoughts about it? As we think of the non-clear cell subtypes, do you think we should think of IO-TKI in those histologies or should we keep them aside and think of other strategies?
Jiwei Huang: So I think if you want to distinguish the different subtypes, for example, the FH or other subtypes, I think the best way maybe, you can choose, for example, plan A for subtype one and plan B for subtype two. I think this is a better way. But if you do this, maybe you must have more patients included in the study. For example, for lactate cell RCC, I think the outcome may be not so good. It may be not comparable, for example, to the chemotherapy. But in this study, because it's a phase II study, so we want to include all the subtypes. Maybe in the next study, we will differentiate all the subtypes to different groups. I think maybe this is a better way to have more good results.
Pedro Barata: I see. Gotcha. So if I understand correctly, because I don't remember, I saw that breakdown, is it fair to say there was limited activity in chromophobe, collecting duct, and maybe spindle cell?
Jiwei Huang: Yeah.
Pedro Barata: Okay. Okay, gotcha. So you do see that. And so, in my final question, you did highlight, interesting, the rapid progressors on your study, which you defined progressing within four months, essentially in the first or the second set of scans, both patients had sarcomatoid features. Did you got a deep dive into that? Do you have any rationale to why that happened, or is just hypothesis generator at this point? We've seen some rapid progressions on some non-clear cell subtypes reported out there, including RMC, et cetera, but I'm curious your thoughts.
Jiwei Huang: I think if we can maybe do some maybe WES or RNA sequencing, maybe we'll find some interesting story in it. But now, we have not just do this now. But maybe we will do this in the future as the study have finished, I think. Maybe this will provide some interesting information about it.
Pedro Barata: Got you. Okay, wonderful. And before I let you go, of course, we're looking forward to read the manuscript. Remind me, what is the complete sample or cohort of patients you're going to include in this study, and when we would expect a manuscript on this?
Jiwei Huang: Total number, 39.
Pedro Barata: 39. So we're done with the cohort for the phase II, and it's basically to get outcomes of these patients for publication, is that right?
Jiwei Huang: Yeah.
Pedro Barata: Gotcha. Okay. Dr. Huang, this is so great. Great job. I know it's not easy. I know you're a busy provider and there's a lot of non-clear cell patients needing important novel strategies, so it's great that you ran the study. Congratulations on a great presentation. I'm certainly looking forward to read the details in a manuscript, so kudos to you to put this together into your team as well. And thanks for taking the time to talk to us today.
Jiwei Huang: Thank you so much.
Pedro Barata: I'll see you soon. Thank you.