Darren Feldman: Thanks. I'm super excited to be here and appreciate you giving me some time.
Tian Zhang: Absolutely. So tell us a bit about the work you're presenting here at ASCO.
Darren Feldman: Sure. So we're presenting an investigator-initiated Phase II single center trial of cabozantinib plus nivolumab in patients with non-clear cell RCC. It's actually something that's been published and reported on before, but these are the final results with now additional patients, so about 60 total patients in the cohort and about 50 months of median follow-up for survivors.
Tian Zhang: That's a long time for follow-up, which is amazing to see that longer term data. So tell us the spread of variant non-clear cell histologies and what does that look like and what did you find?
Darren Feldman: So it was set up into two cohorts. We had a cohort, one that had papillary RCC, unclassified RCC, or translocation RCC, as it was originally set out. And then, cohort two was chromophobe RCC. And they each had separate statistical designs. Cohort two, which was the chromophobe, didn't show any responses and we closed it early after only seven patients. And then, the other 53 patients are the subject of the presentation, which are the patients with the papillary, unclassified, and translocation.
For this presentation, we actually looked a little closer into the papillary RCC and selected out FH-deficient RCC based on genomics, as well as many confirmed with IHC. And so, we just report the overall results for the patients in cohort one, so now 53 patients, and the response rate was good. It was overall about 43%, and patients who were treated in the first-line, it was about 46%. And we found a very high response rate in the small group of patients with FH-deficient RCC. So eight patients with FH-deficient RCC, seven of the eight responded, and the median for PFS was about 16 months in that group.
Tian Zhang: That's great to hear, that for FH-deficient papillary, cabo-nivo seems to have a really good effect. Did you see those were quite durable? You said median progression-free was 16 months?
Darren Feldman: Yeah. I mean, it was only eight patients, so it's a wide confidence interval, but of the patients who responded, they had some of the longer responses. The average duration of response or median duration of response was about 17 months.
Tian Zhang: 17 months for the FH-deficient or for all-comers?
Darren Feldman: For all patients who responded.
Tian Zhang: Oh, great.
Darren Feldman: I don't know if I have it specifically for the FH-deficient, just because it was such a small subgroup.
Tian Zhang: No, but I think we're doing more molecular characterization now, so it's helpful to know, when we find the FH deficiency, what might work for that patient population. Fantastic. What are the median overall survival? Do you have that in this presentation as well?
Darren Feldman: Yeah. The median overall survival was 28 months, and at two years, it was about 55%.
Tian Zhang: Good to hear. It's hard to treat non-clear cell kidney cancer, so any meaningful push in survival is important. Great. For the UroToday audience, community oncologists, what are your takeaways? Are you using cabo-nivo for non-clear cells? In which populations? Should we not do them for a subset, maybe the chromophobe?
Darren Feldman: Yeah. So just a couple of highlights. One is that there's also the big KEYNOTE-B61 study with lenvatinib plus pembro, but that was all first-line patients, and I just did want to highlight that this included about 25% of patients who had been previously treated, so a little bit different there. And then, in terms of treatment, for chromophobe RCC, we would not use cabo-nivo. We would probably lean more toward a regimen like lenvatinib plus pembrolizumab. But we do think for other patients with non-clear cell histologies, like papillary, unclassified with or without papillary features, or translocation, that this is a good option for patients. And we're encouraged by the high response rate with the small group of FH-deficient, so that needs to be further expanded upon in future series.
Tian Zhang: Fantastic. Next steps? Are you designing another trial for these folks?
Darren Feldman: We are not currently designing another trial with cabozantinib plus nivo, but we are looking into our patients that we've treated since the trial closed with cabo-nivo off-protocol with these histologies, and hoping to be able to report somewhere around a hundred patients in total that have been treated just for increased numbers and tighter confidence intervals.
Tian Zhang: Great. Well, I know we're all looking forward to seeing that larger cohort and the continued, hopefully, success of cabozantinib and nivolumab in this patient population. Thanks so much, Darren.
Darren Feldman: Great. Thank you. Appreciate it.