ASCO 2025 | Phase II trial of nivolumab and axitinib in mucosal melanoma

A huge shout out to my mentor, Dr Alex Shoushtari, who designed and is the principal investigator of this trial and an expert in rare melanomas. It is a really hard space to do clinical trials in with such a rare cancer. Mucosal melanoma counts only for about 1% to 2% of cases of melanoma in the US. That’s a different demographic to our Asian colleagues who see a much more like 20-25% of their melanoma cases. But it’s a rare and aggressive subtype. It doesn’t have the same features, lower TMB, lower rate of BRAF mutations, all these kind of structural variants that make it just a more resistant cancer to our standard treatments in melanoma being immunotherapy. So both with PD-1 monotherapy and with combination therapy, we don’t have great evidence because it’s hard to do trials in these groups. So it’s all subgroups or retrospective analyses. But we see a less, you know, they do, our patients with mucosal melanoma do less well stage for stage and also respond less to our immunotherapies that we have. So there’s a real unmet need for these patients. And I think that this study is, you know, built on data that came out of China for the combination of PD-1 and VEGF inhibitor tixitinib, which has been shown in China, both in and in the neoadjuvant setting, the targeting VEGF in mucosal melanoma has a clinical and biological rationale. So this is a study of phase two single center, single arm study as well. 20 patients were enrolled and received nivolumab and anxitinib. We saw a 45% objective response rate, so it met its primary endpoint as a study. That’s nine patients. And for the patients who responded, the median duration of their response was about 14 months. So while the overall progression-free survival was about 6.5 months, the median survival hasn’t yet been reached. So that’s with 19 months of follow-up. So really encouraging efficacy in a group of patients with very few clinical options. And I think that the design of this study, what’s really unique and fantastic about it is that it tagged on after that phase two of phase 1B for patients on progression. So, you know, about 70% of our patients progressed on this trial to date. We still have patients on the first doing really well. But for the patient to progress, they could enroll in the phase 1B section and receive either the addition of ipilimumab, so at one milligram per kilogram for four doses, while continuing on the tixitinib and nivolumab, or go to radiation with SBRT. and this was chosen based on the type of progression. So obviously patients we chose who are radiation are people with single sites of progression and people who got ipilimumab was it’s more, you know, diffuse progressive disease. And what we’ve shown, you know, that is really with the primary endpoint of safety and we’ve shown that it’s safe to combine ipilimumab with the nivolumab and tixitinib in five patients. And we had one patient who had a response And we had two patients who combined radiation with that, and we had one responder there. So I think a glimmer of efficacy in a very small group, but overall a very safe. There were two grade three toxicities in that phase 1B or the triplet arm, and they were both hepatitis in the ipilimumab. So very much what we’ve seen with this drug and know well. And I think that this offers, you know, a real, you know, building in a more diverse Western population, showing data that’s very similar to what our Chinese colleagues have shown and offers, you know, a potential option for our mucosal melanoma patients. But really should be the data to bring us to a trial where we compare it to immune checkpoint inhibitor therapy. And I’m hopeful that we can figure out what is best for these patients and fill an unmet need.

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