ASCO 2025 | C-IT Neo: interim results of neoadjuvant ipilimumab & nivolumab in melanoma

I’m delighted to be here this weekend presenting the results of the C-IT Neo trial. It’s really a trial looking at a single dose, so one dose of ipilimumab and nivolumab in patients with resectable melanoma. And the fancy kind of part of it is the additional imaging with it where we’re doing CD8 PET in conjunction with this treatment in a phase two trial. So really, we know from this time last year here at ASCO, our colleagues from the Dutch group, Dr. Blank, presented the NADINA trial, which was a phase three study of two doses of ipilimumab one milligram and nivolumab three milligrams per kilogram. And it showed that it was superior to surgery, followed by PD-1 alone for patients with resectable melanoma and showed really impressive high pathological response rates of about 59%. And what we know is that that comes with about a 30% grade three toxicity, like grade three or higher toxicity rate. So that’s moderate to severe toxicities for our patients in a curative setting. And then, you know, there’s been multiple studies done in the neoadjuvant setting, be that the SWOG 1801, which looked at pembrolizumab monotherapy pre-doses before surgery, and then completing out the year afterwards. And again, really impressive superior to adjuvant treatment alone. But I suppose the combination of these and other phase two studies is that we don’t know what is the right dose and what is the right combination of drugs for our patients. Who do we pick? Who is Pembro monotherapy enough for? Who needs the ipilimumab-nivolumab? How do we tailor and personalize and drive forward improving our patients’ outcomes, maintaining this efficacy, building on it even, and reducing toxicity? So, that’s kind of where the idea for the C-IT Neo comes from, where we’re doing one dose given pre-surgery. So, they get one dose and then four weeks later undergo surgery and what we’ve shown in this is interim results so the plan for the study design is 28 patients total and it’s assignment two-stage design so in the we’ve completed stage one and we’re in stage two and the reason we’re presenting it is because we’ve had over 12 pathological major pathological responses which meets the study’s primary endpoint for positivity and which is really exciting and we’re delighted to be presenting that this weekend. And that’s showing very similar. You know, 59% of our patients had a major path response. And only 9% of our patients had a grade three or higher toxicity while on treatment. So, you know, I think this is encouraging preliminary, you know, single center, single arm trial, but a really encouraging sign of efficacy of one dose. And I would emphasize the dosing of we giving a higher dose of ipilimumab than was given in NADINA. So this was kind of the secondary end points of the trial. We looked at, you know, how the standard response on CT imaging. And of course, all the neoadjuvant studies I’ve mentioned before, NADINA, SWOG, we’ve seen this discordance between radiographic and pathologic response. And that’s, you know, when we’re doing our standard CTs before we take them to surgery, most patients first have stable disease, and we don’t know what that means. And some people are coming out with major path response with no viable melanoma and some are coming out with like pathologic non-response and not having had a benefit so it’s trying to we saw that is similarly in our um cohort small cohort again but um that the radiographic response didn’t project pathologic response and for the majority of patients who are stable and that is where some novel imaging comes in and that what we have is a CD8 PET tracer so it’s um given to our we did in our patients and 19 patients completed the baseline CD8 PET, so prior to receiving immunotherapy, and a further 17 had a matched or paired CD8 PET prior to surgery. And what we did initially was we looked at that first step of, does this tracer actually show us CD8 cells? And that was our first kind of port of call to make sure that we’re looking for the specificity of the scan. And we looked at patients’ tumors and we stained their tumors for CD8 cells and had a pathologist quantified CD8 staining. And then we saw the uptake of the tracer by autoradiography. And we showed a strong correlation between CD8 cell infiltrate and the intensity of tracer uptake by autoradiography. It’s kind of a proof of concept, proof of principle that we’re seeing when we’re doing the scan, we’re seeing what we want to see in that CD8 cells. However, in that small sample set, we did try to look and see, could the CD8 cell infiltrate predict pathologic response or be associated? And we didn’t at baseline or pre-surgery see an association between CD8 cell infiltrate and uptake or, you know, some of these imaging measurements such as SUV max or mean standards. So that’s the initial results. I think there’s a lot more to be dug out of these scans and a lot more analysis that we’re doing and working on in order to help us figure out how best to use this tool, both in the neoadjuvant setting and in others. in both melanoma and lots of other cancers where, you know, the role of understanding what the immune system is doing and having a non-invasive tool to serially measure it is really exciting.

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