ESMO 2025 | GDFather-NEO: neoadjuvant nivolumab with or without visugromab in MIBC

Yeah, the GDFather-NEOw trial was built on the background of the GDFather-01 trial, which was a phase one study testing visugromab in combination with nivolumab in patients with advanced solid tumors already pre-treated and refractory to immune therapy. Visugromab is a neutralizing antibody against GDF-15 and GDF-15 emerged as a target that was highly expressed in multiple tumor types including urothelial cancer and the phase one data that had been published a few months ago on Nature by Ignacio, Melero and colleagues showed that in the court of urothelial cancer, there was a huge proportion of responses, and responses were maintained as also updated here at the meeting. So, Godfather NEO trial was the first trial in immunotherapy in naive patients combining visugromab with nivolumab in a randomized study with a combination therapy or nivolumab and placebo therapy just before radical cystectomy by providing the three courses every four weeks of therapy and then the patient has the treatment had also to decide on the one as to whether to do with the with the radical cystectomy or retain, so a bladder sparing approach that was very much response driven and patient decision driven depending on the response. The primary endpoint of the study was the pathological response rate and then we also put another primary endpoint represented by radiological response and the results in terms of primary endpoint was predicted. Thirty-three percent of the patients in the combination therapy arm achieved the pathological complete response. Sixty-six percent achieved the pathological downstaging, a major response to non-muscle invasive disease, as compared to the nivolumab and placebo arm. So the results were tripled in terms of pathological complete responses and also the same and it was fourfold higher in terms of radiological responses and we have seen 60% of radiological partial or complete responses in the combination therapy arm. Most importantly the combination therapy was pretty well tolerated and there were no grade four or five events and the time from cycle one day one to the surgery was in line with the protocol allowance so it’s a during the grade three adverse events reported in both arms were pretty well tolerated and in line with what is expected actually with the checkpoint inhibitor so globally it’s um it’s an intriguing combination visu and nivolumab, and certainly warrant a further investigation in the field. It is going complicated, you know, with multiple trials, having read out the data this year at the meeting, but adding additional drug that does not, and the next toxicity, you know, it’s important for combination therapies in these patients, in this curative setting.

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