“Our drug candidate has already shown preliminary positive effects in combination with pembrolizumab in our NeoLIPA study, and this new study gives us the opportunity to generate clinical evidence with the other standard of care backbone in neoadjuvant melanoma. Partnering with Prof. Blank, one of the true pioneers of neoadjuvant immunotherapy in melanoma, on a biomarker-defined study targeting patients who respond poorly to ipilimumab plus nivolumab today makes this an especially valuable addition to our evidence base,” says Øystein Rekdal, CEO, Lytix Biopharma.

The multi-arm Phase II study

The multi-arm Phase II study will enrol patients with resectable stage III melanoma and is designed and run by the Netherlands Cancer Institute (NKI) and the European Institute of Oncology (IEO), together with eight Dutch and Italian melanoma expert centres. It is led by Professor Christian Blank, MD, PhD, a leading figure in neoadjuvant immunotherapy for melanoma whose earlier OpACIN, OpACIN-neo, PRADO, DONIMI and NADINA trials helped establish checkpoint inhibitor treatment before surgery as standard of care in the disease.

“Despite the progress made with checkpoint inhibitor combinations in stage III melanoma, patients with low interferon-gamma signatures continue to have substantially worse outcomes. The preclinical rationale for combining ruxotemitide with ipilimumab and nivolumab in this population is compelling, and I look forward to testing whether this combination can meaningfully improve pathological response rates for patients who are currently underserved by standard of care,” says Professor Christian Blank

Neoadjuvant ipilimumab plus nivolumab and perioperative pembrolizumab are both used today as standard-of-care options ahead of surgery in stage III melanoma. Ruxotemitide has already shown preliminary positive effects in combination with pembrolizumab in Lytix’s own NeoLIPA study; ALETTA will generate the first randomized, controlled data on adding ruxotemitide to the ipilimumab-nivolumab backbone instead, with the comparison arm specifically targeting patients with low interferon-gamma signatures, a biomarker-defined group that responds poorly to ipilimumab plus nivolumab alone. Patient enrolment in that comparison is expected to begin in early 2027.