Genfit has announced encouraging preliminary results from its phase 1b clinical trial evaluating investigational drug GNS561 in combination with a MEK inhibitor (MEKi) in patients with KRAS mutated cholangiocarcinoma (CCA).
The rare and aggressive cancer of the bile ducts is often diagnosed late and has limited treatment options.
The study enrolled patients with advanced CCA who had failed one or two prior lines of therapy. Nine patients with measurable disease were included, with four reaching tumour assessment at week six.
At this point, all four showed disease stabilisation, while a subgroup demonstrated tumour shrinkage, with the best response showing a 20% reduction approaching the partial response threshold. No dose limiting toxicity has been observed to date, allowing recruitment of a third patient cohort.
Dr Mark Yarchoan, Associate Professor of Oncology at John Hopkins Medicine and principal investigator of the programme, said: “Advanced KRAS-mutated cholangiocarcinoma remains a formidable clinical challenge, and the emerging activity seen in this initial study is encouraging.
“Because MEK inhibition alone has historically shown limited efficacy in this setting, the early signs of benefit with dual targeting of autophagy and MAPK signalling provide meaningful rationale for continued evaluation of this combination strategy.”
Pascal Prigent, Chief Executive Officer of Genfit, explained: “These early results suggest a potential breakthrough for patients with limited options, and we are committed to advancing this programme rapidly to individuals impacted by cholangiocarcinoma. We will also explore GNS561 potential in combination with other agents and in other tumours where autophagy inhibition plays a central role.”
Dose escalation will continue into 2026, with recommended phase 2 doses expected in the first half of the year and phase 2 initiation targeted for the second half.
