Genfit Flags Early Signs of Promise for GNS561 Combo for Cholangiocarcinoma
Genfit has announced encouraging preliminary findings from a phase 1b clinical trial evaluating its investigational therapy, GNS561, in combination with a MEK inhibitor (MEKi) in patients with KRAS-mutated cholangiocarcinoma (CCA).
The disease- a rare and aggressive cancer of the bile ducts – is frequently diagnosed at an advanced stage, leaving many patients with limited therapeutic options once standard treatments fail.
The ongoing study focuses on patients with advanced CCA who had already undergone, and not benefited from, one or two prior lines of therapy. In other words, this is a group where treatment success is notoriously difficult to achieve, and where even incremental clinical signals can carry real weight for future development decisions.
In the initial enrolled population, nine patients with measurable disease were included in the analysis set. Of those, four patients reached the first tumour assessment timepoint at week six. At that early checkpoint, all four demonstrated disease stabilisation – an outcome that can be meaningful in an aggressive cancer known for rapid progression.
Within that group, Genfit also reported that a subgroup showed tumour shrinkage, with the best observed response showing a 20% reduction in tumour size – an effect described as approaching the threshold typically associated with a partial response.
While the dataset remains small and early, the company is positioning these findings as an important directional signal, particularly given the clinical setting and the limited options available to this patient population.
Safety readouts, at least so far, have also supported continued recruitment. Genfit reported that no dose-limiting toxicity has been observed to date, a factor that has enabled the trial to move forward with recruitment of a third patient cohort.
In early-phase oncology development, the ability to escalate dose and expand cohorts without encountering dose-limiting toxicity can be a pivotal step – both for determining an appropriate regimen and for sustaining momentum into later-stage evaluation.
Commenting on the programme, the Associate Professor of Oncology at Johns Hopkins Medicine and principal investigator described advanced KRAS-mutated cholangiocarcinoma as a formidable clinical challenge, noting that the emerging activity seen in this initial study is encouraging.
The investigator also pointed to a key scientific rationale underpinning the combination: MEK inhibition alone has historically shown limited efficacy in this setting, which makes the early signs of benefit with dual targeting of autophagy and MAPK signalling particularly noteworthy.
That strategic framing matters. By pairing GNS561 – positioned here as an autophagy-targeting agent – with a MEK inhibitor aimed at MAPK pathway signalling, the approach is attempting to widen the therapeutic net in a tumour context where single-pathway pressure has not reliably delivered durable responses.
Genfit’s Chief Executive Officer echoed the patient-need perspective, stating that the early results suggest a potential breakthrough for individuals with limited options, and that the company is committed to advancing the programme rapidly for those impacted by cholangiocarcinoma.
Beyond this initial combination, Genfit also said it intends to explore GNS561’s potential alongside other agents and in additional tumour types where autophagy inhibition may play a central role – signalling broader ambitions for the mechanism beyond CCA alone.
In terms of what comes next, the company outlined a clear development runway into 2026. Dose escalation is expected to continue into the new year, with recommended phase 2 doses anticipated in the first half of 2026.
Phase 2 initiation is then targeted for the second half of 2026, setting up a progression from early signal detection toward a more robust test of efficacy and durability.
In Conclusion
Taken together, Genfit’s early phase 1b update offers a cautiously optimistic snapshot: stabilisation in all evaluable patients at week six, early shrinkage in a subgroup with a best 20% reduction nearing partial-response territory, and no dose-limiting toxicity observed so far – enough, in the company’s view, to justify continued escalation and expansion.
While the dataset remains small and the story is still being written, the combination’s early activity, coupled with a clear biological rationale, positions GNS561 plus MEKi as a programme to watch as it moves through 2026 and toward the more definitive proving grounds of phase 2.
News Credits: Genfit reports promising phase 1b data in cholangiocarcinoma
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