An open label feasibility study of fecal microbiota transplantation (FMT) in patients with malignancies not responding to immune checkpoint inhibitor therapy (ICI)

The intestinal microbiome forms a symbiotic relationship with the human host and continuously interacts with its immune system. Specific compositions of the intestinal microbiome of patients with cancer have been linked to response to immune checkpoint inhibitor (ICI) therapy.

We hypothesize that fecal microbiota transplantation (FMT) from patients who respond to ICI therapy (FMT-Donor) can modulate the intestinal microbiome of patients with ICI-refractory malignancies (FMT-Recipients) and render them into responders. Successful proof-of-concept studies showed that reversion from an ICI non-responsive to a responsive disease is indeed possible in melanoma patients after FMT. Based on these data, we propose to investigate whether the FMT approach could be successfully adapted to any cancer type when patients receiving cancer immunotherapy lack a significant treatment response. We will also study molecular mechanisms, which characterize therapy response, such as the composition of transplanted microbiome in donor stool and changes in systemic and local response in stool recipients. This will allow us to identify more general mechanisms that are common to all patients not responding to any ICI.

This trial expands the FMT intervention to patients with any malignancy treated with ICI as a standard of care, to demonstrate the feasibility of this FMT approach as a novel option in cancer therapy. Our overarching goal is to identify specific bacteria strains that can be widely used as a cancer therapy.