Fecal Microbiota Transplantation Enhances First-Line ICI Therapy in Metastatic RCC – OncLive News

Fecal microbiota transplantation (FMT) may improve outcomes when combined with immune checkpoint inhibitor (ICI) therapy for patients with metastatic renal cell carcinoma (mRCC), according to recent research presented in OncLive and supported by findings from a phase 1 clinical trial published in Nature Medicine.

The phase 1 trial, known as TACITO, evaluated the safety and efficacy of encapsulated healthy donor FMT (LND101) in combination with various ICI-based regimens in 20 treatment-naive patients with mRCC. Participants received FMT alongside either ipilimumab/nivolumab (n=16), pembrolizumab/axitinib (n=3), or pembrolizumab/lenvatinib (n=1). The primary endpoint was safety, specifically the incidence and severity of immune-related adverse events (irAEs).

Results showed that 50% of patients (10 out of 20) experienced grade 3 irAEs, but there were no serious FMT-related toxicities and no grade 4 or 5 irAEs reported. Among the 18 patients evaluable for response, the objective response rate was 50% (9 out of 18), including two complete responses (11%, 2 out of 18). Notably, most patients who responded to treatment did not develop any grade 3 or higher irAEs.

Further analysis revealed that patients who responded to treatment and experienced lower toxicity showed improvement in alpha (α) diversity of the gut microbiome and durable engraftment of microbial taxa and metabolic functions linked to anti-inflammatory properties. In contrast, patients who developed grade 3 irAEs exhibited an expansion of Segatella copri, particularly in those receiving ipilimumab/nivolumab, along with elevated levels of donor-derived microbial enzymes previously associated with pro-inflammatory activity.

The study suggests that resilience to toxicity and improved treatment response correlated with the maintenance of protective metabolites and increased levels of immune regulatory cells. Conversely, the presence of grade 3 irAEs and Segatella copri enrichment was associated with high immune dysregulation.

These findings support the hypothesis that gut microbiome modulation through FMT can enhance the efficacy of immunotherapy while potentially reducing toxicity in mRCC. Researchers note that while the safety endpoint was met, larger studies are needed to confirm these results and better understand the mechanisms underlying microbiome-immune interactions in cancer treatment.

The research was conducted as part of the TACITO trial and published in Nature Medicine. Additional coverage highlighting the potential of FMT to boost response to pembrolizumab plus axitinib in metastatic RCC has been reported by OncLive.