Journal: Nature medicine
This phase 2a TACITO trial tested whether adding fecal microbiota transplantation (FMT) from “super-responder” donors to standard first-line pembrolizumab plus axitinib improves outcomes in treatment-naive metastatic renal cell carcinoma.
Key design points
- Investigator-initiated, randomized, double-blind, placebo-controlled.
- Patients: 45 with metastatic RCC, no prior systemic therapy.
- Arms:
- Donor FMT (d-FMT) + pembrolizumab/axitinib
- Placebo FMT (p-FMT) + pembrolizumab/axitinib
- FMT donors were patients with complete responses to immune checkpoint inhibitors.
Efficacy
- Primary endpoint (12‑month progression‑free survival rate) was numerically improved but not statistically significant:
- 70% with d-FMT vs 41% with p-FMT (P = 0.053).
- Secondary endpoints favored d-FMT:
- Median PFS: 24.0 months (d-FMT) vs 9.0 months (p-FMT); HR = 0.50, P = 0.035.
- Objective response rate: 52% (d-FMT) vs 32% (p-FMT).
- Overall survival was a secondary endpoint but is not detailed in the abstract.
Microbiome findings
- Donor strains successfully engrafted in recipients.
- d-FMT increased alpha diversity and induced larger compositional shifts (beta diversity) versus baseline.
- Clinical benefit correlated with acquisition or loss of specific strains rather than overall engraftment magnitude.
Safety
- The abstract reports FMT as safe in this setting; no specific new safety signals are described.
Clinical interpretation
- Although the formal primary endpoint was narrowly missed, the magnitude of PFS improvement and higher response rate suggest a clinically meaningful signal that modulating the gut microbiome with carefully selected donor FMT may enhance ICI-based therapy in metastatic RCC.
- Results are hypothesis‑generating and support larger confirmatory studies and further work to define the key bacterial strains driving benefit.