Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial.
- 2026-01-28
- Nature medicine 32(4)
- Serena Porcari
- Chiara Ciccarese
- Vitor Heidrich
- Debora Rondinella
- Gianluca Quaranta
- Andrea Severino
- Daniela Arduini
- Sebastiano Buti
- Giuseppe Fornarini
- Francesca Primi
- Luciano Stumbo
- Diana Giannarelli
- Giulia Claire Giudice
- Alessandra Damassi
- Julio Rodrigo Giron Berríos
- Michal Punčochář
- Thomas B Barbazuk
- Gianmarco Piccinno
- Federica Pinto
- Federica Armanini
- Francesco Asnicar
- Giovanni Schinzari
- Lisa Derosa
- Guido Kroemer
- Maurizio Sanguinetti
- Luca Masucci
- Antonio Gasbarrini
- Giampaolo Tortora
- Giovanni Cammarota
- Laurence Zitvogel
- Nicola Segata
- Roberto Iacovelli
- Gianluca Ianiro
- PubMed: 41606119
- DOI: 10.1038/s41591-025-04189-2
Study Design
- Type
- Randomized Controlled Trial (RCT)
- Population
- 45 treatment-naive patients with metastatic RCC (mRCC) receiving pembrolizumab + axitinib
- Methods
- investigator-initiated, randomized, double-blind placebo-controlled phase 2a TACITO trial; fecal microbiota transplantation (FMT) from complete ICI responders versus placebo FMT
- Blinding
- Double-blind
- Duration
- 12 months
- Funding
- Independent
- Rigorous Journal
Renal cell carcinoma (RCC) is a common malignancy with limited durable responses to first-line immune checkpoint inhibitor (ICI)-based therapies. Emerging evidence implicates the gut microbiome in modulating ICI efficacy. In the investigator-initiated, randomized, double-blind placebo-controlled phase 2a TACITO trial, we evaluated whether fecal microbiota transplantation (FMT) from complete ICI responders enhances clinical outcomes in treatment-naive patients with metastatic RCC (mRCC) receiving pembrolizumab + axitinib. The primary endpoint was the rate of patients free from disease progression at 12 months after randomization (12-month progression-free survival (PFS)). Secondary endpoints were median PFS and median overall survival, objective response rate (ORR), safety and microbiome changes, after randomization. Forty-five patients randomly received donor FMT (d-FMT) or placebo FMT (p-FMT). Although the primary endpoint was not met (70% versus 41% for d-FMT versus p-FMT, respectively, P = 0.053), the secondary endpoint of median PFS was significantly longer with d-FMT (24.0 months in the d-FMT arm versus 9.0 months in the p-FMT arm; hazard ratio = 0.50, P = 0.035). The ORR was 52% of patients in the d-FMT arm and 32% of patients receiving placebo. Microbiome analysis confirmed donor strain engraftment and increased α-diversity and larger microbiome shifts (β-diversity) compared with baseline composition in the d-FMT treatment group. Acquisition or loss of specific strains, but not total engraftment, was associated with the primary endpoint. Our findings support the safety and potential efficacy of selected donor FMT to enhance ICI-based treatment in mRCC, which deserves further investigations. ClinicalTrials.gov identifier: NCT04758507 .