| Title: |
Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial |
| Authors: |
Porcari, Serena; Ciccarese, Chiara; Heidrich, Vitor; Rondinella, Debora; Quaranta, Gianluca; Severino, Andrea; Arduini, Daniela; Buti, Sebastiano; Fornarini, Giuseppe; Primi, Francesca; Stumbo, Luciano; Giannarelli, Diana; Giudice, Giulia, Claire; Damassi, Alessandra; Giron Berríos, Julio, Rodrigo; Barbazuk, Thomas, B; Piccinno, Gianmarco; Pinto, Federica; Armanini, Federica; Asnicar, Francesco; Schinzari, Giovanni; Derosa, Lisa; Kroemer, Guido; Sanguinetti, Maurizio; Masucci, Luca; Gasbarrini, Antonio; Tortora, Giampaolo; Cammarota, Giovanni; Zitvogel, Laurence; Segata, Nicola; Iacovelli, Roberto; Ianiro, Gianluca |
| Contributors: |
Immunologie anti-tumorale et immunothérapie des cancers (ITIC (U1015)); Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay; Université Paris-Saclay; Institut Gustave Roussy (IGR); Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)); École Pratique des Hautes Études (EPHE); Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité); Cancer Research and Personalized Medicine - CARPEM Paris (SIRIC CARPEM); Hôpital Européen Georges Pompidou APHP (HEGP); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Necker - Enfants Malades AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut national du cancer (INCa)-Université Paris Cité (UPCité); Plateforme de métabolomique; Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa); Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS); Institut universitaire de France (IUF); Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.); ANR-16-RHUS-0008,LUMIERE,LUMIERE(2016); ANR-21-RHUS-0017,IMMUNOLIFE,Microbiota-centered interventions to solve antibiotics-induced primary resistance to immune checkpoint inhibitors(2021); ANR-23-RHUS-0010,LUCA-pi,Lung cancer prevention and interception(2023); ANR-22-CE14-0066,VIVORUSH,Le système RUSH : un système chemo-génétique pour la manipulation in vivo de circuits de communication.(2022); ANR-23-CE44-0030,COPPERMAC,Ciblage du cuivre mitochondrial pour moduler l'inflammation(2023); ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018); ANR-21-ESRE-0028,ONCO-PHENO-SCREEN,Next-generation phenotypic screening for oncological applications(2021); ANR-23-R4HC-0006,Ener-LIGHT,Energizing the failing heart(2023); ANR-19-CE15-0029,Ileobiome,Régulation des réponses immunitaires iléales dans l'immunosurveillance du cancer du colon: rôle du microbiote et des antigènes des cellules souches.(2019); European Project: 101045015,ERC-2021-COG,ERC-2021-COG,microTOUCH(2022); European Project: 825410,H2020-SC1-BHC-2018-2020,H2020-SC1-2018-Single-Stage-RTD,ONCOBIOME(2019); European Project: 964590,H2020-SC1-BHC-2018-2020,H2020-SC1-2020-Single-Stage-RTD,IHMCSA(2021); European Project: 101052444,ERC-2021-ADG,ERC-2021-ADG,ICD-Cancer(2023); European Project: 101095604,HORIZON-HLTH-2022-STAYHLTH-02,HORIZON-HLTH-2022-STAYHLTH-02,PREVALUNG EU(2022); European Project: 101168810,HORIZON-MSCA-2023-DN-01,HORIZON-MSCA-2023-DN-01,T-RAFIC(2025) |
| Source: |
ISSN: 1078-8956. |
| Publisher Information: |
CCSD; Nature Publishing Group |
| Publication Year: |
2026 |
| Collection: |
Inserm: HAL (Institut national de la santé et de la recherche médicale) |
| Subject Terms: |
Renal cancer; Cancer immunotherapy; Microbiome; [SDV]Life Sciences [q-bio] |
| Description: |
International audience ; 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/grantAgreement//101045015/EU/Transmission of the human microbiome and its impact on health/microTOUCH; info:eu-repo/grantAgreement//825410/EU/Gut OncoMicrobiome Signatures (GOMS) associated with cancer incidence, prognosis and prediction of treatment response./ONCOBIOME; info:eu-repo/grantAgreement//964590/EU/International Human Microbiome Coordination and Support Action/IHMCSA; info:eu-repo/grantAgreement//101052444/EU/Immunogenic cell death (ICD) in the cancer-immune dialogue/ICD-Cancer; info:eu-repo/grantAgreement//101095604/EU/Biomarkers affecting the transition from cardiovascular disease to lung cancer: towards stratified interception./PREVALUNG EU; info:eu-repo/grantAgreement//101168810/EU/Training network for tracking and controlling therapeutic immune cells in cancer/T-RAFIC |
| DOI: |
10.1038/s41591-025-04189-2 |
| Availability: |
https://hal.science/hal-05613137; https://hal.science/hal-05613137v1/document; https://hal.science/hal-05613137v1/file/41606119.pdf; https://doi.org/10.1038/s41591-025-04189-2 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.ABC7F56F |
| Database: |
BASE |