KETOREIN is a project developed within ClinicObiome at Gustave Roussy, centered on metastatic renal cell cancer (RCC) with dismal prognosis features (intermediate or poor IMDC) amenable to first line combination of immune checkpoint inhibitors (Ipilimumab+Nivolumab). It is a prospective, 4 single-arm, open-label, multicentric phase II study enrolling a total of 60 metastatic Renal Cell Carcinoma patients. The purpose of this study is to assess objective response rate (partial and complete response) of Nivolumab and Ipilimumab concomitant to a special diet (ketogenic diet, continuous or discontinuous) or standard diet with or without BHB according to RECIST v1.1 at 8 weeks. The expected response rate is <40% at 3 months with side effects in all-comers (i.e., unselected). Given the published data (Ferrere et al JCI Insight 2021, supported by Seerave), it is anticipated that preconditioning with ketogenic diet (KD) or the main resulting systemic ketone body beta hydroxybutyrate (BHB) will increase objective responses rates and decreases side effects in human cancer patients undergoing immunotherapy.
For more information on the study, visit NCT05119010 at clinicaltrials.gov
The aim of the study is to investigate whether the induction of ketosis, either with a ketogenic diet or with the intake of beta-Hydroxybutyrate (BHB), will overcome the primary resistance to immunotherapy. The team hypothesizes that the induction of ketosis might shift the gut microbiota, shaping the immune system to favor response to anticancer treatment.
The translational research will focus on two main aspects
- Pharmacokinetics: the detection of ketosis and the bioavailability of BHB, ipilimumab and nivolumab,
- Pharmacodynamics: the identification of biomarkers of treatment response and the characterization of the mechanisms of action.
Internal validation of Ketogenic Diet
Internal validation of commercial ketogenic drink