Targeting Lipid Metabolism and Diet in Patients with Prostate Cancer - Ongoing Clinical Trials

We are thrilled to announce a significant milestone in our ongoing research at Loda's Lab. After dedicating years to in-depth investigations into lipogenesis and the crucial role of the Fatty Acid Synthase enzyme (FASN) in prostate cancer (PC), we are excited to be enrolling patients in the following clinical trial:

Phase I, Open-Label, Dose-Finding Study of TVB-2640 Administered in Combination with Enzalutamide (enza) in Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) [NCT05743621]

Led by Dr. David Nanus, this trial aims to contribute to developing a new treatment in mCRPC by targeting for the first time the intricate interplay between the Androgen Receptor (AR) pathway - which is the primary driver of lethal mCRPC - and the metabolic processes within cancer cells, particularly the FASN enzyme, its rate-limiting step.

This is an open-label, single-arm, Phase I dose-escalation study that enrolls pts with mCRPC who are candidates to receive enza. The primary objective is to determine the maximum tolerated dose  and recommended Phase II dose of TVB-2640 -  a FASN inhibitor developed by Sagimet Bioscience - in combination with enza. Secondary objectives include safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity. Exploratory objectives include the effects of FASN inhibition on metabolites, genetics, and lipids in human blood and tumor tissue, to identify potential predictive and prognostic markers of response.

Pts with a confirmed diagnosis of PC, evidence of metastatic PC on imaging, serum testosterone <50 ng/dl, who had progressed on androgen-depletion therapy,  with documented progressive mCRPC are eligible.

Enrolled patients will receive enza at a daily dose of 160 mg for 36 days to reach a steady state, followed by the addition of oral TVB-2640 starting at 100 mg/daily. The dose escalation will follow the Bayesian optimal interval (BOIN) design with additional dose levels of 150 mg, 200 mg, 250 mg, and 300 mg daily.

This is the first clinical trial to evaluate the targeting of the AR pathway through inhibition of lipid synthesis as a new approach to treating mCRPC. Enrollment of Cohort 1 began in August 2023. ClinicalTrials.gov ID NCT05743621. https://clinicaltrials.gov/study/NCT05743621?cond=prostate%20caner&term=tvb-2640&rank=1