First-in-human study of the safety, pharmacokinetics, and pharmacodynamics of first-in-class fatty acid synthase inhibitor TVB-2640 alone and with a taxane in advanced tumors
Gerald S. Falchook, Jeffrey R. Infante, Hendrik‐Tobias Arkenau, Manish R. Patel, Emma Dean, Erkut Borazanci, Andrew Brenner, Natalie Cook, Juanita Lopez, Shubham Pant, Arthur E. Frankel, Peter Schmid, Kathleen N. Moore, William McCulloch, Katharine Grimmer, Marie O’Farrell, George Kemble, Howard A. Burris
Abstract
BACKGROUND: We conducted a first-in-human dose-escalation study with the oral FASN inhibitor TVB-2640 to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D), as monotherapy and with a taxane. METHODS: This completed open-label outpatient study was conducted at 11 sites in the United States and United Kingdom. Patients with previously-treated advanced metastatic solid tumors and adequate performance status and organ function were eligible. TVB-2640 was administered orally daily until PD. Dose escalation initially followed an accelerated titration design that switched to a standard 3 + 3 design after Grade 2 toxicity occurred. Disease-specific cohorts were enrolled at the MTD. Statistical analyses were primarily descriptive. Safety analyses were performed on patients who received at least 1 dose of study drug. (Clinicaltrials.gov identifier NCT02223247). FINDINGS: NSCLC, ovarian, and breast cancer. INTERPRETATION: lung, ovarian, and breast cancer, is warranted. FUNDING: This trial was funded by 3-V Biosciences, Inc. (now known as Sagimet Biosciences Inc.).