Preliminary activity in the first in human study of the first-in-class fatty acid synthase (FASN) inhibitor, TVB-2640.

2512Background: FASN inhibition is a novel approach to cancer treatment involving selective disruption of palmitate biosynthesis that, in tumor cells, leads to apoptosis. TVB-2640 is an oral, first-in-class, small molecule reversible inhibitor of FASN that demonstrates in vivo antitumor effects. We previously reported the results of dose escalation and now present evidence of preliminary activity from the dose expansion. Methods: This ongoing multicenter Phase I trial enrolled patients (pts) with advanced solid tumors with adequate organ function. TVB-2640 was given orally once daily at the MTD (100 mg/m2) as monotherapy (mono) or in combination (combo) with weekly IV paclitaxel (80 mg/m2). Results: The most common AE’s seen in both groups [mono, N=53; combo, N=47] were: alopecia (57%), palmar-plantar erythrodysesthesia (PPE) (36%), dry eye (13%), and increased lacrimation (11%). Gr 3 AE's include corneal edema (3%) and PPE (10%). Other toxicities were ≤ Gr 2 and only minor GI symptoms occurred. All toxic...