Abstract P6-11-09: Heavily pre-treated breast cancer patients show promising responses in the first in human study of the first-In-class fatty acid synthase (FASN) inhibitor, TVB-2640 in combination with paclitaxel
Authors: Brenner AJ , Falchook G , Patel M , Infante JR , Arkenau H-T , Dean EM , Borazanci E , Lopez JS , Moore K , Schmid P , Frankel AE , Jones S , McCulloch W , Kemble G , Grimmer K , Burris H 
Published: March 2017

Abstract
Introduction
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 in breast cancer patients treated in the dose expansion cohort.
Methods
This ongoing international, multicenter Phase I trial enrolls patients (pts) with advanced solid tumors with adequate organ function. TVB-2640 is 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 observed [mono, N=53; combo, N=47] were: alopecia (57%), palmar-plantar erythrodysesthesia (PPE) (36%), dry eye (13%) and increased lacrimation (11%). Gr. 3 toxicities include corneal edema (3%) and PPE (10%). Other toxicities were ≤ Gr. 2 and only minor GI symptoms occurred. All toxicities were reversible on dose interruption and no enhancement of common paclitaxel toxicity was observed when given with TVB-2640. Rare cases of pneumonitis in combination have been observed but the contribution of TVB-2640 to this effect is uncertain.
14 breast cancer patients were enrolled and treated in combination with weekly paclitaxel while 3 breast patients were given monotherapy (during the dose escalation phase). Among patients treated in combination, three (3) confirmed RECIST partial responses (cPR) were seen and multiple cases of prolonged stable disease (SD) (≥16 wks) despite heavy pre-treatment and taxane resistance in all but 2 cases. One ER+, PR+, Her2+ patient achieved a cPR and was on study for 26 weeks. One ER-/PR-/Her2+ patient whose previous best response to paclitaxel treatment was SD for 24 weeks, reached a cPR at week 12, discontinued paclitaxel at week 21 and remains on monotherapy TVB-2640 with a sustained cPR at week 29. The third responder with cPR is an ER+, PR+, HER2- patient whose previous taxane treatment lasted 15 weeks (response unknown) and she remains on study at week 24. Of the remaining 11 patients, 10 achieved SD &gt; 12 weeks and 8 of the 10 maintained that response for 16-45 weeks. The ongoing SD patient at week 45, discontinued paclitaxel at week 35 and remains on monotherapy TVB-2640.
Summary
TVB-2640 demonstrated multiple cPRs and prolonged SD when combined with weekly paclitaxel in 93% of patients treated. Further exploration of response in patients recently progressed on a taxane (progression within the prior 6 months) and safety with TVB-2640 in combination with docetaxel is being explored.
Citation Format: Brenner AJ, Falchook G, Patel M, Infante JR, Arkenau H-T, Dean EM, Borazanci E, Lopez JS, Moore K, Schmid P, Frankel AE, Jones S, McCulloch W, Kemble G, Grimmer K, Burris H. Heavily pre-treated breast cancer patients show promising responses in the first in human study of the first-In-class fatty acid synthase (FASN) inhibitor, TVB-2640 in combination with paclitaxel [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-11-09.