Phase I study of the investigational oral mTORC1/2 inhibitor sapanisertib (TAK-228): tolerability and food effects of a milled formulation in patients with advanced solid tumours

Authors: Moore KN, Bauer TM, Falchook GS, Chowdhury S, Patel C, Neuwirth R, Enke A, Zohren F, Patel MR
Publication: ESMO Open
Keywords: absorption modeling, ACAT, food effect, Oncology, PBPK
Software: GastroPlus®

Background

Sapanisertib (TAK-228) is an investigational, orally available, potent and highly selective mTORC1/2 inhibitor demonstrating promise in numerous malignancies. This phase I study (NCT02412722) evaluated the safety, tolerability, pharmacokinetics and antitumour activity of single-agent TAK-228 (milled capsules), administered daily (QD) or weekly (QW) and in combination with paclitaxel in patients with advanced solid tumours. Pharmacokinetic comparisons of milled versus unmilled TAK-228 and the impact of food were also investigated.