biostudies-literatureUnknown3(2)Moore KNMillennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA<h4>Background</h4>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.<h4>Methods</h4>Patients were enrolled to receive: TAK-228 QD, TAK-228 3 days/week plus paclitaxel 80 mg/m² days 1, 8, 15 (TAK-228+P) or TAK-228 QW (all 28-day cycles); starting TAK‑228 doses were 4, 6 and 20 mg, respectively.<h4>ResulESMO opene000291https://www.ebi.ac.uk/biostudies/studies/S-EPMC5812400biostudies-literaturePhase 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.PMC5812400Neuwirth RBauer TMZohren FPatel MRPatel CFalchook GSChowdhury SEnke AMoore KNfalsePhase 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.<h4>Background</h4>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.<h4>Methods</h4>Patients were enrolled to receive: TAK-228 QD, TAK-228 3 days/week plus paclitaxel 80 mg/m² days 1, 8, 15 (TAK-228+P) or TAK-228 QW (all 28-day cycles); starting TAK‑228 doses were 4, 6 and 20 mg, respectively.<h4>Resul2018-01-01T00:00:00Z20182026-06-08T03:23:33.192Z2026-06-08T03:14:07.651ZS-EPMC58124002946411010.1136/esmoopen-2017-000291