0000000000017521
AUTHOR
Wai Y. Chan
Antitumor activity of ipatasertib combined with chemotherapy: results from a phase Ib study in solid tumors
Inhibidor d'AKT; Càncer avançat; Fase I Inhibidor de AKT; Cáncer avanzado; Fase I AKT inhibitor; Advanced cancer; Phase I Background This phase Ib study evaluated the safety, tolerability, pharmacokinetics, and preliminary efficacy of the oral AKT inhibitor ipatasertib and chemotherapy or hormonal therapy in patients with advanced or metastatic solid tumors to determine combined dose-limiting toxicities (DLTs), maximum tolerated dose, and recommended phase II doses and schedules. Patients and methods The clinical study comprised four combination treatment arms: arm A (with docetaxel), arm B [with mFOLFOX6 (modified leucovorin, 5-fluorouracil, and oxaliplatin)], arm C (with paclitaxel), and …
A First-in-Human Phase I Study of the ATP-Competitive AKT Inhibitor Ipatasertib Demonstrates Robust and Safe Targeting of AKT in Patients with Solid Tumors.
Abstract Activation of AKT signaling by PTEN loss or PIK3CA mutations occurs frequently in human cancers, but targeting AKT has been difficult due to the mechanism-based toxicities of inhibitors that target the inactive conformation of AKT. Ipatasertib (GDC-0068) is a novel selective ATP-competitive small-molecule inhibitor of AKT that preferentially targets active phosphorylated AKT (pAKT) and is potent in cell lines with evidence of AKT activation. In this phase I study, ipatasertib was well tolerated; most adverse events were gastrointestinal and grade 1–2 in severity. The exposures of ipatasertib ≥200 mg daily in patients correlated with preclinical TGI90, and pharmacodynamic studies co…