PI3K/AKT Activation and Response in Phase IB: AKT Inhibitor GDC-0068 with Docetaxel (D) Or MFOLFOX6 (F) in Refractory Solid Tumors

R. Meng1, L. R. Molife2, L. de Mattos-Arruda3, A. Hollebecque4, S. J. Isakoff5, D. Roda6, Y. Yan1, A. Cervantes6, J. C. Soria4, J. Mateo2, G. Argiles3, J. C. Bendell7 Genentech, South San Francisco, CA, USA, Institute of Cancer Research/ Royal Marsden Hospital, Sutton, United Kingdom, Vall d’Hebron University Hospital, Barcelona, Spain, Institut Gustave Roussy, Villejuif, France, Massachusetts General Hospital, Boston, MA, USA, Institute of Health Research INCLIVA, University of Valenica, Valencia, Spain, Sarah Cannon Research Institute, Nashville, TN, USA

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 …

Abstract P6-12-02: Phase Ib dose-escalation study of an Akt inhibitor ipatasertib (Ipat) in combination with docetaxel (Doc) or paclitaxel (Pac) in patients (pts) with metastatic breast cancer (MBC)

Abstract Background: The Akt pathway is frequently aberrantly activated in MBC (e.g. via PTEN loss, and/or alterations of PIK3CA, AKT1, or AKT3); additionally, Akt activation may occur in response to chemotherapy, leading to cell survival and chemoresistance. Ipat (GDC-0068) is a potent oral, ATP-competitive inhibitor of all Akt isoforms. In preclinical models, Ipat synergistically combined with taxanes. In the Phase I dose-escalation single agent study, Ipat was given to pts including MBC, and downregulated Akt signaling at doses ≥ 100 mg. Methods: Eligible pts with MBC, treated with up to 3 prior systemic chemotherapy regimens, received Doc 75 mg/m2 intravenously (IV) on Day 1 with escala…

Poster session 6. Phase 1 studies