Interrogating two schedules of the AKT inhibitor MK-2206 in patients with advanced solid tumors incorporating novel pharmacodynamic and functional imaging biomarkers.

Cancer Therapy: Clinical Interrogating Two Schedules of the AKT Inhibitor MK-2206 in Patients with Advanced Solid Tumors Incorporating Novel Pharmacodynamic and Functional Imaging Biomarkers

Purpose: Multiple cancers harbor genetic aberrations that impact AKT signaling. MK-2206 is a potent pan-AKT inhibitor with amaximum tolerated dose (MTD) previously established at 60mg on alternate days (QOD). Due to a long half-life (60–80 hours), a weekly (QW)MK-2206 schedule was pursued to compare intermittent QW and continuous QOD dosing. Experimental Design: Patients with advanced cancers w...

Title: Phase 1 study of an AKT-inhibitor (MK-2206) combined with lapatinib in adult solid tumors followed by dose-expansion in advanced HER2+ breast cancer Running title: Phase 1 of MK-2206 and lapatinib in combination Authors: 1)

Results of an abbreviated phase-II study with the Akt Inhibitor MK-2206 in Patients with Advanced Biliary Cancer

Biliary cancers (BC) are rare, chemoresistant and are associated with a poor prognosis. Targeting the Akt pathway is of significance in BC. We hypothesized that the allosteric inhibitor MK-2206 will be active in BC. This was a multi-institutional phase II study of MK-2206 given to patients with advanced, refractory BC. The primary end point was overall response rate. We also characterized pharm...

Phase 1 trial of the oral AKT inhibitor MK-2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors

BACKGROUND Inhibition of AKT with MK-2206 has demonstrated synergism with anticancer agents. This phase 1 study assessed the MTD, DLTs, PK, and efficacy of MK-2206 in combination with cytotoxic and targeted therapies. METHODS Advanced solid tumor patients received oral MK-2206 45 or 60 mg (QOD) with either carboplatin (AUC 6.0) and paclitaxel 200 mg/m2 (arm 1), docetaxel 75 mg/m2 (arm 2), or ...

A Phase I Trial of Combined Ridaforolimus and MK-2206 in Patients with Advanced Malignancies.

PURPOSE The PI3K/Akt/mTOR signaling pathway is aberrantly activated in many cancers. Combining ridaforolimus, an mTOR inhibitor, with MK-2206, an Akt inhibitor, may more completely block the PI3K pathway and inhibit tumor growth. EXPERIMENTAL DESIGN This phase I study assessed dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) for the combination of oral ridaforolimus plus oral M...