0000000000017516
AUTHOR
Rafael Morales-barrera
Translational study associated to a phase II study evaluating the activity of pazopanib in patients (pts) with advanced/metastatic liposarcoma (LPS): A joint Spanish Sarcoma Group (GEIS) and German Interdisciplinary Sarcoma Group (GISG) study.
11067 Background: GEIS 30 was a phase II study showing moderate activity of pazopanib in well-differentiated/dedifferentiated LPS (cohort A:37 pts, Progression free Survival (PFS) at 12 weeks (w) 43.2%) and no activity in Myxoid/round cell LPS (cohort B: 15 pts, PFS at 12w 13.3%). The present study aims to identify tumor and plasma biomarkers that are differently expressed in long responders (LRs) PFS > 24 w. Methods: Serum samples and paraffin-blocks at diagnosis were collected for 28 pts in cohort A and 11 in B. A total of 13 pts were LRs. Serum samples were obtained at baseline, after 3 w of treatment and at progression. A panel of 15 cytokines and growth factors were evaluated using…
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…