Phase 1 study of the PARP inhibitor E7449 as a single agent in patients with advanced solid tumors or B-cell lymphoma.
Published on May 20, 2014in Journal of Clinical Oncology28.349
· DOI :10.1200/jco.2014.32.15_suppl.e19531
e19531^ Background: E7449 is an orally bioavailable, likely brain penetrable, potent small-molecule inhibitor of poly (ADP-ribose) polymerase (PARP) 1 and PARP 2 with an IC50 of 1.0 and 1.2 nmol/L respectively. E7449 is a poor P-gp substrate. Preclinically, E7449 potentiates the antitumor activity of chemotherapy and radiotherapy and has activity as a single-agent in BRCA-deficient and other tumors. A Phase 1 study of E7449 as a single agent is underway to determine the MTD, safety, PK, PD, preliminary activity and perform exploratory biomarker analysis. Methods: Patients (pts) with advanced solid tumors or B-cell lymphoma, ECOG PS 0-1, > 18 years (yrs) and adequate organ function are eligible. E7449 is administered orally, once daily (QD), continuously. Blood samples for PK, PD and biomarkers are collected at multiple time points. Results: 25 pts (median age: 66 yrs; M/F: 14/ 11) have been treated at 6 dose levels: 50, 100, 200, 400, 800 and 600 mg QD. Tumor types included: pancreatic (n=5), lung (n=4), ...