Phase I and pharmacokinetic (PK) study of dasatinib (D) and cetuximab (C) in patients (pts) with advanced solid malignancies

3540 Background: D is a small molecule inhibitor of several kinases, including SRC. SRC can potentiate Epidermal Growth Factor Receptor (EGFR) signaling and is implicated in resistance to EGFR inhibitors. Combined inhibition of EGFR and SRC may lead to improved therapeutic effect. We evaluated the combination of D and C, a chimeric IgG1 monoclonal anti-EGFR antibody. Methods: Eligible pts had advanced solid malignancies treated with any number of prior regimens but without EGFR or SRC inhibitors, ECOG performance status 0–2, QTc interval on baseline EKG <450 msec, and adequate laboratory parameters. C was administered i.v as a loading dose of 400 mg/m2 on cycle 1, day 1 and then weekly at 250 mg/m2 on days 1, 8 and 15. D was administered orally, once daily, on a continuous schedule, on days 1–21. We used a standard up-and-down dose escalation scheme to assign pts on 3 dose levels (DL): 1- 100 mg QD, 2- 150 mg, 3- 200 mg. PK studies of D were performed on days 0 (prior to starting C) and 15 of cycle 1. Res...