Phase I study of MEDI0639 in patients with advanced solid tumors.

3024 Background: MEDI0639 is an investigational monoclonal antibody that selectively binds to Delta-like ligand 4 (DLL4) and blocks its ability to bind to and activate signaling through the Notch receptors, potentially inhibiting tumor growth by multiple mechanisms. Methods: This study (NCT01577745) included patients (pts) with advanced solid tumors who had ECOG performance status 0–1 and adequate organ function. MEDI0639 10–200 mg was given every 21 days with a 3+3 dose-escalation design. Primary objective was to determine maximum tolerated dose (MTD) and safety. Other objectives included pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity (IG), and antitumor activity. Results: As of Jan 7, 2015, 20 pts were enrolled (median age 61y [range 40–83y]; median number of prior therapies: 5). The most common tumors were colorectal (n = 5), small cell lung cancer (n = 4), and melanoma (n = 4). No dose-limiting toxicities were identified through the 150 mg dose; the 200 mg dose is currently being evaluat...