Safety, pharmacokinetics, and antitumor activity of MEDI3617, a selective angiopoietin inhibitor, in adult patients with advanced solid tumors.
TPS2621 Background: MEDI3617 is an investigational monoclonal antibody that inhibits angiogenesis by preventing the interaction of angiopoietin-1 and angiopoietin-2 (Ang2) ligands with the Tie2 receptor. Methods: This is an ongoing phase 1 dose-escalation and dose-expansion study in patients with advanced solid tumors, Karnofsky performance status ≥70, and adequate organ function. Patients were treated with escalating IV doses of MEDI3617 on day 1 of each 21 day cycle in cohorts of 3-6 patients. The objectives are to evaluate the safety profile and determine the maximum tolerated dose, dose-limiting toxicities (DLT), pharmacokinetics, pharmacodynamics, and clinical activity of MEDI3617. Results: Preliminary data are presented for 21 patients (14M/7F), median age 65 yrs, evaluable for DLT. One DLT occurred: grade 4 neutropenia lasting more than 7 days. The most frequently reported drug-related adverse events (% of patients) were fatigue (24%), diarrhea (19%), nausea (19%), dysgeusia (14%), and headache (14%), all of which were ≤ grade 2. All monotherapy dose levels have completely enrolled patients without exceeding the maximum tolerated dose. The exposure of MEDI3617 after the first dose showed a more than dose-proportional increase. Suppression of free Ang2 was dose-dependent. Maximum accumulation of total Ang2 was observed at the lowest administered dose. No anti-MEDI3617 neutralizing antibodies were detected. Of the 21 patients, 4 continue on treatment (maximum of 6+ months in a patient with carcinoid tumor of the jejunum) as of the data cut-off date. Of the 17 patients for whom response data are available, 5 had stabilization of disease of 12 weeks or greater. Conclusions: Preliminary safety and activity signals warrant continued evaluation of MEDI3617. This study was funded by MedImmune, LLC.