Safety, Pharmacokinetics, Pharmacodynamics, And Antitumor Activity Of Necuparanib Combined With Nab-Paclitaxel And Gemcitabine In Patients With Metastatic Pancreatic Cancer: Updated Phase 1 Results.

4114 Background: Preclinical studies have shown necuparanib (necu)’s ability to bind growth factors, adhesion molecules, and chemokines to inhibit tumor progression, invasion, metastasis, and angiogenesis. Necu is being evaluated in a phase I/II trial with nab-paclitaxel (nabP) + gemcitabine (gem) in patients (pts) with metastatic pancreatic cancer (ClinicalTrials.gov NCT01621243). Part A is an open-label safety/pharmacokinetic (PK)/pharmacodynamic (PD) study to determine a Part B dose; Part B will evaluate efficacy, safety, and PK/PD relative to nabP + gem. Methods: In Part A, necu was given as daily escalating s.c. doses in combination with i.v. 125 mg/m2 nabP and 1000 mg/m2 gem (Days 1, 8, 15 of each 28-day cycle). The necu start dose was 0.5 mg/kg, with escalation via a modified 3+3 design until the maximum tolerated dose (MTD) was determined. The protocol was amended to include nabP after 2 necu + gem cohorts were completed. Results: As of January 15, 2015, 39 pts in 7 cohorts (0.5 and 1 mg/kg + gem;...