Phase Ib Of Anticancer Stem Cell Antibody Omp-59r5 (Anti-Notch2/3) In Combination With Nab-Paclitaxel And Gemcitabine (Nab-P Plus Gem) In Patients (Pts) With Untreated Metastatic Pancreatic Cancer (Mpc)

220 Background: OMP-59R5, a fully human IgG2 antibody, inhibits signaling of Notch2 and 3 receptors. Tumor regression was seen in Notch3 expressing patient-derived pancreatic cancer xenografts when OMP-59R5 was combined with Nab-P+Gem. The maximum tolerated dose (MTD) of single agent OMP-59R5 was 7.5 mg/kg every other week (Smith, EORTC 2012); the main dose limiting toxicity (DLT) was grade 3 diarrhea. This study is to determine the MTD, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of OMP-59R5 in combination with Nab-P+Gem in mPC. Methods: Cohorts of 3 to 6 pts were treated at each dose level of OMP-59R5. OMP-59R5 is given intravenously every other week (days 1 and 15) with GEM 1,000 mg/m2 alone (first two cohorts) or nab-P 125 mg/m2 and GEM 1,000 mg/m2 on days 1, 8, and 15 of every 28-day cycle. Results: By August 30, 2013, 24 pts were treated. No DLTs have occurred. Frequently reported (≥10%) OMP-59R5 treatment-related adverse events (AEs) were: diarrhea (44%), fatigue (44%), and nausea (16%); most were grade 1 or 2 and managed with supportive care. Frequent chemo-related AEs (≥10%) were cytopenia, fatigue, diarrhea, and nausea. GEM or Nab-P+Gem did not alter PK of OMP-59R5. See table for additional data. Conclusions: OMP-59R5 with Nab-P+ Gem is well tolerated. The MTD has not been reached. Encouraging anti-tumor activity is observed. Updated Safety, PK/PD, and efficacy data will be presented. Clinical trial information: NCT01647828. [Table: see text]