Final Results Of Phase Ib Of Anticancer Stem Cell Antibody Tarextumab (Omp-59r5, Trxt, Anti-Notch 2/3) In Combination With Nab-Paclitaxel And Gemcitabine (Nab-P Plus Gem) In Patients (Pts) With Untreated Metastatic Pancreatic Cancer (Mpc).

278 Background: Tarextumab (TRXT), fully human IgG2 antibody, inhibits signaling Notch 2, 3 receptors. Tumor regression seen in Notch 3 patient-derived PC xenografts when TRXT added to Nab-P+Gem. The maximum tolerated dose (MTD) of single agent TRXT was 7.5mg/kg every other week (Smith, EORTC 2012); the main dose limiting toxicity (DLT) was Grade 3 diarrhea. This study evaluates MTD, pharmacokinetics (PK), pharmacodynamics (PD) and early efficacy of TRXT + Nab-P+Gem in mPC. Methods: Cohorts of 3-6 pts treated at 6 dose levels of TRXT. TRXT IV Days 1 + 15 with GEM 1000mg/m2 alone (first two cohorts) or nab-P 125 mg/m2 and GEM 1000mg/m2on Days 1, 8, 15 of every 28-day cycle. Biomarker analysis of surrogate tissue and tumor undertaken. Results: By 08/22/14, N= 40 treated. TRXT 15 mg/kg selected as Phase 2 dose. 1 DLT Grade 3 diarrhea in 15 mg/kg cohort. Frequently reported (≥15%) TRXT adverse events(AEs) were: diarrhea(60%), fatigue(43%), anemia(28%), decreased appetite (18%) and nausea(15%); most grade 1 or...