PD-006Final analysis of stage 1 data from a randomized phase 2 study of PEGPH20 plus nab-paclitaxel/gemcitabine in stage IV previously untreated pancreatic cancer patients, utilizing Ventana companion diagnostic assay

Introduction: Poor outcome in pancreatic ductal adenocarcinoma (PDA) is associated partly with stromal hyaluronan (HA) accumulation, which compromises chemotherapy perfusion. PEGPH20 (PEGylated recombinant human hyaluronidase) potentiates chemotherapy by degrading HA. An ongoing, Phase 2, randomized study is comparing PEGPH20 + nab-paclitaxel (Nab) + Gemcitabine (Gem) (PAG) vs Nab + Gem (AG) in untreated Stage IV PDA. Interim data were presented at ASCO 2015 using a prototype assay to determine the HA-high subpopulation. Final efficacy data are now available with a newly developed Ventana HA CDx Assay and scoring algorithm that identifies HA-HIGH (≥ 50% staining in the extracellular matrix) tumors in patients requiring treatment. Methods: Patients received PEGPH20 3 µg/kg twice weekly (Cycle 1), then weekly (Cycles 2+) with standard AG dosing. The protocol was amended after a temporary clinical hold (April-July 2014) for an imbalance in thromboembolic (TE) events to exclude high-TE-risk patients and add enoxaparin (LMWH) prophylaxis to both treatment arms. Primary endpoints include progression-free survival (PFS) and TE events. PFS and ORR data through Dec 2014 are presented for patients enrolled up to clinical hold (Stage 1). TE data through Dec 2015 (Stage 2) are presented. Results: 135 patients were treated (74 PAG, 61 AG).PFS results are shown below (median follow-up 7 months). In patients with HA-HIGH tumors receiving PAG vs AG, ORR was 55% (1 CR) and 33%, respectively. Incidences of TE events (PAG vs AG) were: Stage 1 (no LMWH) 42% vs 25%; Stage 2 (+LMWH 1 mg/kg/d) 7% vs 4%; overall (+LMWH 40 mg/d or 1 mg/kg/d) 12% vs 9%. No Grade 5 events have occurred with 1 mg/kg/day LMWH. Conclusion: Patients with HA-high tumors receiving PAG vs AG showed clinically meaningful improvements in PFS and ORR. TE events reduced with LMWH. A global phase 3 trial of PAG has been initiated in Q1 2016. Tabled 1 Open table in a new tab