Background: Poor outcomes in pancreatic cancer (PDA) are associated in part with tumor stroma limiting chemotherapy perfusion. PDAs express high levels of hyaluronan (HA), which contributes to elevated interstitial pressures. PEGylated recombinant human hyaluronidase, PEGPH20, depletes HA in tumors. In a Phase Ib study of PEGPH20 with Gemcitabine (Gem), patients (pts) whose tumors were HA^high had improved ORR, PFS and OS compared to those with tumors that were HA^Low. Methods: This is an ongoing phase II, open-label, randomized study of PEGPH20 +Nab-Paclitaxel (Nab) + Gem (PAG) vs. Nab + Gem (AG) in previously untreated pts with Stage IV PDA. Pts receive 3 µg/kg twice weekly (Cycle 1) and then weekly (Cycle 2+) PEGPH20 in combination with standard dosing of AG. HA status was tested retrospectively. Primary endpoint is PFS, secondary endpoints include: ORR, OS and Safety. Due to a temporary clinical hold, ORR is from data through April 2014; and PFS is data through December 2014. Results: 146 pts were enrolled and 135 pts received at least one dose of study drug. The mean age was 65.1 yrs. (Range 29-83 yrs), 93% had a KPS of ≥ 80. The most common AEs related to study drugs (PAG vs. AG) were: fatigue (68% vs. 69%), nausea (55% vs. 44%), anemia (42% vs. 53%) peripheral edema (58% vs. 31%) and muscle spasms (55% vs. 2%). There was an imbalance of thromboembolic (TE) events with 42% vs. 25% of subjects having at least one TE event. Overall RR and PFS are shown in the table below. Conclusions: PEGPH20 + Nab/Gem is generally well tolerated in advanced PDA. Patients with HA^high tumors receiving PAG had greater ORR and longer PFS than HA^high patients receiving AG. Overall survival will be presented at the time of the meeting. ClinicalTrials.gov Identifier NCT01839487. Clinical trial information: NCT01839487