Randomized phase II study of PEGPH20 plus nab-paclitaxel/gemcitabine (PAG) vs AG in patients (Pts) with untreated, metastatic pancreatic ductal adenocarcinoma (mPDA).

• DOI: 10.1200/jco.2017.35.15_suppl.4008
• Publication Date: 2018-09-06T15:43:43Z
• Authors: Sunil R. Hingorani; Andrea J. Bullock; Tara Elisabeth Seery; Lei Zheng; Darren Sigal; Paul S. Ritch; Fadi S. Braiteh; Mark Zalupski; Nathan Bahary; William Proctor H...; Jie Pu; Carrie Aldrich; Sihem Khelifa; Xionghua W. Wu; Joaquina Baranda; Ping Jiang; Andrew Eugene Hen...
• Keywords: 0301 basic medicine; 03 medical and health sciences; 3. Good health

4008 Background: Hyaluronan (HA) accumulation in the tumor microenvironment produces elevated tumor pressure, vascular compression, and reduced drug delivery. PEGPH20 degrades HA, increasing the access and therapeutic index of anticancer agents. Methods: In Stage 1 of this phase II study, pts with untreated mPDA were randomized 1:1 to PAG (P; 3 µg/kg IV 2x/wk x 3 wks in C1, then 1x/wk x 3 wks in C2+, plus AG) vs AG every 28 days. An imbalance in thromboembolic (TE) events in the PAG arm led to a clinical hold (~40% of pts discontinued PEGPH20), exclusion of pts at high risk for TE events and enoxaparin prophylaxis in both study arms. In Stage 2, randomization was 2:1 to PAG vs AG. Tumor HA was tested using a novel assay (VENTANA HA RxDx). Primary endpoints were PFS (evaluable pts) and TE event rate (Stage 2). Secondary endpoints were PFS by HA level and ORR. Results: 279 pts were randomized; 231 are evaluable for efficacy. Of 246 pts with HA data, 84 (34%) were HA-High. As of December 16, 2016, the primary PFS endpoint was statistically significant for PAG vs AG (HR 0.73, 95% CI 0.53-1.00; p = 0.048) (Table). PFS in HA-High pts was also statistically significant in the PAG vs AG arm (HR 0.51; 95% CI 0.26-1.00; p = 0.048). ORR in HA-High pts was 46% (PAG) vs 34% (AG). Overall survival in HA-High pts (exploratory) was 11.5 months (mo) (PAG) and 8.5 mo (AG) (HR 0.96, 95% CI 0.57-1.61). TE events were similar (PAG 14% vs AG 10%) following enoxaparin initiation. All grade treatment-related AE included peripheral edema (PAG 63% vs AG 26%), muscle spasms (56% vs 3%), neutropenia (34% vs 19%), and myalgia (26% vs 7%). Conclusions: Randomized Phase II study met both primary endpoints (PFS and TE event rate), with the largest improvement in the secondary endpoint of PFS in HA-High pts. These data support HA as a potential predictive biomarker for patient selection of PEGPH20, currently investigated in the ongoing global Phase III HALO 301 study with PFS and OS as co-primary endpoints. Clinical trial information: NCT01839487. [Table: see text]