A phase Ib study of gemcitabine plus PEGPH20 (pegylated recombinant human hyaluronidase) in patients with stage IV previously untreated pancreatic cancer.

Gastrointestinal (Noncolorectal) Cancer
Session Type and Session Title: 
Poster Discussion Session, Gastrointestinal (Noncolorectal) Cancer
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 4010)
Sunil R. Hingorani, William Proctor Harris, J. Thaddeus Beck, Boris A. Berdov, Stephanie Ann Wagner, Eduard M. Pshevlotsky, Sergei Tjulandin, Oleg Gladkov, Randall F. Holcombe, Ping Jiang, Daniel C. Maneval, Joy Zhu, Craig E. Devoe; Fred Hutchinson Cancer Research Center, Seattle, WA; University of Washington School of Medicine, Seattle, WA; Highlands Oncology Group, Fayetteville, AR; Medical Radiological Research Center, Obninsk, Russia; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN; Omsk Regional Budget Medical Institution: Clinical Oncological Center, Omsk, Russia; Russian Oncology Research Center; N.N. Blokhin Cancer Research Center, Moscow, Russia; Chelyabinsk Regional Clinical Oncology Center, Chelyabinsk, Russia; Mount Sinai School of Medicine, New York, NY; Halozyme Therapeutics, San Diego, CA; Monter Cancer Center, Lake Success, NY

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Abstract Disclosures


Background: PEGPH20 is a PEGylated version of human recombinant hyaluronidase. In preclinical studies, PEGPH20 depleted pancreatic cancers of their high hyaluronan (HA) content. In a genetically-engineered murine model of PDA, PEGPH20 + gemcitabine (Gem) significantly prolonged survival compared to Gem alone. In Ph1 PEGPH20 monotherapy studies, the MTD was 3.0 μg/kg. The most common AEs were musculoskeletal events (MSEs). Methods: This was a dose-escalation study to find the recommended Phase 2 dose (RP2D) of PEGPH20 in combination with Gem in patients (pts) with Stage IV previously untreated pancreatic cancer. Pts received PEGPH20 at 1, 1.6, or 3 μg/kg IV twice a week for Wks 1-4, weekly for Wks 5-7, then 1 wk rest. Dose escalation was based on safety. Gem was given at 1000 mg/m2 IV once a week for Wks 1-7, then 1 wk rest. Thereafter, PEGPH20 + Gem were given once a week for 3 wks in 4-wk cycles. Dexamethasone was given pre and post PEGPH20 doses. Results: Of the 28 pts enrolled, the majority had a Karnofsky performance status of 80%, and 85%/19%/26% of pts had liver/lung/visceral metastases. The median age was 58 yrs. Four pts received PEGPH20 at 1 μg/kg, 4 at 1.6 μg/kg, and 20 at 3 μg/kg. The RP2D was 3 μg/kg. Treatment duration ranged from 1-274 days; 5 pts remain on study. Treatment was generally well tolerated. Ten pts had 1 Gem dose reduction, 2 pts had 1 PEGPH20 dose reduction (3 to 1.6 µg/kg), but no pt had a DLT. The most common PEGPH20-related AEs were MSEs (25% Gr1; 18% Gr2) and fatigue (21% Gr1; 11% Gr2). Objective response was assessed by an independent central radiologist using RECIST 1.1. Of the 21 pts evaluable for efficacy, 7 had partial response (PR) for an overall response rate (ORR) of 33%, and 9 had stable disease for ≥ 2 mo. Tumor biopsies from 12 pts were evaluable for HA staining. HA was high in 9 and low in 3. Of the 9 with high HA staining, 5 had PR (56% ORR); HA data were not available for the other 2 PR pts. PK results show dose-dependent exposure consistent with data from PEGPH20 monotherapy studies. Conclusions: PEGPH20 in combination with Gem is generally well tolerated in advanced pancreatic cancer and shows promising efficacy, especially in pts with high intratumoral HA content. Clinical trial information: NCT01453153.