Halozyme Therapeutics Inc (HALO)

[rod5247]

Published OnlineFirst January 26, 2016; doi: 10.1158/1078-0432.CCR-15-2010

Phase 1b Study of PEGylated Recombinant Human Hyaluronidase and Gemcitabine in Patients with Advanced Pancreatic Cancer

Sunil R Hingorani1,*,
William P Harris2,
J. Thaddeus Beck3,
Boris A Berdov4,
Stephanie A Wagner5,
Eduard M Pshevlotsky6,
Sergei Tjulandin7,
Oleg Gladkov8,
Randall F Holcombe9,
Ronald Korn10,
Natarajan Raghunand11,
Samuel Dychter12,
Ping Jiang13,
H. Michael Shepard13, and
Craig E Devoe14


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Author Affiliations
1Clinical Research Division, Fred Hutchinson Cancer Research Center
2Human Biology, Fred Hutchinson Cancer Research Center
3Oncology, Highlands Oncology Group, PA
4Radiation and Surgery Department, Medical Radiological Research Center
5IU, Indiana University Melvin and Bren Simon Cancer Center
6Clinical Oncological Center, Omsk Regional Budget Medical Institution
7Department of Clinical Pharmacology and Chemotherapy, N.N. Blokhin Russian Cancer Research Center
8Clinical Oncology, Chelyabinsk Regional Clinical Oncology Center
9HEMATOLOGY AND ONCOLOGY, Mt. Sinai School of Medicine
10Radiology, Scottsdale Medical Imaging
11Cancer Imaging & Metabolism, Moffitt Cancer Center
12Halozyme, Halozyme Therapeutics
13Research, Halozyme Therapeutics
14Division of Hematology and Medical Oncology, Hofstra North Shore-LIJ School of Medicine
?* Corresponding Author:
Sunil R Hingorani, Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M5-C800, Seattle, WA, 98109, United States [e-mail]


Abstract

Purpose: This Phase 1b study evaluated the safety and tolerability of PEGylated human recombinant hyaluronidase (PEGPH20) in combination with gemcitabine (Gem), and established a Phase 2 dose for patients with untreated Stage IV metastatic pancreatic ductal adenocarcinoma (PDA). Objective response rate and treatment efficacy using biomarker and imaging measurements were also evaluated. Experimental Design: Patients received escalating intravenous doses of PEGPH20 in combination with Gem using a standard 3+3 dose-escalation design. In Cycle 1 (8 weeks), PEGPH20 was administrated twice weekly for 4 weeks, then once weekly for 3 weeks; Gem was administrated once weekly for 7 weeks, followed by 1 week off treatment. In each subsequent 4-week cycle, PEGPH20 and Gem were administered once weekly for 3 weeks, followed by 1 week off. Dexamethasone (8 mg) was given pre- and post-PEGPH20 administration. Several safety parameters were evaluated. Results: Twenty-eight patients were enrolled and received PEGPH20 at 1.0 (n=4), 1.6 (n=4), or 3.0 µg/kg (n=20), respectively. The most common PEGPH20-related adverse events were musculoskeletal and extremity pain, peripheral edema, and fatigue. The incidence of thromboembolic events was 29%. Median progression-free survival (PFS) and overall survival (OS) were 5.0 and 6.6 months, respectively. In 17 patients evaluated for pre-treatment tissue hyaluronan (HA) levels, median PFS and OS were 7.2 and 13.0 months for "high"-HA patients (n=6), and 3.5 and 5.7 months for "low"-HA patients (n=11), respectively. Conclusion: PEGPH20 in combination with Gem was well tolerated and may have therapeutic benefit in patients with advanced PDA, especially in those with high-HA tumors.
Received September 3, 2015.
Revision received December 18, 2015.
Accepted December 24, 2015.
Copyright © 2016, American Association for Cancer Research.

http://clincancerres.aacrjournals.org/content/early/2016/01/28/1078-0432.CCR-15-2010.abstract