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Br J Cancer. 2018 Jan;118(2):153-161. doi: 10.1038/bjc.2017.327. Epub 2017 Sep 26.

Phase 1 trials of PEGylated recombinant human hyaluronidase PH20 in patients with advanced solid tumours.

Author information

1
Early Development Oncology, Janssen Research & Development, LLC, Welsh & McKean Roads, Spring House, PA 19477, USA.
2
Scottsdale Medical Imaging, 9700 N. 91st Suite C-200, Scottsdale, AZ 85258, USA.
3
Division of Hematology-Oncology, University of California - Los Angeles, 2020 Santa Monica Boulevard, Suite 600, Santa Monica, CA 90404, USA.
4
Yale Cancer Center, PO Box 208028, New Haven, CT 06520, USA.
5
Fate Therapeutics, Inc., 3535 General Atomics Court, San Diego, CA 92121, USA.
6
SBIO Pte, Ltd., 1 Science Park Road, #05-09, The Capricorn Science Park 2, Singapore, 117 528, Singapore.
7
Halozyme Therapeutics, Inc., 11388 Sorrento Valley Road, San Diego, CA 92121, USA.
8
F1 Bioventures LLC, 505 S. Flagler Drive, West Palm Beach, FL 33401, USA.
9
Translational Genomics Research Institute (TGen), 445 N. Fifth Street, Phoenix, AZ 85004, USA.
10
Mayo Clinic, 13400 E. Shea Boulevard, Scottsdale, AZ 85259, USA.

Abstract

BACKGROUND:

Hyaluronan accumulation in tumour stroma is associated with reduced survival in preclinical cancer models. PEGPH20 degrades hyaluronan to facilitate tumour access for cancer therapies. Our objective was to assess safety and antitumour activity of PEGPH20 in patients with advanced solid tumours.

METHODS:

In HALO-109-101 (N=14), PEGPH20 was administered intravenously once or twice weekly (0.5 or 50 μg kg-1) or once every 3 weeks (0.5-1.5 μg kg-1). In HALO-109-102 (N=27), PEGPH20 was administered once or twice weekly (0.5-5.0 μg kg-1), with dexamethasone predose and postdose.

RESULTS:

Dose-limiting toxicities included grade ⩾3 myalgia, arthralgia, and muscle spasms; the maximum tolerated dose was 3.0 μg kg-1 twice weekly. Plasma hyaluronan increased in a dose-dependent manner, achieving steady state by Day 8 in multidose studies. A decrease in tumour hyaluronan level was observed in 5 of the 6 patients with pretreatment and posttreatment tumour biopsies. Exploratory imaging showed changes in tumour perfusion and decreased tumour metabolic activity, consistent with observations in animal models.

CONCLUSIONS:

The tumour stroma has emerging importance in the development of cancer therapeutics. PEGPH20 3.0 μg kg-1 administered twice weekly is feasible in patients with advanced cancers; exploratory analyses indicate antitumour activity supporting further evaluation of PEGPH20 in solid tumours.

PMID:
28949957
PMCID:
PMC5785735
DOI:
10.1038/bjc.2017.327
[Indexed for MEDLINE]
Free PMC Article

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