Phase 1 Trials of PEGylated Recombinant Human Hyaluronidase PH20 in Patients with Advanced Solid Tumours

Overview

Journal Br J Cancer

Specialty Oncology

Date 2017 Sep 27

PMID 28949957

Citations 37

Authors

Jeffrey R Infante

Ronald L Korn

Lee S Rosen

Patricia LoRusso

Samuel S Dychter

Joy Zhu

Daniel C Maneval

Ping Jiang

H Michael Shepard

Gregory Frost

Daniel D Von Hoff

Mitesh J Borad

Ramesh K Ramanathan

Affiliations

Soon will be listed here.

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) or once every 3 weeks (0.5-1.5 μg kg). In HALO-109-102 (N=27), PEGPH20 was administered once or twice weekly (0.5-5.0 μg kg), 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 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 administered twice weekly is feasible in patients with advanced cancers; exploratory analyses indicate antitumour activity supporting further evaluation of PEGPH20 in solid tumours.

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