Phase 1 trials of PEGylated recombinant human hyaluronidase PH20 in patients with advanced solid tumours
Open accessAbstract
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. In HALO-109-101 ( N =14), PEGPH20 was administered intravenously once or twice weekly (0.5 or 50 μ g kg −1 ) or once every 3 weeks (0.5–1.5 μ g kg −1 ). In HALO-109-102 ( N =27), PEGPH20 was administered once or twice weekly (0.5–5.0 μ g kg −1 ), with dexamethasone predose and postdose. Dose-limiting toxicities included grade ⩾ 3 myalgia, arthralgia, and muscle spasms; the maximum tolerated dose was 3.0 μ g 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. The tumour stroma has emerging importance in the development of cancer therapeutics. PEGPH20 3.0 μ g 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.
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HA-degradable PEGPH20 in integration with gemcitabine demonstrated enhanced therapeutic effects in animal models.
“HA-degradable PEGPH20 in integration with gemcitabine has demonstrated enhanced therapeutic effects in animal models [56,57].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [57]
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Research works printed but not linked: 1
- Printz MA, Babson B, Selvam P, Beyerlein D, Jiang P, Maneval DC, Sugarman BJ (2017) A Quantitative Method for Determining Hyaluronan Content in Plasma by LC/MS/MS and Plasma HA as a Pharmacodynamic Marker for PEGylated-Hyaluronidase PH20 (PEGPH20) in a Phase 1b Trial for Pancreatic Ductal Adenocarcinoma [poster]. Exhibited at the American Association of Pharmaceutical Sciences National Biotechnology Conference, 1-3 May 2017; San Diego, CA, USA.
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“HA-degradable PEGPH20 in integration with gemcitabine has demonstrated enhanced therapeutic effects in animal models [56,57].”
Background
- Authors
- Infante, J. R., Korn, R. L., Rosen, L. S., LoRusso, P., Dychter, S. S., Zhu, J., Maneval, D. C., Jiang, P., Shepard, H. M., Frost, G., Von Hoff, D. D., Borad, M. J., & Ramanathan, R. K.
- Affiliations
- Janssen Research & Development (United States) (US)
- University of California, Los Angeles (US)
- Yale Cancer Center (US)
- Fate Therapeutics (United States) (US)
- Halozyme Therapeutics (United States) (US)
- Mayo Clinic (US)
- Corresponding author
- Infante, Jeffrey R
- ORCID
- Venue
- British Journal of Cancer
- Published
- 2017-09-26
- Volume
- 118
- Issue
- 2
- Pages
- 153-161
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC5785735
- OpenAlex
- W2759247220
- Cited by
- 83
- References
- 30
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 7 · 2023: 6 · 2022: 9 · 2021: 11 · 2020: 11 · 2019: 16 · 2018: 7
- FWCI
- 4.96
- Type
- journal article
- Language
- en
- Update notices
- erratum (2018-01-23)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- British Journal of Cancer (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- Halozyme
- National Institutes of Health (UL1TR001863)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- PEGPH20, recombinant human hyaluronidase, hyaluronan degradation, tumor stroma, advanced solid tumors, antitumour activity, safety, maximum tolerated dose, dose-limiting toxicity, tumor perfusion
- MeSH terms
- Adult, Aged, Aged, 80 and over, Dexamethasone, Dose-Response Relationship, Drug, Female, Humans, Hyaluronic Acid, Hyaluronoglucosaminidase, Male, Middle Aged, Neoplasms, Polyethylene Glycols, Recombinant Proteins
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