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Cancer Chemother Pharmacol. 2015 Sep;76(3):631-9. doi: 10.1007/s00280-015-2832-6. Epub 2015 Jul 30.

A Phase I study of MEDI-575, a PDGFRα monoclonal antibody, in Japanese patients with advanced solid tumors.

Author information

1
Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumicho Sunto-Gun, Shizuoka, 411-8777, Japan, ha.murakami@scchr.jp.

Abstract

PURPOSE:

MEDI-575 is a fully human monoclonal antibody that selectively binds to platelet-derived growth factor receptor alpha (PDGFRα). This open-label Phase I study assessed the safety and tolerability of MEDI-575 in Japanese patients with advanced solid tumors.

METHODS:

The study comprised two parts: Part A, dose escalation; Part B, dose expansion in patients with hepatocellular cancer. In Part A, patients were enrolled into three cohorts: MEDI-575 was administered intravenously over a 21-day treatment cycle at doses of 9 and 15 mg/kg/week (cohorts 1, 2) and 35 mg/kg/3-weekly (cohort 3). In Part B, MEDI-575 25 mg/kg/3-weekly was administered. Secondary measures included assessment of the maximum tolerated dose, pharmacokinetics, immunogenicity and anti-tumor activity.

RESULTS:

Ten and 12 patients were treated in Parts A and B, respectively. There were no dose-limiting toxicities; the maximum tolerated dose was not determined. Common treatment-related adverse events were fatigue (30%) and decreased appetite (20%) in Part A and decreased appetite (33.3%) in Part B. All treatment-related adverse events were grade 1 or 2 in severity. No patients discontinued MEDI-575 because of an adverse event and there were no patient deaths due to adverse events. MEDI-575 binding with PDGFRα resulted in a dose-dependent increase in PDGF-AA ligand, with plateau levels observed within 2 days and sustained during the dosing interval. None of the patients in Part A or B experienced complete or partial responses to treatment.

CONCLUSIONS:

MEDI-575 once weekly and 3-weekly was well tolerated with a favorable pharmacokinetic profile in Japanese patients with advanced solid tumors.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT01102400.

PMID:
26223436
DOI:
10.1007/s00280-015-2832-6
[Indexed for MEDLINE]

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