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

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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.

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Acknowledgments

Dr Yuichiro Ohe (National Cancer Center Hospital 5-1-1, Tsukiji, Chuo-ku, Tokyo, Japan) and Dr Junji Furuse (School of Medicine, Kyorin University 6-20-2, Shinkawa, Mitaka-shi, Tokyo, Japan), members of the Data Monitoring Committee/Safety Committee, contributed to the study.

Funding

This study was sponsored by AstraZeneca. Medical writing assistance was provided by Claire Routley PhD from Mudskipper Business Ltd, funded by AstraZeneca.

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Authors and Affiliations

  1. Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumicho Sunto-Gun, Shizuoka, 411-8777, Japan

    Haruyasu Murakami

  2. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center East Hospital, Kashiwa, Chiba, Japan

    Masafumi Ikeda

  3. Division of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tsukiji, Chuo-ku, Tokyo, Japan

    Takuji Okusaka

  4. Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan

    Yoshitaka Inaba

  5. Clinical Research Institute, Shikoku Cancer Center, Matsuyama City, Ehime, Japan

    Haruo Iguchi

  6. R&D, Clinical Science Department, AstraZeneca KK, Osaka, Japan

    Katsuro Yagawa

  7. Third Department of Internal Medicine, Wakayama Medical University School of Medicine, Wakayama, Japan

    Nobuyuki Yamamoto

Authors
  1. Haruyasu Murakami
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  2. Masafumi Ikeda
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  3. Takuji Okusaka
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  4. Yoshitaka Inaba
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  5. Haruo Iguchi
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  6. Katsuro Yagawa
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  7. Nobuyuki Yamamoto
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Corresponding author

Correspondence to Haruyasu Murakami.

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Conflict of interest

HM, TO, YI, and HI have received research funding from AstraZeneca. MI has received honoraria from Bayer Yakuhin, Novartis, Bristol-Myers Squibb, and Abbott Japan and research funding from AstraZeneca. NY has received honoraria and research funding from AstraZeneca. KY is employed by AstraZeneca.

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Murakami, H., Ikeda, M., Okusaka, T. et al. A Phase I study of MEDI-575, a PDGFRα monoclonal antibody, in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol 76, 631–639 (2015). https://doi.org/10.1007/s00280-015-2832-6

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  • DOI: https://doi.org/10.1007/s00280-015-2832-6

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