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Phase I study of the second-generation, recombinant, human EGFR antibody necitumumab in Japanese patients with advanced solid tumors

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Abstract

Purpose

To establish the safety and pharmacokinetic profile of necitumumab in Japanese patients with advanced solid tumors not responsive to standard therapy or for which no standard therapy was available.

Methods

In this phase I study, patients aged ≥20 years with advanced solid tumors, and an Eastern Cooperative Oncology Group performance statuses of 0–1 were enrolled in a 3 + 3 design, with dose-escalation based on dose-limiting toxicity (DLT). Planned dose levels were: cohort 1: 600 mg IV, days 1 and 8, every 3 weeks; cohort 2: 800 mg IV, day 1, every 2 weeks; and cohort 3: 800 mg IV, days 1 and 8, every 3 weeks. After the first 6-week cycle, patients with an objective response or stable disease could continue to receive necitumumab (same dose and schedule) until disease progression or other withdrawal criteria were met. Safety, antitumor activity, and pharmacokinetics were assessed.

Results

Fourteen of 15 enrolled patients received all scheduled infusions in cycle 1 (median cycles: N = 2, range 1–4). No DLTs were observed. The most common treatment-emergent adverse events were headache (73 %), dry skin (67 %), pruritus (60 %), and rash (53 %), mostly grade 1/2. All patients achieved serum trough concentrations >40 µg/mL, a level associated with antitumor activity in preclinical models. No patients had an objective response; stable disease was seen in 67 % of patients.

Conclusions

Necitumumab can be safety administered to Japanese patients at dose levels established in Western patients: 800 mg every 2 weeks, or on days 1 and 8 of a 3-week cycle.

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Acknowledgments

The authors would like to acknowledge that Nancy Sheridan of INC Research, NC, USA provided writing assistance, which was funded by Eli Lilly and Company, Bridgewater, NJ.

Funding

This study was funded by Eli Lilly and Company.

Author information

Author notes

  1. Tomohide Tamura

    Present address: St Luke’s International Hospital, Tokyo, Japan

Authors and Affiliations

  1. Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan

    Yosuke Tamura, Hiroshi Nokihara, Kazunori Honda, Yuko Tanabe, Hajime Asahina, Noboru Yamamoto & Tomohide Tamura

  2. Department of Medical Oncology, Division of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan

    Yasuhide Yamada

  3. Eli Lilly Japan, Kobe, Japan

    Sotaro Enatsu

  4. Lilly Deutschland GmbH, Bad Homburg, Germany

    Raffael Kurek

Authors
  1. Yosuke Tamura
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Correspondence to Tomohide Tamura.

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Conflict of interest

Raffael Kurek and Sotaro Enatsu are employees of Eli Lilly and Company and its subsidiary Eli Lilly Japan K.K., respectively; they also have stock ownership as a part of bonus program.

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Tamura, Y., Nokihara, H., Honda, K. et al. Phase I study of the second-generation, recombinant, human EGFR antibody necitumumab in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol 78, 995–1002 (2016). https://doi.org/10.1007/s00280-016-3154-z

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  • DOI: https://doi.org/10.1007/s00280-016-3154-z

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