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A phase I pharmacokinetic study of matuzumab in combination with paclitaxel in patients with EGFR-expressing advanced non-small cell lung cancer

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Summary

Matuzumab is a humanized IgG1 EGFR monoclonal antibody. This phase I study investigated the tolerability, safety and pharmacokinetics (PK) of matuzumab in combination with paclitaxel in patients with EGFR-expressing advanced non-small cell lung cancer (NSCLC). Six dose levels/schedules of matuzumab were explored in combination with paclitaxel. Dose was escalated from 100 mg to 1,600 mg on a modified Fibonacci scheme according to the incidence of dose-limiting toxicity (DLT) over the first two cycles. DLT was assessed in patients who completed the first two treatment cycles or who stopped treatment because of a DLT during those cycles. Patients with non-progressive disease could then continue to receive study treatment for up to 6 months. The safety population comprised 44 patients, with DLT evaluable in 33. The maximum tolerated dose was not reached, with only one DLT reported at the 1,600 mg 3-weekly dose level. The most frequent grade 3/4 adverse events across all cycles were dyspnea (23 %) and neutropenia (11 %). Matuzumab exhibited non-linear PK, with accumulation after escalation and repeated dosing. Tumor growth control was seen in 15/44 (34 %) patients, including 5/9 (56 %) at the 800 mg weekly dose level. Matuzumab combined with paclitaxel was generally well tolerated in patients with advanced NSCLC. There was some evidence of anticancer activity in relation to the matuzumab 800 mg weekly dose.

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Acknowledgements

The study sponsor, Merck KGaA, was responsible for data management and statistical analysis. The clinical study was designed by Merck KGaA (Global Clinical Development Unit Oncology and Department of Biostatistics) in collaboration with CB. JTH had the final responsibility for the decision to submit the manuscript for publication. Jim Heighway of Cancer Communications and Consultancy Ltd (Knutsford, UK), provided medical writing services, which were funded by the sponsor.

Conflict of interest statement

JTH received honoraria in relation to lectures and advisory boards. SH is a salaried employee of Merck KGaA. CB has served as speaker and chairman for symposia of Merck KGaA as well as on advisory boards and his department has received research funding from Merck KGaA. CK, IC, FM and MMS declared no conflict of interest.

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Authors and Affiliations

  1. Department of Hematology/Oncology, University Hospital Schleswig-Holstein, Christian-Albrechts-University Cancer Center North, Arnold-Heller-Strasse 3, 24105, Kiel, Germany

    J. T. Hartmann

  2. Department of Oncology, Hematology, Immunology, Rheumatology and Pulmonology, University of Tübingen Medical Centre, Tübingen, Germany

    J. T. Hartmann, C. Kollmannsberger, F. Mayer, M. M. Schittenhelm & C. Bokemeyer

  3. Division of Medical Oncology, British Columbia Cancer Agency, Vancouver Cancer Center, Vancouver, Canada

    C. Kollmannsberger

  4. Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

    I. Cascorbi

  5. Global Clinical Development Unit—Oncology, Merck KGaA, Darmstadt, Germany

    S. Heeger

  6. Department of Oncology, Hematology, Bone Marrow Transplantation with Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    C. Bokemeyer

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  1. J. T. Hartmann
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  2. C. Kollmannsberger
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Correspondence to J. T. Hartmann.

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Hartmann, J.T., Kollmannsberger, C., Cascorbi, I. et al. A phase I pharmacokinetic study of matuzumab in combination with paclitaxel in patients with EGFR-expressing advanced non-small cell lung cancer. Invest New Drugs 31, 661–668 (2013). https://doi.org/10.1007/s10637-012-9856-0

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  • DOI: https://doi.org/10.1007/s10637-012-9856-0

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