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A phase 1 study of ABT-806 in subjects with advanced solid tumors

  • PHASE I STUDIES
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Summary

Purpose ABT‐806, a humanized recombinant monoclonal antibody, binds a unique epidermal growth factor receptor (EGFR) epitope exposed in the EGFRde2‐7 (EGFRvIII) deletion mutant and other EGFR proteins in the activated state. This phase I study evaluated the safety, pharmacokinetics, and recommended phase two dose (RP2D) of ABT-806 in patients with solid tumors that commonly overexpress activated EGFR or EGFRvlll. Methods Patients with advanced solid tumors, including glioblastoma, were eligible. Following a dose escalation phase, expanded safety cohorts of patients with solid tumors or EGFR-amplified glioblastoma were enrolled. Adverse events (AEs) were graded by National Cancer Institute Common Terminology Criteria for Adverse Events v4.0; tumor response was assessed by Response Evaluation Criteria in Solid Tumors v1.1. EGFR protein expression was quantified by immunohistochemistry. Results 49 patients were treated. Frequent AEs (≥10 %) possibly/probably related to ABT-806 were fatigue (18 %), nausea (16 %), dermatitis acneiform (12 %), and vomiting (10 %). Only one dose-limiting toxicity (grade three morbilliform rash) occurred. The RP2D was the pre-specified highest dose (24 mg/kg). Systemic exposures were dose proportional between 2 and 24 mg/kg. Median time to progression was 55 days (95 % confidence interval, 53–57) in all patients and 43 days (22–57) for glioblastoma patients. No objective responses occurred; however, two patients had prolonged stable disease. An EGFR-amplified penile cancer patient has stable disease lasting over 2.5 years. Conclusions ABT-806 has unique pharmacokinetic and safety profiles. Toxicities were infrequent and typically low grade at the RP2D. Linear ABT-806 pharmacokinetics suggest lack of significant binding to wild-type EGFR in normal tissues.

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Acknowledgments

Medical writing support was provided by Jacqueline Nielsen, an AbbVie Inc. employee.

Funding

This study was funded by AbbVie Inc.

Author contributions

All authors participated in the collection and analysis of data, manuscript writing or editing, and provided final approval of the manuscript.

Sponsor disclosures

The design, study conduct, analysis, and financial support of the clinical trial were provided by AbbVie Inc. AbbVie Inc. participated in the interpretation of data, review, and approval of this manuscript.

Compliance With Ethical Standards

ᅟ

Conflict of interest

J M Cleary, D A Reardon, N Azad, L Gandhi, G I Shapiro, and Jorge Chaves declare that they have no conflicts of interest. M Pedersen, P Ansell, W Ames, H Xiong, W Munasinghe, M Dudley, E Reilly, K Holen, and R Humerickhouse are employees of AbbVie Inc. and may own AbbVie Inc. stocks or options.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    James M. Cleary, David A. Reardon, Leena Gandhi & Geoffrey I. Shapiro

  2. Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA

    James M. Cleary, David A. Reardon, Leena Gandhi & Geoffrey I. Shapiro

  3. Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, MD, USA

    Nilofer Azad

  4. Northwest Medical Specialties, Tacoma, WA, USA

    Jorge Chaves

  5. AbbVie Inc., North Chicago, IL, USA

    Michelle Pedersen, Peter Ansell, William Ames, Hao Xiong, Wijith Munasinghe, Matt Dudley, Edward B. Reilly, Kyle Holen & Rod Humerickhouse

  6. Early Drug Development Center, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA

    James M. Cleary & Geoffrey I. Shapiro

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  1. James M. Cleary
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Correspondence to James M. Cleary.

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Cleary, J.M., Reardon, D.A., Azad, N. et al. A phase 1 study of ABT-806 in subjects with advanced solid tumors. Invest New Drugs 33, 671–678 (2015). https://doi.org/10.1007/s10637-015-0234-6

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  • DOI: https://doi.org/10.1007/s10637-015-0234-6

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