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

Purpose ABTaEuro806, a humanized recombinant monoclonal antibody, binds a unique epidermal growth factor receptor (EGFR) epitope exposed in the EGFRde2aEuro7 (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 (a parts per thousand yen10 %) 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.