Phase I study of the HER3-targeted antibody patritumab (U3-1287) combined with erlotinib in Japanese patients with non-small cell lung cancer.

Objectives Human epidermal growth factor receptor 3 (HER3) is a key dimerization partner for HER family members and is associated with resistance to other HER family receptor-targeted therapeutics. This study evaluated the safety, tolerability, pharmacokinetics and efficacy of patritumab (U3-1287), a fully human anti-HER3 monoclonal antibody, in combination with erlotinib, an epidermal growth factor receptor-tyrosine kinase inhibitor in patients with previously treated advanced non-small cell lung cancer (NSCLC). Patients and methods This study enrolled patients with stage IIIB/IV NSCLC with Eastern Cooperative Oncology Group performance status 0–1, life expectancy >3 months and who had progressed after at least one prior course of chemotherapy (excluding erlotinib). This open-label study included two parts: dose escalation (Part 1) and dose expansion (Part 2). In Part 1, patients received intravenous patritumab 9 or 18 mg/kg every 3 weeks in addition to per-oral erlotinib 150 mg/day daily. In Part 2, patients received the recommended dose of patritumab as determined in Part 1. Adverse event rates, pharmacokinetics and tumor responses were determined. Results Twenty-four Japanese patients received patritumab at 9 mg/kg ( n = 3) or 18 mg/kg ( n = 21), and erlotinib. No dose-limiting toxicities were reported, indicating the maximum-tolerated dose was not reached. The most frequent adverse events were gastrointestinal or skin toxicities, which were generally mild and manageable. Patritumab pharmacokinetics were similar to those reported in previous studies. The median progression-free survival (95% confidence interval) was 44.0 (22.0–133.0) days for the EGFR wild-type group ( n = 9) and 107.0 (74.0–224.0) days for the EGFR -activating mutation group ( n = 13). Evaluation of biomarkers by immunohistochemical analysis did not indicate a relationship between efficacy and HER3 expression in tumor tissues. Conclusion Patritumab in combination with erlotinib was well tolerated and the efficacy of the combination was encouraging, especially in patients where prior gefitinib treatment failed. [ABSTRACT FROM AUTHOR]