Onartuzumab is a monovalent, humanized, monoclonal antibody that showed 
significant survival benefits in combination with erlotinib in MET-positive 
non-small-cell lung cancer (NSCLC) in pre-specified subgroup analyses of a 
randomized phase II study. We conducted a two-stage, open-label, multicenter, 
phase I study of onartuzumab in Japanese patients. Stage 1 investigated the 
safety, tolerability, pharmacokinetics (PK), and recommended dose of onartuzumab 
in patients with solid tumors, and Stage 2 determined the safety, tolerability, 
and PK of onartuzumab plus erlotinib in patients with MET-positive NSCLC. Nine 
patients received onartuzumab monotherapy (4, 15, or 30 mg/kg on Day 1 of each 
21-day cycle) in Stage 1, and six patients received onartuzumab (15 mg/kg) plus 
erlotinib (150 mg/day) in Stage 2. There were no dose-limiting toxicities in 
either stage. Serious adverse events (AEs) occurred in one patient in Stage 1 
(convulsion), and two patients in Stage 2 (once case each of diarrhea, vomiting, 
and pulmonary embolism), but there were no grade 4 AEs or AEs leading to death. 
Onartuzumab PKs were linear in the dose range of 4 to 30 mg/kg, and were not 
affected by co-administration with erlotinib. PK parameters of onartuzumab were 
similar to those reported in non-Japanese patients. A partial response was 
observed in a patient with MET immunohistochemistry 3+ NSCLC without MET gene 
amplification. Based on these results, the recommended dose of onartuzumab in 
Japanese patients with solid tumors is 15 mg/kg every 21 days. The combination 
of onartuzumab with erlotinib is feasible in Japanese patients with MET-positive 
lung cancer.