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.