Phase I study of the second-generation, recombinant, human EGFR antibody necitumumab in Japanese patients with advanced solid tumors.

PURPOSE: To establish the safety and pharmacokinetic profile of necitumumab in Japanese patients with advanced solid tumors not responsive to standard therapy or for which no standard therapy was available.

METHODS: In this phase I study, patients aged ≥20 years with advanced solid tumors, and an Eastern Cooperative Oncology Group performance statuses of 0-1 were enrolled in a 3 + 3 design, with dose-escalation based on dose-limiting toxicity (DLT). Planned dose levels were: cohort 1: 600 mg IV, days 1 and 8, every 3 weeks; cohort 2: 800 mg IV, day 1, every 2 weeks; and cohort 3: 800 mg IV, days 1 and 8, every 3 weeks. After the first 6-week cycle, patients with an objective response or stable disease could continue to receive necitumumab (same dose and schedule) until disease progression or other withdrawal criteria were met. Safety, antitumor activity, and pharmacokinetics were assessed.

RESULTS: Fourteen of 15 enrolled patients received all scheduled infusions in cycle 1 (median cycles: N = 2, range 1-4). No DLTs were observed. The most common treatment-emergent adverse events were headache (73 %), dry skin (67 %), pruritus (60 %), and rash (53 %), mostly grade 1/2. All patients achieved serum trough concentrations >40 µg/mL, a level associated with antitumor activity in preclinical models. No patients had an objective response; stable disease was seen in 67 % of patients.

CONCLUSIONS: Necitumumab can be safety administered to Japanese patients at dose levels established in Western patients: 800 mg every 2 weeks, or on days 1 and 8 of a 3-week cycle.