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Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Phase I study of the second-generation, recombinant, human EGFR antibody necitumumab in Japanese patients with
Yosuke Tamura1, Hiroshi Nokihara1, Kazunori Honda1
1Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
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.
Insights
Necitumumab is safe for Japanese patients with advanced solid tumors. This phase I study found no dose-limiting toxicities, with common side effects including headache and rash.
Area of Science:
- Oncology
- Pharmacology
Background:
- Necitumumab is a monoclonal antibody targeting the epidermal growth factor receptor.
- Advanced solid tumors often have limited treatment options, necessitating novel therapeutic approaches.
Purpose of the Study:
- To evaluate the safety and pharmacokinetics of necitumumab in Japanese patients with advanced solid tumors.
- To determine the maximum tolerated dose and dose-limiting toxicities of necitumumab in this population.
Main Methods:
- A phase I, open-label, dose-escalation study using a 3+3 design.
- Patients received necitumumab at planned dose levels: 600 mg every 3 weeks, or 800 mg every 2 weeks or every 3 weeks.
- Safety, antitumor activity, and pharmacokinetics were assessed.
Main Results:
- Fourteen patients were enrolled, and no dose-limiting toxicities were observed.
- The most frequent treatment-emergent adverse events were headache, dry skin, pruritus, and rash, primarily grade 1/2.
- All patients achieved target serum trough concentrations; 67% had stable disease, with no objective responses.
Conclusions:
- Necitumumab demonstrated a favorable safety profile in Japanese patients with advanced solid tumors.
- The established dosing regimens of 800 mg every 2 weeks or 800 mg on days 1 and 8 of a 3-week cycle are safe and can be administered to this population.
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