Phase 1 Study of Nimotuzumab in Combination With Cisplatin and Docetaxel for Patients With Advanced Non-small Cell Lung Cancer
Altered expression or constitutive activation of the epidermal growth factor receptor
(EGFR/HER1/erbB1) commonly occurs in primary NSCLC, and is often a critical factor in
progressive growth and resistance to normal mechanisms of cell death. Epidermal growth
factor receptor expression in lung cancer has been correlated with tumor aggressiveness.
Clinical trials already suggest that EGFR targeted therapy may improve the antitumor
activity of chemotherapy for treatment of lung carcinoma. Monoclonal antibodies specific to
EGFR can be combined safely and effectively with chemotherapy. Nimotuzumab (hR3) is a
humanized monoclonal antibody (mAb) that binds to the EGFR. In preclinical studies the
antibody has shown potent antitumor activity. A previous phase II study in children with
high grade brain tumors showed activity of Nimotuzumab as a monotherapeutic agent, even in
prognostic very unfavourable diffuse, intrinsic pontine glioma. No drug related side effects
were reported. Nimotuzumab (hR3) in combination with radiotherapy for treatment of locally
advanced squamous cell carcinomas of the head and neck resulted in high rates of antitumor
response, and was accompanied by a favourable safety profile.
This is a dose-escalation study of Nimotuzumab. Nimotuzumab in combination with chemotherapy
will be administered to the patients with advanced NSCLC. The patients' blood test and liver
and renal function tests will be monitored weekly, a physical exam and reassessment of the
tumor will be performed and every 6 weeks. When the total result is the CR or PR, the
results of the 6th, 12th, 18th and the 22th week should be compared.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety and toxicity of this new treatment. Both acute and chronic toxicity will be evaluated.
within study period
Yuankai Shi, Professor
China: Food and Drug Administration