The purpose of the run-in phase of this study is to determine the appropriate and tolerable dose of ZD6474 (200mg or 300mg) to be administered in combination with paclitaxel and carboplatin in subjects with previously untreated locally advanced or metastatic NSCLC. This phase of the trial is closed to enrollment.

The purpose of the randomized phase of this study is to determine the efficacy of ZD6474 alone versus that of ZD6474 in combination with paclitaxel and carboplatin versus that of paclitaxel and carboplatin alone in subjects with previously untreated locally advanced or metastatic NSCLC. This phase of the trial is closed to enrollment.

Inclusion Criteria:

• Signed informed consent
• 18 years or older
• Histologically or cytologically confirmed locally advanced or metastatic NSCLC
• No prior chemotherapy/biological therapy/radiation therapy
• One or more measurable lesions
• Life expectancy more than 12 weeks

Exclusion Criteria:

• Brain metastases or spinal cord compression
• Currently active skin disease
• History of significant hemoptysis
• Abnormal blood chemistry
• Cardiac abnormalities
• Recent significant cardiac event
• Coexisting malignancies