Phase II Safety and Efficacy Study of Crizotinib in East Asian Patients With ROS1 Positive, ALK Negative Advanced NSCLC

Phase II, Open Label, Single Arm Study of the Efficacy and Safety of Crizotinib in East Asian Patients With Advanced ALK-Negative NSCLC Harboring a Translocation or Inversion Involving the c-ROS Oncogene (ROS1) Locus

To assess treatment effectiveness and safety of oral crizotinib administered to East Asian patients with Advanced Non-Small Cell Lung Cancer (NSCLC) that is confirmed to be positive for a ROS1 positive gene mutation (translocation or inversion) and confirmed negative for an ALK mutation

Inclusion Criteria:

• Histologically or cytologically proven diagnosis of NSCLC that is locally advanced or metastatic
• treatment-naïve or have received no more than 3 systemic treatment regimen(s)
• Positive for translocation or inversion events involving the ROS1 gene
• Negative for translocation or inversion events involving the ALK gene
• Patients with brain metastases are eligible if asymptomatic, or if treated, must be neurologically stable for at least 2 weeks and are not taking any contraindicated medications
• Any prior treatment (chemotherapy, radiation [except for palliative], or surgery) must have been completed at least 2 weeks prior to initiation of study medication
• At least 1 measurable tumor lesion as per RECIST v1.1
• Female or male, 18 years of age or older
• ECOG performance status 0 to 1
• Adequate organ function
• Signed and dated informed consent
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including completion of the PRO measures
• Agree to use effective contraception during the study period and for at least 90 days after completion of the study treatment

Exclusion Criteria:

• Current treatment on another therapeutic clinical trial
• Prior therapy specifically directed against ALK or ROS1 fusion genes
• Spinal cord compression unless treated with the patient attaining good pain control and stable or recovered neurologic function, carcinomatous meningitis, or leptomeningeal disease
• known interstitial fibrosis or interstitial lung disease
• myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, or cerebrovascular accident including transient ischemic attack within 3 months prior to start of study treatment
• Ongoing cardiac dysrhythmias of NCI CTCAE v4.03 Grade >/=2, uncontrolled atrial fibrillation of any grade, or QTc >470 msec
• Pregnant or breast feeding
• Use of drugs or foods that are known potent CYP3A4 inhibitors or inducers
• Use of other anti-cancer drugs including traditional Chinese medicine on the SFDA list
• Evidence of active malignancy within last 3 years