A Phase I/II Clinical Study of SAF-189s in Non-small Cell Lung Cancer (NSCLC) Patients

Exclusion Criteria12

• Has had prior chemotherapy, anti-cancer treatment with biological drugs, or other investigational agents within 28 days or received TKI or targeted therapies within 14 days prior to enrollment;
• Received radiotherapy within 21 days prior to the 1st dose or continuance of toxicities due to prior radiotherapy that do not recover to Grade 0 or 1;
• Patients who received major surgery within 3 weeks before enrollment or have not adequately recovered from prior surgery;
• Patients with central nervous system (CNS) metastases requiring
• Clinical local intervention such as surgical excision, radiotherapy or other therapies
• Phase I dose escalation: patients requiring systemic treatment with corticosteroids (\>10 mg/day prednisone or equivalent) are not eligible for dose escalation study (not applicable to patients participating Phase I cohort expansion or Phase II).
• Diabetics without stable control and with insulin therapy (patients with fasting blood glucose below 7mmol/L, who are receiving stable hypoglycemic drug regimen, and whose blood glucose control is stable as evaluated by specialist doctors are allowed to be enrolled); 6）Difficulty in swallowing or having an active digestive disorder or having undergone major gastrointestinal surgery may significantly affect the administration or absorption of SAF189s (e.g. ulcerative lesions, uncontrollable nausea, vomiting, diarrhoea, malabsorption syndrome, and enteroctomies) 7）Patients who are taking the following medicines:
• Repaglinide (cytochrome \[CYP\]2C8) and drugs metabolized via CYP3A4 enzyme within 1 week before enrollment;
• Medicines which are known to cause QT prolongation or torsade de pointes;
• Coumarin anticoagulants within 1 week before enrollment (low molecular weight heparin is permitted);
• Illegal drugs;
• \) Has a history of acute pancreatitis within 1 year before enrollment, or past history of chronic pancreatitis; 9) Patients have positive laboratory test for anti-HCV, or are diagnosed with human immunodeficiency virus (HIV) infection, or who refuse to receive HIV screen test; 10) Patients have other malignant tumor history or with other malignant tumors simultaneously; 11) Impairment of cardiac function or clinically significant heart disease, including New York College of Cardiology (NYHA) grade ≥ 3 congestive heart failure, arrhythmias, conduction abnormalities requiring treatment, cardiomyopathy, or uncontrolled hypertension； 12) Corrected QT interval using Fridericia formula \> 450 msec for male patients and \> 470 msec for female patients; 13) Patients have uncured interstitial lung disease history or non-infectious pneumonitis prior to enrollment, except for those induced by radiation therapy; 14）Any other clinically significant disease or condition (such as uncontrolled diabetes, active or uncontrolled infections, etc.) that the investigator believes could affect protocol adherence or affect the patient's ability to sign up for ICF; 15）Spinal cord metastases with potential risk or symptoms of spinal cord compression； 16）The second cohort received ROS1 inhibitors other than crizotinib； 17）The patient had uncontrollable amounts of pleural effusion, ascites, and pericardial effusion.