RET fusions are present in 1% to 2% of unselected population of non-small cell lung cancer (NSCLC). Existing US Food and Drug Administration-approved inhibitors of RET tyrosine kinase show promising therapeutic effects in a non-small cell lung cancer patients. Apatinib is an oral multi-kinase inhibitors including RET fusions. This study is designed to evaluate the safety and tolerability of Apatinib in patients with RET fusion positive advanced NSCLC.

To observe objective response rate (ORR) of apatinib in RET fusion positive pre-treated advanced NSCLC.

To observe Progression free survival （PFS）. To assess the overall survival (OS). To assess safety and tolerability. To evaluate quality of life. To explore the relationship between biomarkers and the toxicity/efficacy of apatinib.

Inclusion Criteria:

• Aged ≥18 and ≤80 years.
• ECOG performance status of 0 to 1.
• Life expectancy of more than 12 weeks.
• At least one measurable lesion exists.(RECIST 1.1)
• Histologically or cytologic confirmed RET fusion positive advanced Non-small cell lung cancer who failed to prior therapies.
• Required laboratory values including following parameters: ANC: ≥ 1.5 x 10^9/L, Platelet count: ≥ 80 x 10^9/L, Hemoglobin: ≥ 90 g/L, Total bilirubin: ≤ 1.5 x upper limit of normal, ULN, ALT and AST: ≤ 1.5 x ULN, BUN and creatine clearance rate: ≥ 50 mL/min LVEF: ≥ 50% QTcF: < 470 ms
• Signed informed consent
• Females of child-bearing potential must have negative serum pregnancy test. Sexually active male and those having childbearing potential must practice contraception during the study.

Exclusion Criteria:

• Squamous carcinoma (including adeno-squamous carcinoma), small cell lung cancer
• Subjects with third space fluid that can not be controled by drainage or other methods.
• Obvious cavity or necrosis formed in the tumor
• Uncontrolled hypertension
• Hymoptysis, more than 2.5ml daily
• Thrombosis in 12 months, including pulmonary thrombosis, stroke, or deep venous thrombosis
• Received big surgery, had bone fracture or ulcer in 4 weeks
• Urine protein >++, or urine protein in 24 hours> 1.0g
• pregnant or lactating woman
• Receiving any other antitumor therapy.
• Known history of hypersensitivity to apatinib or any of it components.