Vandetanib in Advanced NSCLC With RET Rearrangement

Inclusion Criteria: * Provision of informed consent * Female or male aged 18 years or over * Histologically confirmed locally advanced or metastatic (stage IIIB or IV) NSCLC * Failure after platinum-based chemotherapy * Presence of a RET fusion in an archival or newly acquired NSCLC tumor specimen (RET fusion should be performed in central laboratory by FISH) * ECOG performance status of 0, 1 or 2 * Negative pregnancy test (urine or serum) for female patients of childbearing potential * Measurable disease according to RECIST 1.1 criteria * Life expectancy of \>12 weeks * Able to swallow study medication * If the subject is on the course of radiotherapy, one can be enrolled after radiotherapy Exclusion Criteria: * Involvement in the planning/conduct of this study * Previous enrollment in the present study * Previous exposure to vandetanib * Unstable brain metastases or spinal cord compression that requires treatment (The patients with treated brain metastases who are on a stable dose of steroids can be included) * Major surgery within 28 days before starting treatment * The last dose of prior chemotherapy received less than 28 days prior to starting treatment * Any unresolved chronic toxicity greater than CTCAE grade 2 from previous anticancer therapy * Serum bilirubin greater than 1.5 x the upper limit of reference range (ULRR) * Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) greater than 2.5 x ULRR, or greater than 5.0 x ULRR if judged by the investigator to be related to liver metastases * Creatinine clearance \<30 mL/min (Patients with moderate renal impairment defined as screening creatinine clearance ≥30 to \<50 mL/min will start vandetanib at a reduced dose of 200 mg once daily and will continue this dose throughout the study, unless further dose reduction is required) * Unacceptable electrolyte imbalance (Potassium \<4.0 mmol/L despite supplementation, Magnesium below normal range despite supplementation, Calcium as evaluated by either ionized or standard serum tests: ionized calcium below the normal range or serum calcium above the CTCAE grade I upper limit) * Significant cardiac event (e.g. myocardial infarction), superior vena cava syndrome, NYHA classification of heart disease ≥2 within 12 weeks before starting treatment, or presence of cardiac disease that in the opinion of the investigator increases the risk of ventricular arrhythmia * History of ventricular arrhythmia, which is symptomatic or requires treatment (CTCAE grade 3), symptomatic or uncontrolled atrial fibrillation, or asymptomatic sustained ventricular tachycardia. (Patients with atrial fibrillation controlled by medication are permitted) * Uncontrolled hypertension (systolic blood pressure \>160 mmHg or diastolic blood pressure \> 100 mmHg) * Past medical history of, or clinically active interstitial lung disease * Evidence of severe or uncontrolled systemic disease * Previous or current malignancies of other histologies within the last 3 years. (In situ carcinoma of the cervix, adequately treated basal cell or squamous cell carcinoma of the skin is exceptionally permitted) * Congenital long QT syndrome * Any concomitant medications that are known to be associated with Torsades de Pointes or potent inducers of cytochrome P450 3A4 (CYP3A4) function and/or any prohibited medications * History of QT prolongation associated with other medication that required discontinuation of that medication * QTcB correction unmeasurable or \>480 ms on screening ECG * Participation in a clinical study and/or receipt of an investigational drug within 28 days prior to enrollment * Females only - currently pregnant or breast feeding