['carcinoma, non-small-cell lung']
['lorlatinib']

        Inclusion Criteria:

          1. Written informed consent;

          2. Male or female patient ages ≥ 18 years;

          3. Histologically/cytologically confirmed diagnosis of NSCLC with evidence of ROS1
             rearrangement;

          4. Possibility to perform a new tumor biopsy or tumor tissue collected at the time or
             after crizotinib failure;

          5. Patient pretreated with crizotinib with evidence of disease progression during
             crizotinib therapy;

          6. At least one radiological measurable disease according to RECIST criteria;

          7. At least 1 previous standard chemotherapy regimen;

          8. Performance status 0-2 (ECOG);

          9. Patient compliance to trial procedures

         10. Adequate bone marrow function (ANC ≥ 1.5x109/L, platelets ≥ 100x109/L, haemoglobin > 9
             g/dl);

         11. Adequate liver function (bilirubin < grade 2, transaminases no more than 3xULN/<5xULN
             in present of liver metastases);

         12. Normal level of alkaline phosphatase and creatinine;

         13. If female: childbearing potential either terminated by surgery, radiation, or
             menopause, or attenuated by use of approved contraceptive method [intrauterine
             contraceptive device (IUD), birth control pills, or barrier device] during and for
             ninety (90) days after end of treatment.

        Exclusion Criteria:

        1. No ROS1 rearrangement 2. No previous therapy with crizotinib; 3. No evidence of
        crizotinib failure; 4. No post-crizotinib tumor tissue available; 5. Absence of any
        measurable lesions; 6. No previous chemotherapy; 7. Concomitant radiotherapy or
        chemotherapy; 8. Symptomatic brain metastases; 9. Diagnosis of any other malignancy during
        the last 5 years, except for in situ carcinoma of cervix uteri and squamous cell carcinoma
        of the skin; 10. Predisposing factors for acute pancreatitis (e.g., uncontrolled
        hyperglycaemia, current gallstone disease, alcoholism); 11. History of extensive
        disseminated/bilateral or known presence of Grade 3 or 4 interstitial fibrosis or
        interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis,
        interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis and pulmonary
        fibrosis (but not history of prior radiation pneumonitis); 12. Pregnancy or lactating
        female; 13. Other serious illness or medical condition potentially interfering with the
        study.

        -
      