PF-06463922 for Crizotinib Pretreated ROS1 Positive Non-small-cell Lung Cancer

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.

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