E GFR TKI and EGF-P TI C Ombination in EGFR mutA nt NSCL C

Inclusion Criteria

• •1. Age 18 years or older.
• •2. Histological confirmation of locally advanced or metastatic, non-squamous NSCLC with an activating EGFR mutation who are not candidates for local curative treatment.
• •3. Stage IV, according to TNM Version 8, including M1a (malignant effusion) or M1b (distant metastasis), or locally advanced disease for which there is no curative treatment (including patients who progress after chemoradiotherapy in Stage III disease).
• •4. Centrally confirmed EGFR exon 19 deletion, exon 21 (L858R, L861Q) or exon 18 (G719X) mutation before treatment (concomitant T790M pre-treatment mutation is permitted).
• •5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• •6. Existence of measurable or evaluable disease (according to RECIST 1.1 criteria). Patients with asymptomatic and stable brain metastases are eligible for the study.
• •7. Possibility of obtaining tissue samples, via a biopsy or surgical resection of the primary tumour or metastatic tumour tissue, within 60 days prior to the start of treatment.
• •8. Life expectancy ≥12 weeks.
• •9. Adequate haematological function, defined as: absolute neutrophil count (ANC) \>1.5 x 109/L, platelet count \>100.0 x 109/L, and haemoglobin \>9.0 g/dL (\>6.2 mmol/L).
• •10. Adequate coagulation, defined as: international normalised ratio (INR) ≤1.5.
• •11. Adequate liver function, defined as: total bilirubin \<1.5 x upper limit of normal (ULN), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \<2.5 x ULN, alkaline phosphatase \<5 ULN, except in the presence of single bone metastases and in the absence of any liver disorders.
• •12. Adequate renal function, defined as: calculated creatinine clearance \>50 mL/min (Cockcroft-Gault formula) and proteinuria \<2+ (dipstick).
• •13. Ability to complete the study, and residing within geographical proximity allowing for adequate follow-up.
• •14. Resolution of all acute toxic effects of any previous anti-cancer therapy (which can only be adjuvant or neoadjuvant) or previous surgical interventions not exceeding grade ≤1 according to the National Cancer Institute CTCAE Version 4.0 (except for alopecia or other side effects that the investigator does not consider to be a risk to patient safety).
• •17. Patients who have had a surgical procedure unrelated to the study within 7 days prior to the first administration of EGF-PTI, or a significant traumatic lesion during the 4 weeks prior to starting the first dose of EGF-PTI, patients who have not recovered from the side effects of any major surgery or patients who might need major surgery during the course of the study.
• •18. Pregnant or breastfeeding women. Women of childbearing potential, including women who had their last menstrual period within the last 2 years, must have a negative serum or urine pregnancy test in the 7 days prior to the first dose of EGF-PTI.
• •19. Patients with a serious concomitant systemic disorder (e.g., active infection, including HIV or heart disease) that is incompatible with the study (in the opinion of the investigator), history of bleeding diathesis or anticoagulant therapy (the use of low molecular weight heparin is permitted provided that it is used for prophylaxis).
• •20. Treatment with any of the prohibited concomitant medications that cannot be stopped for the duration of trial participation.
• •21. Any other reason that the investigator deems to be incompatible with the patient's participation in the study.