Osimertinib (AZD9291) in First-line Locally Advanced or Metastatic NSCLC Patients With EGFR and EGFR T790M

Inclusion Criteria

• •Patient aged 18 years or older
• •Patients with histological confirmation of locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC) with an activating EGFR mutation and concomitant T790M mutation who are not candidates for local curative treatment.
• •Patients with a M1a stage according to the TNM version 7 including M1a (malignant effusion) or M1b (distant metastasis), or locally advanced disease that is not a candidate for curative treatment (including patients who progress after chemoradiotherapy in stage III disease).
• •Patients with a EGFR deletion or mutation in exon 19, exon 21 (L858R, L861Q) or exon 18 (G719X) and concomitant T790M mutation before treatment confirmed centrally.
• •ECOG (Eastern Cooperative Oncology Group) performance status less than or equal to 2.
• •Existence of measurable or evaluable disease (as per RECIST 1.1 criteria). Patients with asymptomatic and stable brain metastases are eligible for the study.
• •Possibility of obtaining sufficient tissue sample, via a biopsy or surgical resection of the primary tumor or metastatic tumor tissue, within the 60 days prior to study entry.
• •Life expectancy ≥12 weeks.
• •Adequate hematologic function:
• •* Absolute neutrophil count (ANC) \> 1.5 x 109/L
• •* platelet count \> 100.0 x109/L
• •* hemoglobin \> 9.0 g/dL (\> 6.2 mmol/L).
• •Adequate coagulation: INR ≤ 1.5.
• •Adequate liver function
• •Adequate renal function.
• •Capacity to swallow, patient capable of completing treatment and accessible, ensuring proper follow-up.
• •Patients able to complete study and within geographical proximity allowing for adequate follow-up.
• •Resolution of all acute toxic effects of previous anti-cancer therapy (which can only be adjuvant or neoadjuvant) or surgical interventions not exceeding grade ≤ 1 according to the NCI CTCAE version 4.0 (except for alopecia or other side effects that the investigator does not consider to be a risk to patient safety).
• •All men or women of childbearing potential must use a contraception method during the study treatment and for at least 12 months after the last dose of the study drug.
• •Signed and dated informed consent form
• •Refractory nauseas and vomiting, chronic gastrointestinal disease, inability to swallow study drug or significant intestinal resection that restricts the adequate absorption of osimertinib (AZD9291).
• •Patients who have had a surgical procedure unrelated to the study within 7 days prior to the administration of the drug or a significant traumatic lesion during the 4 weeks prior to starting the administration of the study drug, 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.
• •Pregnant or breastfeeding women. Women of childbearing potential, including women who had their last menstrual period within the last two years, must have a negative serum or urine pregnancy test in the 7 days prior to the start of the treatment.
• •Patients who are not willing to use an adequate contraception method until 12 months after the last dose of study treatment.
• •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).
• •Patients with a history of cancer that has been completely treated, with no evidence of malignant disease currently cannot be enrolled in the study if their chemotherapy was completed less than 6 months prior and/or have received a bone marrow transplant less than 2 years before the first day of study treatment.
• •Prior treatment with cytotoxic chemotherapy for advanced NSCLC; neoadjuvant/adjuvant chemotherapy is permitted if at least 6 months have elapsed between the end of chemotherapy and the first day of study treatment.
• •Patients who have received prior EGFR treatments for lung cancer.
• •Patients who have received treatment with an investigational drug within 3 weeks before the first day of study treatment.
• •Treatment with prohibited drugs within 14 days before the first day of study treatment.