Olmutinib Trial in T790M (+) NSCLC Patients Detected by Liquid Biopsy Using BALF Extracellular Vesicular DNA

1. Male or female, aged at least 19 years

2. Obtained written informed consent

3. Histologically- or cytologically confirmed diagnosis of unresectable Stage IIIB or IV non-small cell lung cancer.

4. Confirmation that the tumor harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q).

5. Eastern Cooperative Oncology Group performance status of 0 to 2

6. Prior treatment with at least one line of a single agent EGFR TKI (gefitinib, erlotinib, afatinib) and confirmed progressive disease after treatment with EGFR TKI

* Regardless of treatment sequence between previous chemotherapy and EGFR TKI

* Regardless of whether they were administered conventional chemotherapy, if therapy were treated with at least one EGFR TKI

7. Subjects who will undergo bronchoscopy/ BAL procedures and sufficient amount of BAL fluid is carefully collected for EGFR mutation analysis.

8. Confirmation that the extracellular vesicles (EV) extracted from bronchoalveolar lavage fluid (BALF) harbour T790M mutation (It can be replaced previous the same result throughout the follow up period before enrollment.)

9. At least one measurable disease (except brain) at baseline according to RECIST version 1.1

10. Female subjects must be postmenopausal (for at least one year), or, if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study; and, for those of childbearing potential, have a negative urinary β-hCG pregnancy test at screening.

11. Male subjects should be willing to use barrier methods which are suitable for sexual partner throughout the study.

12. Subjects must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. The subject also must sign and date the consent form before specific procedures or sampling.

13. Adequate organ function as defined by liver, kidney, and hematologic laboratory testing as below

* Absolute neutrophil count (ANC) ≥ 1500/mm3, Platelet ≥ 100,000 /mm3 Hemoglobin (Hb) ≥ 9.0g/dL

* Serum creatinine ≤ upper limit of normal (ULN)

* AST/ALT/ALP ≤ 3 times ULN, Total bilirubin ≤2.0 mg/dL AST/ALT/ALP ≤ 5 times ULN in patients with metastatic lesions to the liver ALP ≤ 5 times ULN in patients with metastatic lesions to the bone

14. Expected survival of at least 12 weeks

11. Uncontrolled active infectious disease (with the exception of those that are considered to be needed topical antibiotics, however subjects can be enrolled into the study after they complete their treatment)

12. Unable to attend all the study visits or comply with study procedures

13. Patients who had received other investigational product within 30 days prior to the first administration of study drug except for gefitinib, erlotinib, or afatinib

What this study is about