X-396(Ensartinib) Capsules in ALK-Positive NSCLC Patients With Brain Metastases

In this phase Ⅱ, open-label, single arm, multicenter study, efficacy and safety of oral X-396 capsule (Ensartinib) in 37 Chinese ALK-positive NSCLC patients with brain metastases will be assessed. Eligible patients will receive 225mg X-396 capsules once daily and objective responses of brain metastasis based on investigator assessment according to Response Assessment in Neuro-Oncology (RANO) are primary outcome measures.

Inclusion criteria

• 1. Histologically or cytologically confirmed locally advance or recurrent/metastatic NSCLC that was positive for ALK mutations.

• Contrast-enhanced MRI or CT confirmed parenchymal brain metastases with at least one measurable lesion (according to RANO and RECIST 1.1), which was not previously treated with radiotherapy.

• At most once treated with chemotherapy, which must have been completed at least 4 weeks before the initiation of study treatment. Any adverse events related to previous chemotherapy treatment have disappeared.

• Female or male, 18 years of age or older 5. A Karnofsky Performance Status score of at least 60. 6. An expected survival time of at least 12 weeks. 7. Adequate organ functions, defined as absolute neutrophils count ≥1.5*10^9/L，platelets count ≥80*10^9/L, hemoglobin concentration≥ 9 g/dL, total bilirubin ≤1.5 *ULN (upper limits of normal), ALT≤2.5 *ULN, AST≤2.5 *ULN, creatinine≤1.5 *ULN.

• Drug related toxicities has been relieved to grade 1 (based on NCI CTCAE v4.03), except for hair loss.

• Being willing and able to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.

• Signed and dated informed consent.

Exclusion criteria

• 1. Currently under treatment of other systemic anti-cancer therapies. 2. Evidence of active malignancy within last 5 years. 3. Patients who participated in other clinical trials within last 4 weeks before the initiation of study treatment.

• Patients who received surgery or immunotherapy within last 4 weeks before the initiation of study treatment, or received radiotherapy within last 2 weeks before the initiation of study treatment.

• Patients who previously received organ transplantation or stem cell transplantation.

• Patients with clinically significant cardiovascular and cerebrovascular diseases.

• Patients with dysphagia, active gastrointestinal diseases or other conditions that will interfere significantly with the absorption, distribution, metabolism or excretion of study medication.

• Patients who are active carrier of hepatitis B (HBsAg positive and HBV-DNA ≥500IU/mL), hepatitis C virus antibody, treponema pallidum antibody or HIV antibody.

• Patients with interstitial lung disease history or signs of active interstitial lung disease.

• Pregnant and lactating women. 11. Patients with known allergy or delayed hypersensitivity reaction to study drug or its excipients.

• Patients who need to receive drugs which could induce QT/QTc interval prolongation or torsade de pointes, or drugs which are potent CYP3A4 inhibitors or inducers within last 14 days before the initiation of study treatment and during the study.

• Patients who are currently under treatment of warfarin or other coumarin anticoagulants.

• Patients with other illness or medical conditions potentially interfering with the study treatment.