Study of Alkotinib in Patients With Advanced Non Small Cell Lung Cancer

The study is a randomized, double-blind phase 1 trial including 2 sequential parts: single ascending dose(SAD) part,multiple ascending dose(MAD) part. SAD and MAD are dose-escalated tolerant study designing. The aims of the study as below:

• Evaluating the safety and tolerance of ZG0418 in ALK+ NSCLC.
• Evaluating the fasting pharmacokinetic parameters of ZG0418 in ALK+ NSCLCJaktinib.
• Evaluating the postprandial pharmacokinetic parameters of ZG0418 in ALK+ NSCLC.
• Analysis the metabolites of ZG0418

Inclusion criteria

• Advanced ALK+ or ROS1+ NSCLC And Previously Treated with Chemotherapy or Crizotinib
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 to 2.
• Life expectancy of at least 12 weeks.
• Ability to swallow and retain oral medication.
• Adequate organ system function, defined as follows:

• Absolute neutrophil count (ANC) ≥1.5 x 10^9/L
• Platelets ≥75 x 10^9/L
• Hemoglobin ≥9 g/dL (≥90 g/L) Note that transfusions are allowed to meet the required hemoglobin level
• Total bilirubin ≤1.5 times the upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)

≤2.5 x ULN if no liver involvement or ≤5 x ULN with liver involvement.

• Creatinine 1.5 x ULN.
• Brain metastases allowed if asymptomatic at study baseline.
• Patients must have measurable disease per RECIST v. 1.1.

Exclusion criteria

• chemotherapy, radiation therapy, immunotherapy within 4 weeks.
• Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of study medications.
• uncontrolled mass of pleural effusion, pericardial effusion, and peritoneal effusion.