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

A Phase I Tolerance, Safety and Efficacy Study of Alkotinib in Patients With Advanced ALK Positive /ROS1 Positive NSCLC and Previously Treated With Chemotherapy or Crizotinib

To explore the DLT of ZG0418 for Patients with Advanced ALK+ or ROS1+ NSCLC And Previously Treated with Chemotherapy or Crizotinib, and to determine the MTD or the R2PD.

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:

1. Evaluating the safety and tolerance of ZG0418 in ALK+ NSCLC.
2. Evaluating the fasting pharmacokinetic parameters of ZG0418 in ALK+ NSCLCJaktinib.
3. Evaluating the postprandial pharmacokinetic parameters of ZG0418 in ALK+ NSCLC.
4. Analysis the metabolites of ZG0418

Inclusion Criteria:

1. Advanced ALK+ or ROS1+ NSCLC And Previously Treated with Chemotherapy or Crizotinib

2. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 to 2.

3. Life expectancy of at least 12 weeks.

4. Ability to swallow and retain oral medication.

5. Adequate organ system function, defined as follows:

   1. Absolute neutrophil count (ANC) ≥1.5 x 10^9/L

   2. Platelets ≥75 x 10^9/L

   3. Hemoglobin ≥9 g/dL (≥90 g/L) Note that transfusions are allowed to meet the required hemoglobin level

   4. Total bilirubin ≤1.5 times the upper limit of normal (ULN)

   5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)

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

   6. Creatinine 1.5 x ULN.

6. Brain metastases allowed if asymptomatic at study baseline.

7. Patients must have measurable disease per RECIST v. 1.1.

Exclusion Criteria:

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