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

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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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

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Alkotinib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ZG0418 200mg QD<br>ZG0418 200mg/day,oral | Drug: Alkotinib<br>* Alkotinib 200mg QD、 Alkotinib 300mg QD、 Alkotinib 400mg QD、 Alkotinib 500mg QD、 Alkotinib 600mg QD<br>* Other names: ZG0418;|
| Experimental: ZG0418 300mg QD<br>ZG0418 300mg/day,oral | Drug: Alkotinib<br>* Alkotinib 200mg QD、 Alkotinib 300mg QD、 Alkotinib 400mg QD、 Alkotinib 500mg QD、 Alkotinib 600mg QD<br>* Other names: ZG0418;|
| Experimental: ZG0418 400mg QD<br>ZG0418 400mg/day,oral | Drug: Alkotinib<br>* Alkotinib 200mg QD、 Alkotinib 300mg QD、 Alkotinib 400mg QD、 Alkotinib 500mg QD、 Alkotinib 600mg QD<br>* Other names: ZG0418;|
| Experimental: ZG0418 500mg QD<br>ZG0418 500mg/day,oral | Drug: Alkotinib<br>* Alkotinib 200mg QD、 Alkotinib 300mg QD、 Alkotinib 400mg QD、 Alkotinib 500mg QD、 Alkotinib 600mg QD<br>* Other names: ZG0418;|
| Experimental: ZG0418 600mg QD<br>ZG0418 600mg/day,oral | Drug: Alkotinib<br>* Alkotinib 200mg QD、 Alkotinib 300mg QD、 Alkotinib 400mg QD、 Alkotinib 500mg QD、 Alkotinib 600mg QD<br>* Other names: ZG0418;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MTD | Evaluating Dose-Limiting Toxicities (DLTs) from the individuals taking orally dose-escalated Alkotinib | Day1 to Day25 |