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

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.

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Alkotinib

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Shanghai Eastern Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ZG0418 200mg QD; ZG0418 200mg/day,oral	Drug: Alkotinib; Alkotinib 200mg QD、 Alkotinib 300mg QD、 Alkotinib 400mg QD、 Alkotinib 500mg QD、 Alkotinib 600mg QD; Other Names: ZG0418
Experimental: ZG0418 300mg QD; ZG0418 300mg/day,oral	Drug: Alkotinib; Alkotinib 200mg QD、 Alkotinib 300mg QD、 Alkotinib 400mg QD、 Alkotinib 500mg QD、 Alkotinib 600mg QD; Other Names: ZG0418
Experimental: ZG0418 400mg QD; ZG0418 400mg/day,oral	Drug: Alkotinib; Alkotinib 200mg QD、 Alkotinib 300mg QD、 Alkotinib 400mg QD、 Alkotinib 500mg QD、 Alkotinib 600mg QD; Other Names: ZG0418
Experimental: ZG0418 500mg QD; ZG0418 500mg/day,oral	Drug: Alkotinib; Alkotinib 200mg QD、 Alkotinib 300mg QD、 Alkotinib 400mg QD、 Alkotinib 500mg QD、 Alkotinib 600mg QD; Other Names: ZG0418
Experimental: ZG0418 600mg QD; ZG0418 600mg/day,oral	Drug: Alkotinib; Alkotinib 200mg QD、 Alkotinib 300mg QD、 Alkotinib 400mg QD、 Alkotinib 500mg QD、 Alkotinib 600mg QD; Other Names: ZG0418

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Suzhou Zelgen Biopharmaceuticals Co.,Ltd
• Investigators: Principal Investigator: Jin Li, Doctor, Shanghai Eastern Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2018
• Primary Completion (Actual): October 17, 2022
• Study Completion (Actual): October 17, 2022

Study Registration Dates

• First Submitted: July 23, 2018
• First Submitted That Met QC Criteria: July 23, 2018
• First Posted (Actual): July 31, 2018

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: ZGALK001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No