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

Efficacy and Safety of X-396(Ensartinib) in ALK-Positive NSCLC Patients With Brain Metastases: A Phase Ⅱ, Open-Label, Single Arm, Multicenter Study

To assess efficacy and safety of oral X-396 (Ensartinib) capsule in Chinese ALK-positive NSCLC patients with brain metastases, eligible patients will be enrolled with objective responses being primary outcome measures.

Study Overview

• Status: Active, not recruiting
• Conditions: Nonsmall Cell Lung Cancer; Brain Metastases
• Intervention / Treatment: Drug: X-396(Ensartinib) Capsule

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518100
      • Cancer Hospital Chinese Academy of Medical Sciences, ShenZhen center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

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

  2. 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.

  3. 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.

  4. 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.

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

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

  10. 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.

  4. 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.

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

  6. Patients with clinically significant cardiovascular and cerebrovascular diseases.

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

  8. 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.

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

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

  12. 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.

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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: X-396(Ensartinib) Capsule	Drug: X-396(Ensartinib) Capsule; All consented, enrolled, eligible patients receive X-396 capsules, 225mg once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracranial objective response rate (iORR) based on investigator assessment according to RNAO-BM.	iORR per RANO-BM calculated as the proportion of patients with a best intracranial overall response defined as complete response (CR) or partial response (PR), based on investigator assessment.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate based on intracranial response (iDCR) according to RANO-BM.	Defined as the percentage of patients who have achieved intracranial overall response of CR, PR and stable disease (SD), assessed by investigator.	12 weeks
Progression-free survival based on intracranial response (iPFS) according to RANO-BM	Defined as time from first dose of X-396 capsule to intracranial disease progression or death due to any causes, assessed by investigator.	36 months
Time to progression based on intracranial response (iTTP) according to RANO-BM.	Defined as time from first dose of X-396 capsule to intracranial disease progression, assessed by investigator.	36 months
Duration of response based on intracranial response (iDOR) according to RANO-BM.	Defined as time from documentation of intracranial response (CR or PR) to intracranial disease progression or death, assessed by investigator.	36 months
Disease control rate based on intracranial response (iDCR) according to RECIST 1.1	Defined as the percentage of patients who have achieved intracranial overall response of CR, PR and stable disease (SD), assessed by investigator.	12 weeks
Progression-free survival based on intracranial response (iPFS) according to RECIST 1.1	Defined as time from first dose of X-396 capsule to intracranial disease progression or death due to any causes, assessed by investigator.	36 months
Time to progression based on intracranial response (iTTP) according to RECIST 1.1	Defined as time from first dose of X-396 capsule to intracranial disease progression, assessed by investigator.	36 months
Objective response rate (ORR) based on overall response according to RECIST 1.1.	ORR per RECIST 1.1 calculated as the proportion of patients with a best overall response defined as complete response (CR) or partial response (PR), based on investigator assessment.	12 weeks
Disease control rate based on overall response (DCR) according to RECIST 1.1	Defined as the percentage of patients who have achieved overall response of CR, PR and stable disease (SD), assessed by investigator.	12 weeks
Progression-free survival based on overall response (PFS) according to RECIST 1.1	Defined as time from first dose of X-396 capsule to overall disease progression or death due to any causes, assessed by investigator.	36 months
Time to progression based on overall response (TTP) according to RECIST 1.1	Defined as time from first dose of X-396 capsule to overall disease progression, assessed by investigator.	36 months
Overall survival (OS)	Defined as time from first dose of X-396 to death due to any causes.	36 months
Intracranial objective response rate (iORR) based on intracranial response according to RECIST 1.1	iORR per RECIST 1.1 calculated as the proportion of patients with a best intracranial overall response defined as complete response (CR) or partial response (PR), based on investigator assessment.	12 weeks
Duration of response based on intracranial response (iDOR) according to RECIST 1.1	Defined as time from documentation of intracranial response (CR or PR) to intracranial disease progression or death, assessed by investigator.	36 months
Duration of response based on overall response (DOR) according to RECIST 1.1	Defined as time from documentation of overall response (CR or PR) to overall disease progression or death, assessed by investigator.	36 months
Incidence of patients experiencing adverse events.	Incidence of adverse events occurred during the study (from the timeoint of signing a informed consent form to 30days after the end of trial).	36 months

Collaborators and Investigators

• Sponsor: Fudan University
• Collaborators: Betta Pharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2019
• Primary Completion (Actual): June 30, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: November 22, 2018
• First Submitted That Met QC Criteria: November 22, 2018
• First Posted (Actual): November 27, 2018

Study Record Updates

• Last Update Posted (Actual): July 23, 2025
• Last Update Submitted That Met QC Criteria: July 18, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: NSCLC; Brain metastases; ALK mutations; X-396 (Ensartinib)
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Lung Neoplasms; Nervous System Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Central Nervous System Neoplasms; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung; Brain Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Ensartinib
• Other Study ID Numbers: BTP-42324-IIT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No