X-396 Capsule in Advanced NSCLC Patients With ROS1 Gene Rearrangement

Phase II, Open-Label, Single Arm Study of the Efficacy and Safety of X-396 Capsule in Patients With ROS1 Positive Advanced NSCLC

To assess treatment effectiveness and safety of oral X-396 capsule (Ensartinib) administered to Chinese patients with Advanced Non-Small Cell Lung Cancer (NSCLC) that is confirmed to be positive for a c-ROS Oncogene (ROS1) positive gene mutation (translocation or inversion).

Study Overview

• Status: Unknown
• Conditions: Lung Cancer; ROS1 Gene Rearrangement
• Intervention / Treatment: Drug: X-396 Capsule

Detailed Description

This is a phase II, multicenter, single-arm study in which the efficacy and safety of X-396 capsule (Ensartinib) will be assessed in adult Chinese patients with ROS1-positive (rearrangement or inversion) non-small cell lung cancer (NSCLC). Approximately 69 patients (59 for never-treated, and 10 for previously treated with crizotinib) with locally advanced or metastatic NSCLC carrying ROS1-rearrangement will be enrolled in the study.

• Study Type: Interventional
• Enrollment (Anticipated): 69
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Recruiting
      • Chest hospital affiliated to Shanghai jiao tong university
      • Principal Investigator: Shun Lu, Ph.D

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Female or male, 18 years of age or older
• Histologically or cytologically proven diagnosis of NSCLC that is locally advanced or metastatic
• Positive for translocation or inversion events involving the ROS1 gene
• Tyrosine kinase inhibitor (TKI) treatment-naive or have previously received no more than one systemic treatment regimen(s) such as chemotherapy (After a 3-week washout period)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
• Predicted survival ≥ 3 months
• Drug related toxicities were relieved to grade 1, except for hair loss (based on NCI CTCAE v4.03)
• Adequate organ function
• At least 1 measurable tumor lesion as per RECIST v1.1
• Asymptomatic central nervous system (CNS) metastases do not require the use of steroids or anticonvulsants.
• Signed and dated informed consent
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
• Agree to use effective contraception during the study period and for at least 90 days after completion of the study treatment

Exclusion Criteria:

• Current treatment on another systemic anti-cancer therapy
• Prior therapy specifically directed against ROS1 fusion genes (except for the exploratory arm that will enroll patients pretreated with crizotinib)
• Evidence of active malignancy within last 3 years
• Previous therapeutic clinical trial must have completed at least 4 week prior to initiation of study drug
• Prior surgery or immunotherapy must have completed at least 4 weeks, and radiation must have been completed at least 2 weeks prior to initiation of study drug
• Known interstitial fibrosis or interstitial lung disease
• Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of study medication
• Clinically significant cardiovascular disease
• Patients with a known allergy or delayed hypersensitivity reaction to study drug or its excipient
• Pregnant or breast feeding
• Use of drugs or foods that are known potent CYP3A4 inhibitors or inducers
• Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol
• Other serious illness or medical condition potentially interfering with the study

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 Capsule; Single-arm trial whereby all consented, enrolled, eligible patients receive X-396 capsule, 225 mg once daily.	Drug: X-396 Capsule; 225 mg once daily; Other Names: Ensartinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) based on independent radiology review (IRC) 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 IRC.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	OS, defined as time from first dose of X-396 to death due to any cause.	36 months
ORR based on investigator assessment according to RECIST 1.1	ORR per RECIST 1.1 calculated as the proportion of patients with a best overall response defined as CR or PR, based on investigator's assessment	12 weeks
Disease control rate (DCR) according to RECIST 1.1	DCR defined as the percentage of patients who have achieved CR, PR and stable disease (SD), based on RECIST 1.1 measured by IRC or investigator	12 weeks
Intracranial overall response rate (iORR) by IRC and investigator assessment according to RECIST 1.1	iORR calculated as the ORR (CR+PR) of lesions in the brain for patients who have measurable disease in the brain at baseline.	12 weeks
Progression-free survival (PFS) based on IRC or investigator according to RECIST 1.1	PFS defined as time from first dose of X-396 capsule to disease progression or death due to any cause, based on RECIST 1.1.	36 months
Time to progression (TTP) based on IRC or investigator according to RECIST 1.1	TTP defined as time from first dose of X-396 capsule to disease progression, based on RECIST 1.1.	36 months
Duration of response (DOR) based on IRC or investigator according to RECIST 1.1	DOR defined as time from documentation of tumor response (CR or PR) to disease progression or death, based on RECIST 1.1	36 months
Change From Baseline Scores on the functional assessment of cancer therapy - Lung (FACT-L) quality of life questionnaire	The FACT-L questionnaire consisted of several major aspects of life (Physical, social/family, emotional, and functional well-being) as well as lung cancer subscale (symptoms, cognitive function, regret of smoking). Scores for item ranging from 0 (not at all) to 4 (very much).	36 months
Incidence of patients experiencing adverse events (AE)	Adverse events are graded according to CTCAE 4.03	36 months

Collaborators and Investigators

• Sponsor: Betta Pharmaceuticals Co., Ltd.
• Investigators: Principal Investigator: Shun Lu, phd

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2018
• Primary Completion (Anticipated): March 1, 2020
• Study Completion (Anticipated): September 1, 2020

Study Registration Dates

• First Submitted: May 16, 2018
• First Submitted That Met QC Criteria: July 23, 2018
• First Posted (Actual): July 31, 2018

Study Record Updates

• Last Update Posted (Actual): January 9, 2020
• Last Update Submitted That Met QC Criteria: January 6, 2020
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: X-396; ROS1 NSCLC
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Ensartinib
• Other Study ID Numbers: BTP-42723

Drug and device information, study documents

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