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

Phase 2
Conditions
Lung Cancer
ROS1 Gene Rearrangement
Interventions
Registration Number
NCT03608007
Lead Sponsor
Betta Pharmaceuticals Co., Ltd.
Brief Summary

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).

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
69
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
X-396 CapsuleX-396 CapsuleSingle-arm trial whereby all consented, enrolled, eligible patients receive X-396 capsule, 225 mg once daily.
Primary Outcome Measures
NameTimeMethod
Objective response rate (ORR) based on independent radiology review (IRC) according to RECIST 1.112 weeks

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.

Secondary Outcome Measures
NameTimeMethod
Incidence of patients experiencing adverse events (AE)36 months

Adverse events are graded according to CTCAE 4.03

Disease control rate (DCR) according to RECIST 1.112 weeks

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

ORR based on investigator assessment according to RECIST 1.112 weeks

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

Progression-free survival (PFS) based on IRC or investigator according to RECIST 1.136 months

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.

Overall survival (OS)36 months

OS, defined as time from first dose of X-396 to death due to any cause.

Time to progression (TTP) based on IRC or investigator according to RECIST 1.136 months

TTP defined as time from first dose of X-396 capsule to disease progression, based on RECIST 1.1.

Duration of response (DOR) based on IRC or investigator according to RECIST 1.136 months

DOR defined as time from documentation of tumor response (CR or PR) to disease progression or death, based on RECIST 1.1

Change From Baseline Scores on the functional assessment of cancer therapy - Lung (FACT-L) quality of life questionnaire36 months

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).

Intracranial overall response rate (iORR) by IRC and investigator assessment according to RECIST 1.112 weeks

iORR calculated as the ORR (CR+PR) of lesions in the brain for patients who have measurable disease in the brain at baseline.

Trial Locations

Locations (1)

Chest hospital affiliated to Shanghai jiao tong university

🇨🇳

Shanghai, Shanghai, China

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