X-396 Capsule in Advanced NSCLC Patients With ROS1 Gene Rearrangement
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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 Design
Arms and Interventions
| 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:
|
Outcome Measures
Primary Outcome Measures
- Objective response rate (ORR) based on independent radiology review (IRC) according to RECIST 1.1 [12 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
- ORR based on investigator assessment according to RECIST 1.1 [12 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
- Disease control rate (DCR) according to RECIST 1.1 [12 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
- Intracranial overall response rate (iORR) by IRC and investigator assessment according to RECIST 1.1 [12 weeks]
iORR calculated as the ORR (CR+PR) of lesions in the brain for patients who have measurable disease in the brain at baseline.
- Progression-free survival (PFS) based on IRC or investigator according to RECIST 1.1 [36 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.
- Time to progression (TTP) based on IRC or investigator according to RECIST 1.1 [36 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 1.1 [36 months]
DOR defined as time from documentation of tumor response (CR or PR) to disease progression or death, 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.
- Change From Baseline Scores on the functional assessment of cancer therapy - Lung (FACT-L) quality of life questionnaire [36 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).
- Incidence of patients experiencing adverse events (AE) [36 months]
Adverse events are graded according to CTCAE 4.03
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Female or male, 18 years of age or older
-
Histologically or cytologically proven diagnosis of NSCLC that is locally advanced or metastatic
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Positive for translocation or inversion events involving the ROS1 gene
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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)
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Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
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Predicted survival ≥ 3 months
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Drug related toxicities were relieved to grade 1, except for hair loss (based on NCI CTCAE v4.03)
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Adequate organ function
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At least 1 measurable tumor lesion as per RECIST v1.1
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Asymptomatic central nervous system (CNS) metastases do not require the use of steroids or anticonvulsants.
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Signed and dated informed consent
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Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
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Agree to use effective contraception during the study period and for at least 90 days after completion of the study treatment
Exclusion Criteria:
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Current treatment on another systemic anti-cancer therapy
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Prior therapy specifically directed against ROS1 fusion genes (except for the exploratory arm that will enroll patients pretreated with crizotinib)
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Evidence of active malignancy within last 3 years
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Previous therapeutic clinical trial must have completed at least 4 week prior to initiation of study drug
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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
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Known interstitial fibrosis or interstitial lung disease
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Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of study medication
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Clinically significant cardiovascular disease
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Patients with a known allergy or delayed hypersensitivity reaction to study drug or its excipient
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Pregnant or breast feeding
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Use of drugs or foods that are known potent CYP3A4 inhibitors or inducers
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Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol
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Other serious illness or medical condition potentially interfering with the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Chest hospital affiliated to Shanghai jiao tong university | Shanghai | Shanghai | China | 200000 |
Sponsors and Collaborators
- Betta Pharmaceuticals Co., Ltd.
Investigators
- Principal Investigator: Shun Lu, PHD
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BTP-42723