Lung Cancer, ROS1 Gene Rearrangement
Conditions
Keywords
ROS1 NSCLC, X-396
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.
Interventions
DRUGX-396 Capsule
225 mg once daily
Sponsors
Betta Pharmaceuticals Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| 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 |
| 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 |
Countries
China
Contacts
Primary ContactJinxiao Xu
Outcome results
None listed