Clinical trial NCT03608007: X-396 Capsule in Advanced NSCLC Patients With ROS1 Gene Rearrangement
Official title: Phase II, Open-Label, Single Arm Study of the Efficacy and Safety of X-396 Capsule in Patients With ROS1 Positive Advanced NSCLC
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Lung Cancer
ROS1 Gene Rearrangement
Keywords: ROS1 NSCLC
X-396
Lead sponsor: Betta Pharmaceuticals Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-07-31
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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
* 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

Primary outcomes:
measure: Objective response rate (ORR) based on independent radiology review (IRC) according to RECIST 1.1
timeFrame: 12 weeks
Secondary outcomes:
measure: ORR based on investigator assessment according to RECIST 1.1
timeFrame: 12 weeks
measure: Disease control rate (DCR) according to RECIST 1.1
timeFrame: 12 weeks
measure: Intracranial overall response rate (iORR) by IRC and investigator assessment according to RECIST 1.1
timeFrame: 12 weeks
measure: Progression-free survival (PFS) based on IRC or investigator according to RECIST 1.1
timeFrame: 36 months
measure: Time to progression (TTP) based on IRC or investigator according to RECIST 1.1
timeFrame: 36 months
measure: Duration of response (DOR) based on IRC or investigator according to RECIST 1.1
timeFrame: 36 months
measure: Overall survival (OS)
timeFrame: 36 months
measure: Change From Baseline Scores on the functional assessment of cancer therapy - Lung (FACT-L) quality of life questionnaire
timeFrame: 36 months
measure: Incidence of patients experiencing adverse events (AE)
timeFrame: 36 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Chest hospital affiliated to Shanghai jiao tong university
state: Shanghai
Study officials:
affiliation: PHD
name: Shun Lu
role: PRINCIPAL_INVESTIGATOR
References: