Patient case: 72-year-old male with lung adenocarcinoma; genetic feature: EZR-ROS1 fusion

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

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: 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 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

Relevance to patient case: possibly relevant