Entrectinib

RANDOMIZED, OPEN LABEL, MULTICENTER, PHASE III STUDY OF ENTRECTINIB VERSUS CRIZOTINIB IN PATIENTS WITH LOCALLYADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER HARBORING ROS1 GENE REARRANGEMENTS WITH AND WITHOUT CENTRAL NERVOUS SYSTEM METASTASES

• Histologically- or cytologically-confirmed diagnosis of advanced or recurrent (Stage IIIB/C, not amenable for radical treatment) or metastatic (Stage IV) NSCLC that harbors a documented ROS1 gene rearrangement
  • For a patient to be considered for this study, documented positivity for ROS1 gene rearrangements must have been determined locally at CLIA-certified or equivalently-accredited diagnostic laboratories using nucleic acid-based testing methods that rely on direct assessment of ROS1 gene rearrangements in tumor tissue. Examples of acceptable methods include next-generation sequencing (NGS), Sanger sequencing, reverse transcriptase-polymerase chain reaction (RT-PCR), NanoString and EdgeSeq. Fluorescence in situ hybridization (FISH) is also an acceptable method, with ROS1 positivity defined as the detection of at least 15% of neoplastic nuclei with ROS1 gene rearrangements among a minimum of 50 total neoplastic nuclei. Immunohistochemistry (IHC) is not an acceptable method
• No prior treatment with a ROS1 tyrosine kinase inhibitor, chemotherapy or other systemic therapy for advanced or recurrent (Stage IIIB/C not amenable for radical treatment) or metastatic (Stage IV) NSCLC
• Prior radiotherapy is allowed if more than 14 days have elapsed between the end of treatment and randomization. Patients who received brain irradiation must have completed whole brain radiotherapy at least 14 days prior and/or stereotactic radiosurgery at least 7 days prior to the start of entrectinib treatment

• Current participation in another therapeutic clinical trial
• Prior treatment with a ROS1 tyrosine kinase inhibitor, chemotherapy or other systemic therapy for advanced or recurrent (Stage IIIB/C not amenable for radical treatment) or metastatic (Stage IV) NSCLC
• NCI-CTCAE v5.0 Grade 3 or higher toxicities due to any prior therapy (excluding alopecia, fatigue, nausea and lack of appetite), which have not shown improvement and are strictly considered to interfere with current study medication
• History of recent (within the past 3 months) symptomatic congestive heart failure or ejection fraction ≤ 50% observed during screening for the study