A Study to Compare the Efficacy and Safety of Entrectinib and Crizotinib in Participants With Advanced or Metastatic ROS1 Non-small Cell Lung Cancer (NSCLC) With and Without Central Nervous System (CNS) Metastases

Inclusion Criteria:

• Histologically or cytologically-confirmed diagnosis of advanced or recurrent (StageIIIB/C not amenable for radical treatment) or metastatic (Stage IV) NSCLC thatharbors a documented ROS1 gene rearrangement.

• No prior treatment with a ROS1 tyrosine kinase inhibitor, chemotherapy or othersystemic therapy for advanced or recurrent (Stage IIIB/C not amenable for radicaltreatment) or metastatic (Stage IV) NSCLC

• Prior radiotherapy is allowed if more than 14 days have elapsed between the end oftreatment and randomization

• Measurable systemic disease according to RECIST v1.1

• Participants with measurable and non-measurable CNS lesions per RECIST v1.1,including leptomeningeal carcinomatosis

• Life expectancy of at least 12 weeks

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

• Adequate hematologic, renal, liver functions

• Participants must have recovered from effects of any major surgery or significanttraumatic injury at least 28 days before the first dose of study treatment

• Ability to swallow entrectinib and crizotinib intact without chewing, crushing, oropening the capsules

• For women of childbearing potential: agreement to remain abstinent (refrain fromheterosexual intercourse) or use contraceptive methods with a failure rate of <1%per year during the treatment period and for up to 5 weeks after the last dose ofentrectinib or for at least 90 days after the last dose of crizotinib

• For men: agreement to remain abstinent (refrain from heterosexual intercourse) oruse contraceptive measures, and agreement to refrain from donating sperm.

Exclusion Criteria:

• Prior treatment with a ROS1 tyrosine kinase inhibitor, chemotherapy or othersystemic therapy for advanced or recurrent (Stage IIIB/C not amenable for radicaltreatment) or metastatic (Stage IV) NSCLC

• NCI-CTCAE v5.0 Grade 3 or higher toxicities due to any prior therapy (excludingalopecia, fatigue, nausea and lack of appetite), which have not shown improvementand are strictly considered to interfere with current study drug

• History of recent (within the past 3 months) symptomatic congestive heart failure orejection fraction ≤ 50% observed during screening for the study

• History of prolonged corrected QTc interval

• Peripheral sensory neuropathy ≥ Grade 2

• Known interstitial lung disease, interstitial fibrosis, or history of tyrosinekinase inhibitor-induced pneumonitis

• Previous malignancy within the past 3 years

• Incomplete recovery from any surgery prior to the start of study treatment

• Active GI disease (e.g., Crohn's disease, ulcerative colitis or short gut syndrome)or other malabsorption syndrome that would reasonably impact drug absorption

• History of prior therapy-induced pneumonitis

• Any condition (in the past 3 months) e.g., myocardial infarction, unstable angina,coronary/peripheral artery bypass graft, cerebrovascular accident or transientischemic attack, stroke, symptomatic bradycardia, or uncontrolled arrhythmiasrequiring medication

• Known active infections (bacterial, fungal or viral, including humanimmunodeficiency virus positive)

• History of hypersensitivity to any of the additives in the entrectinib and/orcrizotinib drug formulations

• Pregnant or lactating women

• Known human immunodeficiency virus (HIV) positivity or acquired immunodeficiencysyndrome (AIDS)-related illness

• Any clinically significant concomitant disease or condition that could interferewith, or for which the treatment might interfere with, the conduct of the study orthe absorption of oral medications.