∙ Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:

• Diagnosis:

∙ Study Population: Patients with histologically or cytologically confirmed diagnosis of locally advanced \[(Stage IIIB/C not amenable for multimodality treatment) or metastatic (Stage IV) by American Joint Committee on Cancer (AJCC) v 7.0\] ALK-positive NSCLC where ALK status is determined by the Ventana ALK (D5F3) Companion Diagnostic (CDx) IHC test performed on the Ventana ULTRA or XT Platforms, FISH, PCR, or next generation sequencing (NGS), or circulating tumor DNA (ctDNA).

‣ Tumor Requirements: At least 1 extracranial measurable target lesion per RECIST v. 1.1 that has not been previously irradiated. CNS metastases are allowed if asymptomatic and:

‣ Either untreated and not currently requiring corticosteroid treatment, or on a stable or decreasing dose of ≤10 mg QD prednisone or equivalent; or

⁃ Local treatment has been completed with full recovery from the acute effects of radiation therapy or surgery prior to randomization, and if corticosteroid treatment for these metastases has been withdrawn for at least 4 weeks with neurological stability; or

⁃ In case of leptomeningeal disease (LMD) or carcinomatous meningitis (CM) if visualized on magnetic resonance imaging (MRI), or if baseline CSF positive cytology is available.

‣ Tissue Requirements: All patients must have an archival formalin fixed, paraffin embedded (FFPE) tissue specimen available and collected prior to randomization. If archived tissue is unavailable, then a mandatory de novo biopsy must be performed.

• No prior systemic NSCLC treatment for advanced (Stage IIIB/C not amenable for multimodality treatment) or metastatic (Stage IV) disease, including molecularly targeted agents (e.g., ALK TKIs), angiogenesis inhibitors, immunotherapy, or chemotherapy. Prior treatment for earlier Stages of the NSCLC only allowed if completed more than 12 months prior to randomization.

• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, 1, or 2.

• Age ≥18 years.

• Adequate Bone Marrow Function, including:

∙ Absolute Neutrophil Count (ANC) ≥ 1,500/mm3 or ≥1.5 x 109/L;

‣ Platelets ≥100,000/mm3 or ≥100 x 109/L;

‣ Hemoglobin ≥9 g/dL.

• Adequate Pancreatic Function, including:

∙ Serum total amylase ≤1.5 x upper limit of normal (ULN)\*;

‣ Serum lipase ≤1.5 x ULN. \*if total amylase \>1.5 x ULN, but pancreatic amylase is within the ULN, then patient may be enrolled.

• Adequate Renal Function, including:

• a. Serum creatinine ≤1.5 x ULN or estimated creatinine clearance ≥60 mL/min as calculated using the method standard for the institution.

• Adequate Liver Function, including:

∙ Total serum bilirubin ≤1.5 x ULN;

‣ Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤2.5 x ULN (≤5.0 x ULN in case of liver metastases).

• Acute effects of prior radiotherapy resolved to baseline severity or to CTCAE Grade ≤1 except for AEs that in the investigator's judgment do not constitute a safety risk for the patient.

⁃ Serum pregnancy test (for females of childbearing potential) negative at screening. Female patients of non-childbearing potential must meet at least 1 of the following criteria:

• Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause (which may be confirmed with a serum follicle-stimulating hormone \[FSH\] level confirming the postmenopausal state if appropriate);

∙ Have undergone a documented hysterectomy and/or bilateral oophorectomy;

∙ Have medically confirmed ovarian failure. All other female patients (including female patients with tubal ligations) are considered to be of childbearing potential.

⁃ Evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study.

⁃ Willing and able to comply with scheduled visits, treatment plans, laboratory tests and other procedures.

• Diagnosed as ALK-positive NSCLC as in CC cohort, but not fulfilled CC cohort inclusion criteria 2\

∙ 9 as above mentioned.

• No prior ALK TKI treatment for advanced (Stage IIIB/C not amenable for multimodality treatment) or metastatic (Stage IV) disease (e.g., alectinib, brigatinib).

• Serum pregnancy test (for females of childbearing potential) negative at screening.

• Evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study.

• Willing and able to comply with scheduled visits, treatment plans, laboratory tests and other procedures.