PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeter (mm) and the appearance of new lesions.

ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.

Overall response rate in subjects with confirmed CNS response (C-ORR) was defined as the percentage of subjects who attained Complete Response (CR) or Partial Response (PR) for lesions in the CNS. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

ITT population with measurable CNS metastasis (mc-ITT) included all participants in ITT population with measurable CNS metastasis at baseline (as per IRC).

PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions.

This outcome measure was assessed as part of the primary analysis and was not repeated during final analysis.

ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.

ORR was defined as the percentage of participants who attained CR or PR. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

The IRC assessment was part of the primary analysis and was not repeated during final analysis.

ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.

Disease control rate (DCR) was defined as the percentage of participants who attained CR, PR, or stable disease (SD) of at least 5 weeks. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters, SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters since the treatment started.

The IRC assessment was part of the primary analysis and was not repeated during final analysis.

ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.

DOR was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death, whichever occurred first. DOR was evaluated for participants who had a best overall response (BOR) of CR or PR.

The IRC assessment was part of the primary analysis and was not repeated during final analysis.

ITT population included all participants randomized in the study, irrespective of whether or not they received study drug. Number analyzed indicates number of participants with a BOR of CR or PR.

PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions.

This outcome measure assessment was part of the primary analysis and was not repeated during final analysis.

Intent-to-treat population with CNS metastasis (C-ITT) included participants in ITT population with CNS metastasis at baseline (as per IRC assessment).

Time to CNS progression was defined as the time from randomization until radiographic evidence of CNS progression. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions.

This outcome measure assessment was part of the primary analysis and was not repeated during final analysis.

C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment).

Disease Control Rate (DCR) was defined as the percentage of participants who attained CR, PR, or stable disease (SD) of at least 5 weeks. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters, SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters since the treatment started.

C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment).

ORR was defined as the percentage of participants who attained CR or PR. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment).

DOR was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death, whichever occurred first. C-DOR was defined in a similar way for lesions in the CNS, taking into account all lesions in the body. DOR was evaluated for participants who had a BOR of CR or PR.

C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment). Number analyzed indicates number of participants with a BOR of CR or PR.

Overall survival (OS) was defined as the time from randomization to death from any cause. OS was confounded by cross-over of participants to the alectinib arm.

ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.

The Pharmacokinetic (PK) Evaluable Population included all participants who received any dose of alectinib and who had at least one post-baseline PK sample available.

The PK Evaluable Population included all participants who received any dose of alectinib and who had at least one post-baseline PK sample available.

Percentage of participants who filled out an EORTC QLQ-C30 questionnaire at a visit. The EORTC QLQ-C30 questionnaire consisted of 30 questions generating five functional scores (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale score; three symptom scale scores (fatigue, pain, and nausea and vomiting); and six stand alone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and perceived financial burden.

ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.

Percentage of participants who filled out an EORTC QLQ-LC13 questionnaire at a visit. The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis.

ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.

Percentage of participants who filled out an ED-5D-5L questionnaire at a visit. EQ-5D-5L: A generic preference-based health utility measure that provides a single index value for health status. The instrument consists of two parts. The first part, health-state classification, contains five dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.

ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.

TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea [single item and multi-item scales] chest pain [single item], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-LC13.

ITT population included all participants randomized in the study, irrespective of whether or not they received study drug. Number analyzed indicates number of participants evaluated for specified categories.

TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea [single item and multi-item scales] chest pain [single item], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-LC13.

C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment). Number analyzed indicates number of participants evaluated for specified categories.

TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea [single item and multi-item scales] chest pain [single item], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-C30.

ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.

TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea [single item and multi-item scales] chest pain [single item], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-C30.

C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment).

TTD for a composite of three symptoms (cough, dyspnea, chest pain) in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for any component of the composite of the three following symptoms [cough, dyspnea [multi-item subscales QLQ-LC13] and chest pain]) as measured by the EORTC QLQ-LC13.

C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment).

TTD for a composite of three symptoms (cough, dyspnea, chest pain) in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for any component of the composite of the three following symptoms [cough, dyspnea [multi-item subscales QLQ-LC13] and chest pain]) as measured by the EORTC QLQ-LC13.

ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.

An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Safety (SAF) population included all participants who received at least one dose of any study drug.