Alectinib Versus Pemetrexed or Docetaxel in Anaplastic Lymphoma Kinase (ALK)-Positive Advanced Non-Small Cell Lung Cancer (NSCLC) Participants Previously Treated With Platinum-Based Chemotherapy and Crizotinib

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02604342
• Collaborator: (none)
• Enrollment: 119
• Locations: 54
• Arms: 2
• Actual Duration (Months): 33.3
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This randomized active-controlled multicenter Phase III open-label study will evaluate and compare between treatment groups the efficacy of alectinib versus chemotherapy in participants with ALK-positive advanced NSCLC who were previously treated with chemotherapy and crizotinib, as measured by investigator-assessed progression-free survival (PFS) and to evaluate and compare between treatment groups the central nervous system (CNS) objective response rate (C-ORR) in participants with measurable CNS metastases at baseline, as assessed by an Independent Review Committee (IRC).

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Drug: Alectinib; Drug: Docetaxel; Drug: Pemetrexed	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 119 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized, Multicenter, Phase III, Open-Label Study of Alectinib Versus Pemetrexed or Docetaxel in Anaplastic Lymphoma Kinase-Positive Advanced Non Small Cell Lung Cancer Patients Previously Treated With Platinum-Based Chemotherapy and Crizotinib
• Actual Study Start Date: Nov 3, 2015
• Actual Primary Completion Date: Jan 26, 2017
• Actual Study Completion Date: Aug 13, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Alectinib Participants will receive oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food until disease progression, unacceptable toxicity, withdrawal of consent or death.	Drug: Alectinib; Participants will receive oral alectinib at a dose of 600 mg twice daily, taken with food until disease progression, unacceptable toxicity, withdrawal of consent or death.
Active Comparator: Premetrexed/Docetaxel Participants will receive chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.	Drug: Docetaxel; Participants will receive docetaxel at a dose of 75 mg/m^2 of body surface area intravenously every 3 weeks, until disease progression, unacceptable toxicity, withdrawal of consent or death.; Other Names: Taxotere® ; Drug: Pemetrexed; Participants will receive pemetrexed at a dose of 500 mg/m^2 of body surface area intravenously every 3 weeks, until disease progression, unacceptable toxicity, withdrawal of consent or death.; Other Names: Alimta®

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator [Randomization to first documented disease progression, death from any cause, or study end (up to 33 months)]

   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.

Secondary Outcome Measures

1. Percentage of Participants With CNS Objective Response Rate (ORR) With Measurable CNS Metastases at Baseline Using RECIST Version 1.1 as Assessed By IRC [Baseline through study end (up to 33 months)]

   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.

2. PFS Using RECIST Version 1.1 as Assessed by IRC [Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)]

   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.

3. Percentage of Participants With Objective Response of CR or PR Using RECIST Version 1.1 as Assessed by Investigator and IRC [Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)]

   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.

4. Percentage of Participants With Disease Control Using RECIST Version 1.1 as Assessed by Investigator and IRC [Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)]

   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.

5. Duration of Response (DOR) Using RECIST Version 1.1 as Assessed by Investigator and IRC [From the first documented CR or PR to the first documented disease progression, death, or study end (up to 33 months)]

   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.

6. PFS in C-ITT Population Using RECIST Version 1.1 as Assessed by Investigator and IRC [Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)]

   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.

7. Time to CNS Progression in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC [Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)]

   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.

8. Percentage of Participants With Disease Control in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC [From first documented CR, PR, or SD lasting at least 5 weeks through study end (up to 33 months)]

   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.

9. Percentage of Participants With ORR in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC [Baseline through study end (up to 33 months)]

   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.

10. Duration of Response for Lesions in the CNS (C-DOR) Using RECIST Version 1.1 as Assessed by IRC [From the first documented CR or PR to the first documented disease progression, death, or study end (up to 33 months)]

    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.

11. Overall Survival (OS) [Randomization to death from any cause, through study end (up to 33 months)]

    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.

12. Plasma Concentration of Alectinib [Predose (2 hours) at Baseline, Week 3 and Week 6]

13. Plasma Concentration of Alectinib Metabolite [Predose (2 hours) at Baseline, Week 3 and Week 6]

14. Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time [Baseline through Week 138]

    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.

15. Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time [Baseline through Week 138]

    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.

16. Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time [Baseline through Week 60]

    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.

17. Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for ITT Population [Baseline through study end (up to 33 months)]

    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.

18. Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for C-ITT Population [Baseline through study end (up to 33 months)]

    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.

19. Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for ITT Population [Baseline through study end (up to 33 months)]

    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.

20. Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for C-ITT Population [Baseline through study end (up to 33 months)]

    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.

21. TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for C-ITT Population [Baseline through study end (up to 33 months)]

    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.

22. TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for ITT Population [Baseline through study end (up to 33 months)]

    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.

23. Percentage of Participants With Adverse Events (AEs) [Baseline through study end (up to 33 months)]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive. ALK positivity must have been determined by a validated fluorescence in situ hybridization (FISH) test (recommended probe, Vysis ALK Break-Apart Probe) or a validated immunohistochemistry (IHC) test (recommended antibody, clone D5F3)

• Participant had received two prior systemic lines of therapy, which must have included one line of platinum-based chemotherapy and one line of crizotinib

• Prior CNS or leptomeningeal metastases allowed if asymptomatic

• Participants with symptomatic CNS metastases for whom radiotherapy is not an option will be allowed to participate in this study

• Measurable disease by RECIST Version 1.1 prior to the administration of study treatment

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• For all females of childbearing potential, a negative pregnancy test must be obtained within 3 days before starting study treatment

Exclusion Criteria:

• Participants with a previous malignancy within the past 3 years are excluded (other than curatively treated basal cell carcinoma of the skin, early gastrointestinal [GI] cancer by endoscopic resection or in situ carcinoma of the cervix)

• Participants who have received any previous ALK inhibitor other than crizotinib

• Any GI disorder that may affect absorption of oral medications

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GHdC Site Notre Dame	Charleroi		Belgium	6000
2	UZ Antwerpen	Edegem		Belgium	2650
3	UZ Gent	Gent		Belgium	9000
4	MBAL Serdika EOOD	Sofia		Bulgaria	1632
5	Centre Francois Baclesse	Caen		France	14076
6	Hopital Bichat Claude Bernard ; Service de Pneumologie	Paris		France	75877
7	Hopital Du Haut Leveque; Service Des Maladies Respiratoires	Pessac		France	33600
8	Hopital Foch; Pneumologie	Suresnes		France	92151
9	Hopital Sainte Musse; Pneumologie	Toulon		France	83056
10	Hopital Larrey; Pneumologie	Toulouse		France	31059
11	Hopital Robert Schuman; Pneumologie	Vantoux		France	57070
12	Zentralklinik Bad Berka GmbH; Abteilung Onkologie und Hämatologie	Bad Berka		Germany	99437
13	Evang. Lungenklinik Berlin Klinik für Pneumologie	Berlin		Germany	13125
14	Asklepios-Fachkliniken Muenchen-Gauting; Onkologie	Gauting		Germany	82131
15	Fachklinik für Lungenerkrankungen	Immenhausen		Germany	34376
16	Pius-Hospital; Klinik fuer Haematologie und Onkologie	Oldenburg		Germany	26121
17	Queen Elizabeth Hospital; Clinical Oncology	Hong Kong		Hong Kong
18	Queen Mary Hospital; Dept. of Clinical Oncology	Hong Kong		Hong Kong
19	Semmelweis Egyetem X; Pulmonologiai Klinika	Budapest		Hungary	1083
20	Azienda Ospedaliera di Rilievo Nazionale e di Alta Specialita San Giuseppe Moscati	Avellino	Campania	Italy	83100
21	AORN Ospedali dei Colli Ospedale Monaldi; UOC Pneumologia ad indirizzo Oncologico	Napoli	Campania	Italy	80131
22	Istituto Nazionale Tumori Fondazione G. Pascale; U.O.C. Oncologia Medica Toraco Polmonare	Napoli	Campania	Italy	80131
23	Ospedale Provinciale Santa Maria Delle Croci; Oncologia Medica	Ravenna	Emilia-Romagna	Italy	48100
24	Azienda Ospedaliera San Camillo Forlanini; U.O.C. Pneumologia Ad Indirizzo Oncologico 1	Roma	Lazio	Italy	00152
25	Irccs Ospedale San Raffaele;Oncologia Medica	Milano	Lombardia	Italy	20132
26	Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica	Milano	Lombardia	Italy	20141
27	POLICLINICO RODOLICO, U.O. di Oncologia Medica	Catania	Sicilia	Italy	95100
28	A.O. Universitaria Pisana-Ospedale Cisanello; Dipartimento Cardio Toracico-Pneumologia Ii	Pisa	Toscana	Italy	56124
29	Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica	Perugia	Umbria	Italy	06156
30	Chonnam National University Hwasun Hospital	Jeollanam-do		Korea, Republic of	58128
31	Korea University Guro Hospital; Oncology	Seoul		Korea, Republic of	152-703
32	Oslo Universitetssykehus HF; Radiumhospitalet	Oslo		Norway	0310
33	Medical University of Gdansk	Gdansk		Poland	80-952
34	Hospital Geral; Servico de Pneumologia	Coimbra		Portugal	3041-801
35	IPO do Porto; Servico de Oncologia Medica	Porto		Portugal	4200-072
36	CHVNG/E_Unidade 1; Servico de Pneumologia	Vila Nova De Gaia		Portugal	4434-502
37	FSBI"National Medical Research Center of Oncology named after N.N.Petrov" MHRF	St Petersburg	Leningrad	Russian Federation	197758
38	University сlinic of headaches	Moscow	Moskovskaja Oblast	Russian Federation	121467
39	Main Military Clinical Hospital named after N.N. Burdenko	Moscow		Russian Federation	105229
40	City Clinical Oncology Hospital	Moscow		Russian Federation	143423
41	City Clinical Oncology Dispensary	Saint-Petersburg		Russian Federation	197022
42	S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)	Saint-Petersburg		Russian Federation	197758
43	FNsP F. D. Roosevelta Banska Bystrica, II.Ocna klinika SZU	Banska Bystrica		Slovakia	975 17
44	Vychodoslovensky onkologicky ustav	Košice		Slovakia	040 01
45	Hospital Universitario de Torrejon	Torrejon de Ardoz	Madrid	Spain	28850
46	Hospital de Cruces; Servicio de Oncologia	Bilbao	Vizcaya	Spain	48903
47	Hospital Universitario La Paz; Servicio de Oncologia	Madrid		Spain	28046
48	Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia	Malaga		Spain	29010
49	Hospital Universitari i Politecnic La Fe de Valencia	Valencia		Spain	46026
50	Adana Acıbadem Hospital Oncology Department	Adana		Turkey	01130
51	Hacettepe Uni Medical Faculty Hospital; Oncology Dept	Ankara		Turkey	06100
52	Istanbul Uni Capa Medical Faculty; Inst. of Oncology	Istanbul		Turkey	34093
53	Ege University Medical Faculty; Chest Diseases	Izmir		Turkey	35040
54	Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department	Malatya		Turkey	44280

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol - Dec 1, 2017
• Statistical Analysis Plan - Aug 21, 2018

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02604342
• Other Study ID Numbers: MO29750; 2015-000634-29
• First Posted: Nov 13, 2015
• Last Update Posted: Oct 29, 2019
• Last Verified: Oct 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Docetaxel; Pemetrexed

Study Results

Participant Flow

Recruitment Details	The study recruited participants with Anaplastic Lymphoma Kinase (ALK)-positive advanced Non-Small Cell Lung Cancer (NSCLC) in 13 countries from November 2015 to March 2017.
Pre-assignment Detail	A total of 119 participants were enrolled and randomized into the study: 79 participants in the alectinib arm, and 40 participants in the chemotherapy arm.

Arm/Group Title	Experimental: Alectinib	Active Comparator: Premetrexed/Docetaxel
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Period Title: Overall Study
STARTED	79	40
COMPLETED	36	17
NOT COMPLETED	43	23

Baseline Characteristics

Arm/Group Title	Experimental: Alectinib	Active Comparator: Premetrexed/Docetaxel	Total
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.	Total of all reporting groups
Overall Participants	79	40	119
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.6 (13.0)	58.8 (10.5)	56.0 (12.4)
Sex: Female, Male (Count of Participants)
Female	33 41.8%	20 50%	53 44.5%
Male	46 58.2%	20 50%	66 55.5%
Race/Ethnicity, Customized (Number) [Number]
Hispanic or Latino	5 6.3%	4 10%	9 7.6%
Not Hispanic or Latino	68 86.1%	34 85%	102 85.7%
Not reported	4 5.1%	1 2.5%	5 4.2%
Unknown	0 0%	1 2.5%	1 0.8%
Missing	2 2.5%	0 0%	2 1.7%
Race/Ethnicity, Customized (Number) [Number]
White	67 84.8%	32 80%	99 83.2%
Asian	6 7.6%	8 20%	14 11.8%
Unknown	5 6.3%	0 0%	5 4.2%
Native Hawaiian or other Pacific Islander	1 1.3%	0 0%	1 0.8%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator
Description	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.
Time Frame	Randomization to first documented disease progression, death from any cause, or study end (up to 33 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Experimental: Alectinib	Active Comparator: Premetrexed/Docetaxel
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Measure Participants	79	40
Median (95% Confidence Interval) [months]	10.9	1.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Alectinib, Active Comparator: Premetrexed/Docetaxel
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Stratified log-rank test
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.20
	Confidence Interval	(2-Sided) 95%; 0.12 to 0.33
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated hazard ratio obtained from stratified Cox model with treatment group as covariate.

2. Secondary Outcome

Title	Percentage of Participants With CNS Objective Response Rate (ORR) With Measurable CNS Metastases at Baseline Using RECIST Version 1.1 as Assessed By IRC
Description	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.
Time Frame	Baseline through study end (up to 33 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Experimental: Alectinib	Active Comparator: Premetrexed/Docetaxel
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Measure Participants	24	17
Number [percentage of participants]	66.7 84.4%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Alectinib, Active Comparator: Premetrexed/Docetaxel
	Comments	95% confidence interval of the difference (alectinib - chemotherapy) computed using Hauck-Anderson approach.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in C-ORR
	Estimated Value	0.667
	Confidence Interval	(2-Sided) 95%; 0.39 to 0.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	PFS Using RECIST Version 1.1 as Assessed by IRC
Description	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.
Time Frame	Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Experimental: Alectinib	Active Comparator: Premetrexed/Docetaxel
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Measure Participants	72	35
Median (95% Confidence Interval) [months]	7.1	1.6

4. Secondary Outcome

Title	Percentage of Participants With Objective Response of CR or PR Using RECIST Version 1.1 as Assessed by Investigator and IRC
Description	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.
Time Frame	Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Experimental: Alectinib	Active Comparator: Premetrexed/Docetaxel
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Measure Participants	79	40
Assessed by Investigator	50.6 64.1%	2.5 6.3%
Assessed by IRC	36.1 45.7%	11.4 28.5%

5. Secondary Outcome

Title	Percentage of Participants With Disease Control Using RECIST Version 1.1 as Assessed by Investigator and IRC
Description	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.
Time Frame	Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Experimental: Alectinib	Active Comparator: Premetrexed/Docetaxel
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Measure Participants	79	40
Assessed by Investigator	86.1 109%	25.0 62.5%
Assessed by IRC	76.4 96.7%	48.6 121.5%

6. Secondary Outcome

Title	Duration of Response (DOR) Using RECIST Version 1.1 as Assessed by Investigator and IRC
Description	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.
Time Frame	From the first documented CR or PR to the first documented disease progression, death, or study end (up to 33 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Experimental: Alectinib	Active Comparator: Premetrexed/Docetaxel
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Measure Participants	79	40
Assessed by Investigator	12.0	2.7
Assessed by IRC	9.7	NA

7. Secondary Outcome

Title	PFS in C-ITT Population Using RECIST Version 1.1 as Assessed by Investigator and IRC
Description	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.
Time Frame	Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Experimental: Alectinib	Active Comparator: Premetrexed/Docetaxel
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Measure Participants	50	26
Assessed by Investigator	9.7	1.4
Assessed by IRC	8.1	1.5

8. Secondary Outcome

Title	Time to CNS Progression in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC
Description	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.
Time Frame	Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Experimental: Alectinib	Active Comparator: Premetrexed/Docetaxel
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Measure Participants	50	26
Median (95% Confidence Interval) [months]	NA	1.6

9. Secondary Outcome

Title	Percentage of Participants With Disease Control in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC
Description	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.
Time Frame	From first documented CR, PR, or SD lasting at least 5 weeks through study end (up to 33 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Experimental: Alectinib	Active Comparator: Premetrexed/Docetaxel
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Measure Participants	52	28
Number [percentage of participants]	82.7 104.7%	25.0 62.5%

10. Secondary Outcome

Title	Percentage of Participants With ORR in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC
Description	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.
Time Frame	Baseline through study end (up to 33 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Experimental: Alectinib	Active Comparator: Premetrexed/Docetaxel
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Measure Participants	52	28
Number [percentage of participants]	48.1 60.9%	0.0 0%

11. Secondary Outcome

Title	Duration of Response for Lesions in the CNS (C-DOR) Using RECIST Version 1.1 as Assessed by IRC
Description	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.
Time Frame	From the first documented CR or PR to the first documented disease progression, death, or study end (up to 33 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Experimental: Alectinib	Active Comparator: Premetrexed/Docetaxel
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Measure Participants	52	28
Median (95% Confidence Interval) [months]	13.9	NA

12. Secondary Outcome

Title	Overall Survival (OS)
Description	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.
Time Frame	Randomization to death from any cause, through study end (up to 33 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Experimental: Alectinib	Active Comparator: Premetrexed/Docetaxel
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Measure Participants	79	40
Median (95% Confidence Interval) [months]	27.8	NA

13. Secondary Outcome

Title	Plasma Concentration of Alectinib
Time Frame	Predose (2 hours) at Baseline, Week 3 and Week 6

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Experimental: Alectinib
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Measure Participants	56
Geometric Mean (Geometric Coefficient of Variation) [nanogram/milliliter (ng/mL)]	559 (48.0)

14. Secondary Outcome

Title	Plasma Concentration of Alectinib Metabolite
Time Frame	Predose (2 hours) at Baseline, Week 3 and Week 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Experimental: Alectinib
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.
Measure Participants	56
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	240 (44.8)

15. Secondary Outcome

Title	Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time
Description	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.
Time Frame	Baseline through Week 138

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Experimental: Alectinib	Active Comparator: Premetrexed/Docetaxel
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Measure Participants	79	40
Baseline	92.4 117%	85.0 212.5%
Treatment - Week 3	96.1 121.6%	83.3 208.3%
Treatment - Week 6	97.2 123%	60.0 150%
Treatment - Week 12	95.5 120.9%	80.0 200%
Treatment - Week 18	88.5 112%	50.0 125%
Treatment - Week 24	91.1 115.3%	100 250%
Treatment - Week 30	96.2 121.8%	66.7 166.8%
Treatment - Week 36	89.8 113.7%	66.7 166.8%
Treatment - Week 42	95.3 120.6%	66.7 166.8%
Treatment - Week 48	100 126.6%	100 250%
Treatment - Week 54	97.1 122.9%	100 250%
Treatment - Week 60	100 126.6%	100 250%
Treatment - Week 66	89.7 113.5%	100 250%
Treatment - Week 72	88.9 112.5%	100 250%
Treatment - Week 78	84.6 107.1%
Treatment - Week 84	78.3 99.1%
Treatment - Week 90	88.9 112.5%
Treatment - Week 96	93.8 118.7%
Treatment - Week 102	84.6 107.1%
Treatment - Week 108	100 126.6%
Treatment - Week 114	83.3 105.4%
Treatment - Week 120	100 126.6%
Treatment - Week 126	100 126.6%
Treatment - Week 132	100 126.6%
Treatment - Week 138	100 126.6%

16. Secondary Outcome

Title	Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time
Description	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.
Time Frame	Baseline through Week 138

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Experimental: Alectinib	Active Comparator: Premetrexed/Docetaxel
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Measure Participants	79	40
Baseline	92.4 117%	82.5 206.3%
Treatment - Week 3	96.1 121.6%	83.3 208.3%
Treatment - Week 6	97.2 123%	63.3 158.3%
Treatment - Week 12	95.5 120.9%	80.0 200%
Treatment - Week 18	88.5 112%	50.0 125%
Treatment - Week 24	91.1 115.3%	100 250%
Treatment - Week 30	96.2 121.8%	66.7 166.8%
Treatment - Week 36	87.8 111.1%	66.7 166.8%
Treatment - Week 42	95.3 120.6%	66.7 166.8%
Treatment - Week 48	100 126.6%	100 250%
Treatment - Week 54	97.1 122.9%	100 250%
Treatment - Week 60	100 126.6%	100 250%
Treatment - Week 66	89.7 113.5%	100 250%
Treatment - Week 72	88.9 112.5%	100 250%
Treatment - Week 78	84.6 107.1%
Treatment - Week 84	78.3 99.1%
Treatment - Week 90	88.9 112.5%
Treatment - Week 96	100 126.6%
Treatment - Week 102	84.6 107.1%
Treatment - Week 108	100 126.6%
Treatment - Week 114	83.3 105.4%
Treatment - Week 120	80.0 101.3%
Treatment - Week 126	100 126.6%
Treatment - Week 132	100 126.6%
Treatment - Week 138	100 126.6%

17. Secondary Outcome

Title	Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time
Description	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.
Time Frame	Baseline through Week 60

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Experimental: Alectinib	Active Comparator: Premetrexed/Docetaxel
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Measure Participants	72	35
Treatment - Week 0	88.9 112.5%	82.9 207.3%
Treatment - Week 3	86.6 109.6%	78.8 197%
Treatment - Week 6	91.9 116.3%	58.6 146.5%
Treatment - Week 12	86.8 109.9%	80 200%
Treatment - Week 18	72.1 91.3%	66.7 166.8%
Treatment - Week 24	82.4 104.3%	100 250%
Treatment - Week 30	80 101.3%	66.7 166.8%
Treatment - Week 36	80 101.3%	50 125%
Treatment - Week 42	91.7 116.1%	50 125%
Treatment - Week 48	62.5 79.1%	0 0%
Treatment - Week 54	100 126.6%
Treatment - Week 60	50 63.3%

18. Secondary Outcome

Title	Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for ITT Population
Description	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.
Time Frame	Baseline through study end (up to 33 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Experimental: Alectinib	Active Comparator: Premetrexed/Docetaxel
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Measure Participants	79	40
Coughing score	18.1	16.6
Dyspnoea score	4.1	3.3
Pain in chest score	NA	NA
Pain in arm or shoulder score	12.5	1.9

19. Secondary Outcome

Title	Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for C-ITT Population
Description	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.
Time Frame	Baseline through study end (up to 33 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Experimental: Alectinib	Active Comparator: Premetrexed/Docetaxel
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Measure Participants	52	28
Coughing score	NA	16.6
Dyspnoea score	9.7	1.4
Pain in chest score	NA	NA
Pain in arm or shoulder score	11.1	1.7

20. Secondary Outcome

Title	Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for ITT Population
Description	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.
Time Frame	Baseline through study end (up to 33 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Experimental: Alectinib	Active Comparator: Premetrexed/Docetaxel
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Measure Participants	79	40
Dyspnoea score	13.3	8.3
Fatigue score	5.6	1.2

21. Secondary Outcome

Title	Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for C-ITT Population
Description	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.
Time Frame	Baseline through study end (up to 33 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Experimental: Alectinib	Active Comparator: Premetrexed/Docetaxel
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Measure Participants	52	26
Dyspnoea score	16.6	8.3
Fatigue score	14.4	1.0

22. Secondary Outcome

Title	TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for C-ITT Population
Description	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.
Time Frame	Baseline through study end (up to 33 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Experimental: Alectinib	Active Comparator: Premetrexed/Docetaxel
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Measure Participants	52	28
Median (95% Confidence Interval) [months]	2.8	1.4

23. Secondary Outcome

Title	TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for ITT Population
Description	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.
Time Frame	Baseline through study end (up to 33 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Experimental: Alectinib	Active Comparator: Premetrexed/Docetaxel
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Measure Participants	79	40
Median (95% Confidence Interval) [months]	1.4	1.4

24. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs)
Description	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.
Time Frame	Baseline through study end (up to 33 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Experimental: Alectinib	Active Comparator: Premetrexed/Docetaxel
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
Measure Participants	77	37
Number [Percentage of Participants]	89.6 113.4%	89.2 223%

Adverse Events

Time Frame	Approximately 15 months
Adverse Event Reporting Description	SAF population included all participants who received at least one dose of any study drug.
Arm/Group Title	Experimental: Alectinib		Active Comparator: Premetrexed/Docetaxel
Arm/Group Description	Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.		Participants received chemotherapy with either pemetrexed (500 milligrams per square meter [mg/m^2] of body surface area) or docetaxel (75 mg/m^2) intravenously.
All Cause Mortality
	Experimental: Alectinib		Active Comparator: Premetrexed/Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/77 (33.8%)		4/37 (10.8%)
Serious Adverse Events
	Experimental: Alectinib		Active Comparator: Premetrexed/Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/77 (26%)		7/37 (18.9%)
Blood and lymphatic system disorders
Anaemia	0/77 (0%)		2/37 (5.4%)
Febrile neutropenia	0/77 (0%)		2/37 (5.4%)
Neutropenia	0/77 (0%)		1/37 (2.7%)
Cardiac disorders
Myocardial infarction	1/77 (1.3%)		0/37 (0%)
Gastrointestinal disorders
Abdominal pain	1/77 (1.3%)		1/37 (2.7%)
Diarrhoea	0/77 (0%)		1/37 (2.7%)
Nausea	0/77 (0%)		1/37 (2.7%)
Stomatitis	0/77 (0%)		1/37 (2.7%)
General disorders
Death	1/77 (1.3%)		0/37 (0%)
Hepatobiliary disorders
Cholelithiasis	1/77 (1.3%)		0/37 (0%)
Infections and infestations
Abscess jaw	1/77 (1.3%)		0/37 (0%)
Bronchitis	1/77 (1.3%)		0/37 (0%)
Lung infection	0/77 (0%)		1/37 (2.7%)
Pneumonia	4/77 (5.2%)		0/37 (0%)
Pneumonia bacterial	0/77 (0%)		1/37 (2.7%)
Diverticulitis	1/77 (1.3%)		0/37 (0%)
Erysipelas	1/77 (1.3%)		0/37 (0%)
H1N1 Influenza	1/77 (1.3%)		0/37 (0%)
Pharyngitis	1/77 (1.3%)		0/37 (0%)
Gastroenteritis	0/77 (0%)		1/37 (2.7%)
Injury, poisoning and procedural complications
Ankle fracture	1/77 (1.3%)		0/37 (0%)
Jaw fracture	1/77 (1.3%)		0/37 (0%)
Skull fractured base	1/77 (1.3%)		0/37 (0%)
Wound Complication	1/77 (1.3%)		0/37 (0%)
Investigations
Blood creatine phosphokinase increased	1/77 (1.3%)		0/37 (0%)
Blood Creatinine Increased	1/77 (1.3%)		0/37 (0%)
Musculoskeletal and connective tissue disorders
Osteoporotic fracture	1/77 (1.3%)		0/37 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Invasive ductal breast carcinoma	1/77 (1.3%)		0/37 (0%)
Nervous system disorders
Cerebellar ataxia	1/77 (1.3%)		0/37 (0%)
Epilepsy	1/77 (1.3%)		0/37 (0%)
Syncope	1/77 (1.3%)		0/37 (0%)
Psychiatric disorders
Depression	1/77 (1.3%)		0/37 (0%)
Renal and urinary disorders
Acute kidney injury	2/77 (2.6%)		0/37 (0%)
Respiratory, thoracic and mediastinal disorders
Haemoptysis	1/77 (1.3%)		0/37 (0%)
Vascular disorders
Deep vein thrombosis	1/77 (1.3%)		0/37 (0%)
Hypertension	1/77 (1.3%)		0/37 (0%)
Other (Not Including Serious) Adverse Events
	Experimental: Alectinib		Active Comparator: Premetrexed/Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	57/77 (74%)		31/37 (83.8%)
Blood and lymphatic system disorders
Anaemia	12/77 (15.6%)		4/37 (10.8%)
Neutropenia	0/77 (0%)		4/37 (10.8%)
Ear and labyrinth disorders
Tinnitus	2/77 (2.6%)		2/37 (5.4%)
Gastrointestinal disorders
Constipation	16/77 (20.8%)		4/37 (10.8%)
Diarrhoea	5/77 (6.5%)		2/37 (5.4%)
Nausea	3/77 (3.9%)		6/37 (16.2%)
Vomiting	3/77 (3.9%)		2/37 (5.4%)
Abdominal Pain	5/77 (6.5%)		0/37 (0%)
General disorders
Asthenia	9/77 (11.7%)		6/37 (16.2%)
Fatigue	5/77 (6.5%)		9/37 (24.3%)
Oedema peripheral	11/77 (14.3%)		2/37 (5.4%)
Pyrexia	3/77 (3.9%)		3/37 (8.1%)
Immune system disorders
Drug Hypersensitivity	0/77 (0%)		2/37 (5.4%)
Infections and infestations
Bronchitis	5/77 (6.5%)		1/37 (2.7%)
Nasopharyngitis	4/77 (5.2%)		1/37 (2.7%)
Pneumonia	6/77 (7.8%)		0/37 (0%)
Upper Respiratory Tract Infection	7/77 (9.1%)		1/37 (2.7%)
Investigations
Blood bilirubin increased	6/77 (7.8%)		0/37 (0%)
Blood Creatinine Increased	5/77 (6.5%)		0/37 (0%)
Electrocardiogram QT Prolonged	4/77 (5.2%)		0/37 (0%)
Metabolism and nutrition disorders
Decreased appetite	7/77 (9.1%)		4/37 (10.8%)
Musculoskeletal and connective tissue disorders
Back pain	10/77 (13%)		2/37 (5.4%)
Myalgia	11/77 (14.3%)		4/37 (10.8%)
Pain in extremity	2/77 (2.6%)		2/37 (5.4%)
Arthralgia	4/77 (5.2%)		3/37 (8.1%)
Musculoskeletal Chest Pain	2/77 (2.6%)		2/37 (5.4%)
Nervous system disorders
Dizziness	3/77 (3.9%)		2/37 (5.4%)
Headache	5/77 (6.5%)		3/37 (8.1%)
Neuropathy peripheral	1/77 (1.3%)		2/37 (5.4%)
Paraesthesia	1/77 (1.3%)		3/37 (8.1%)
Respiratory, thoracic and mediastinal disorders
Cough	8/77 (10.4%)		4/37 (10.8%)
Dyspnoea	9/77 (11.7%)		0/37 (0%)
Skin and subcutaneous tissue disorders
Alopecia	1/77 (1.3%)		8/37 (21.6%)
Pruritus Generalised	0/77 (0%)		3/37 (8.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.