Trial Outcomes & Findings for A Study of Alectinib (RO5424802) in Participants With Non-Small Cell Lung Cancer Who Have Anaplastic Lymphoma Kinase (ALK) Mutation and Failed Crizotinib Treatment (NCT NCT01801111)
NCT ID: NCT01801111
Last Updated: 2018-11-02
Results Overview
RP2D was to be determined based on the safety and tolerability profile of the study treatment.
COMPLETED
PHASE1/PHASE2
138 participants
Cycle 1 (up to 28 days)
2018-11-02
Participant Flow
Overall study status was confirmed as completed. Here, 'study terminated by sponsor' in reason for study not completed means participants were transitioned to commercial supply of alectinib (where it was available) or transitioned to a roll-over study BO39694 (NCT03194893) where they continued to receive alectinib treatment.
Part 1 of study was planned to determine recommended Phase 2 dose (RP2D) of alectinib to be used in Part 2. During the conduct of Part 1 for this study, RP2D was confirmed in Study NP28761 (NCT01871805). Hence Part 1 participants were merged into Part 2. Part 3 was post-progression treatment period.
Participant milestones
| Measure |
Alectinib
Participants received alectinib at a dose of 600 milligrams (mg) via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until disease progression (PD), death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
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|---|---|
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Overall Study
STARTED
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138
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Overall Study
COMPLETED
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0
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Overall Study
NOT COMPLETED
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138
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Reasons for withdrawal
| Measure |
Alectinib
Participants received alectinib at a dose of 600 milligrams (mg) via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until disease progression (PD), death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
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|---|---|
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Overall Study
Adverse Event
|
12
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Overall Study
Death
|
8
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Overall Study
Physician Decision
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5
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Overall Study
Other
|
1
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Overall Study
Withdrawal by Subject
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4
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Overall Study
Study Terminated by Sponsor
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27
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Overall Study
Progressive Disease
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81
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Baseline Characteristics
A Study of Alectinib (RO5424802) in Participants With Non-Small Cell Lung Cancer Who Have Anaplastic Lymphoma Kinase (ALK) Mutation and Failed Crizotinib Treatment
Baseline characteristics by cohort
| Measure |
Alectinib
n=138 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
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|---|---|
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Age, Continuous
|
51.5 years
STANDARD_DEVIATION 11.1 • n=5 Participants
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Sex: Female, Male
Female
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77 Participants
n=5 Participants
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Sex: Female, Male
Male
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61 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: Cycle 1 (up to 28 days)Population: The endpoint was not analyzed in this study as the RP2D was confirmed in study NP28761 (NCT01871805).
RP2D was to be determined based on the safety and tolerability profile of the study treatment.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Cycle 1 (up to 28 days)Population: The endpoint was not analyzed in this study as the RP2D was confirmed in study NP28761 (NCT01871805).
DLTs were to be assessed based on the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.3 (NCI-CTCAE v 4.3). DLTs: drug-related toxicities that meet any one of the following criteria: Grade 4 thrombocytopenia; Grade 3 thrombocytopenia with bleeding; Grade 4 neutropenia continuing for greater than or equal to (\>/=) 7 consecutive days or neutropenic fever; Non-hematological toxicity of Grade 3 or higher; Adverse events that require interruption of treatment for a total of \>/=7 days.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)Population: Analysis was performed on RE population (IRC) which included all participants with measurable disease at baseline according to the IRC, who had baseline tumor assessment and received at least one dose of alectinib.
Tumor response was assessed by IRC according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Objective response was defined as percentage of participants with a CR or PR that was confirmed by repeat assessments \>/=4 weeks after initial documentation. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level; and reduction in all lymph nodes size to less than (\<) 10 millimeters (mm). PR was defined as \>/=30 percent (%) decrease in the sum of diameters (SoD) of target lesions (taking as reference the baseline SoD). The 95% confidence interval (CI) was computed using Clopper-Pearson method.
Outcome measures
| Measure |
Alectinib
n=122 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
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|---|---|
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Percentage of Participants Achieving Objective Response (Complete Response [CR] or Partial Response [PR]) as Assessed by Independent Radiological Review Committee (IRC) in Response Evaluable (RE) Population
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50.8 percentage of participants
Interval 41.62 to 59.98
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PRIMARY outcome
Timeframe: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)Population: Analysis was performed on RE population (IRC) participants who received prior chemotherapy.
Tumor response was assessed by IRC according to RECIST v1.1. Objective response was defined as percentage of participants with a CR or PR that was confirmed by repeat assessments \>/=4 weeks after initial documentation. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level; and reduction in all lymph nodes size to \<10 mm. PR was defined as \>/=30% decrease in the SoD of target lesions (taking as reference the baseline SoD). The 95% CI was computed using Clopper-Pearson method.
Outcome measures
| Measure |
Alectinib
n=96 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
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|---|---|
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Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by IRC in Chemotherapy-Pretreated Participants
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44.8 percentage of participants
Interval 34.63 to 55.29
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SECONDARY outcome
Timeframe: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)Population: Analysis was performed on RE population (IRC) participants who did not receive prior chemotherapy.
Tumor response was assessed by IRC according to RECIST v1.1. Objective response was defined as percentage of participants with a CR or PR that was confirmed by repeat assessments \>/=4 weeks after initial documentation. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level; and reduction in all lymph nodes size to \<10 mm. PR was defined as \>/=30% decrease in the SoD of target lesions (taking as reference the baseline SoD).
Outcome measures
| Measure |
Alectinib
n=26 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
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|---|---|
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Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by IRC in Chemotherapy-Naive Participants
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73.1 percentage of participants
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SECONDARY outcome
Timeframe: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)Population: Analysis was performed on RE population (Investigator) which included all participants with measurable disease at baseline according to the investigator, who had baseline tumor assessment and received at least one dose of alectinib.
Tumor response was assessed by the investigator according to RECIST v1.1. Objective response was defined as percentage of participants with a CR or PR that was confirmed by repeat assessments \>/=4 weeks after initial documentation. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level; and reduction in all lymph nodes size to \<10 mm. PR was defined as \>/=30% decrease in the SoD of target lesions (taking as reference the baseline SoD). The 95% CI was computed using Clopper-Pearson method.
Outcome measures
| Measure |
Alectinib
n=138 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
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|---|---|
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Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in RE Population
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51.4 percentage of participants
Interval 42.8 to 60.04
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SECONDARY outcome
Timeframe: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)Population: Analysis was performed on RE population (investigator) participants who received prior chemotherapy.
Tumor response was assessed by the investigator according to RECIST v1.1. Objective response was defined as percentage of participants with a CR or PR that was confirmed by repeat assessments \>/=4 weeks after initial documentation. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level; and reduction in all lymph nodes size to \<10 mm. PR was defined as \>/=30% decrease in the SoD of target lesions (taking as reference the baseline SoD).
Outcome measures
| Measure |
Alectinib
n=110 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
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|---|---|
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Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in Chemotherapy-Pretreated Participants
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50.0 percentage of participants
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SECONDARY outcome
Timeframe: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)Population: Analysis was performed on RE population (investigator) participants who did not receive prior chemotherapy.
Tumor response was assessed by the investigator according to RECIST v1.1. Objective response was defined as percentage of participants with a CR or PR that was confirmed by repeat assessments \>/=4 weeks after initial documentation. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level; and reduction in all lymph nodes size to \<10 mm. PR was defined as \>/=30% decrease in the SoD of target lesions (taking as reference the baseline SoD).
Outcome measures
| Measure |
Alectinib
n=28 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
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|---|---|
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Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in Chemotherapy-Naive Participants
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57.1 percentage of participants
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SECONDARY outcome
Timeframe: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)Population: Analysis was performed on RE population (IRC) participants with documented objective response as assessed by IRC according to RECIST v1.1.
DoR was defined as the time from the first observation of an objective tumor response (CR or PR) until first observation of progressive disease (PD) according to RECIST v1.1 or death from any cause. CR: disappearance of all target, non-target lesions; normalization of tumor marker level; and reduction in all lymph nodes size to \<10 mm. PR: \>/=30% decrease in the SoD of target lesions (taking as reference the baseline SoD). PD: \>/=20% relative increase and \>/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-target lesions. Duration of response was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley. Participants who did not progress or die after a confirmed objective response were censored at the date of their last tumor assessment.
Outcome measures
| Measure |
Alectinib
n=62 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
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|---|---|
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Duration of Response (DoR) as Assessed by IRC in RE Population
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15.2 months
Interval 11.2 to 24.9
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SECONDARY outcome
Timeframe: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)Population: Analysis was performed on safety population.
According to RECIST v1.1, PD was defined as \>/=20% relative increase and \>/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-target lesions.
Outcome measures
| Measure |
Alectinib
n=138 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
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|---|---|
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Percentage of Participants With PD as Assessed by IRC According to RECIST v1.1 or Death From Any Cause in Safety Population
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71.0 percentage of participants
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SECONDARY outcome
Timeframe: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)Population: Analysis was performed on safety population.
PFS was defined as the time interval between the date of the first treatment and the date of PD or death from any cause, whichever occurred first. PD: \>/=20% relative increase and \>/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-target lesions. PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley. Participants who neither progressed nor died at the time of assessment or who were lost to follow-up were censored at the date of the last tumor assessment. Participants with no post-baseline assessments were censored at the date of first dose.
Outcome measures
| Measure |
Alectinib
n=138 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
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|---|---|
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Progression Free Survival (PFS) as Assessed by IRC in Safety Population
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8.9 months
Interval 5.6 to 12.8
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SECONDARY outcome
Timeframe: Baseline up to death from any cause (up to approximately 4 years)Population: Analysis was performed on safety population.
Percentage of participants who died of any cause was reported.
Outcome measures
| Measure |
Alectinib
n=138 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
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|---|---|
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Percentage of Participants Who Died of Any Cause
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54.3 percentage of participants
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SECONDARY outcome
Timeframe: Baseline up to death from any cause (up to approximately 4 years)Population: Analysis was performed on safety population.
OS was defined as the time from the date of first treatment to the date of death, regardless of the cause of death. OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley. Participants who did not die were censored at the date last known to be alive.
Outcome measures
| Measure |
Alectinib
n=138 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
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|---|---|
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Overall Survival (OS)
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29.2 months
Interval 21.5 to 44.4
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SECONDARY outcome
Timeframe: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)Population: Analysis was performed on RE population which included all participants with measurable disease at baseline, who had baseline tumor assessment, and who received at least one dose of alectinib. Here, 'Number Analyzed'=number of participant evaluable for specified category.
The disease control rate (DCR) was defined as the percentage of participants achieving CR, PR, or SD that lasted for at least 16 weeks. Tumor response was assessed by the investigator and IRC according to RECIST v1.1. CR: disappearance of all target, non-target lesions; normalization of tumor marker level; and reduction in all lymph nodes size to \<10 mm. PR: \>/=30% decrease in the SoD of target lesions (taking as reference the baseline SoD). PD: \>/=20% relative increase and \>/=5 mm of absolute increase in the SoD, taking as reference the smallest SoD recorded since treatment started; 1 or more new lesion(s); and/or unequivocal progression of non-target lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SoD while on study. The 95% CI was computed using Clopper-Pearson method.
Outcome measures
| Measure |
Alectinib
n=138 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
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|---|---|
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Percentage of Participants Achieving CR, PR or Stable Disease (SD) According to RECIST v1.1 in RE Population
IRC Assessment
|
63.9 percentage of participants
Interval 54.75 to 72.43
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Percentage of Participants Achieving CR, PR or Stable Disease (SD) According to RECIST v1.1 in RE Population
Investigator Assessment
|
69.6 percentage of participants
Interval 61.16 to 77.11
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SECONDARY outcome
Timeframe: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)Population: Analysis was performed on safety population participants with measurable CNS lesions at baseline.
CNS response was assessed by IRC according to RECIST v1.1. CNS Objective response was defined as percentage of participants with a CR or PR. CR was defined as disappearance of all CNS lesions. PR was defined as \>/=30% decrease in the SoD of measurable CNS lesions (taking as reference the baseline SoD). The 95% CI was computed using Clopper-Pearson method.
Outcome measures
| Measure |
Alectinib
n=34 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
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|---|---|
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Percentage of Participants Achieving Central Nervous System (CNS) Objective Response as Assessed by IRC According to RECIST v1.1
|
58.8 percentage of participants
Interval 40.7 to 75.35
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SECONDARY outcome
Timeframe: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up until cutoff 18 August 2014 (up to approximately 53 weeks)Population: Analysis was performed on safety population participants with measurable CNS lesions at baseline.
CNS response was assessed by IRC according to RANO criteria. CNS Objective response: percentage of participants with a CR or PR that was confirmed by repeat assessments \>/=4 weeks after initial documentation. CR was defined as complete disappearance of all enhancing measurable, non-measurable disease; stable or improved non-enhancing lesions; no new lesions; no corticosteroids (or only physiologic replacement dose), and clinically stable or improved. PR was defined as \>/=50% decrease compared to screening in the sum of the products of the diameters (SPD) of enhancing measurable lesions; no progression of non-measurable disease (enhancing and non-enhancing lesions); no new lesions; no corticosteroids (or only physiologic replacement dose), and clinically stable or improved. The 95% CI was computed using Clopper-Pearson method.
Outcome measures
| Measure |
Alectinib
n=34 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
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|---|---|
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Percentage of Participants Achieving CNS Objective Response as Assessed by IRC According to Radiology Assessment in Neuro-Oncology (RANO) Criteria
|
44.1 percentage of participants
Interval 27.19 to 62.11
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SECONDARY outcome
Timeframe: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)Population: Analysis was performed on safety population participants with measurable CNS lesions at baseline and who had CNS objective response as assessed by IRC according to RECIST v1.1.
CDoR was defined as the time from the first observation of a CNS objective response (CR or PR) until first observation of CNS progression as assessed by IRC according to RECIST v 1.1 or death from any cause. CR: disappearance of all CNS lesions. PR: \>/=30% decrease in the SoD of measurable CNS lesions (taking as reference the baseline SoD). CNS progression: \>/=20% increase in the SoD of measurable CNS lesions (with an absolute increase of at least 5 mm), taking as reference the baseline SoD; 1 or more new CNS lesion(s); and/or unequivocal progression of non-measurable CNS lesions. CDoR was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Outcome measures
| Measure |
Alectinib
n=20 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
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|---|---|
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CNS Duration of Response (CDoR) as Assessed by IRC According to RECIST v1.1
|
11.1 months
Interval 7.1 to
The upper limit of 95% CI could not be estimated due to high number of censored participants.
|
SECONDARY outcome
Timeframe: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up until cutoff 18 August 2014 (up to approximately 53 weeks)Population: Analysis was performed on safety population participants with measurable CNS lesions at baseline and who had CNS objective response as assessed by IRC according to RANO criteria.
CDoR: time from the CNS objective response until CNS progression as assessed by IRC according to RANO criteria or death from any cause. CR: complete disappearance of all enhancing measurable, non-measurable disease; stable/improved non-enhancing lesions; no new lesions; no corticosteroids, and clinically stable/improved. PR: \>/=50% decrease compared to screening in SPD of enhancing measurable lesions; no progression of non-measurable disease; no new lesions; no corticosteroids, and clinically stable/improved. Progression: \>/=25% increase in SPD of enhancing measurable lesions compared to best response on study; stable/increasing doses of corticosteroids; significant increase in non-enhancing lesions not caused by co-morbid events; any new lesions; progression of non-measurable disease; or clinical deterioration not attributable to other non-tumor causes. CDoR was estimated by Kaplan-Meier method and 95% CI was assessed using method of Brookmeyer and Crowley.
Outcome measures
| Measure |
Alectinib
n=15 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
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|---|---|
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CDoR as Assessed by IRC According to RANO Criteria
|
7.6 months
Interval 7.4 to 7.6
|
SECONDARY outcome
Timeframe: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up until cutoff 18 August 2014 (up to approximately 53 weeks)Population: Analysis was performed on safety population.
According to RECIST v 1.1, CNS progression was defined as \>/=20% increase in the SoD of measurable CNS lesions (with an absolute increase of at least 5 mm), taking as reference the baseline SoD; 1 or more new CNS lesion(s); and/or unequivocal progression of non-measurable CNS lesions.
Outcome measures
| Measure |
Alectinib
n=138 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
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|---|---|
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Percentage of Participants With CNS Progression as Assessed by IRC According to RECIST v 1.1
|
18.8 percentage of participants
|
SECONDARY outcome
Timeframe: Pre-dose (0 hours [hrs]), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1Population: Analysis was performed on Pharmacokinetic (PK) Evaluable Population, which included all participants who received any dose of alectinib and who had at least one post-baseline PK sample available. Here, 'Number Analyzed'=number of participant evaluable for specified category.
Cmax for alectinib was estimated from plasma concentration versus time data by non-compartmental methods of analysis using Phoenix WinNonlin v6.2 (Pharsight Corporation) software.
Outcome measures
| Measure |
Alectinib
n=28 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
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|---|---|
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Maximum Observed Plasma Concentration (Cmax) of Alectinib
Day 1
|
204 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 47.6
|
|
Maximum Observed Plasma Concentration (Cmax) of Alectinib
Day 21
|
933 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 34.8
|
SECONDARY outcome
Timeframe: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1Population: Analysis was performed on PK Evaluable Population. Here, 'Number Analyzed'=number of participant evaluable for specified category.
Tmax for alectinib was estimated from plasma concentration versus time data by non-compartmental methods of analysis using Phoenix WinNonlin v6.2 software.
Outcome measures
| Measure |
Alectinib
n=28 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
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|---|---|
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Time to Cmax (Tmax) of Alectinib
Day 1
|
5.89 hrs
Interval 2.0 to 10.0
|
|
Time to Cmax (Tmax) of Alectinib
Day 21
|
4.12 hrs
Interval 0.0 to 11.18
|
SECONDARY outcome
Timeframe: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1Population: Analysis was performed on PK Evaluable Population. Here, 'Number Analyzed'=number of participant evaluable for specified category.
Tlast for alectinib was estimated from plasma concentration versus time data by non-compartmental methods of analysis using Phoenix WinNonlin v6.2 software.
Outcome measures
| Measure |
Alectinib
n=28 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
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|---|---|
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Time to Last Measurable Plasma Concentration (Tlast) of Alectinib
Day 1
|
11.59 hrs
Geometric Coefficient of Variation 3.9
|
|
Time to Last Measurable Plasma Concentration (Tlast) of Alectinib
Day 21
|
11.65 hrs
Geometric Coefficient of Variation 3.8
|
SECONDARY outcome
Timeframe: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1Population: Analysis was performed on PK Evaluable Population. Here, 'Number Analyzed'=number of participant evaluable for specified category.
The AUC(0-10) of alectinib was calculated using the linear trapezoidal rule and actual sampling times (with the exception of pre-dose which was set to zero).
Outcome measures
| Measure |
Alectinib
n=28 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
|
|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time 0 to 10 Hours Post-dose (AUC[0-10]) of Alectinib
Day 1
|
1140 hrs*nanograms per milliliter (hrs*ng/mL)
Geometric Coefficient of Variation 44.5
|
|
Area Under the Plasma Concentration-Time Curve From Time 0 to 10 Hours Post-dose (AUC[0-10]) of Alectinib
Day 21
|
7860 hrs*nanograms per milliliter (hrs*ng/mL)
Geometric Coefficient of Variation 37.2
|
SECONDARY outcome
Timeframe: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1Population: Analysis was performed on PK Evaluable Population. Here, 'Number Analyzed'=number of participant evaluable for specified category.
The AUC(0-last) of alectinib was calculated using the linear trapezoidal rule and actual sampling times (with the exception of pre-dose which was set to zero).
Outcome measures
| Measure |
Alectinib
n=28 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
|
|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time 0 to Tlast (AUC[0-last]) of Alectinib
Day 1
|
1340 hrs*ng/mL
Geometric Coefficient of Variation 44.9
|
|
Area Under the Plasma Concentration-Time Curve From Time 0 to Tlast (AUC[0-last]) of Alectinib
Day 21
|
9090 hrs*ng/mL
Geometric Coefficient of Variation 36.9
|
SECONDARY outcome
Timeframe: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1Population: Analysis was performed on PK Evaluable Population. Here, 'Number Analyzed'=number of participant evaluable for specified category.
Cmax for alectinib metabolite was estimated from plasma concentration versus time data by non-compartmental methods of analysis using Phoenix WinNonlin v6.2 software.
Outcome measures
| Measure |
Alectinib
n=28 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
|
|---|---|
|
Cmax of Alectinib Metabolite
Day 1
|
57.2 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 68.6
|
|
Cmax of Alectinib Metabolite
Day 21
|
303 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 33.5
|
SECONDARY outcome
Timeframe: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1Population: Analysis was performed on PK Evaluable Population. Here, 'Number Analyzed'=number of participant evaluable for specified category.
Tmax for alectinib metabolite was estimated from plasma concentration versus time data by non-compartmental methods of analysis using Phoenix WinNonlin v6.2 software.
Outcome measures
| Measure |
Alectinib
n=28 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
|
|---|---|
|
Tmax of Alectinib Metabolite
Day 1
|
8.03 hrs
Interval 5.97 to 11.18
|
|
Tmax of Alectinib Metabolite
Day 21
|
7.00 hrs
Interval 0.0 to 12.0
|
SECONDARY outcome
Timeframe: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1Population: Analysis was performed on PK Evaluable Population. Here, 'Number Analyzed'=number of participant evaluable for specified category.
Tlast for alectinib metabolite was estimated from plasma concentration versus time data by non-compartmental methods of analysis using Phoenix WinNonlin v6.2 software.
Outcome measures
| Measure |
Alectinib
n=28 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
|
|---|---|
|
Tlast of Alectinib Metabolite
Day 1
|
11.59 hrs
Geometric Coefficient of Variation 3.9
|
|
Tlast of Alectinib Metabolite
Day 21
|
11.65 hrs
Geometric Coefficient of Variation 3.8
|
SECONDARY outcome
Timeframe: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1Population: Analysis was performed on PK Evaluable Population. Here, 'Number Analyzed'=number of participant evaluable for specified category.
The AUC(0-10) of alectinib metabolite was calculated using the linear trapezoidal rule and actual sampling times (with the exception of pre-dose which was set to zero).
Outcome measures
| Measure |
Alectinib
n=28 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
|
|---|---|
|
AUC(0-10) of Alectinib Metabolite
Day 1
|
300 hrs*ng/mL
Geometric Coefficient of Variation 68.4
|
|
AUC(0-10) of Alectinib Metabolite
Day 21
|
2590 hrs*ng/mL
Geometric Coefficient of Variation 35.0
|
SECONDARY outcome
Timeframe: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1Population: Analysis was performed on PK Evaluable Population. Here, 'Number Analyzed'=number of participant evaluable for specified category.
The AUC(0-last) of alectinib metabolite was calculated using the linear trapezoidal rule and actual sampling times (with the exception of pre-dose which was set to zero).
Outcome measures
| Measure |
Alectinib
n=28 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
|
|---|---|
|
AUC(0-last) of Alectinib Metabolite
Day 1
|
378 hrs*ng/mL
Geometric Coefficient of Variation 67.5
|
|
AUC(0-last) of Alectinib Metabolite
Day 21
|
3040 hrs*ng/mL
Geometric Coefficient of Variation 34.9
|
SECONDARY outcome
Timeframe: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1Population: Analysis was performed on PK Evaluable Population. Here, 'Number Analyzed'=number of participant evaluable for specified category.
Metabolite to parent ratio based on AUC(0-10) was computed as AUC(0-10) of metabolite divided by AUC(0-10) of parent drug (alectinib) corrected for the molecular weight of parent divided by the molecular weight of the metabolite.
Outcome measures
| Measure |
Alectinib
n=28 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
|
|---|---|
|
Metabolite to Parent Ratio Based on AUC(0-10)
Day 1
|
0.278 Ratio
Geometric Coefficient of Variation 41.0
|
|
Metabolite to Parent Ratio Based on AUC(0-10)
Day 21
|
0.349 Ratio
Geometric Coefficient of Variation 28.7
|
SECONDARY outcome
Timeframe: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1Population: Analysis was performed on PK Evaluable Population. Here, 'Number Analyzed'=number of participant evaluable for specified category.
Metabolite to parent ratio based on AUC(0-last) was computed as AUC(0-last) of metabolite divided by AUC(0-last) of parent drug (alectinib) corrected for the molecular weight of parent divided by the molecular weight of the metabolite.
Outcome measures
| Measure |
Alectinib
n=28 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
|
|---|---|
|
Metabolite to Parent Ratio Based on AUC(0-last)
Day 1
|
0.298 Ratio
Geometric Coefficient of Variation 41.2
|
|
Metabolite to Parent Ratio Based on AUC(0-last)
Day 21
|
0.354 Ratio
Geometric Coefficient of Variation 28.7
|
SECONDARY outcome
Timeframe: Pre-dose (0 hrs) on Day 21 of Cycle 1Population: Analysis was performed on PK Evaluable Population. Here, 'Overall Number of Participants Analyzed'=number of participant evaluable for this outcome measure.
Outcome measures
| Measure |
Alectinib
n=26 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
|
|---|---|
|
Trough Plasma Concentration (Ctrough) of Alectinib
|
761 ng/mL
Geometric Coefficient of Variation 42.9
|
SECONDARY outcome
Timeframe: Pre-dose (0 hrs) on Day 21 of Cycle 1Population: Analysis was performed on PK Evaluable Population. Here, 'Overall Number of Participants Analyzed'=number of participant evaluable for this outcome measure.
Outcome measures
| Measure |
Alectinib
n=26 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
|
|---|---|
|
Ctrough of Alectinib Metabolite
|
244 ng/mL
Geometric Coefficient of Variation 37.8
|
SECONDARY outcome
Timeframe: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hours post-dose on Day 21 of Cycle 1Population: Analysis was performed on PK Evaluable Population. Here, 'Overall Number of Participants Analyzed'=number of participant evaluable for this outcome measure.
Outcome measures
| Measure |
Alectinib
n=26 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
|
|---|---|
|
Peak to Trough Ratio of Alectinib
|
1.23 Ratio
Geometric Coefficient of Variation 14.4
|
SECONDARY outcome
Timeframe: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hours post-dose on Day 1 and Day 21 of Cycle 1Population: Analysis was performed on PK Evaluable Population. Here, 'Overall Number of Participants Analyzed'=number of participant evaluable for this outcome measure.
Accumulation ratio after repeat dosing was computed as AUC(0-10) on Day 21 divided by AUC(0-10) on Day 1.
Outcome measures
| Measure |
Alectinib
n=26 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
|
|---|---|
|
Accumulation Ratio of Alectinib
|
6.95 Ratio
Geometric Coefficient of Variation 42.1
|
SECONDARY outcome
Timeframe: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hours post-dose on Day 1 and Day 21 of Cycle 1Population: Analysis was performed on PK Evaluable Population. Here, 'Overall Number of Participants Analyzed'=number of participant evaluable for this outcome measure.
Accumulation ratio after repeat dosing was computed as AUC(0-10) on Day 21 divided by AUC(0-10) on Day 1.
Outcome measures
| Measure |
Alectinib
n=26 Participants
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
|
|---|---|
|
Accumulation Ratio of Alectinib Metabolite
|
8.68 Ratio
Geometric Coefficient of Variation 64.2
|
Adverse Events
Alectinib
Serious adverse events
| Measure |
Alectinib
n=138 participants at risk
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
|
|---|---|
|
Cardiac disorders
Myocardial infarction
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Eye disorders
Retinal detachment
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Constipation
|
1.4%
2/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Intestinal perforation
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Oesophagitis
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Vomiting
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
General disorders
Malaise
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
2.2%
3/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Infections and infestations
Appendicitis perforated
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Infections and infestations
Intervertebral discitis
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Infections and infestations
Pleural infection
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Infections and infestations
Pneumonia
|
1.4%
2/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Infections and infestations
Sepsis
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Injury, poisoning and procedural complications
Head injury
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Injury, poisoning and procedural complications
Ligament rupture
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Investigations
Alanine aminotransferase increased
|
1.4%
2/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Investigations
Aspartate aminotransferase increased
|
1.4%
2/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Psychiatric disorders
Depression
|
1.4%
2/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.2%
3/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
2.2%
3/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Vascular disorders
Haemorrhage
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Cardiac disorders
Cardiac arrest
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Enterovesical fistula
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Hepatobiliary disorders
Cholecystitis
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Infections and infestations
Appendicitis
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Infections and infestations
Bronchitis
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Infections and infestations
Endocarditis
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Infections and infestations
Enterocolitis infectious
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Infections and infestations
Infection
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Infections and infestations
Influenza
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Infections and infestations
Lower respiratory tract infection
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Infections and infestations
Lung infection
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Infections and infestations
Urosepsis
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Investigations
International normalised ratio increased
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Musculoskeletal and connective tissue disorders
Muscle haemorrhage
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Nervous system disorders
Seizure
|
1.4%
2/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Renal and urinary disorders
Ureterolithiasis
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Reproductive system and breast disorders
Menorrhagia
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Reproductive system and breast disorders
Pelvic floor muscle weakness
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Blood and lymphatic system disorders
Anaemia
|
0.72%
1/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
Other adverse events
| Measure |
Alectinib
n=138 participants at risk
Participants received alectinib at a dose of 600 mg via capsule, orally, twice daily, continuously starting on Day 1 Cycle 1 (in 28-day cycles) until PD, death, or withdrawal for any other reasons, whichever occurred first. After PD, participants were allowed to continue treatment with alectinib as per the discretion of the treating physician.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
13.8%
19/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Abdominal pain
|
8.0%
11/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
12.3%
17/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Constipation
|
38.4%
53/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Diarrhoea
|
19.6%
27/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Nausea
|
23.2%
32/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Vomiting
|
15.9%
22/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
General disorders
Asthenia
|
22.5%
31/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
General disorders
Fatigue
|
31.2%
43/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
General disorders
Oedema
|
6.5%
9/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
General disorders
Oedema peripheral
|
30.4%
42/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
General disorders
Pyrexia
|
12.3%
17/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Infections and infestations
Upper respiratory tract infection
|
15.2%
21/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Investigations
Alanine aminotransferase increased
|
10.9%
15/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Investigations
Asparatate aminotransferase increased
|
13.0%
18/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Investigations
Blood bilirubin increased
|
13.0%
18/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
12.3%
17/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
11.6%
16/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
15.2%
21/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
5.8%
8/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
8.0%
11/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
10.1%
14/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
26.1%
36/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
10.9%
15/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Nervous system disorders
Dizziness
|
11.6%
16/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Nervous system disorders
Headache
|
19.6%
27/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
23.2%
32/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
15.9%
22/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
11.6%
16/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
8.0%
11/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
7.2%
10/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
9.4%
13/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Skin and subcutaneous tissue disorders
Photosensitivity reaction
|
11.6%
16/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Skin and subcutaneous tissue disorders
Rash
|
17.4%
24/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Ear and labyrinth disorders
Vertigo
|
5.8%
8/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Dyspepsia
|
7.2%
10/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
General disorders
Chest pain
|
7.2%
10/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
General disorders
Influenza like illness
|
5.8%
8/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Infections and infestations
Bronchitis
|
5.8%
8/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Infections and infestations
Influenza
|
5.1%
7/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Infections and infestations
Sinusitis
|
5.1%
7/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Infections and infestations
Urinary tract infection
|
5.1%
7/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Infections and infestations
Viral upper respiratory tract infection
|
10.9%
15/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Investigations
Blood creatinine increased
|
5.1%
7/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Investigations
Weight increased
|
13.0%
18/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
5.1%
7/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
7.2%
10/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
5.8%
8/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Nervous system disorders
Dysgeusia
|
5.1%
7/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Nervous system disorders
Paraesthesia
|
5.1%
7/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Psychiatric disorders
Insomnia
|
10.1%
14/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
5.1%
7/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
5.1%
7/138 • From Baseline until 28 days after the last dose of study drug (overall up to approximately 4 years)
Analysis was performed on safety population.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER