A Phase II Study to Evaluate the Efficacy and Safety of O... | NCT02336451 | Trialant
NCT02336451
Sponsor
Novartis Pharmaceuticals
Status
Completed
Last Update Posted
Apr 21, 2020Actual
Enrollment
156Actual
Phase
Phase 2
Conditions
ALK-positive Non-small Cell Lung Cancer
Interventions
Ceritinib
Countries
United States
Australia
Belgium
Brazil
Canada
France
Germany
Hong Kong
Italy
Netherlands
Russia
Singapore
South Korea
Spain
Taiwan
Turkey (Türkiye)
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT02336451
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CLDK378A2205
Secondary IDs
ID
Type
Description
Link
2014-000578-20
EudraCT Number
Brief Title
A Phase II Study to Evaluate the Efficacy and Safety of Oral Ceritinib in Patients With ALK-positive NSCLC Metastatic to the Brain and/or to Leptomeninges
Official Title
A Phase II, Multi-center, Open-label, Five-arm Study to Evaluate the Efficacy and Safety of Oral Ceritinib Treatment for Patients With ALK-positive Non-small Cell Lung Cancer (NSCLC) Metastatic to the Brain and/or to Leptomeninges
Acronym
Ascend-7
Organization
NovartisINDUSTRY
Status Module
Record Verification Date
Apr 2020
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Apr 1, 2015Actual
Primary Completion Date
Feb 6, 2019Actual
Completion Date
Feb 6, 2019Actual
First Submitted Date
Jan 8, 2015
First Submission Date that Met QC Criteria
Jan 12, 2015
First Posted Date
Jan 13, 2015Estimated
Results Waived
Not provided
Results First Submitted Date
Feb 6, 2020
Results First Submitted that Met QC Criteria
Feb 6, 2020
Results First Posted Date
Feb 21, 2020Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Apr 8, 2020
Last Update Posted Date
Apr 21, 2020Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Novartis PharmaceuticalsINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This was a phase II, multi-center, open-label, five-arm study in which the efficacy and safety of oral ceritinib treatment was assessed in patients with NSCLC metastatic to the brain and/or to leptomeninges harboring a confirmed ALK rearrangement, using the FDA approved Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular Inc.) test and scoring algorithm (including positivity criteria). If documentation of ALK rearrangement as described above was not locally available, a test to confirm ALK rearrangement was performed by a Novartis designated central laboratory. Patients waited for the central laboratory result of the ALK rearrangement status before initiating treatment with ceritinib.
Detailed Description
Approximately 160 patients diagnosed with ALK-positive metastatic NSCLC (according to the 7th edition of the AJCC [American Joint Committee on Cancer] Cancer Staging Manual) and active lesions in the brain and/or diagnosed with leptomeningeal carcinomatosis were included in the study, approximately 40 patients in Arm 1 and Arm 2, approximately 30 patients in Arms 3 and Arm 4, and approximately 20 patients in Arm 5. Additional patients were enrolled in Arm 4 to achieve approximately 60 patients in Arms 3 and 4 together (i.e. ALKi naïve patients), if enrollment rate in Arm 3 was slow.
Arm 1 included patients with metastases in the brain without evidence of leptomeningeal carcinomatosis, previously treated with radiation to the brain and with prior exposure to an ALKi.
Arm 2 included patients with metastases in the brain without evidence of leptomeningeal carcinomatosis, previously untreated with radiation to the brain but with prior exposure to an ALKi.
Arm 3 included patients with metastases in the brain without evidence of leptomeningeal carcinomatosis, previously treated with radiation to the brain but with no prior exposure to an ALKi.
Arm 4 included patients with metastases in the brain without evidence of leptomeningeal carcinomatosis, previously untreated with radiation to the brain and with no prior exposure to an ALKi
Arm 5 included any patients with leptomeningeal carcinomatosis with or without evidence of active lesion at the baseline Gadolinium-enhanced brain MRI.
Note: Previous treatment with ALK inhibitors other than crizotinib was not allowed in Arms 1, 2, and 5.
Ceritinib was administered orally once daily at a dose of 750 mg (five 150 mg capsules) on a continuous dosing schedule. The treatment period started on Cycle 1 Day 1.
Complete tumor assessments including gadolinium enhanced brain MRI was repeated at Week 8 (on Cycle 3 Day 1) and every 8 weeks (i.e. every 2 cycles) thereafter or earlier if clinically indicated. Safety evaluations included (S)AEs, physical examination, vital signs, ECGs, laboratory parameters and WHO performance status. Blood and CSF samples for PK were also collected.
Conditions Module
Conditions
ALK-positive Non-small Cell Lung Cancer
Keywords
ALK-positive
NSCLC
non-small cell lung cancer
brain metastasis
metastatic to the brain and/or to leptomeninges
ceritinib
LDK378
NSCLC metastatic to the brain
leptomeninges harboring a confirmed ALK rearrangement
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
156Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Arm 1 (PrALKi=Y, PrBRad=Y)
Experimental
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
Drug: Ceritinib
Arm 2 (PrALKi=Y, PrBRad=N)
Experimental
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
Drug: Ceritinib
Arm 3 (PrALKi=N, PrBRad=Y)
Experimental
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
Drug: Ceritinib
Arm 4 (PrALKi=N, PrBRad=N)
Experimental
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Ceritinib
Drug
LDK378 is a gelatin capsule, administered orally once daily at a dose of 750 mg (five 150 mg capsules) on a continuous dosing schedule on an empty stomach.
Arm 1 (PrALKi=Y, PrBRad=Y)
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Overall Response Rate (ORR) Per Investigator Assessment
Overall response rate (ORR) is defined as the percentage of participants with a best overall confirmed response of complete response (CR) or partial response (PR) in the whole body as assessed per RECIST 1.1 by the investigator. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
43 months
Secondary Outcomes
Measure
Description
Time Frame
Disease Control Rate (DCR) Per Investigator Assessment
DCR: percentage of parts. with best overall response of CR, PR or stable disease (SD) in the whole body, as assessed per RECIST 1.1 by investigator. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), & no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed and non-target lesions are not in progression or in complete response. SD: Neither sufficient shrinkage in the target lesion to qualify for PR or CR nor an increase in lesions which would qualify for PD & non-target lesions are not in unequivocal progression.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically confirmed diagnosis of metastatic NSCLC according to the 7th edition of the AJCC Cancer Staging Manual. In addition, the NSCLC must harbor an ALK rearrangement, as assessed using the FDA approved Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular Inc.) test and scoring algorithm (including positivity criteria). If documentation of ALK rearrangement as described above was not locally available, a test to confirm ALK rearrangement was to be performed by a Novartis designated central laboratory. Patients had to wait for the central laboratory result of the ALK rearrangement status before initiating treatment with ceritinib
At least one extracranial measurable lesion as defined by RECIST 1.1. A previously irradiated site lesion could only be counted as a target lesion if there was clear sign of progression since the irradiation.
Patients could or could not have neurological symptoms but must have been able to swallow and retain oral medication.
Patients had to be neurologically stable within at least 1 week prior to the first dose of study drug.
Patients could have received prior chemotherapy, crizotinib (other ALK inhibitors were not allowed), biologic therapy or other investigational agents.
Patients must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 1 (CTCAE v 4.03). Patients with any grade of alopecia were allowed to enter the study.
Patient had life expectancy ≥ 6 weeks.
Patient had a WHO performance status 0-2.
Patients in Arm 1 to 4 had to also meet the following inclusion criteria:
- Patients had to have active brain metastases from NSCLC, confirmed by Gadolinium-enhanced MRI without concomitant leptomeningeal carcinomatosis. Dose of steroids had to be stable for 5 days before the baseline brain MRI.
Patients in Arm 5 had to also meet the following inclusion criteria:
- Patients must have been diagnosed with leptomeningeal carcinomatosis.
Exclusion Criteria:
Patients who needed whole brain radiation to control the brain metastases. Patients were not eligible unless treated brain lesions were progressive or new brain lesions were observed since the post whole brain radiation therapy MRI.
Planning of any brain local treatment (including but not limited to surgery, stereotactic radiosurgery, whole brain radiation, intrathecal chemotherapy) following the administration of the first dose of study drug.
Patient with a concurrent malignancy or history of a malignant disease other than NSCLC that had been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion included the following: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.
Patient had impairment of GI function or GI disease that could significantly alter the absorption of ceritinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome).
Patient was receiving unstable or increasing doses of corticosteroids.
Patient had other severe, acute, or chronic medical conditions including uncontrolled diabetes mellitus or psychiatric conditions or laboratory abnormalities that in the opinion of the investigator could increase the risk associated with study participation, or that could interfere with the interpretation of study results.
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
Not provided
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
USC Kenneth Norris Comprehensive Cancer Center SC-3
Chow LQM, Barlesi F, Bertino EM, van den Bent MJ, Wakelee HA, Wen PY, Chiu CH, Orlov S, Chiari R, Majem M, McKeage M, Yu CJ, Garrido P, Hurtado FK, Arratia PC, Song Y, Branle F, Shi M, Kim DW. ASCEND-7: Efficacy and Safety of Ceritinib Treatment in Patients with ALK-Positive Non-Small Cell Lung Cancer Metastatic to the Brain and/or Leptomeninges. Clin Cancer Res. 2022 Jun 13;28(12):2506-2516. doi: 10.1158/1078-0432.CCR-21-1838.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
Plan to Share IPD
Yes
Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
Approximately 160 patients were planned to be enrolled.
Recruitment Details
A total of 156 patients were enrolled and treated with ceritinib. The FAS (N=156) included all patients who received at least one dose of ceritinib with 42, 40, 12, 44 and 18 patients in arms 1 to 5 respectively. The Safety set was identical to full analysis set in this study.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
SAP
No
Yes
No
Statistical Analysis Plan
Mar 11, 2019
Feb 6, 2020
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
New Zealand
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Non-Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Drug: Ceritinib
Arm 5 (LepDis)
Experimental
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Drug: Ceritinib
Arm 2 (PrALKi=Y, PrBRad=N)
Arm 3 (PrALKi=N, PrBRad=Y)
Arm 4 (PrALKi=N, PrBRad=N)
Arm 5 (LepDis)
LDK378
43 months
Overall Intracranial Response Rate (OIRR) Per Modified RECIST 1.1 Per Investigator Assessment
OIRR was calculated based on response assessments in the brain for patients having measurable brain metastases at baseline. OIRR was defined as the percentage of participants with a best overall confirmed response of CR or PR in the brain as assessed per modified RECIST 1.1. This was applied to the brain only. CR: Disappearance of all non-nodal target & non-target lesions. All lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), & no new lesion is identified. PR: When all target lesions have disappeared or decreased by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) & non-target lesions are not in progression or in complete response.
43 months
Overall Intracranial Response Rate (OIRR) Per Modified RECIST 1.1 Per Blinded Independent Review Committee (BIRC) Assessment
OIRR was calculated based on response assessments in the brain for patients having measurable brain metastases at baseline. OIRR was defined as the percentage of participants with a best overall confirmed response of CR or PR in the brain as assessed per modified RECIST 1.1. This was applied to the brain only. CR: Disappearance of all non-nodal target & non-target lesions. All lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), & no new lesion is identified. PR: When all target lesions have disappeared or decreased by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) & non-target lesions are not in progression or in complete response.
43 months
Intracranial Disease Control Rate (IDCR) Per Modified RECIST 1.1 Per Investigator Assessment at Weeks 8 & 16
IDCR overall: percentage of participants with a best overall response of CR, PR, SD or non-CR/non-PD in the brain, as assessed per modified RECIST 1.1 by the Investigator. This was applied to the brain only. CR: Disappearance of all non-nodal target & non-target lesions. All lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), & no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response. SD: Neither sufficient shrinkage in the target lesion to qualify for PR or CR nor an increase in lesions which would qualify for PD & non-target lesions are not in unequivocal progression.
Week 8 and Week 16
Intracranial Disease Control Rate (IDCR) Per Modified RECIST 1.1 Per Investigator Assessment - Overall
IDCR overall: percentage of participants with a best overall response of CR, PR, SD or non-CR/non-PD in the brain, as assessed per modified RECIST 1.1 by the Investigator. This was applied to the brain only. CR: Disappearance of all non-nodal target & non-target lesions. All lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), & no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response. SD: Neither sufficient shrinkage in the target lesion to qualify for PR or CR nor an increase in lesions which would qualify for PD & non-target lesions are not in unequivocal progression.
43 months
Intracranial Disease Control Rate (IDCR) Per Modified RECIST 1.1 Per BIRC Assessment at Weeks 8 & 16
IDCR overall: percentage of participants with a best overall response of CR, PR, SD or non-CR/non-PD in the brain, as assessed per modified RECIST 1.1 by Investigator. This was applied to the brain only. CR: Disappearance of all non-nodal target & non-target lesions. All lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), & no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response. SD: Neither sufficient shrinkage in the target lesion to qualify for PR or CR nor an increase in lesions which would qualify for PD & non-target lesions are not in unequivocal progression.
Week 8 and Week 16
Intracranial Disease Control Rate (IDCR) Per Modified RECIST 1.1 Per BIRC Assessment - Overall
IDCR overall: percentage of participants with a best overall response of CR, PR, SD or non-CR/non-PD in the brain, as assessed per modified RECIST 1.1 by Investigator. This was applied to the brain only. CR: Disappearance of all non-nodal target & non-target lesions. All lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), & no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response. SD: Neither sufficient shrinkage in the target lesion to qualify for PR or CR nor an increase in lesions which would qualify for PD & non-target lesions are not in unequivocal progression.
43 months
Time to Intracranial Tumor Response (TTIR) Per Modified RECIST 1.1 Per Investigator Assessment
TTIR was defined as the time from the date of the first dose of ceritinib to the date of the first documented response (CR or PR) in the brain as assessed per modified RECIST 1.1 criteria for patients with measurable brain metastases at baseline. This was applied to the brain only. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
43 months
Time to Intracranial Tumor Response (TTIR) Per Modified RECIST 1.1 Per BIRC Assessment
TTIR was defined as the time from the date of the first dose of ceritinib to the date of the first documented response (CR or PR) in the brain as assessed per modified RECIST 1.1 criteria for patients with measurable brain metastases at baseline. This was applied to the brain only. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
43 months
Duration of Intracranial Response (DOIR) by Modified RECIST 1.1 Per Investigator Assessment
Defined as the time from the first documented response (PR or CR) in the brain to the date of the first documented disease progression in the brain or death due to any cause, amongst participants with measurable brain metastases at baseline and a confirmed response (PR or CR) in the brain as per modified RECIST 1.1. This was applied to the brain only. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
43 months
Duration of Intracranial Response (DOIR) by Modified RECIST 1.1 Per BIRC Assessment
Defined as the time from the first documented response (PR or CR) in the brain to the date of the first documented disease progression in the brain or death due to any cause, amongst participants with measurable brain metastases at baseline and a confirmed response (PR or CR) in the brain as per modified RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
43 months
Overall Extracranial Response Rate (OERR) Per RECIST 1.1 Per Investigator & BIRC Assessment
OERR was defined as the percentage of participants with a best overall confirmed response of CR or PR outside of the brain, as assessed per RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
43 months
Extracranial Disease Control Rate (EDCR) Per RECIST 1.1 Per Investigator & BIRC Assessment - Overall
EDCR overall was defined as the percentage of participants with a best overall response of CR, PR or SD outside of the brain as assessed per RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), & no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed and non-target lesions are not in progression or in complete response. SD: Neither sufficient shrinkage in the target lesion to qualify for PR or CR nor an increase in lesions which would qualify for PD & non-target lesions are not in unequivocal progression.
43 months
Extracranial Disease Control Rate (EDCR) Per RECIST 1.1 Per Investigator & BIRC Assessment at Weeks 8 & 16
EDCR at weeks 8 & 16: defined as percentage of parts. with CR, PR or SD outside of the brain at Wk 8 & 16 extracranial tumor evaluations respectively, per RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), & no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed and non-target lesions are not in progression or in complete response. SD: Neither sufficient shrinkage in the target lesion to qualify for PR or CR nor an increase in lesions which would qualify for PD & non-target lesions are not in unequivocal progression.
Week 8 and Week 16
Time to Extracranial Tumor Response (TTER) Per RECIST 1.1 Per Investigator Assessment
TTER was defined as the time from the date of the first dose of ceritinib to the date of the first documented response (CR or PR) outside of the brain as assessed per RECIST 1.1 criteria. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
43 months
Time to Extracranial Tumor Response (TTER) Per RECIST 1.1 Per BIRC Assessment
TTER was defined as the time from the date of the first dose of ceritinib to the date of the first documented response (CR or PR) outside of the brain as assessed per RECIST 1.1 criteria. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
43 months
Duration of Extracranial Response (DOER) Per RECIST 1.1 Per Investigator Assessment
DOER was defined as the time from the first documented response (PR or CR) outside of the brain to the date of the first documented disease progression outside of the brain or death due to any cause, amongst patients with a confirmed response (PR or CR) outside of the brain per RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
43 months
Duration of Extracranial Response (DOER) Per RECIST 1.1 Per BIRC Assessment
DOER was defined as the time from the first documented response (PR or CR) outside of the brain to the date of the first documented disease progression outside of the brain or death due to any cause, amongst patients with a confirmed response (PR or CR) outside of the brain per RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
43 months
Overall Response Rate (ORR) (Whole Body) Per RECIST 1.1 Per BIRC Assessment
Overall response rate ORR is defined as the percentage of participants with a best overall confirmed response of complete response (CR) or partial response (PR) in the whole body as assessed per RECIST 1.1 by BIRC. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
43 months
Disease Control Rate (DCR) (Whole Body) Per RECIST 1.1 Per BIRC Assessment
DCR: defined as percentage of participants with a best overall response of CR, PR or stable disease (SD) in the whole body, per RECIST 1.1 by BIRC. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), & no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed and non-target lesions are not in progression or in complete response. SD: Neither sufficient shrinkage in the target lesion to qualify for PR or CR nor an increase in lesions which would qualify for PD & non-target lesions are not in unequivocal progression.
43 months
Time to Tumor Response (TTR) (Whole Body) Per RECIST 1.1 Per Investigator Assessment
TTR was defined as the time from the date of the first dose of ceritinib to the date of the first documented response (CR or PR) in the whole body as assessed per RECIST 1.1 criteria per Investigator. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
43 months
Time to Tumor Response (TTR) (Whole Body) Per RECIST 1.1 Per BIRC Assessment
TTR was defined as the time from the date of the first dose of ceritinib to the date of the first documented response (CR or PR) in the whole body as assessed by RECIST 1.1 criteria per BIRC assessment. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
43 months
Duration of Response (DOR) (Whole Body) Per RECIST 1.1 Per Investigator Assessment
DOR was defined as the time from the first documented response (PR or CR) to the date of the first documented disease progression or death due to any cause, amongst patients with a confirmed response (PR or CR) in the whole body per RECIST 1.1 per Investigator. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
43 months
Duration of Response (DOR) (Whole Body) Per RECIST 1.1 Per BIRC Assessment
DOR was defined as the time from the first documented response (PR or CR) to the date of the first documented disease progression or death due to any cause, amongst patients with a confirmed response (PR or CR) in the whole body per RECIST 1.1 per BIRC. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
43 months
Progression Free Survival (PFS) (Whole Body) Per RECIST 1.1 Per Investigator & BIRC Assessment
PFS was defined as the time from the date of the first dose of ceritinib to the date of the first radiologically documented disease progression in the whole body per RECIST 1.1 or death due to any cause. A patient who had not progressed or died at the date of the analysis was censored at the time of the last adequate tumor evaluation on or before the cut-off date.
43 months
Overall Survival (OS)
OS was defined as time from the date of first dose of ceritinib to the date of death due to any cause. The OS time for patients who were alive at the end of the study or were lost to follow-up was censored at the date of last contact.
24 weeks
Pharmacokinetics (PK) of Ceritinib in Study Population: Cmax & Cmin (Trough)
Cmax is the maximum (peak) concentration of drug in plasma. Cmin is the minimum (trough) concentration of drug in plasma. Sparse blood samples for ceritinib PK evaluation in plasma were collected on C1D1 up to C6D1 from all patients who received at least one dose of investigational study treatment.
Cmax: Cycle 2 Day 1 (C2D1); Cmin: C1D1, C1D8, C1D15, C2D1, C3D1, C4D1, C5D1, C6D1 - all 0hr (pre dose)
Stanford Universtiy Medical Center SC-5
Stanford
California
94304
United States
Memorial Hospital of South Bend
South Bend
Indiana
46601
United States
Dana Farber Cancer Institute SC-12
Boston
Massachusetts
02215
United States
The Ohio State University Comprehensive Cancer Center Ohio State University
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
FG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
FG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
FG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
FG00042 subjects
FG00140 subjects
FG00212 subjects
FG00344 subjects
FG00418 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
NOT COMPLETED
FG00042 subjects
FG00140 subjects
FG00212 subjects
FG00344 subjects
FG00418 subjects
Type
Comment
Reasons
Adverse Event
FG0001 subjects
FG0012 subjects
FG0020 subjects
FG0036 subjects
FG0044 subjects
Death
FG0006 subjects
FG0012 subjects
FG0023 subjects
FG0036 subjects
FG004
Physician Decision
FG0009 subjects
FG0016 subjects
FG0027 subjects
FG00316 subjects
FG004
Progressive disease
FG00023 subjects
FG00126 subjects
FG0022 subjects
FG00314 subjects
FG004
Protocol Violation
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Patient/guardian decision
FG0002 subjects
FG0014 subjects
FG0020 subjects
FG0032 subjects
FG004
The Full Analysis Set (FAS) comprised of all patients who received at least one dose of ceritinib.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
BG001
Arm 2 (PrALKi=Y, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
BG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
BG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
BG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
BG005
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00042
BG00140
BG00212
BG00344
BG00418
BG005156
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
The Full Analysis Set (FAS) comprised of all patients who received at least one dose of ceritinib.
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00048.6± 11.37
BG00154.5± 12.32
BG00250.0± 9.67
BG003
Sex: Female, Male
The Full Analysis Set (FAS) comprised of all patients who received at least one dose of ceritinib.
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00021
BG00119
BG002
Race/Ethnicity, Customized
Number
Participants
Title
Denominators
Categories
Asian
Title
Measurements
BG00018
BG00111
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Overall Response Rate (ORR) Per Investigator Assessment
Overall response rate (ORR) is defined as the percentage of participants with a best overall confirmed response of complete response (CR) or partial response (PR) in the whole body as assessed per RECIST 1.1 by the investigator. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
The Full Analysis Set (FAS) comprised of all patients who received at least one dose of ceritinib.
Posted
Number
95% Confidence Interval
Percentage of participants
43 months
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG001
Arm 2 (PrALKi=Y, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00042
OG00140
OG00212
OG003
Title
Denominators
Categories
Title
Measurements
OG00035.7(21.6 to 52.0)
OG00130.0(16.6 to 46.5)
OG00250.0(21.1 to 78.9)
OG003
Secondary
Disease Control Rate (DCR) Per Investigator Assessment
DCR: percentage of parts. with best overall response of CR, PR or stable disease (SD) in the whole body, as assessed per RECIST 1.1 by investigator. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), & no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed and non-target lesions are not in progression or in complete response. SD: Neither sufficient shrinkage in the target lesion to qualify for PR or CR nor an increase in lesions which would qualify for PD & non-target lesions are not in unequivocal progression.
The Full Analysis Set (FAS) comprised of all patients who received at least one dose of ceritinib.
Posted
Number
95% Confidence Interval
Percentage of participants
43 months
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG001
Secondary
Overall Intracranial Response Rate (OIRR) Per Modified RECIST 1.1 Per Investigator Assessment
OIRR was calculated based on response assessments in the brain for patients having measurable brain metastases at baseline. OIRR was defined as the percentage of participants with a best overall confirmed response of CR or PR in the brain as assessed per modified RECIST 1.1. This was applied to the brain only. CR: Disappearance of all non-nodal target & non-target lesions. All lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), & no new lesion is identified. PR: When all target lesions have disappeared or decreased by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) & non-target lesions are not in progression or in complete response.
A subset of FAS (comprised of all patients who received at least one dose of ceritinib) where participants had measurable brain metastases at baseline.
Posted
Number
95% Confidence Interval
Percentage of participants
43 months
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
Secondary
Overall Intracranial Response Rate (OIRR) Per Modified RECIST 1.1 Per Blinded Independent Review Committee (BIRC) Assessment
OIRR was calculated based on response assessments in the brain for patients having measurable brain metastases at baseline. OIRR was defined as the percentage of participants with a best overall confirmed response of CR or PR in the brain as assessed per modified RECIST 1.1. This was applied to the brain only. CR: Disappearance of all non-nodal target & non-target lesions. All lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), & no new lesion is identified. PR: When all target lesions have disappeared or decreased by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) & non-target lesions are not in progression or in complete response.
A subset of FAS (comprised of all patients who received at least one dose of ceritinib) where participants had measurable brain metastases at baseline.
Posted
Number
95% Confidence Interval
Percentage of participants
43 months
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
Secondary
Intracranial Disease Control Rate (IDCR) Per Modified RECIST 1.1 Per Investigator Assessment at Weeks 8 & 16
IDCR overall: percentage of participants with a best overall response of CR, PR, SD or non-CR/non-PD in the brain, as assessed per modified RECIST 1.1 by the Investigator. This was applied to the brain only. CR: Disappearance of all non-nodal target & non-target lesions. All lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), & no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response. SD: Neither sufficient shrinkage in the target lesion to qualify for PR or CR nor an increase in lesions which would qualify for PD & non-target lesions are not in unequivocal progression.
The Full Analysis Set (FAS) comprised of all patients who received at least one dose of ceritinib.
Posted
Number
95% Confidence Interval
Percentage of participants
Week 8 and Week 16
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
Secondary
Intracranial Disease Control Rate (IDCR) Per Modified RECIST 1.1 Per Investigator Assessment - Overall
IDCR overall: percentage of participants with a best overall response of CR, PR, SD or non-CR/non-PD in the brain, as assessed per modified RECIST 1.1 by the Investigator. This was applied to the brain only. CR: Disappearance of all non-nodal target & non-target lesions. All lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), & no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response. SD: Neither sufficient shrinkage in the target lesion to qualify for PR or CR nor an increase in lesions which would qualify for PD & non-target lesions are not in unequivocal progression.
The Full Analysis Set (FAS) comprised of all patients who received at least one dose of ceritinib.
Posted
Number
95% Confidence Interval
Percentage of participants
43 months
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
Secondary
Intracranial Disease Control Rate (IDCR) Per Modified RECIST 1.1 Per BIRC Assessment at Weeks 8 & 16
IDCR overall: percentage of participants with a best overall response of CR, PR, SD or non-CR/non-PD in the brain, as assessed per modified RECIST 1.1 by Investigator. This was applied to the brain only. CR: Disappearance of all non-nodal target & non-target lesions. All lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), & no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response. SD: Neither sufficient shrinkage in the target lesion to qualify for PR or CR nor an increase in lesions which would qualify for PD & non-target lesions are not in unequivocal progression.
The Full Analysis Set (FAS) comprised of all patients who received at least one dose of ceritinib.
Posted
Number
95% Confidence Interval
Percentage of participants
Week 8 and Week 16
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
Secondary
Intracranial Disease Control Rate (IDCR) Per Modified RECIST 1.1 Per BIRC Assessment - Overall
IDCR overall: percentage of participants with a best overall response of CR, PR, SD or non-CR/non-PD in the brain, as assessed per modified RECIST 1.1 by Investigator. This was applied to the brain only. CR: Disappearance of all non-nodal target & non-target lesions. All lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), & no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response. SD: Neither sufficient shrinkage in the target lesion to qualify for PR or CR nor an increase in lesions which would qualify for PD & non-target lesions are not in unequivocal progression.
The Full Analysis Set (FAS) comprised of all patients who received at least one dose of ceritinib.
Posted
Number
95% Confidence Interval
Percentage of participants
43 months
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
Secondary
Time to Intracranial Tumor Response (TTIR) Per Modified RECIST 1.1 Per Investigator Assessment
TTIR was defined as the time from the date of the first dose of ceritinib to the date of the first documented response (CR or PR) in the brain as assessed per modified RECIST 1.1 criteria for patients with measurable brain metastases at baseline. This was applied to the brain only. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
A subset of FAS (comprised of all patients who received at least one dose of ceritinib) where participants had measurable brain metastases at baseline and confirmed CR or PR.
Posted
Median
Full Range
months
43 months
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
Secondary
Time to Intracranial Tumor Response (TTIR) Per Modified RECIST 1.1 Per BIRC Assessment
TTIR was defined as the time from the date of the first dose of ceritinib to the date of the first documented response (CR or PR) in the brain as assessed per modified RECIST 1.1 criteria for patients with measurable brain metastases at baseline. This was applied to the brain only. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
A subset of FAS (comprised of all patients who received at least one dose of ceritinib) where participants had measurable brain metastases at baseline and confirmed CR or PR.
Posted
Median
Full Range
months
43 months
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
Secondary
Duration of Intracranial Response (DOIR) by Modified RECIST 1.1 Per Investigator Assessment
Defined as the time from the first documented response (PR or CR) in the brain to the date of the first documented disease progression in the brain or death due to any cause, amongst participants with measurable brain metastases at baseline and a confirmed response (PR or CR) in the brain as per modified RECIST 1.1. This was applied to the brain only. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
A subset of FAS (comprised of all patients who received at least one dose of ceritinib) where participants had measurable brain metastases at baseline and confirmed CR or PR.
Posted
Median
95% Confidence Interval
months
43 months
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
Secondary
Duration of Intracranial Response (DOIR) by Modified RECIST 1.1 Per BIRC Assessment
Defined as the time from the first documented response (PR or CR) in the brain to the date of the first documented disease progression in the brain or death due to any cause, amongst participants with measurable brain metastases at baseline and a confirmed response (PR or CR) in the brain as per modified RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
A subset of FAS (comprised of all patients who received at least one dose of ceritinib) where participants had measurable brain metastases at baseline and confirmed CR or PR.
Posted
Median
95% Confidence Interval
months
43 months
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
Secondary
Overall Extracranial Response Rate (OERR) Per RECIST 1.1 Per Investigator & BIRC Assessment
OERR was defined as the percentage of participants with a best overall confirmed response of CR or PR outside of the brain, as assessed per RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
The Full Analysis Set (FAS) comprised of all patients who received at least one dose of ceritinib.
Posted
Number
95% Confidence Interval
Percentage of participants
43 months
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG001
Arm 2 (PrALKi=Y, PrBRad=N)
Secondary
Extracranial Disease Control Rate (EDCR) Per RECIST 1.1 Per Investigator & BIRC Assessment - Overall
EDCR overall was defined as the percentage of participants with a best overall response of CR, PR or SD outside of the brain as assessed per RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), & no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed and non-target lesions are not in progression or in complete response. SD: Neither sufficient shrinkage in the target lesion to qualify for PR or CR nor an increase in lesions which would qualify for PD & non-target lesions are not in unequivocal progression.
The Full Analysis Set (FAS) comprised of all patients who received at least one dose of ceritinib.
Posted
Number
95% Confidence Interval
Percentage of participants
43 months
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
Secondary
Extracranial Disease Control Rate (EDCR) Per RECIST 1.1 Per Investigator & BIRC Assessment at Weeks 8 & 16
EDCR at weeks 8 & 16: defined as percentage of parts. with CR, PR or SD outside of the brain at Wk 8 & 16 extracranial tumor evaluations respectively, per RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), & no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed and non-target lesions are not in progression or in complete response. SD: Neither sufficient shrinkage in the target lesion to qualify for PR or CR nor an increase in lesions which would qualify for PD & non-target lesions are not in unequivocal progression.
The Full Analysis Set (FAS) comprised of all patients who received at least one dose of ceritinib.
Posted
Number
95% Confidence Interval
Percentage of participants
Week 8 and Week 16
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
Secondary
Time to Extracranial Tumor Response (TTER) Per RECIST 1.1 Per Investigator Assessment
TTER was defined as the time from the date of the first dose of ceritinib to the date of the first documented response (CR or PR) outside of the brain as assessed per RECIST 1.1 criteria. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
A subset of FAS (comprised of all patients who received at least one dose of ceritinib) where participants had confirmed CR or PR.
Posted
Median
Full Range
months
43 months
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG001
Arm 2 (PrALKi=Y, PrBRad=N)
Secondary
Time to Extracranial Tumor Response (TTER) Per RECIST 1.1 Per BIRC Assessment
TTER was defined as the time from the date of the first dose of ceritinib to the date of the first documented response (CR or PR) outside of the brain as assessed per RECIST 1.1 criteria. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
A subset of FAS (comprised of all patients who received at least one dose of ceritinib) where participants had confirmed CR or PR.
Posted
Median
Full Range
months
43 months
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG001
Arm 2 (PrALKi=Y, PrBRad=N)
Secondary
Duration of Extracranial Response (DOER) Per RECIST 1.1 Per Investigator Assessment
DOER was defined as the time from the first documented response (PR or CR) outside of the brain to the date of the first documented disease progression outside of the brain or death due to any cause, amongst patients with a confirmed response (PR or CR) outside of the brain per RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
A subset of FAS (comprised of all patients who received at least one dose of ceritinib) where participants had confirmed CR or PR.
Posted
Median
95% Confidence Interval
months
43 months
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG001
Secondary
Duration of Extracranial Response (DOER) Per RECIST 1.1 Per BIRC Assessment
DOER was defined as the time from the first documented response (PR or CR) outside of the brain to the date of the first documented disease progression outside of the brain or death due to any cause, amongst patients with a confirmed response (PR or CR) outside of the brain per RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
A subset of FAS (comprised of all patients who received at least one dose of ceritinib) where participants had confirmed CR or PR.
Posted
Median
95% Confidence Interval
months
43 months
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG001
Secondary
Overall Response Rate (ORR) (Whole Body) Per RECIST 1.1 Per BIRC Assessment
Overall response rate ORR is defined as the percentage of participants with a best overall confirmed response of complete response (CR) or partial response (PR) in the whole body as assessed per RECIST 1.1 by BIRC. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
The Full Analysis Set (FAS) comprised of all patients who received at least one dose of ceritinib.
Posted
Number
95% Confidence Interval
Percentage of participants
43 months
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG001
Arm 2 (PrALKi=Y, PrBRad=N)
Secondary
Disease Control Rate (DCR) (Whole Body) Per RECIST 1.1 Per BIRC Assessment
DCR: defined as percentage of participants with a best overall response of CR, PR or stable disease (SD) in the whole body, per RECIST 1.1 by BIRC. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), & no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed and non-target lesions are not in progression or in complete response. SD: Neither sufficient shrinkage in the target lesion to qualify for PR or CR nor an increase in lesions which would qualify for PD & non-target lesions are not in unequivocal progression.
The Full Analysis Set (FAS) comprised of all patients who received at least one dose of ceritinib.
Posted
Number
95% Confidence Interval
Percentage of participants
43 months
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
Secondary
Time to Tumor Response (TTR) (Whole Body) Per RECIST 1.1 Per Investigator Assessment
TTR was defined as the time from the date of the first dose of ceritinib to the date of the first documented response (CR or PR) in the whole body as assessed per RECIST 1.1 criteria per Investigator. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
A subset of FAS (comprised of all patients who received at least one dose of ceritinib) where participants had confirmed CR or PR.
Posted
Median
Full Range
months
43 months
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG001
Arm 2 (PrALKi=Y, PrBRad=N)
Secondary
Time to Tumor Response (TTR) (Whole Body) Per RECIST 1.1 Per BIRC Assessment
TTR was defined as the time from the date of the first dose of ceritinib to the date of the first documented response (CR or PR) in the whole body as assessed by RECIST 1.1 criteria per BIRC assessment. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
A subset of FAS (comprised of all patients who received at least one dose of ceritinib) where participants had confirmed CR or PR.
Posted
Median
Full Range
months
43 months
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG001
Arm 2 (PrALKi=Y, PrBRad=N)
Secondary
Duration of Response (DOR) (Whole Body) Per RECIST 1.1 Per Investigator Assessment
DOR was defined as the time from the first documented response (PR or CR) to the date of the first documented disease progression or death due to any cause, amongst patients with a confirmed response (PR or CR) in the whole body per RECIST 1.1 per Investigator. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
A subset of FAS (comprised of all patients who received at least one dose of ceritinib) where participants had confirmed CR or PR.
Posted
Median
95% Confidence Interval
months
43 months
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG001
Secondary
Duration of Response (DOR) (Whole Body) Per RECIST 1.1 Per BIRC Assessment
DOR was defined as the time from the first documented response (PR or CR) to the date of the first documented disease progression or death due to any cause, amongst patients with a confirmed response (PR or CR) in the whole body per RECIST 1.1 per BIRC. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
A subset of FAS (comprised of all patients who received at least one dose of ceritinib) where participants had confirmed CR or PR.
Posted
Median
95% Confidence Interval
months
43 months
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG001
Arm 2 (PrALKi=Y, PrBRad=N)
Secondary
Progression Free Survival (PFS) (Whole Body) Per RECIST 1.1 Per Investigator & BIRC Assessment
PFS was defined as the time from the date of the first dose of ceritinib to the date of the first radiologically documented disease progression in the whole body per RECIST 1.1 or death due to any cause. A patient who had not progressed or died at the date of the analysis was censored at the time of the last adequate tumor evaluation on or before the cut-off date.
The Full Analysis Set (FAS) comprised of all patients who received at least one dose of ceritinib
Posted
Median
95% Confidence Interval
months
43 months
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG001
Arm 2 (PrALKi=Y, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
Secondary
Overall Survival (OS)
OS was defined as time from the date of first dose of ceritinib to the date of death due to any cause. The OS time for patients who were alive at the end of the study or were lost to follow-up was censored at the date of last contact.
The Full Analysis Set (FAS) comprised of all patients who received at least one dose of ceritinib
Posted
Median
95% Confidence Interval
months
24 weeks
ID
Title
Description
OG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG001
Arm 2 (PrALKi=Y, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
Secondary
Pharmacokinetics (PK) of Ceritinib in Study Population: Cmax & Cmin (Trough)
Cmax is the maximum (peak) concentration of drug in plasma. Cmin is the minimum (trough) concentration of drug in plasma. Sparse blood samples for ceritinib PK evaluation in plasma were collected on C1D1 up to C6D1 from all patients who received at least one dose of investigational study treatment.
The Pharmacokinetic Analysis Set (PAS) comprised of all the patients who received at least one (full or partial) dose of ceritinib and provided at least one evaluable PK blood sample.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Cmax: Cycle 2 Day 1 (C2D1); Cmin: C1D1, C1D8, C1D15, C2D1, C3D1, C4D1, C5D1, C6D1 - all 0hr (pre dose)
ID
Title
Description
OG000
Ceritinib 750mg
Participants all received a dose of 750 mg orally in fasted state
Units
Counts
Participants
OG000
Time Frame
Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to maximum duration of approx. 168 weeks.
Description
Adverse Event (AE): Any sign or symptom that occurs during the study treatment plus 30 days post treatment.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Arm 1 (PrALKi=Y, PrBRad=Y)
Participants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
8
42
28
42
42
42
EG001
Arm 2 (PrALKi=Y, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
5
40
17
40
40
40
EG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
3
12
4
12
11
12
EG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation
6
44
15
44
43
44
EG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
9
18
11
18
18
18
EG005
All Participants
All participants who participated in the study and received at least one (full or partial) dose of ceritinib and provided at least one evaluable PK blood sample
31
156
75
156
154
156
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Lymphadenopathy
Blood and lymphatic system disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG0031 affected44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
Atrial fibrillation
Cardiac disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Left ventricular dysfunction
Cardiac disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Pericardial effusion
Cardiac disorders
MedDRA (20.1)
Systematic Assessment
EG0002 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Pericarditis
Cardiac disorders
MedDRA (20.1)
Systematic Assessment
EG0002 affected42 at risk
EG0012 affected40 at risk
EG0020 affected12 at risk
EG003
Tachycardia
Cardiac disorders
MedDRA (20.1)
Systematic Assessment
EG0002 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Keratitis
Eye disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Oesophagopleural fistula
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Salivary hypersecretion
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Small intestinal obstruction
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Subileus
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Upper gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Adverse drug reaction
General disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Disease progression
General disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
General physical health deterioration
General disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Hyperthermia
General disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Pyrexia
General disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Sudden death
General disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Hepatitis
Hepatobiliary disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Colonic abscess
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Herpes zoster
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Lower respiratory tract infection
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Lung infection
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Lung infection pseudomonal
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Nocardia sepsis
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Pneumonia
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0004 affected42 at risk
EG0014 affected40 at risk
EG0021 affected12 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Septic shock
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Staphylococcal bacteraemia
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Staphylococcal infection
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0021 affected12 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Post procedural complication
Injury, poisoning and procedural complications
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Blood creatinine increased
Investigations
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0021 affected12 at risk
EG003
General physical condition abnormal
Investigations
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Hepatic enzyme increased
Investigations
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Inflammatory marker increased
Investigations
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Platelet count decreased
Investigations
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA (20.1)
Systematic Assessment
EG0002 affected42 at risk
EG0010 affected40 at risk
EG0021 affected12 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0021 affected12 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Malignant neoplasm progression
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Aphasia
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Ataxia
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Cerebral haemorrhage
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Dysarthria
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Dysmetria
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Epilepsy
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Extrapyramidal disorder
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Haemorrhage intracranial
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Headache
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Hemiparesis
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Loss of consciousness
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Memory impairment
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Partial seizures
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Seizure
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0003 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Spinal cord compression
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Bradyphrenia
Psychiatric disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Confusional state
Psychiatric disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Delirium
Psychiatric disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Acute kidney injury
Renal and urinary disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0021 affected12 at risk
EG003
Nephrolithiasis
Renal and urinary disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Acute respiratory failure
Respiratory, thoracic and mediastinal disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Interstitial lung disease
Respiratory, thoracic and mediastinal disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Lung disorder
Respiratory, thoracic and mediastinal disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Pneumonia aspiration
Respiratory, thoracic and mediastinal disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0021 affected12 at risk
EG003
Pneumothorax
Respiratory, thoracic and mediastinal disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0021 affected12 at risk
EG003
Respiratory failure
Respiratory, thoracic and mediastinal disorders
MedDRA (20.1)
Systematic Assessment
EG0002 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Vascular purpura
Skin and subcutaneous tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Aortic aneurysm rupture
Vascular disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Embolism
Vascular disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Peripheral ischaemia
Vascular disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Thrombosis
Vascular disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA (20.1)
Systematic Assessment
EG0008 affected42 at risk
EG0016 affected40 at risk
EG0020 affected12 at risk
EG0035 affected44 at risk
EG0043 affected18 at risk
EG00522 affected156 at risk
Neutropenia
Blood and lymphatic system disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0011 affected40 at risk
EG0021 affected12 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Bradycardia
Cardiac disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Palpitations
Cardiac disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0013 affected40 at risk
EG0020 affected12 at risk
EG003
Sinus bradycardia
Cardiac disorders
MedDRA (20.1)
Systematic Assessment
EG0003 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Vertigo
Ear and labyrinth disorders
MedDRA (20.1)
Systematic Assessment
EG0004 affected42 at risk
EG0010 affected40 at risk
EG0021 affected12 at risk
EG003
Cushingoid
Endocrine disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Vitreous detachment
Eye disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0021 affected12 at risk
EG003
Abdominal discomfort
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0005 affected42 at risk
EG0014 affected40 at risk
EG0021 affected12 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0007 affected42 at risk
EG00112 affected40 at risk
EG0024 affected12 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0006 affected42 at risk
EG0016 affected40 at risk
EG0021 affected12 at risk
EG003
Bowel movement irregularity
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG00010 affected42 at risk
EG0019 affected40 at risk
EG0022 affected12 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG00027 affected42 at risk
EG00134 affected40 at risk
EG0028 affected12 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0007 affected42 at risk
EG0016 affected40 at risk
EG0021 affected12 at risk
EG003
Dysphagia
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0003 affected42 at risk
EG0011 affected40 at risk
EG0021 affected12 at risk
EG003
Epigastric discomfort
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0002 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Faecaloma
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Ileus
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Mouth ulceration
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0003 affected42 at risk
EG0010 affected40 at risk
EG0021 affected12 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG00023 affected42 at risk
EG00129 affected40 at risk
EG0028 affected12 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0003 affected42 at risk
EG0012 affected40 at risk
EG0020 affected12 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG00022 affected42 at risk
EG00124 affected40 at risk
EG0024 affected12 at risk
EG003
Asthenia
General disorders
MedDRA (20.1)
Systematic Assessment
EG00011 affected42 at risk
EG0019 affected40 at risk
EG0024 affected12 at risk
EG003
Fatigue
General disorders
MedDRA (20.1)
Systematic Assessment
EG00013 affected42 at risk
EG00114 affected40 at risk
EG0023 affected12 at risk
EG003
Feeling cold
General disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Gait disturbance
General disorders
MedDRA (20.1)
Systematic Assessment
EG0004 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
General physical health deterioration
General disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0011 affected40 at risk
EG0021 affected12 at risk
EG003
Hyperthermia
General disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0021 affected12 at risk
EG003
Influenza like illness
General disorders
MedDRA (20.1)
Systematic Assessment
EG0002 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Malaise
General disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0013 affected40 at risk
EG0021 affected12 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA (20.1)
Systematic Assessment
EG0009 affected42 at risk
EG0017 affected40 at risk
EG0021 affected12 at risk
EG003
Oedema peripheral
General disorders
MedDRA (20.1)
Systematic Assessment
EG0008 affected42 at risk
EG0016 affected40 at risk
EG0021 affected12 at risk
EG003
Pain
General disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Pyrexia
General disorders
MedDRA (20.1)
Systematic Assessment
EG0006 affected42 at risk
EG00114 affected40 at risk
EG0020 affected12 at risk
EG003
Influenza
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0012 affected40 at risk
EG0021 affected12 at risk
EG003
Mucosal infection
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0002 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0012 affected40 at risk
EG0021 affected12 at risk
EG003
Oral candidiasis
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0002 affected42 at risk
EG0013 affected40 at risk
EG0020 affected12 at risk
EG003
Pneumonia
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0011 affected40 at risk
EG0021 affected12 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Tuberculosis
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0021 affected12 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0003 affected42 at risk
EG0012 affected40 at risk
EG0022 affected12 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0003 affected42 at risk
EG0014 affected40 at risk
EG0020 affected12 at risk
EG003
Vulvovaginal candidiasis
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Procedural dizziness
Injury, poisoning and procedural complications
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0021 affected12 at risk
EG003
Subcutaneous haematoma
Injury, poisoning and procedural complications
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0021 affected12 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA (20.1)
Systematic Assessment
EG00018 affected42 at risk
EG00124 affected40 at risk
EG0023 affected12 at risk
EG003
Amylase increased
Investigations
MedDRA (20.1)
Systematic Assessment
EG0002 affected42 at risk
EG0012 affected40 at risk
EG0021 affected12 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA (20.1)
Systematic Assessment
EG00018 affected42 at risk
EG00119 affected40 at risk
EG0022 affected12 at risk
EG003
Bilirubin conjugated increased
Investigations
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Blood alkaline phosphatase increased
Investigations
MedDRA (20.1)
Systematic Assessment
EG0003 affected42 at risk
EG0018 affected40 at risk
EG0021 affected12 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Blood creatinine increased
Investigations
MedDRA (20.1)
Systematic Assessment
EG0004 affected42 at risk
EG0014 affected40 at risk
EG0022 affected12 at risk
EG003
Blood lactate dehydrogenase increased
Investigations
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Blood phosphorus decreased
Investigations
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Cardiac murmur
Investigations
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Electrocardiogram QT prolonged
Investigations
MedDRA (20.1)
Systematic Assessment
EG0006 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Gamma-glutamyltransferase increased
Investigations
MedDRA (20.1)
Systematic Assessment
EG0008 affected42 at risk
EG00113 affected40 at risk
EG0022 affected12 at risk
EG003
Lipase increased
Investigations
MedDRA (20.1)
Systematic Assessment
EG0003 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Neutrophil count decreased
Investigations
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0021 affected12 at risk
EG003
Weight decreased
Investigations
MedDRA (20.1)
Systematic Assessment
EG0006 affected42 at risk
EG0018 affected40 at risk
EG0024 affected12 at risk
EG003
Weight increased
Investigations
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0012 affected40 at risk
EG0020 affected12 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA (20.1)
Systematic Assessment
EG00021 affected42 at risk
EG00114 affected40 at risk
EG0023 affected12 at risk
EG003
Hypercalcaemia
Metabolism and nutrition disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0021 affected12 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA (20.1)
Systematic Assessment
EG0004 affected42 at risk
EG0012 affected40 at risk
EG0021 affected12 at risk
EG003
Hypoalbuminaemia
Metabolism and nutrition disorders
MedDRA (20.1)
Systematic Assessment
EG0002 affected42 at risk
EG0012 affected40 at risk
EG0021 affected12 at risk
EG003
Hypocalcaemia
Metabolism and nutrition disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA (20.1)
Systematic Assessment
EG0008 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Hypomagnesaemia
Metabolism and nutrition disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0011 affected40 at risk
EG0021 affected12 at risk
EG003
Hypophagia
Metabolism and nutrition disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0021 affected12 at risk
EG003
Hypophosphataemia
Metabolism and nutrition disorders
MedDRA (20.1)
Systematic Assessment
EG0004 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0005 affected42 at risk
EG0015 affected40 at risk
EG0022 affected12 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0009 affected42 at risk
EG0018 affected40 at risk
EG0021 affected12 at risk
EG003
Coccydynia
Musculoskeletal and connective tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Flank pain
Musculoskeletal and connective tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Joint swelling
Musculoskeletal and connective tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Muscle hypertrophy
Musculoskeletal and connective tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0003 affected42 at risk
EG0015 affected40 at risk
EG0020 affected12 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0004 affected42 at risk
EG0013 affected40 at risk
EG0020 affected12 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0003 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Musculoskeletal discomfort
Musculoskeletal and connective tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0021 affected12 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0006 affected42 at risk
EG0011 affected40 at risk
EG0021 affected12 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0012 affected40 at risk
EG0021 affected12 at risk
EG003
Myopathy
Musculoskeletal and connective tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0011 affected40 at risk
EG0021 affected12 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0002 affected42 at risk
EG0012 affected40 at risk
EG0021 affected12 at risk
EG003
Amnesia
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Aphasia
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Balance disorder
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0021 affected12 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0006 affected42 at risk
EG0018 affected40 at risk
EG0021 affected12 at risk
EG003
Dysarthria
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0013 affected40 at risk
EG0021 affected12 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Headache
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG00012 affected42 at risk
EG00113 affected40 at risk
EG0023 affected12 at risk
EG003
Memory impairment
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0004 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0004 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Partial seizures
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Seizure
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0002 affected42 at risk
EG0014 affected40 at risk
EG0020 affected12 at risk
EG003
Somnolence
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Tremor
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0013 affected40 at risk
EG0020 affected12 at risk
EG003
Aggression
Psychiatric disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Agitation
Psychiatric disorders
MedDRA (20.1)
Systematic Assessment
EG0003 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0011 affected40 at risk
EG0021 affected12 at risk
EG003
Bradyphrenia
Psychiatric disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Depression
Psychiatric disorders
MedDRA (20.1)
Systematic Assessment
EG0003 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Disorientation
Psychiatric disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Hallucination, auditory
Psychiatric disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Hallucinations, mixed
Psychiatric disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA (20.1)
Systematic Assessment
EG0003 affected42 at risk
EG0014 affected40 at risk
EG0021 affected12 at risk
EG003
Acute kidney injury
Renal and urinary disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Proteinuria
Renal and urinary disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Urinary incontinence
Renal and urinary disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Pelvic pain
Reproductive system and breast disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA (20.1)
Systematic Assessment
EG00010 affected42 at risk
EG0018 affected40 at risk
EG0021 affected12 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (20.1)
Systematic Assessment
EG0004 affected42 at risk
EG0018 affected40 at risk
EG0022 affected12 at risk
EG003
Dyspnoea exertional
Respiratory, thoracic and mediastinal disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0011 affected40 at risk
EG0021 affected12 at risk
EG003
Haemoptysis
Respiratory, thoracic and mediastinal disorders
MedDRA (20.1)
Systematic Assessment
EG0003 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0021 affected12 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0013 affected40 at risk
EG0020 affected12 at risk
EG003
Productive cough
Respiratory, thoracic and mediastinal disorders
MedDRA (20.1)
Systematic Assessment
EG0003 affected42 at risk
EG0011 affected40 at risk
EG0021 affected12 at risk
EG003
Alopecia
Skin and subcutaneous tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0012 affected40 at risk
EG0021 affected12 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0002 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Eczema
Skin and subcutaneous tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0003 affected42 at risk
EG0013 affected40 at risk
EG0022 affected12 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0004 affected42 at risk
EG0016 affected40 at risk
EG0024 affected12 at risk
EG003
Rash maculo-papular
Skin and subcutaneous tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0003 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Skin fissures
Skin and subcutaneous tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0021 affected12 at risk
EG003
Skin striae
Skin and subcutaneous tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0010 affected40 at risk
EG0020 affected12 at risk
EG003
Hypertension
Vascular disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected42 at risk
EG0013 affected40 at risk
EG0021 affected12 at risk
EG003
Hypotension
Vascular disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected42 at risk
EG0011 affected40 at risk
EG0020 affected12 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00042
OG00140
OG00212
OG00344
OG00418
Title
Denominators
Categories
Title
Measurements
OG00066.7(50.5 to 80.4)
OG00182.5(67.2 to 92.7)
OG00266.7(34.9 to 90.1)
OG00370.5(54.8 to 83.2)
OG00466.7(41.0 to 86.7)
OG001
Arm 2 (PrALKi=Y, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00028
OG00129
OG0027
OG00333
OG0048
Title
Denominators
Categories
Title
Measurements
OG00039.3(21.5 to 59.4)
OG00127.6(12.7 to 47.2)
OG00228.6(3.7 to 71.0)
OG00351.5(33.5 to 69.2)
OG00412.5(0.3 to 52.7)
OG001
Arm 2 (PrALKi=Y, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00030
OG00129
OG0026
OG00334
OG00410
Title
Denominators
Categories
Title
Measurements
OG00033.3(17.3 to 52.8)
OG00124.1(10.3 to 43.5)
OG00233.3(4.3 to 77.7)
OG00358.8(40.7 to 75.4)
OG00420.0(2.5 to 55.6)
OG001
Arm 2 (PrALKi=Y, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00042
OG00140
OG00212
OG00344
OG00418
Title
Denominators
Categories
IDCR at Week 8
Title
Measurements
OG00071.4(55.4 to 84.3)
OG00175.0(58.8 to 87.3)
OG00258.3(27.7 to 84.8)
OG00368.2(52.4 to 81.4)
OG00466.7(41.0 to 86.7)
IDCR at Week 16
Title
Measurements
OG00059.5(43.3 to 74.4)
OG00162.5(45.8 to 77.3)
OG00258.3(27.7 to 84.8)
OG003
OG001
Arm 2 (PrALKi=Y, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00042
OG00140
OG00212
OG00344
OG00418
Title
Denominators
Categories
Title
Measurements
OG00071.4(55.4 to 84.3)
OG00185.0(70.2 to 94.3)
OG00275.0(42.8 to 94.5)
OG00375.0(59.7 to 86.8)
OG00466.7(41.0 to 86.7)
OG001
Arm 2 (PrALKi=Y, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00042
OG00140
OG00212
OG00344
OG00418
Title
Denominators
Categories
IDCR at 8 weeks
Title
Measurements
OG00076.2(60.5 to 87.9)
OG00180.0(64.4 to 90.9)
OG00258.3(27.7 to 84.8)
OG00368.2(52.4 to 81.4)
OG00466.7(41.0 to 86.7)
IDCR at 16 weeks
Title
Measurements
OG00069.0(52.9 to 82.4)
OG00162.5(45.8 to 77.3)
OG00258.3(27.7 to 84.8)
OG003
OG001
Arm 2 (PrALKi=Y, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00042
OG00140
OG00212
OG00344
OG00418
Title
Denominators
Categories
Title
Measurements
OG00073.8(58.0 to 86.1)
OG00185.0(70.2 to 94.3)
OG00266.7(34.9 to 90.1)
OG00375.0(59.7 to 86.8)
OG00466.7(41.0 to 86.7)
OG001
Arm 2 (PrALKi=Y, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00011
OG0018
OG0022
OG00317
OG0041
Title
Denominators
Categories
Title
Measurements
OG0001.87(1.7 to 7.5)
OG0011.84(1.6 to 9.1)
OG0023.56(1.8 to 5.3)
OG0031.77(1.3 to 7.4)
OG0041.80(1.8 to 1.8)
OG001
Arm 2 (PrALKi=Y, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00010
OG0017
OG0022
OG00320
OG0042
Title
Denominators
Categories
Title
Measurements
OG0001.91(1.7 to 5.6)
OG0011.68(1.6 to 7.2)
OG0026.31(3.5 to 9.1)
OG0031.81(1.3 to 9.2)
OG0041.22(0.7 to 1.8)
OG001
Arm 2 (PrALKi=Y, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00011
OG0018
OG0022
OG00317
OG0041
Title
Denominators
Categories
Title
Measurements
OG0009.2(3.7 to NA)NA: Not estimable due to small number of responders
OG00110.1(3.8 to 17.3)
OG002NA(NA to NA)NA: Not estimable due to no responders
OG0037.5(5.6 to 11.2)
OG0045.5(NA to NA)NA:there was only 1 responder in arm 5, for which the 95% CI was not estimable using Kaplan-Meier method
OG001
Arm 2 (PrALKi=Y, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00010
OG0017
OG0022
OG00320
OG0042
Title
Denominators
Categories
Title
Measurements
OG00011.0(3.8 to NA)NA: Not estimable due to small number of responders
OG0014.6(3.5 to 20.3)
OG002NA(18.4 to NA)NA: Not estimable due to small number of responders
OG0039.2(5.7 to 11.3)
OG0043.4(2.0 to 4.7)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00042
OG00140
OG00212
OG00344
OG00418
Title
Denominators
Categories
OERR per Investigator assessment
Title
Measurements
OG00031.0(17.6 to 47.1)
OG00142.5(27.0 to 59.1)
OG00241.7(15.2 to 72.3)
OG00361.4(45.5 to 75.6)
OG00422.2(6.4 to 47.6)
OERR per BIRC assessment
Title
Measurements
OG00026.2(13.9 to 42.0)
OG00125.0(12.7 to 41.2)
OG00250.0(21.1 to 78.9)
OG003
OG001
Arm 2 (PrALKi=Y, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00042
OG00140
OG00212
OG00344
OG00418
Title
Denominators
Categories
EDCR per Investigator assessment
Title
Measurements
OG00069.0(52.9 to 82.4)
OG00192.5(79.6 to 98.4)
OG00266.7(34.9 to 90.1)
OG00372.7(57.2 to 85.0)
OG00472.2(46.5 to 90.3)
EDCR per BIRC assessment
Title
Measurements
OG00064.3(48.0 to 78.4)
OG00180.0(64.4 to 90.9)
OG00266.7(34.9 to 90.1)
OG003
OG001
Arm 2 (PrALKi=Y, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00042
OG00140
OG00212
OG00344
OG00418
Title
Denominators
Categories
EDCR per Investigator @ Week 8
Title
Measurements
OG00069.0(52.9 to 82.4)
OG00182.5(67.2 to 92.7)
OG00258.3(27.7 to 84.8)
OG00363.6(47.8 to 77.6)
OG00472.2(46.5 to 90.3)
EDCR per Investigator @ Week 16
Title
Measurements
OG00057.1(41.0 to 72.3)
OG00182.5(67.2 to 92.7)
OG00266.7(34.9 to 90.1)
OG003
EDCR per BIRC @ Week 8
Title
Measurements
OG00066.7(50.5 to 80.4)
OG00172.5(56.1 to 85.4)
OG00258.3(27.7 to 84.8)
OG003
EDCR per BIRC @ Week 16
Title
Measurements
OG00054.8(38.7 to 70.2)
OG00170.0(53.5 to 83.4)
OG00266.7(34.9 to 90.1)
OG003
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00013
OG00117
OG0025
OG00327
OG0044
Title
Denominators
Categories
Title
Measurements
OG0001.87(1.7 to 18.2)
OG0011.87(1.6 to 9.3)
OG0021.81(1.2 to 12.7)
OG0031.77(1.3 to 5.7)
OG0042.73(1.8 to 3.6)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00010
OG0016
OG0024
OG00327
OG0044
Title
Denominators
Categories
Title
Measurements
OG0001.81(1.7 to 12.9)
OG0011.86(1.6 to 22.9)
OG0022.66(1.7 to 5.5)
OG0031.77(1.3 to 22.0)
OG0041.81(1.8 to 1.9)
Arm 2 (PrALKi=Y, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00013
OG00117
OG0025
OG00327
OG0044
Title
Denominators
Categories
Title
Measurements
OG00018.4(5.6 to NA)NA = Not estimable due to small number of responders
OG00119.3(5.7 to NA)NA = Not estimable due to small number of responders
OG002NA(NA to NA)NA = Not estimable due to no responders
OG003NA(24.4 to NA)NA = Not estimable due to small number of responders
OG0044.6(1.9 to NA)NA = Not estimable due to small sample size
Arm 2 (PrALKi=Y, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00011
OG00110
OG0026
OG00327
OG0043
Title
Denominators
Categories
Title
Measurements
OG000NA(5.5 to NA)NA = Not estimable due to small number of responders
OG0016.0(3.7 to 27.7)
OG002NA(16.5 to NA)NA = Not estimable due to small sample size
OG003NA(11.5 to NA)NA = Not estimable due to small number of responders
OG0045.5(3.8 to NA)NA = Not estimable due to small sample size
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00042
OG00140
OG00212
OG00344
OG00418
Title
Denominators
Categories
Title
Measurements
OG00023.8(12.1 to 39.5)
OG00115.0(5.7 to 29.8)
OG00233.3(9.9 to 65.1)
OG00361.4(45.5 to 75.6)
OG00411.1(1.4 to 34.7)
OG001
Arm 2 (PrALKi=Y, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00042
OG00140
OG00212
OG00344
OG00418
Title
Denominators
Categories
Title
Measurements
OG00061.9(45.6 to 76.4)
OG00180.0(64.4 to 90.9)
OG00266.7(34.9 to 90.1)
OG00368.2(52.4 to 81.4)
OG00472.2(46.5 to 90.3)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00015
OG00112
OG0026
OG00326
OG0043
Title
Denominators
Categories
Title
Measurements
OG0001.87(1.7 to 9.3)
OG0012.00(1.7 to 9.3)
OG0021.82(1.2 to 30.1)
OG0031.81(1.3 to 3.7)
OG0041.91(1.8 to 3.6)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00010
OG0016
OG0024
OG00327
OG0042
Title
Denominators
Categories
Title
Measurements
OG0002.00(1.7 to 12.9)
OG0011.76(1.6 to 1.9)
OG0021.82(1.7 to 26.5)
OG0031.81(1.3 to 22.0)
OG0041.86(1.8 to 1.9)
Arm 2 (PrALKi=Y, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00015
OG00112
OG0026
OG00326
OG0043
Title
Denominators
Categories
Title
Measurements
OG00010.8(4.1 to NA)NA =Not estimable due to small sample size
OG00112.8(3.7 to 17.3)
OG002NA(11.7 to NA)NA = Not estimable due to small number of responders/sample size
OG0039.2(7.3 to 23.9)
OG0045.5(3.7 to 9.9)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00010
OG0016
OG0024
OG00327
OG0042
Title
Denominators
Categories
Title
Measurements
OG00011.0(2.0 to NA)NA = Not estimable due to small sample size
OG00110.6(3.7 to 20.3)
OG002NA(16.5 to NA)NA = Not estimable due to small sample size
OG0039.2(5.7 to 14.3)
OG0045.7(5.5 to 6.0)
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00042
OG00140
OG00212
OG00344
OG00418
Title
Denominators
Categories
PFS per Investigator assessment
ParticipantsOG00032
ParticipantsOG00135
ParticipantsOG0026
ParticipantsOG00333
ParticipantsOG00414
Title
Measurements
OG0007.2(3.3 to 10.9)
OG0015.6(3.6 to 9.2)
OG002NA(1.0 to NA)NA = Not estimable due to small sample size
OG003
PFS per BIRC assessment
ParticipantsOG00034
ParticipantsOG00136
ParticipantsOG0028
ParticipantsOG00333
OG002
Arm 3 (PrALKi=N, PrBRad=Y)
Participants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG003
Arm 4 (PrALKi=N, PrBRad=N)
Participants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
OG004
Arm 5 (LepDis)
Participants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Units
Counts
Participants
OG00042
OG00140
OG00212
OG00344
OG00418
Title
Denominators
Categories
Title
Measurements
OG00024.0(12.6 to NA)NA = Not estimable due to small number of responders
OG001NA(16.2 to NA)NA = Not estimable due to small number of responders
OG002NA(1.0 to NA)NA = Not estimable due to small sample size
OG003NA(26.5 to NA)NA = Not estimable due to small number of responders
OG0047.2(1.6 to 16.9)
145
Title
Denominators
Categories
Cmin C1D1: 0hr. (pre dose)
ParticipantsOG000130
Title
Measurements
OG0000± 0.0
Cmin C1D8: 0hr. (pre dose)
ParticipantsOG000107
Title
Measurements
OG000658± 59.2
Cmin C1D15: 0hr. (pre dose)
ParticipantsOG000106
Title
Measurements
OG000846± 52.9
Cmin C2D1: 0hr. (pre dose)
ParticipantsOG00084
Title
Measurements
OG0001000± 50.0
Cmax C2D1: 4 - 10 hrs. (post dose)
ParticipantsOG00073
Title
Measurements
OG0001100± 47.8
Cmin C3D1: 0hr. (pre dose)
ParticipantsOG00061
Title
Measurements
OG000982± 59.1
Cmin C4D1: 0hr. (pre dose)
ParticipantsOG00046
Title
Measurements
OG000978± 75.4
Cmin C5D1: 0hr. (pre dose)
ParticipantsOG00045
Title
Measurements
OG000885± 75.5
Cmin C6D1: 0hr. (pre dose)
ParticipantsOG00040
Title
Measurements
OG000785± 120.4
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0053 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0054 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0052 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0052 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0052 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0053 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0052 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
1 affected
44 at risk
EG0042 affected18 at risk
EG00512 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
3 affected
44 at risk
EG0041 affected18 at risk
EG0057 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0052 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
1 affected
44 at risk
EG0041 affected18 at risk
EG0052 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0052 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0053 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
2 affected
44 at risk
EG0041 affected18 at risk
EG0056 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
1 affected
44 at risk
EG0041 affected18 at risk
EG0052 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0053 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0052 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0052 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0052 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
2 affected
44 at risk
EG0042 affected18 at risk
EG0057 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0052 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0054 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0054 affected156 at risk
2 affected
44 at risk
EG0040 affected18 at risk
EG0057 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG00511 affected156 at risk
6 affected
44 at risk
EG0044 affected18 at risk
EG00533 affected156 at risk
10 affected
44 at risk
EG0042 affected18 at risk
EG00525 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
7 affected
44 at risk
EG0044 affected18 at risk
EG00532 affected156 at risk
32 affected
44 at risk
EG0046 affected18 at risk
EG005107 affected156 at risk
2 affected
44 at risk
EG0040 affected18 at risk
EG00516 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0055 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0053 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0055 affected156 at risk
19 affected
44 at risk
EG0048 affected18 at risk
EG00587 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0056 affected156 at risk
13 affected
44 at risk
EG0049 affected18 at risk
EG00572 affected156 at risk
9 affected
44 at risk
EG0045 affected18 at risk
EG00538 affected156 at risk
9 affected
44 at risk
EG0043 affected18 at risk
EG00542 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
1 affected
44 at risk
EG0041 affected18 at risk
EG0056 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0053 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0052 affected156 at risk
3 affected
44 at risk
EG0040 affected18 at risk
EG0055 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0055 affected156 at risk
3 affected
44 at risk
EG0040 affected18 at risk
EG00520 affected156 at risk
2 affected
44 at risk
EG0042 affected18 at risk
EG00519 affected156 at risk
1 affected
44 at risk
EG0042 affected18 at risk
EG0054 affected156 at risk
3 affected
44 at risk
EG0041 affected18 at risk
EG00524 affected156 at risk
2 affected
44 at risk
EG0040 affected18 at risk
EG0056 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0054 affected156 at risk
3 affected
44 at risk
EG0040 affected18 at risk
EG0056 affected156 at risk
1 affected
44 at risk
EG0041 affected18 at risk
EG0057 affected156 at risk
0 affected
44 at risk
EG0042 affected18 at risk
EG0055 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0052 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
4 affected
44 at risk
EG0040 affected18 at risk
EG00511 affected156 at risk
2 affected
44 at risk
EG0042 affected18 at risk
EG00511 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
23 affected
44 at risk
EG0046 affected18 at risk
EG00574 affected156 at risk
3 affected
44 at risk
EG0041 affected18 at risk
EG0059 affected156 at risk
13 affected
44 at risk
EG0044 affected18 at risk
EG00556 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
6 affected
44 at risk
EG0042 affected18 at risk
EG00520 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
10 affected
44 at risk
EG0042 affected18 at risk
EG00522 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0058 affected156 at risk
9 affected
44 at risk
EG0043 affected18 at risk
EG00535 affected156 at risk
8 affected
44 at risk
EG0042 affected18 at risk
EG00513 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0052 affected156 at risk
2 affected
44 at risk
EG0043 affected18 at risk
EG00523 affected156 at risk
1 affected
44 at risk
EG0041 affected18 at risk
EG0054 affected156 at risk
6 affected
44 at risk
EG0046 affected18 at risk
EG00550 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
5 affected
44 at risk
EG0044 affected18 at risk
EG00516 affected156 at risk
2 affected
44 at risk
EG0041 affected18 at risk
EG0058 affected156 at risk
2 affected
44 at risk
EG0041 affected18 at risk
EG0054 affected156 at risk
1 affected
44 at risk
EG0044 affected18 at risk
EG00514 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0053 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0053 affected156 at risk
1 affected
44 at risk
EG0041 affected18 at risk
EG0057 affected156 at risk
3 affected
44 at risk
EG0040 affected18 at risk
EG00515 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG00519 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0052 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0052 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
4 affected
44 at risk
EG0040 affected18 at risk
EG00512 affected156 at risk
0 affected
44 at risk
EG0043 affected18 at risk
EG00510 affected156 at risk
2 affected
44 at risk
EG0041 affected18 at risk
EG0057 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
2 affected
44 at risk
EG0041 affected18 at risk
EG00511 affected156 at risk
2 affected
44 at risk
EG0040 affected18 at risk
EG0055 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0053 affected156 at risk
1 affected
44 at risk
EG0041 affected18 at risk
EG0057 affected156 at risk
0 affected
44 at risk
EG0042 affected18 at risk
EG0052 affected156 at risk
1 affected
44 at risk
EG0041 affected18 at risk
EG0052 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0052 affected156 at risk
4 affected
44 at risk
EG0043 affected18 at risk
EG00522 affected156 at risk
1 affected
44 at risk
EG0043 affected18 at risk
EG0059 affected156 at risk
5 affected
44 at risk
EG0041 affected18 at risk
EG0056 affected156 at risk
10 affected
44 at risk
EG0044 affected18 at risk
EG00542 affected156 at risk
1 affected
44 at risk
EG0041 affected18 at risk
EG0057 affected156 at risk
3 affected
44 at risk
EG0041 affected18 at risk
EG0059 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
2 affected
44 at risk
EG0043 affected18 at risk
EG00511 affected156 at risk
1 affected
44 at risk
EG0042 affected18 at risk
EG0055 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0055 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0054 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0054 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0053 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
4 affected
44 at risk
EG0041 affected18 at risk
EG00513 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0052 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
6 affected
44 at risk
EG0044 affected18 at risk
EG00529 affected156 at risk
5 affected
44 at risk
EG0042 affected18 at risk
EG00521 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0054 affected156 at risk
3 affected
44 at risk
EG0040 affected18 at risk
EG0056 affected156 at risk
1 affected
44 at risk
EG0041 affected18 at risk
EG0054 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0055 affected156 at risk
4 affected
44 at risk
EG0041 affected18 at risk
EG00510 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0053 affected156 at risk
4 affected
44 at risk
EG0040 affected18 at risk
EG0056 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0052 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0052 affected156 at risk
1 affected
44 at risk
EG0040 affected18 at risk
EG0059 affected156 at risk
7 affected
44 at risk
EG0041 affected18 at risk
EG00522 affected156 at risk
2 affected
44 at risk
EG0040 affected18 at risk
EG0055 affected156 at risk
0 affected
44 at risk
EG0040 affected18 at risk
EG0051 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0051 affected156 at risk
1 affected
44 at risk
EG0041 affected18 at risk
EG0057 affected156 at risk
0 affected
44 at risk
EG0041 affected18 at risk
EG0052 affected156 at risk
65.9
(50.1 to 79.5)
OG00450.0(26.0 to 74.0)
68.2
(52.4 to 81.4)
OG00438.9(17.3 to 64.3)
61.4
(45.5 to 75.6)
OG00416.7(3.6 to 41.4)
68.2
(52.4 to 81.4)
OG00472.2(46.5 to 90.3)
65.9
(50.1 to 79.5)
OG00450.0(26.0 to 74.0)
61.4
(45.5 to 75.6)
OG00472.2(46.5 to 90.3)
68.2
(52.4 to 81.4)
OG00444.4(21.5 to 69.2)
7.9
(5.5 to 9.4)
OG0045.2(1.6 to 7.2)
ParticipantsOG00414
Title
Measurements
OG0005.0(3.3 to 9.1)
OG0015.5(3.6 to 7.3)
OG00215.5(1.0 to NA)NA = Not estimable due to small sample size