Trial Outcomes & Findings for LGX818 and MEK162 in Combination With a Third Agent (BKM120, LEE011, BGJ398 or INC280) in Advanced BRAF Melanoma (NCT NCT02159066)
NCT ID: NCT02159066
Last Updated: 2024-03-05
Results Overview
ORR: percentage of participants with confirmed complete response (CR) and partial response (PR). Response evaluation criteria in solid tumors (RECIST) v1.1: a) CR = disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions that had a reduction in short axis to less than (\<) 10 millimeter (mm). Disappearance of all non-target lesions. In addition, all lymph nodes assigned a non-target lesion must be non-pathological in size (\<10 mm short axis) and b) PR = at least a 30 percent (%) decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Any radiological assessments taken more than 30 days after the last dose of study therapy or after antineoplastic agents other than study treatments taken by the participants was excluded from the best overall response derivation. Confirmation of CR or PR was to be at least 4 weeks apart from the previous radiological assessment.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
158 participants
Primary outcome timeframe
From the start of the treatment until disease/clinical progression or death or early study discontinuation, whichever happened earlier (maximum treatment exposure for Part II was 97.0 weeks)
Results posted on
2024-03-05
Participant Flow
This study had 2 parts. In Part I, 158 participants were enrolled and treated with encorafenib/ binimetinib (LGX818/MEK162) combination until disease progression (PD) \[as per RECISTv1.1\]. Based on the genetic assessment of a tumor biopsy obtained at PD, participants from Part I entered Part II. In Part II, 58 participants received tailored combination treatment in one of the 4 arms: encorafenib/ binimetinib + buparlisib (BKM120), infigratinib (BGJ398), capmatinib (INC280) or ribociclib (LEE011).
Participant milestones
| Measure |
Part I: Encorafenib + Binimetinib (Naive)
Participants naive to selective V-raf murine sarcoma viral oncogene homolog B1 (BRAF) and mitogen-activated protein kinase (MEK) inhibitors, received encorafenib 450 milligram (mg) once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit and initiation of triple combination treatment. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for encorafenib and binimetinib was defined as 21 days of daily continuous treatment.
|
Part I: Encorafenib + Binimetinib (Non-naive)
Participants non-naive to selective BRAF and MEK inhibitors, received encorafenib 450 mg once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit and initiation of triple combination treatment. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for both drugs was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Ribociclib
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
|---|---|---|---|---|---|---|
|
Part I
STARTED
|
75
|
83
|
0
|
0
|
0
|
0
|
|
Part I
COMPLETED
|
0
|
4
|
0
|
0
|
0
|
0
|
|
Part I
NOT COMPLETED
|
75
|
79
|
0
|
0
|
0
|
0
|
|
Part II
STARTED
|
0
|
0
|
38
|
1
|
13
|
6
|
|
Part II
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Part II
NOT COMPLETED
|
0
|
0
|
38
|
1
|
13
|
6
|
Reasons for withdrawal
| Measure |
Part I: Encorafenib + Binimetinib (Naive)
Participants naive to selective V-raf murine sarcoma viral oncogene homolog B1 (BRAF) and mitogen-activated protein kinase (MEK) inhibitors, received encorafenib 450 milligram (mg) once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit and initiation of triple combination treatment. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for encorafenib and binimetinib was defined as 21 days of daily continuous treatment.
|
Part I: Encorafenib + Binimetinib (Non-naive)
Participants non-naive to selective BRAF and MEK inhibitors, received encorafenib 450 mg once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit and initiation of triple combination treatment. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for both drugs was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Ribociclib
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
|---|---|---|---|---|---|---|
|
Part I
Adverse Event
|
7
|
5
|
0
|
0
|
0
|
0
|
|
Part I
Death
|
11
|
9
|
0
|
0
|
0
|
0
|
|
Part I
Progressive Disease
|
37
|
46
|
0
|
0
|
0
|
0
|
|
Part I
New Therapy for Study Indication
|
5
|
4
|
0
|
0
|
0
|
0
|
|
Part I
Termination of participants from the study
|
3
|
3
|
0
|
0
|
0
|
0
|
|
Part I
Physician Decision
|
2
|
9
|
0
|
0
|
0
|
0
|
|
Part I
Participant/Guardian Decision
|
9
|
3
|
0
|
0
|
0
|
0
|
|
Part I
Missing Data
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Part II
Adverse Event
|
0
|
0
|
1
|
0
|
1
|
1
|
|
Part II
Death
|
0
|
0
|
1
|
0
|
2
|
1
|
|
Part II
Progressive Disease
|
0
|
0
|
35
|
1
|
7
|
4
|
|
Part II
New Therapy for Study Indication
|
0
|
0
|
0
|
0
|
1
|
0
|
|
Part II
Physician Decision
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Part II
Participant/Guardian Decision
|
0
|
0
|
0
|
0
|
2
|
0
|
Baseline Characteristics
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
Baseline characteristics by cohort
| Measure |
Part I: Encorafenib + Binimetinib (Naive)
n=75 Participants
Participants naive to selective V-raf murine sarcoma viral oncogene homolog B1 (BRAF) and mitogen-activated protein kinase (MEK) inhibitors, received encorafenib 450 milligram (mg) once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for encorafenib and binimetinib was defined as 21 days of daily continuous treatment.
|
Part I: Encorafenib + Binimetinib (Non-naive)
n=83 Participants
Participants non-naive to selective BRAF and MEK inhibitors, received encorafenib 450 mg once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit and initiation of triple combination treatment. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for both drugs was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Ribociclib
n=38 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=1 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=13 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=6 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Total
n=216 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Customized
Part I · 18-44 years
|
14 Participants
n=75 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
24 Participants
n=83 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
38 Participants
n=158 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
|
Age, Customized
Part I · 45-64 years
|
43 Participants
n=75 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
37 Participants
n=83 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
80 Participants
n=158 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
|
Age, Customized
Part I · 65 years and over
|
18 Participants
n=75 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
22 Participants
n=83 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
40 Participants
n=158 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
|
Age, Customized
Part I · Not disclosed
|
0 Participants
n=75 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=83 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=158 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
|
Age, Customized
Part II · 18-44 years
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
9 Participants
n=38 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=1 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=13 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
1 Participants
n=6 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
10 Participants
n=58 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
|
Age, Customized
Part II · 45-64 years
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
19 Participants
n=38 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=1 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
7 Participants
n=13 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
4 Participants
n=6 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
30 Participants
n=58 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
|
Age, Customized
Part II · 65 years and over
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
10 Participants
n=38 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=1 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
6 Participants
n=13 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
1 Participants
n=6 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
17 Participants
n=58 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
|
Age, Customized
Part II · Not disclosed
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=38 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
1 Participants
n=1 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=13 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=6 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
1 Participants
n=58 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
|
Sex/Gender, Customized
Part I · Female
|
28 Participants
n=75 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
39 Participants
n=83 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
67 Participants
n=158 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
|
Sex/Gender, Customized
Part I · Male
|
47 Participants
n=75 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
44 Participants
n=83 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
91 Participants
n=158 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
|
Sex/Gender, Customized
Part I · Not Disclosed
|
0 Participants
n=75 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=83 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=158 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
|
Sex/Gender, Customized
Part II · Female
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
22 Participants
n=38 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=1 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
5 Participants
n=13 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
1 Participants
n=6 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
28 Participants
n=58 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
|
Sex/Gender, Customized
Part II · Male
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
16 Participants
n=38 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=1 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
8 Participants
n=13 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
5 Participants
n=6 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
29 Participants
n=58 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
|
Sex/Gender, Customized
Part II · Not Disclosed
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=38 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
1 Participants
n=1 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=13 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=6 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
1 Participants
n=58 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
|
Race/Ethnicity, Customized
Race: Part I · Caucasian
|
74 Participants
n=75 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
82 Participants
n=83 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
156 Participants
n=158 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
|
Race/Ethnicity, Customized
Race: Part I · Asian
|
1 Participants
n=75 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
1 Participants
n=83 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
2 Participants
n=158 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
|
Race/Ethnicity, Customized
Race: Part I · Not Disclosed
|
0 Participants
n=75 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=83 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=158 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
|
Race/Ethnicity, Customized
Race: Part II · Caucasian
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
37 Participants
n=38 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=1 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
13 Participants
n=13 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
6 Participants
n=6 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
56 Participants
n=58 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
|
Race/Ethnicity, Customized
Race: Part II · Asian
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
1 Participants
n=38 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=1 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=13 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=6 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
1 Participants
n=58 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
|
Race/Ethnicity, Customized
Race: Part II · Not Disclosed
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=38 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
1 Participants
n=1 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=13 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=6 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
1 Participants
n=58 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
|
Race/Ethnicity, Customized
Ethnicity: Part I · Hispanic or Latino
|
3 Participants
n=75 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
7 Participants
n=83 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
10 Participants
n=158 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
|
Race/Ethnicity, Customized
Ethnicity: Part I · Not Hispanic or Latino
|
72 Participants
n=75 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
76 Participants
n=83 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
148 Participants
n=158 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
|
Race/Ethnicity, Customized
Ethnicity: Part I · Not Disclosed
|
0 Participants
n=75 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=83 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=158 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
|
Race/Ethnicity, Customized
Ethnicity: Part II · Hispanic or Latino
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
1 Participants
n=38 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=1 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=13 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=6 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
1 Participants
n=58 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
|
Race/Ethnicity, Customized
Ethnicity: Part II · Not Hispanic or Latino
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
37 Participants
n=38 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=1 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
13 Participants
n=13 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
6 Participants
n=6 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
56 Participants
n=58 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
|
Race/Ethnicity, Customized
Ethnicity: Part II · Not Disclosed
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=38 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
1 Participants
n=1 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=13 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
0 Participants
n=6 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
1 Participants
n=58 Participants • Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive.
|
PRIMARY outcome
Timeframe: From the start of the treatment until disease/clinical progression or death or early study discontinuation, whichever happened earlier (maximum treatment exposure for Part II was 97.0 weeks)Population: For Part II, full analysis set (FAS) consisted of all participants who received at least 1 dose of encorafenib or binimetinib or the assigned third agent following the assignment of the triple combination treatment.
ORR: percentage of participants with confirmed complete response (CR) and partial response (PR). Response evaluation criteria in solid tumors (RECIST) v1.1: a) CR = disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions that had a reduction in short axis to less than (\<) 10 millimeter (mm). Disappearance of all non-target lesions. In addition, all lymph nodes assigned a non-target lesion must be non-pathological in size (\<10 mm short axis) and b) PR = at least a 30 percent (%) decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Any radiological assessments taken more than 30 days after the last dose of study therapy or after antineoplastic agents other than study treatments taken by the participants was excluded from the best overall response derivation. Confirmation of CR or PR was to be at least 4 weeks apart from the previous radiological assessment.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=38 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=1 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=13 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=6 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Overall Response Rate (ORR): Part II
|
2.6 Percentage of participants
Interval 0.1 to 13.8
|
0 Percentage of participants
Only 1 participant evaluable.
|
0 Percentage of participants
Interval 0.0 to 24.7
|
0 Percentage of participants
Interval 0.0 to 45.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 (21 days following the first dose of the combination treatment with buparlisib and capmatinib; 28 days for the combination with ribociclib and infigratinib)Population: Dose-determining analysis set (DDS) consisted of all participants from the safety set for Part II who met the minimum requirements for safety evaluation and minimum exposure or experienced DLT during the first cycle of the assigned triple combination treatment. No participants were included in the dose-determining analysis set in the encorafenib/binimetinib+ infigratinib or buparlisib arm, hence no participants analyzed for these reporting arms for this outcome measure.
DLT was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first cycle (first 21 days for infigratinib and capmatinib; 28 days for ribociclib and buparlisib) of treatment initiation and met the defined criteria for study.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=34 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=12 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Dose Limiting Toxicities (DLTs) in Cycle 1: Part II
|
1 Participants
|
—
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks)Population: Safety set included all participants who received at least 1 dose of encorafenib or binimetinib for Part I and had at least 1 valid post-baseline safety assessment.
An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occurred after participants' signed informed consent has been obtained. An SAE was an AE resulting in any of the following outcomes: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. AEs included both SAEs and all Non-SAEs.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=75 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=83 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs): Part I
AEs
|
75 Participants
|
78 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs): Part I
SAEs
|
47 Participants
|
37 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 up to 30 days after last dose (maximum treatment exposure for Part II was 97.0 weeks)Population: Safety set included all participants who received at least 1 dose of 3rd combination agent for Part II and had at least 1 valid post-baseline safety assessment.
An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occurred after participants' signed informed consent has been obtained. An SAE was an AE resulting in any of the following outcomes: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. AEs included both SAEs and all Non-SAEs.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=38 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=1 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=13 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=6 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With AEs and SAEs: Part II
AEs
|
37 Participants
|
1 Participants
|
12 Participants
|
6 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With AEs and SAEs: Part II
SAEs
|
19 Participants
|
0 Participants
|
6 Participants
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to last dose (maximum treatment exposure for Part I was 403.7 weeks)Population: Safety set included all participants who received at least 1 dose of encorafenib or binimetinib for Part I and had at least 1 valid post-baseline safety assessment.
Parameters evaluated were: Activated partial thromboplastin time (APTT) (seconds \[sec\]) - CTCAE graded high, fibrinogen (gram per liter \[g/L\]) - CTCAE graded low, hemoglobin (g/L) - CTCAE graded low, hemoglobin (g/L) - CTCAE graded high, prothrombin international normalized ratio (PINR) - CTCAE graded high, lymphocytes (10\^9 cells/L) - CTCAE graded low, lymphocytes (10\^9 cells/L) - CTCAE graded high, neutrophils (10\^9 cells/L) - CTCAE graded low, platelets (10\^9 cells/L) - CTCAE graded low, leukocytes (10\^9 cells/L) - CTCAE graded low, leukocytes (10\^9 cells/L) - CTCAE graded high. CTCAE version 4.03 was used: grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening consequences; grade 0 = values not meeting any of the criteria for grade 1 or higher. Baseline = last non-missing value prior to the first dose of study treatment.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=75 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=83 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Hemoglobin - CTCAE graded high · Worst post-baseline value Grade 1
|
4 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
APTT -CTCAE graded high · Worst post-baseline value Grade 0
|
46 Participants
|
54 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
APTT -CTCAE graded high · Worst post-baseline value Grade 1
|
1 Participants
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
APTT -CTCAE graded high · Worst post-baseline value Grade 2
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
APTT -CTCAE graded high · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
APTT -CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
APTT -CTCAE graded high · Worst post-baseline value Missing
|
28 Participants
|
25 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Fibrinogen - CTCAE graded low · Worst post-baseline value Grade 0
|
28 Participants
|
36 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Fibrinogen - CTCAE graded low · Worst post-baseline value Grade 1
|
8 Participants
|
9 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Fibrinogen - CTCAE graded low · Worst post-baseline value Grade 2
|
5 Participants
|
7 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Fibrinogen - CTCAE graded low · Worst post-baseline value Grade 3
|
4 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Fibrinogen - CTCAE graded low · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Fibrinogen - CTCAE graded low · Worst post-baseline value Missing
|
30 Participants
|
30 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Hemoglobin - CTCAE graded low · Worst post-baseline value Grade 0
|
21 Participants
|
17 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Hemoglobin - CTCAE graded low · Worst post-baseline value Grade 1
|
28 Participants
|
39 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Hemoglobin - CTCAE graded low · Worst post-baseline value Grade 2
|
18 Participants
|
20 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Hemoglobin - CTCAE graded low · Worst post-baseline value Grade 3
|
8 Participants
|
6 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Hemoglobin - CTCAE graded low · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Hemoglobin - CTCAE graded low · Worst post-baseline value Missing
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Hemoglobin - CTCAE graded high · Worst post-baseline value Grade 0
|
70 Participants
|
80 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Hemoglobin - CTCAE graded high · Worst post-baseline value Grade 2
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Hemoglobin - CTCAE graded high · Worst post-baseline value Grade 3
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Hemoglobin - CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Hemoglobin - CTCAE graded high · Worst post-baseline value Missing
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
PINR -CTCAE graded high · Worst post-baseline value Grade 0
|
44 Participants
|
34 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
PINR -CTCAE graded high · Worst post-baseline value Grade 1
|
0 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
PINR -CTCAE graded high · Worst post-baseline value Grade 2
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
PINR -CTCAE graded high · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
PINR -CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
PINR -CTCAE graded high · Worst post-baseline value Missing
|
31 Participants
|
47 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Lymphocytes - CTCAE graded low · Worst post-baseline value Grade 0
|
23 Participants
|
27 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Lymphocytes - CTCAE graded low · Worst post-baseline value Grade 1
|
22 Participants
|
24 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Lymphocytes - CTCAE graded low · Worst post-baseline value Grade 2
|
13 Participants
|
12 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Lymphocytes - CTCAE graded low · Worst post-baseline value Grade 3
|
6 Participants
|
10 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Lymphocytes - CTCAE graded low · Worst post-baseline value Grade 4
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Lymphocytes - CTCAE graded low · Worst post-baseline value Missing
|
11 Participants
|
9 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Lymphocytes - CTCAE graded high · Worst post-baseline value Grade 0
|
61 Participants
|
68 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Lymphocytes - CTCAE graded high · Worst post-baseline value Grade 1
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Lymphocytes - CTCAE graded high · Worst post-baseline value Grade 2
|
2 Participants
|
6 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Lymphocytes - CTCAE graded high · Worst post-baseline value Grade 3
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Lymphocytes - CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Lymphocytes - CTCAE graded high · Worst post-baseline value Missing
|
11 Participants
|
9 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Neutrophils - CTCAE graded low · Worst post-baseline value Grade 0
|
52 Participants
|
62 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Neutrophils - CTCAE graded low · Worst post-baseline value Grade 1
|
4 Participants
|
6 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Neutrophils - CTCAE graded low · Worst post-baseline value Grade 2
|
5 Participants
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Neutrophils - CTCAE graded low · Worst post-baseline value Grade 3
|
3 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Neutrophils - CTCAE graded low · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Neutrophils - CTCAE graded low · Worst post-baseline value Missing
|
11 Participants
|
10 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Platelets - CTCAE graded low · Worst post-baseline value Grade 0
|
59 Participants
|
71 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Platelets - CTCAE graded low · Worst post-baseline value Grade 1
|
14 Participants
|
11 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Platelets - CTCAE graded low · Worst post-baseline value Grade 2
|
2 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Platelets - CTCAE graded low · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Platelets - CTCAE graded low · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Platelets - CTCAE graded low · Worst post-baseline value Missing
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Leukocytes - CTCAE graded low · Worst post-baseline value Grade 0
|
52 Participants
|
61 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Leukocytes - CTCAE graded low · Worst post-baseline value Grade 1
|
11 Participants
|
14 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Leukocytes - CTCAE graded low · Worst post-baseline value Grade 2
|
3 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Leukocytes - CTCAE graded low · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Leukocytes - CTCAE graded low · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Leukocytes - CTCAE graded low · Worst post-baseline value Missing
|
9 Participants
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Leukocytes - CTCAE graded high · Worst post-baseline value Grade 0
|
66 Participants
|
78 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Leukocytes - CTCAE graded high · Worst post-baseline value Grade 1
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Leukocytes - CTCAE graded high · Worst post-baseline value Grade 2
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Leukocytes - CTCAE graded high · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Leukocytes - CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Leukocytes - CTCAE graded high · Worst post-baseline value Missing
|
9 Participants
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to last dose (maximum treatment exposure for Part II was 97.0 weeks)Population: Safety set included all participants who received at least 1 dose of 3rd combination agent for Part II and had at least 1 valid post-baseline safety assessment.
Parameters evaluated were: APTT (sec) - CTCAE graded high, fibrinogen (g/L) - CTCAE graded low, hemoglobin (g/L) - CTCAE graded low, hemoglobin (g/L) - CTCAE graded high, PINR - CTCAE graded high, lymphocytes (10\^9 cells/L) - CTCAE graded low, lymphocytes (10\^9 cells/L) - CTCAE graded high, neutrophils (10\^9 cells/L) - CTCAE graded low, platelets (10\^9 cells/L) - CTCAE graded low, leukocytes (10\^9 cells/L) - CTCAE graded low, leukocytes (10\^9 cells/L) - CTCAE graded high. CTCAE version 4.03 was used: grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening consequences; grade 0 = values not meeting any of the criteria for grade 1 or higher. Baseline = last non-missing value prior to the first dose of study treatment in Part II.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=38 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=1 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=13 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=6 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Hemoglobin- CTCAE graded low · Worst post-baseline value Missing
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Hemoglobin- CTCAE graded high · Worst post-baseline value Grade 0
|
37 Participants
|
1 Participants
|
11 Participants
|
6 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Hemoglobin- CTCAE graded high · Worst post-baseline value Grade 1
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Hemoglobin- CTCAE graded high · Worst post-baseline value Grade 2
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Hemoglobin- CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Hemoglobin- CTCAE graded high · Worst post-baseline value Missing
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
PINR- CTCAE graded high · Worst post-baseline value Grade 0
|
14 Participants
|
1 Participants
|
8 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
PINR- CTCAE graded high · Worst post-baseline value Grade 2
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
PINR- CTCAE graded high · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
PINR- CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Neutrophils- CTCAE graded low · Worst post-baseline value Grade 2
|
6 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Neutrophils- CTCAE graded low · Worst post-baseline value Missing
|
11 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
APTT- CTCAE graded high · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Fibrinogen: CTCAE graded low · Worst post-baseline value Grade 1
|
3 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Fibrinogen: CTCAE graded low · Worst post-baseline value Grade 2
|
2 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Fibrinogen: CTCAE graded low · Worst post-baseline value Grade 3
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Fibrinogen: CTCAE graded low · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Fibrinogen: CTCAE graded low · Worst post-baseline value Missing
|
19 Participants
|
0 Participants
|
5 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Hemoglobin- CTCAE graded low · Worst post-baseline value Grade 3
|
4 Participants
|
0 Participants
|
1 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Hemoglobin- CTCAE graded low · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Hemoglobin- CTCAE graded high · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Lymphocytes -CTCAE graded low · Worst post-baseline value Grade 3
|
7 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Lymphocytes -CTCAE graded low · Worst post-baseline value Grade 4
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
PINR- CTCAE graded high · Worst post-baseline value Grade 1
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Neutrophils- CTCAE graded low · Worst post-baseline value Grade 1
|
9 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
PINR- CTCAE graded high · Worst post-baseline value Missing
|
24 Participants
|
0 Participants
|
5 Participants
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Lymphocytes -CTCAE graded low · Worst post-baseline value Grade 0
|
5 Participants
|
0 Participants
|
4 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Lymphocytes -CTCAE graded low · Worst post-baseline value Grade 1
|
7 Participants
|
0 Participants
|
4 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Lymphocytes -CTCAE graded low · Worst post-baseline value Missing
|
9 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Lymphocytes- CTCAE graded high · Worst post-baseline value Grade 0
|
29 Participants
|
0 Participants
|
11 Participants
|
6 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Lymphocytes- CTCAE graded high · Worst post-baseline value Grade 1
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Neutrophils- CTCAE graded low · Worst post-baseline value Grade 3
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Lymphocytes- CTCAE graded high · Worst post-baseline value Grade 2
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Neutrophils- CTCAE graded low · Worst post-baseline value Grade 4
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Lymphocytes- CTCAE graded high · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Lymphocytes- CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Lymphocytes- CTCAE graded high · Worst post-baseline value Missing
|
9 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Platelets- CTCAE graded low · Worst post-baseline value Grade 0
|
33 Participants
|
1 Participants
|
11 Participants
|
6 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Lymphocytes -CTCAE graded low · Worst post-baseline value Grade 2
|
9 Participants
|
0 Participants
|
3 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Platelets- CTCAE graded low · Worst post-baseline value Grade 1
|
4 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Platelets- CTCAE graded low · Worst post-baseline value Grade 2
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Platelets- CTCAE graded low · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Platelets- CTCAE graded low · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Platelets- CTCAE graded low · Worst post-baseline value Missing
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Leukocytes- CTCAE graded low · Worst post-baseline value Grade 0
|
8 Participants
|
0 Participants
|
11 Participants
|
6 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Leukocytes- CTCAE graded low · Worst post-baseline value Grade 1
|
8 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Leukocytes- CTCAE graded low · Worst post-baseline value Grade 2
|
12 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Leukocytes- CTCAE graded low · Worst post-baseline value Grade 3
|
3 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Leukocytes- CTCAE graded low · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Leukocytes- CTCAE graded low · Worst post-baseline value Missing
|
7 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Leukocytes - CTCAE graded high · Worst post-baseline value Grade 0
|
31 Participants
|
0 Participants
|
11 Participants
|
6 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Leukocytes - CTCAE graded high · Worst post-baseline value Grade 1
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Leukocytes - CTCAE graded high · Worst post-baseline value Grade 2
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Leukocytes - CTCAE graded high · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Leukocytes - CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Leukocytes - CTCAE graded high · Worst post-baseline value Missing
|
7 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Neutrophils- CTCAE graded low · Worst post-baseline value Grade 0
|
10 Participants
|
0 Participants
|
11 Participants
|
6 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
APTT- CTCAE graded high · Worst post-baseline value Grade 0
|
27 Participants
|
1 Participants
|
9 Participants
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
APTT- CTCAE graded high · Worst post-baseline value Grade 1
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
APTT- CTCAE graded high · Worst post-baseline value Grade 2
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
APTT- CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
APTT- CTCAE graded high · Worst post-baseline value Missing
|
11 Participants
|
0 Participants
|
4 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Fibrinogen: CTCAE graded low · Worst post-baseline value Grade 0
|
13 Participants
|
0 Participants
|
6 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Hemoglobin- CTCAE graded low · Worst post-baseline value Grade 0
|
4 Participants
|
0 Participants
|
4 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Hemoglobin- CTCAE graded low · Worst post-baseline value Grade 1
|
15 Participants
|
1 Participants
|
5 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Hemoglobin- CTCAE graded low · Worst post-baseline value Grade 2
|
14 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to last dose (maximum treatment exposure for Part I was 403.7 weeks)Population: Safety set included all participants who received at least 1 dose of encorafenib or binimetinib for Part I and had at least 1 valid post-baseline safety assessment.
Parameters evaluated were: albumin (g/L)- CTCAE graded low, alkaline phosphatase (units per liter \[U/L\])- CTCAE graded high, alanine aminotransferase (U/L)- CTCAE graded high, amylase (U/L - CTCAE graded high, aspartate aminotransferase(U/L)- CTCAE graded high, bilirubin (micromole per liter \[umol/L\])- CTCAE graded high, creatinine (umol/L) - CTCAE graded high, creatine kinase (U/L)- CTCAE graded high, gamma glutamyl transferase (U/L)- CTCAE graded high, glucose (millimole per liter \[mmol/L\])- CTCAE graded low, high, potassium (mmol/L)- CTCAE graded low, potassium (mmol/L)- CTCAE graded high, magnesium (mmol/L)- CTCAE graded low, high, phosphate (mmol/L)- CTCAE graded low, sodium (mmol/L)- CTCAE graded low, sodium (mmol/L)- CTCAE graded high, urate (umol/L)- CTCAE graded high. CTCAE version 4.03 was used: grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening consequences; grade 0 = values not meeting any of the criteria for grade 1 or higher.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=75 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=83 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Albumin - CTCAE graded low · Worst post-baseline value Grade 0
|
32 Participants
|
40 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Albumin - CTCAE graded low · Worst post-baseline value Grade 1
|
35 Participants
|
29 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Albumin - CTCAE graded low · Worst post-baseline value Grade 2
|
8 Participants
|
12 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Albumin - CTCAE graded low · Worst post-baseline value Grade 3
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Albumin - CTCAE graded low · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Albumin - CTCAE graded low · Worst post-baseline value Missing
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Alkaline Phosphatase - CTCAE graded high · Worst post-baseline value Grade 0
|
39 Participants
|
43 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Alkaline Phosphatase - CTCAE graded high · Worst post-baseline value Grade 1
|
28 Participants
|
31 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Alkaline Phosphatase - CTCAE graded high · Worst post-baseline value Grade 2
|
5 Participants
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Alkaline Phosphatase - CTCAE graded high · Worst post-baseline value Grade 3
|
3 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Alkaline Phosphatase - CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Alkaline Phosphatase - CTCAE graded high · Worst post-baseline value Missing
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Alanine Aminotransferase - CTCAE graded high · Worst post-baseline value Grade 0
|
38 Participants
|
51 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Alanine Aminotransferase - CTCAE graded high · Worst post-baseline value Grade 1
|
27 Participants
|
28 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Alanine Aminotransferase - CTCAE graded high · Worst post-baseline value Grade 2
|
5 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Alanine Aminotransferase - CTCAE graded high · Worst post-baseline value Grade 3
|
5 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Alanine Aminotransferase - CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Alanine Aminotransferase - CTCAE graded high · Worst post-baseline value Missing
|
0 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Amylase - CTCAE graded high · Worst post-baseline value Grade 0
|
53 Participants
|
52 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Amylase - CTCAE graded high · Worst post-baseline value Grade 1
|
14 Participants
|
6 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Amylase - CTCAE graded high · Worst post-baseline value Grade 2
|
5 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Amylase - CTCAE graded high · Worst post-baseline value Grade 3
|
2 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Amylase - CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Amylase - CTCAE graded high · Worst post-baseline value Missing
|
1 Participants
|
20 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Aspartate Aminotransferase - CTCAE graded high · Worst post-baseline value Grade 0
|
38 Participants
|
50 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Aspartate Aminotransferase - CTCAE graded high · Worst post-baseline value Grade 1
|
30 Participants
|
29 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Aspartate Aminotransferase - CTCAE graded high · Worst post-baseline value Grade 2
|
4 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Aspartate Aminotransferase - CTCAE graded high · Worst post-baseline value Grade 3
|
3 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Aspartate Aminotransferase - CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Aspartate Aminotransferase - CTCAE graded high · Worst post-baseline value Missing
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Bilirubin - CTCAE graded high · Worst post-baseline value Grade 0
|
73 Participants
|
81 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Bilirubin - CTCAE graded high · Worst post-baseline value Grade 1
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Bilirubin - CTCAE graded high · Worst post-baseline value Grade 2
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Bilirubin - CTCAE graded high · Worst post-baseline value Grade 3
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Bilirubin - CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Bilirubin - CTCAE graded high · Worst post-baseline value Missing
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Creatine Kinase - CTCAE graded high · Worst post-baseline value Grade 0
|
22 Participants
|
56 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Creatine Kinase - CTCAE graded high · Worst post-baseline value Grade 1
|
30 Participants
|
15 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Creatine Kinase - CTCAE graded high · Worst post-baseline value Grade 2
|
18 Participants
|
8 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Creatine Kinase - CTCAE graded high · Worst post-baseline value Grade 3
|
4 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Creatine Kinase - CTCAE graded high · Worst post-baseline value Grade 4
|
1 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Creatine Kinase - CTCAE graded high · Worst post-baseline value Missing
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Creatinine - CTCAE graded high · Worst post-baseline value Grade 0
|
2 Participants
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Creatinine - CTCAE graded high · Worst post-baseline value Grade 1
|
57 Participants
|
56 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Creatinine - CTCAE graded high · Worst post-baseline value Grade 2
|
14 Participants
|
22 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Creatinine - CTCAE graded high · Worst post-baseline value Grade 3
|
2 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Creatinine - CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Creatinine - CTCAE graded high · Worst post-baseline value Missing
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Gamma Glutamyl Transferase - CTCAE graded high · Worst post-baseline value Grade 0
|
20 Participants
|
33 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Gamma Glutamyl Transferase - CTCAE graded high · Worst post-baseline value Grade 1
|
19 Participants
|
18 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Gamma Glutamyl Transferase - CTCAE graded high · Worst post-baseline value Grade 2
|
14 Participants
|
13 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Gamma Glutamyl Transferase - CTCAE graded high · Worst post-baseline value Grade 3
|
20 Participants
|
15 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Gamma Glutamyl Transferase - CTCAE graded high · Worst post-baseline value Grade 4
|
2 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Gamma Glutamyl Transferase - CTCAE graded high · Worst post-baseline value Missing
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Glucose - CTCAE graded low · Worst post-baseline value Grade 0
|
55 Participants
|
67 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Glucose - CTCAE graded low · Worst post-baseline value Grade 1
|
15 Participants
|
7 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Glucose - CTCAE graded low · Worst post-baseline value Grade 2
|
1 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Glucose - CTCAE graded low · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Glucose - CTCAE graded low · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Glucose - CTCAE graded low · Worst post-baseline value Missing
|
4 Participants
|
8 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Glucose - CTCAE graded high · Worst post-baseline value Grade 0
|
56 Participants
|
60 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Glucose - CTCAE graded high · Worst post-baseline value Grade 1
|
4 Participants
|
10 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Glucose - CTCAE graded high · Worst post-baseline value Grade 2
|
3 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Glucose - CTCAE graded high · Worst post-baseline value Grade 3
|
7 Participants
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Glucose - CTCAE graded high · Worst post-baseline value Grade 4
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Glucose - CTCAE graded high · Worst post-baseline value Missing
|
4 Participants
|
8 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Potassium - CTCAE graded low · Worst post-baseline value Grade 0
|
65 Participants
|
74 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Potassium - CTCAE graded low · Worst post-baseline value Grade 1
|
7 Participants
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Potassium - CTCAE graded low · Worst post-baseline value Grade 2
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Potassium - CTCAE graded low · Worst post-baseline value Grade 3
|
3 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Potassium - CTCAE graded low · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Potassium - CTCAE graded low · Worst post-baseline value Missing
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Potassium - CTCAE graded high · Worst post-baseline value Grade 0
|
54 Participants
|
66 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Potassium - CTCAE graded high · Worst post-baseline value Grade 1
|
18 Participants
|
15 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Potassium - CTCAE graded high · Worst post-baseline value Grade 2
|
2 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Potassium - CTCAE graded high · Worst post-baseline value Grade 3
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Potassium - CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Potassium - CTCAE graded high · Worst post-baseline value Missing
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Magnesium - CTCAE graded low · Worst post-baseline value Grade 0
|
66 Participants
|
68 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Magnesium - CTCAE graded low · Worst post-baseline value Grade 1
|
8 Participants
|
14 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Magnesium - CTCAE graded low · Worst post-baseline value Grade 2
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Magnesium - CTCAE graded low · Worst post-baseline value Grade 3
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Magnesium - CTCAE graded low · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Magnesium - CTCAE graded low · Worst post-baseline value Missing
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Magnesium - CTCAE graded high · Worst post-baseline value Grade 0
|
74 Participants
|
79 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Magnesium - CTCAE graded high · Worst post-baseline value Grade 1
|
1 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Magnesium - CTCAE graded high · Worst post-baseline value Grade 2
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Magnesium - CTCAE graded high · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Magnesium - CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Magnesium - CTCAE graded high · Worst post-baseline value Missing
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Phosphate - CTCAE graded low · Worst post-baseline value Grade 0
|
40 Participants
|
62 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Phosphate - CTCAE graded low · Worst post-baseline value Grade 1
|
3 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Phosphate - CTCAE graded low · Worst post-baseline value Grade 2
|
24 Participants
|
12 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Phosphate - CTCAE graded low · Worst post-baseline value Grade 3
|
8 Participants
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Phosphate - CTCAE graded low · Worst post-baseline value Grade 4
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Phosphate - CTCAE graded low · Worst post-baseline value Missing
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Sodium - CTCAE graded low · Worst post-baseline value Grade 0
|
54 Participants
|
53 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Sodium - CTCAE graded low · Worst post-baseline value Grade 1
|
21 Participants
|
24 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Sodium - CTCAE graded low · Worst post-baseline value Grade 2
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Sodium - CTCAE graded low · Worst post-baseline value Grade 3
|
0 Participants
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Sodium - CTCAE graded low · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Sodium - CTCAE graded low · Worst post-baseline value Missing
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Sodium - CTCAE graded high · Worst post-baseline value Grade 0
|
66 Participants
|
75 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Sodium - CTCAE graded high · Worst post-baseline value Grade 1
|
9 Participants
|
6 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Sodium - CTCAE graded high · Worst post-baseline value Grade 2
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Sodium - CTCAE graded high · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Sodium - CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Sodium - CTCAE graded high · Worst post-baseline value Missing
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Urate - CTCAE graded high · Worst post-baseline value Grade 0
|
75 Participants
|
82 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Urate - CTCAE graded high · Worst post-baseline value Grade 1
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Urate - CTCAE graded high · Worst post-baseline value Grade 2
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Urate - CTCAE graded high · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Urate - CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Urate - CTCAE graded high · Worst post-baseline value Missing
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to last dose (maximum treatment exposure for Part II was 97.0 weeks)Population: Safety set included all participants who received at least 1 dose of 3rd combination agent for Part II and had at least 1 valid post-baseline safety assessment.
Parameters evaluated were: albumin (g/L)- CTCAE graded low, alkaline phosphatase (U/L)- CTCAE graded high, alanine aminotransferase (U/L)- CTCAE graded high, amylase (U/L) - CTCAE graded high, aspartate aminotransferase(U/L)- CTCAE graded high, bilirubin (umol/L)- CTCAE graded high, creatinine (umol/L) - CTCAE graded high, creatine kinase (U/L)- CTCAE graded high, gamma glutamyl transferase (U/L)- CTCAE graded high, glucose (mmol/L)- CTCAE graded low, high, potassium (mmol/L)- CTCAE graded low, potassium (mmol/L)- CTCAE graded high, magnesium (mmol/L)- CTCAE graded low, high, phosphate (mmol/L)- CTCAE graded low, sodium (mmol/L)- CTCAE graded low, sodium (mmol/L)- CTCAE graded high, urate (umol/L)- CTCAE graded high. CTCAE version 4.03 was used: grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening consequences; grade 0 = values not meeting any of the criteria for grade 1 or higher.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=38 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=1 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=13 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=6 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Bilirubin - CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Bilirubin - CTCAE graded high · Worst post-baseline value Missing
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Creatine Kinase - CTCAE graded high · Worst post-baseline value Grade 0
|
20 Participants
|
0 Participants
|
6 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Creatine Kinase - CTCAE graded high · Worst post-baseline value Grade 1
|
14 Participants
|
1 Participants
|
4 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Creatine Kinase - CTCAE graded high · Worst post-baseline value Grade 2
|
3 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Creatine Kinase - CTCAE graded high · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Creatine Kinase - CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Creatine Kinase - CTCAE graded high · Worst post-baseline value Missing
|
1 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Creatinine - CTCAE graded high · Worst post-baseline value Grade 0
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Creatinine - CTCAE graded high · Worst post-baseline value Grade 1
|
25 Participants
|
1 Participants
|
4 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Albumin- CTCAE graded low · Worst post-baseline value Grade 0
|
16 Participants
|
1 Participants
|
1 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Albumin- CTCAE graded low · Worst post-baseline value Grade 1
|
13 Participants
|
0 Participants
|
6 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Albumin- CTCAE graded low · Worst post-baseline value Grade 2
|
7 Participants
|
0 Participants
|
3 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Albumin- CTCAE graded low · Worst post-baseline value Grade 3
|
1 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Albumin- CTCAE graded low · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Albumin- CTCAE graded low · Worst post-baseline value Missing
|
1 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Alkaline Phosphatase - CTCAE graded high · Worst post-baseline value Grade 0
|
22 Participants
|
1 Participants
|
7 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Alkaline Phosphatase - CTCAE graded high · Worst post-baseline value Grade 1
|
10 Participants
|
0 Participants
|
3 Participants
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Alkaline Phosphatase - CTCAE graded high · Worst post-baseline value Grade 2
|
3 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Alkaline Phosphatase - CTCAE graded high · Worst post-baseline value Grade 3
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Alkaline Phosphatase - CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Alkaline Phosphatase - CTCAE graded high · Worst post-baseline value Missing
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Alanine Aminotransferase - CTCAE graded high · Worst post-baseline value Grade 0
|
27 Participants
|
1 Participants
|
9 Participants
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Alanine Aminotransferase - CTCAE graded high · Worst post-baseline value Grade 1
|
6 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Alanine Aminotransferase - CTCAE graded high · Worst post-baseline value Grade 2
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Alanine Aminotransferase - CTCAE graded high · Worst post-baseline value Grade 3
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Alanine Aminotransferase - CTCAE graded high · Worst post-baseline value Grade 4
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Alanine Aminotransferase - CTCAE graded high · Worst post-baseline value Missing
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Amylase - CTCAE graded high · Worst post-baseline value Grade 0
|
27 Participants
|
1 Participants
|
9 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Amylase - CTCAE graded high · Worst post-baseline value Grade 1
|
1 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Amylase - CTCAE graded high · Worst post-baseline value Grade 2
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Amylase - CTCAE graded high · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Amylase - CTCAE graded high · Worst post-baseline value Grade 4
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Amylase - CTCAE graded high · Worst post-baseline value Missing
|
8 Participants
|
0 Participants
|
2 Participants
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Aspartate Aminotransferase - CTCAE graded high · Worst post-baseline value Grade 0
|
27 Participants
|
1 Participants
|
8 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Aspartate Aminotransferase - CTCAE graded high · Worst post-baseline value Grade 1
|
6 Participants
|
0 Participants
|
4 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Aspartate Aminotransferase - CTCAE graded high · Worst post-baseline value Grade 2
|
3 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Aspartate Aminotransferase - CTCAE graded high · Worst post-baseline value Grade 3
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Aspartate Aminotransferase - CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Aspartate Aminotransferase - CTCAE graded high · Worst post-baseline value Missing
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Bilirubin - CTCAE graded high · Worst post-baseline value Grade 0
|
37 Participants
|
1 Participants
|
12 Participants
|
6 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Bilirubin - CTCAE graded high · Worst post-baseline value Grade 1
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Bilirubin - CTCAE graded high · Worst post-baseline value Grade 2
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Bilirubin - CTCAE graded high · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Creatinine - CTCAE graded high · Worst post-baseline value Grade 2
|
11 Participants
|
0 Participants
|
8 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Creatinine - CTCAE graded high · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Creatinine - CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Creatinine - CTCAE graded high · Worst post-baseline value Missing
|
1 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Gamma Glutamyl Transferase - CTCAE graded high · Worst post-baseline value Grade 0
|
20 Participants
|
1 Participants
|
5 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Gamma Glutamyl Transferase - CTCAE graded high · Worst post-baseline value Grade 1
|
9 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Gamma Glutamyl Transferase - CTCAE graded high · Worst post-baseline value Grade 2
|
1 Participants
|
0 Participants
|
2 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Gamma Glutamyl Transferase - CTCAE graded high · Worst post-baseline value Grade 3
|
7 Participants
|
0 Participants
|
3 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Gamma Glutamyl Transferase - CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Gamma Glutamyl Transferase - CTCAE graded high · Worst post-baseline value Missing
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Glucose - CTCAE graded low · Worst post-baseline value Grade 0
|
24 Participants
|
0 Participants
|
11 Participants
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Glucose - CTCAE graded low · Worst post-baseline value Grade 1
|
6 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Glucose - CTCAE graded low · Worst post-baseline value Grade 2
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Glucose - CTCAE graded low · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Glucose - CTCAE graded low · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Glucose - CTCAE graded low · Worst post-baseline value Missing
|
8 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Glucose - CTCAE graded high · Worst post-baseline value Grade 0
|
26 Participants
|
1 Participants
|
10 Participants
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Glucose - CTCAE graded high · Worst post-baseline value Grade 1
|
2 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Glucose - CTCAE graded high · Worst post-baseline value Grade 2
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Glucose - CTCAE graded high · Worst post-baseline value Grade 3
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Glucose - CTCAE graded high · Worst post-baseline value Grade 4
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Glucose - CTCAE graded high · Worst post-baseline value Missing
|
8 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Potassium - CTCAE graded low · Worst post-baseline value Grade 0
|
34 Participants
|
1 Participants
|
11 Participants
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Potassium - CTCAE graded low · Worst post-baseline value Grade 1
|
3 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Potassium - CTCAE graded low · Worst post-baseline value Grade 2
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Potassium - CTCAE graded low · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Potassium - CTCAE graded low · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Potassium - CTCAE graded low · Worst post-baseline value Missing
|
1 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Potassium - CTCAE graded high · Worst post-baseline value Grade 0
|
32 Participants
|
1 Participants
|
9 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Potassium - CTCAE graded high · Worst post-baseline value Grade 1
|
4 Participants
|
0 Participants
|
3 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Potassium - CTCAE graded high · Worst post-baseline value Grade 2
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Potassium - CTCAE graded high · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Potassium - CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Potassium - CTCAE graded high · Worst post-baseline value Missing
|
1 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Magnesium - CTCAE graded low · Worst post-baseline value Grade 0
|
35 Participants
|
1 Participants
|
10 Participants
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Magnesium - CTCAE graded low · Worst post-baseline value Grade 1
|
2 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Magnesium - CTCAE graded low · Worst post-baseline value Grade 2
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Magnesium - CTCAE graded low · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Magnesium - CTCAE graded low · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Magnesium - CTCAE graded low · Worst post-baseline value Missing
|
1 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Magnesium - CTCAE graded high · Worst post-baseline value Grade 0
|
36 Participants
|
1 Participants
|
12 Participants
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Magnesium - CTCAE graded high · Worst post-baseline value Grade 1
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Magnesium - CTCAE graded high · Worst post-baseline value Grade 2
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Magnesium - CTCAE graded high · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Magnesium - CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Magnesium - CTCAE graded high · Worst post-baseline value Missing
|
1 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Phosphate - CTCAE graded low · Worst post-baseline value Grade 0
|
25 Participants
|
1 Participants
|
7 Participants
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Phosphate - CTCAE graded low · Worst post-baseline value Grade 1
|
2 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Phosphate - CTCAE graded low · Worst post-baseline value Grade 2
|
7 Participants
|
0 Participants
|
3 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Phosphate - CTCAE graded low · Worst post-baseline value Grade 3
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Phosphate - CTCAE graded low · Worst post-baseline value Grade 4
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Phosphate - CTCAE graded low · Worst post-baseline value Missing
|
1 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Sodium -CTCAE graded low · Worst post-baseline value Grade 0
|
28 Participants
|
1 Participants
|
10 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Sodium -CTCAE graded low · Worst post-baseline value Grade 1
|
7 Participants
|
0 Participants
|
2 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Sodium -CTCAE graded low · Worst post-baseline value Grade 2
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Sodium -CTCAE graded low · Worst post-baseline value Grade 3
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Sodium -CTCAE graded low · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Sodium -CTCAE graded low · Worst post-baseline value Missing
|
1 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Sodium - CTCAE graded high · Worst post-baseline value Grade 0
|
35 Participants
|
1 Participants
|
12 Participants
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Sodium - CTCAE graded high · Worst post-baseline value Grade 1
|
2 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Sodium - CTCAE graded high · Worst post-baseline value Grade 2
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Sodium - CTCAE graded high · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Sodium - CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Sodium - CTCAE graded high · Worst post-baseline value Missing
|
1 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Urate - CTCAE graded high · Worst post-baseline value Grade 0
|
37 Participants
|
1 Participants
|
12 Participants
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Urate - CTCAE graded high · Worst post-baseline value Grade 1
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Urate - CTCAE graded high · Worst post-baseline value Grade 2
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Urate - CTCAE graded high · Worst post-baseline value Grade 3
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Urate - CTCAE graded high · Worst post-baseline value Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Urate - CTCAE graded high · Worst post-baseline value Missing
|
1 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: During study treatment (maximum treatment exposure for Part I was 403.7 weeks)Population: Safety set included all participants who received at least 1 dose of encorafenib or binimetinib for Part I and had at least 1 valid post-baseline safety assessment. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified rows.
Vital signs evaluated were: Low/high systolic blood pressure (BP) (millimeter of Mercury \[mmHg\]): less than or equal to (\<=) 90 mmHg with decrease from baseline of \>=20 mmHg / \>=160 mmHg with increase from baseline of \>=20 mmHg; low/high diastolic BP \[mmHg\]: \<=50 mmHg with decrease from baseline of \>=15 mmHg / \>=100 mmHg with increase from baseline of \>=15 mmHg; low/high pulse rate (beats per minute \[bpm\]): \<=50 bpm with decrease from baseline of \>=15 bpm / \>=120 bpm with increase from baseline of \>=15 bpm; low/high weight (kilogram \[kg\]): \>=20% decrease/increase from baseline; and low/high body temperature (degree Celsius \[C\]): \<=36 C / \>= 37.5 C.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=75 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=83 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part I
Sitting Pulse Rate: High
|
2 Participants
|
8 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part I
Sitting Pulse Rate: Low
|
5 Participants
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part I
Sitting Systolic BP: High
|
18 Participants
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part I
Sitting Systolic BP: Low
|
3 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part I
Sitting Diastolic BP: High
|
11 Participants
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part I
Sitting Diastolic BP: Low
|
5 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part I
Weight: High
|
0 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part I
Weight: Low
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part I
Body temperature: High
|
14 Participants
|
14 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part I
Body temperature: Low
|
44 Participants
|
36 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: During study treatment (maximum treatment exposure for Part II was 97.0 weeks)Population: Safety set included all participants who received at least 1 dose of 3rd combination agent for Part II and had at least 1 valid post-baseline safety assessment. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified rows.
Vital signs evaluated were: Low/high systolic BP (mmHg): \<=90 mmHg with decrease from baseline of \>=20 mmHg / \>=160 mmHg with increase from baseline of \>=20 mmHg; low/high diastolic BP \[mmHg\]: \<=50 mmHg with decrease from baseline of \>=15 mmHg / \>=100 mmHg with increase from baseline of \>=15 mmHg; low/high pulse rate (bpm): \<=50 bpm with decrease from baseline of \>=15 bpm / \>=120 bpm with increase from baseline of \>=15 bpm; low/high weight (kg): \>=20% decrease/increase from baseline; and low/high body temperature (C): \<=36 C / \>= 37.5 C.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=38 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=1 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=13 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=6 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part II
Sitting Pulse Rate: High
|
2 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part II
Sitting Pulse Rate: Low
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part II
Sitting Systolic BP: High
|
2 Participants
|
0 Participants
|
4 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part II
Sitting Systolic BP: Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part II
Sitting Diastolic BP: High
|
2 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part II
Sitting Diastolic BP: Low
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part II
Weight: High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part II
Weight: Low
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part II
Body temperature: High
|
3 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part II
Body temperature: Low
|
14 Participants
|
1 Participants
|
6 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: During study treatment (maximum treatment exposure for Part I was 403.7 weeks)Population: Safety set included all participants who received at least 1 dose of encorafenib or binimetinib for Part I and had at least 1 valid post-baseline safety assessment. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified rows.
Number of participants with notable ECG values were reported in this outcome measure. Abnormality categories were: Heart rate (HR): increase from baseline \>25% and to a value \>100 bpm, decrease from baseline \>25% and to a value \<60 bpm; PR: increase from baseline \>25% and to a value \>200 millisecond (ms); QRS: increase from baseline \>25% and to a value \>110 ms; QT: increase from baseline \>30 ms, increase from baseline \>60 ms, new interval \>450 ms, new interval \>480 ms, new interval \>500 ms; and Corrected QT interval by Fridericia (QTcF): increase from baseline \>30 ms, increase from baseline \>60 ms, new interval \>450 ms, new interval \>480 ms, new interval \>500 ms. New = newly occurred post-baseline value.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=75 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=83 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Notable Electrocardiograms (ECG) Values: Part I
QTcF: New Interval >450 ms
|
28 Participants
|
15 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable Electrocardiograms (ECG) Values: Part I
QTcF: New Interval >480 ms
|
4 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable Electrocardiograms (ECG) Values: Part I
QTcF: New Interval >500 ms
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable Electrocardiograms (ECG) Values: Part I
HR: Increase from baseline >25% & to a value >100 bpm
|
10 Participants
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable Electrocardiograms (ECG) Values: Part I
HR: Decrease from baseline >25% & to a value <60 bpm
|
37 Participants
|
23 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable Electrocardiograms (ECG) Values: Part I
PR: Increase from baseline >25% & to a value >200 ms
|
5 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable Electrocardiograms (ECG) Values: Part I
QRS: Increase from baseline >25% & to a value >110 ms
|
3 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable Electrocardiograms (ECG) Values: Part I
QT: Increase from baseline >30 ms
|
61 Participants
|
48 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable Electrocardiograms (ECG) Values: Part I
QT: Increase from baseline >60 ms
|
29 Participants
|
15 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable Electrocardiograms (ECG) Values: Part I
QT: New Interval >450 ms
|
24 Participants
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable Electrocardiograms (ECG) Values: Part I
QT: New Interval >480 ms
|
5 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable Electrocardiograms (ECG) Values: Part I
QT: New Interval >500 ms
|
3 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable Electrocardiograms (ECG) Values: Part I
QTcF: Increase from baseline >30 ms
|
46 Participants
|
31 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable Electrocardiograms (ECG) Values: Part I
QTcF: Increase from baseline >60 ms
|
4 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: During study treatment (maximum treatment exposure for Part II was 97.0 weeks)Population: Safety set included all participants who received at least 1 dose of 3rd combination agent for Part II and had at least 1 valid post-baseline safety assessment. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified rows.
Number of participants with notable ECG values were reported in this outcome measure. Abnormality categories were: HR: increase from baseline \>25% and to a value \>100 bpm, decrease from baseline \>25% and to a value \<60 bpm; PR: increase from baseline \>25% and to a value \>200 ms; QRS: increase from baseline \>25% and to a value \>110 ms; QT: increase from baseline \>30 ms, increase from baseline \>60 ms, new interval \>450 ms, new interval \>480 ms, new interval \>500 ms; and QTcF: increase from baseline \>30 ms, increase from baseline \>60 ms, new interval \>450 ms, new interval \>480 ms, new interval \>500 ms. New = newly occurred post-baseline value.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=38 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=1 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=13 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=6 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Notable ECG Values: Part II
HR: Increase from baseline >25% & to a value >100 bpm
|
3 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable ECG Values: Part II
HR: Decrease from baseline >25% & to a value <60 bpm
|
14 Participants
|
0 Participants
|
7 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable ECG Values: Part II
PR: Increase from baseline >25% & to a value >200 ms
|
1 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable ECG Values: Part II
QRS: Increase from baseline >25% & to a value >110 ms
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable ECG Values: Part II
QT: Increase from baseline >30 ms
|
24 Participants
|
0 Participants
|
9 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable ECG Values: Part II
QT: Increase from baseline >60 ms
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable ECG Values: Part II
QT: New Interval >450 ms
|
3 Participants
|
—
|
3 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable ECG Values: Part II
QT: New Interval >480 ms
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable ECG Values: Part II
QT: New Interval >500 ms
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable ECG Values: Part II
QTcF: Increase from baseline >30 ms
|
11 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable ECG Values: Part II
QTcF: Increase from baseline >60 ms
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable ECG Values: Part II
QTcF: New Interval >450 ms
|
14 Participants
|
0 Participants
|
3 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable ECG Values: Part II
QTcF: New Interval >480 ms
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Notable ECG Values: Part II
QTcF: New Interval >500 ms
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: During study treatment (maximum treatment exposure for Part I was 403.7 weeks)Population: Safety set included all participants who received at least 1 dose of encorafenib or binimetinib for Part I and had at least 1 valid post-baseline safety assessment.
In this outcome measure number of participants with at least 1 dose interruption for encorafenib and binimetinib were reported.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=75 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=83 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With At Least One Dose Interruption: Part I
Encorafenib
|
46 Participants
|
40 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With At Least One Dose Interruption: Part I
Binimetinib
|
44 Participants
|
41 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: During study treatment (maximum treatment exposure for Part II was 97.0 weeks)Population: Safety set included all participants who received at least 1 dose of 3rd combination agent for Part II and had at least 1 valid post-baseline safety assessment. Here, "Number Analyzed" signifies number of participants evaluable for specified treatment in the respective reporting arms.
In this outcome measure number of participants with at least 1 dose interruption for encorafenib, binimetinib, and each third combination agent were reported.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=38 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=1 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=13 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=6 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With At Least One Dose Interruption: Part II
Encorafenib
|
14 Participants
|
0 Participants
|
4 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With At Least One Dose Interruption: Part II
Binimetinib
|
13 Participants
|
0 Participants
|
5 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With At Least One Dose Interruption: Part II
Ribociclib
|
11 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With At Least One Dose Interruption: Part II
Infigratinib
|
—
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With At Least One Dose Interruption: Part II
Capmatinib
|
—
|
—
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With At Least One Dose Interruption: Part II
Buparlisib
|
—
|
—
|
—
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: During study treatment (maximum treatment exposure for Part I was 403.7 weeks)Population: Safety set included all participants who received at least 1 dose of encorafenib or binimetinib for Part I and had at least 1 valid post-baseline safety assessment.
In this outcome measure number of participants with at least 1 dose reduction for encorafenib and binimetinib were reported.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=75 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=83 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With At Least One Dose Reduction: Part I
Encorafenib
|
9 Participants
|
14 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With At Least One Dose Reduction: Part I
Binimetinib
|
32 Participants
|
28 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: During study treatment (maximum treatment exposure for Part II was 97.0 weeks)Population: Safety set included all participants who received at least 1 dose of 3rd combination agent for Part II and had at least 1 valid post-baseline safety assessment. Here, "Number Analyzed" signifies number of participants evaluable for specified treatment in the respective reporting arms.
In this outcome measure number of participants with at least 1 dose reduction for encorafenib, binimetinib, and each third combination agent were reported.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=38 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=1 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=13 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=6 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With At Least One Dose Reduction: Part II
Encorafenib
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With At Least One Dose Reduction: Part II
Binimetinib
|
11 Participants
|
0 Participants
|
5 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With At Least One Dose Reduction: Part II
Ribociclib
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With At Least One Dose Reduction: Part II
Infigratinib
|
—
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With At Least One Dose Reduction: Part II
Capmatinib
|
—
|
—
|
7 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With At Least One Dose Reduction: Part II
Buparlisib
|
—
|
—
|
—
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: During study treatment (maximum treatment exposure for Part I was 403.7 weeks)Population: Safety set included all participants who received at least 1 dose of encorafenib or binimetinib for Part I and had at least 1 valid post-baseline safety assessment.
Dose intensity across all cycles = cumulative dose/duration of exposure. Treatment cycle for encorafenib and binimetinib =21 days.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=75 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=83 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Actual Dose Intensity: Part I
Encorafenib
|
425.311 Milligram per day
Standard Deviation 53.5392
|
408.711 Milligram per day
Standard Deviation 65.5297
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Actual Dose Intensity: Part I
Binimetinib
|
81.920 Milligram per day
Standard Deviation 13.0994
|
82.083 Milligram per day
Standard Deviation 10.9117
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: During study treatment (maximum treatment exposure for Part II was 97.0 weeks)Population: Safety set included all participants who received at least 1 dose of 3rd combination agent for Part II and had at least 1 valid post-baseline safety assessment. Here, "Number Analyzed" signifies number of participants evaluable for specified drug.
Dose intensity = cumulative dose/ duration of exposure. Treatment cycle = 21days for the combination treatment with buparlisib and capmatinib and 28 days for the combination treatment with ribociclib and infigratinib.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=38 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=1 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=13 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=6 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Actual Dose Intensity: Part II
Encorafenib
|
197.856 Milligram per day
Standard Deviation 42.6637
|
450.000 Milligram per day
Standard Deviation NA
Only 1 participant evaluable.
|
195.945 Milligram per day
Standard Deviation 8.4015
|
405.014 Milligram per day
Standard Deviation 102.5218
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Actual Dose Intensity: Part II
Binimetinib
|
79.749 Milligram per day
Standard Deviation 14.7267
|
90.000 Milligram per day
Standard Deviation NA
Only 1 participant evaluable.
|
87.373 Milligram per day
Standard Deviation 3.6593
|
78.791 Milligram per day
Standard Deviation 20.1538
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Actual Dose Intensity: Part II
Ribociclib
|
486.628 Milligram per day
Standard Deviation 79.4485
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Actual Dose Intensity: Part II
Infigratinib
|
—
|
60.227 Milligram per day
Standard Deviation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Actual Dose Intensity: Part II
Capmatinib
|
—
|
—
|
579.519 Milligram per day
Standard Deviation 259.1157
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Actual Dose Intensity: Part II
Buparlisib
|
—
|
—
|
—
|
72.206 Milligram per day
Standard Deviation 15.7019
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From start of study drug until documented PD or death due to any cause or censoring date (maximum treatment exposure for Part I was 403.7 weeks)Population: For Part I, FAS consisted of all participants who received at least 1 dose (partial or full) of encorafenib or binimetinib.
PFS was defined as the time from the start date of study drug in Part I until documented PD or death due to any cause. All participants who had not progressed or died at the time of the data cut-off were censored at the date of last tumor assessment (other than those who were unknown or missing) prior to cut-off date or start date of new anti-neoplastic therapy, whichever is earlier. Per RECIST 1.1, PD= At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Kaplan Meier method used for estimation.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=75 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=83 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Progression-Free Survival (PFS): Part I
|
11.1 Months
Interval 8.1 to 15.0
|
3.3 Months
Interval 2.1 to 4.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From start of study drug until documented PD or death due to any cause or censoring date (maximum treatment exposure for Part II was 97.0 weeks)Population: For Part II, FAS consisted of all participants who received at least 1 dose of encorafenib or binimetinib or the assigned third agent following the assignment of the triple combination treatment.
PFS was defined as the time from the start date of study drug in Part II until documented PD or death due to any cause. All participants who had not progressed or died at the time of the data cut-off were censored at the date of last tumor assessment (other than those who were unknown or missing) prior to cut-off date or start date of new anti-neoplastic therapy, whichever is earlier. Per RECIST 1.1, PD= At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Kaplan Meier method used for estimation.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=38 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=1 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=13 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=6 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
PFS: Part II
|
2.1 Months
Interval 1.7 to 2.1
|
2.1 Months
Only 1 participant evaluable.
|
2.1 Months
Interval 1.0 to 3.7
|
1.4 Months
Interval 0.4 to
Upper limit of 95% CI could not be estimated as there were insufficient number of participants with events.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From date of first documented response (CR or PR) till the date of first documented progression or death due to underlying cancer or censoring date (maximum treatment exposure for Part I was 403.7 weeks)Population: For Part I, FAS consisted of all participants who received at least 1 dose (partial or full) of encorafenib or binimetinib. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure who were confirmed responders. Kaplan Meier method used for estimation.
DOR: time between date of first documented response (CR or PR) and date of first documented progression or death due to underlying cancer. If there was no progression or death due to underlying cancer, then the participant was censored at the date of last tumor assessment other than unknown. RECIST v1.1: CR = disappearance of all non-nodal target lesions. Any pathological lymph nodes assigned as target lesions must had a reduction in short axis to \<10 mm. Disappearance of all non-target lesions. All lymph nodes assigned a non-target lesion must be non-pathological in size (\<10 mm short axis); b) PR = at least a 30% decrease in sum of diameter of all target lesions, taking as reference baseline sum of diameters; c) PD= At least a 20% increase in sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition, sum must also demonstrate an absolute increase of at least 5 mm.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=55 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=21 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Duration of Response (DOR): Part I
|
10.9 Months
Interval 8.1 to 14.1
|
5.6 Months
Interval 3.9 to 13.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From date of first documented response (CR or PR) till the date of first documented progression or death due to underlying cancer or censoring date (maximum treatment exposure for Part II was 97.0 weeks)Population: For Part II, FAS consisted of all participants who received at least 1 dose of encorafenib or binimetinib or the assigned third agent following the assignment of the triple combination treatment. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure who were confirmed responders. Kaplan Meier method used for estimation.
DOR: time between date of first documented response (CR or PR) and date of first documented progression or death due to underlying cancer. If there was no progression or death due to underlying cancer, then the participant was censored at the date of last tumor assessment other than unknown. RECIST v1.1: CR = disappearance of all non-nodal target lesions. Any pathological lymph nodes assigned as target lesions must had a reduction in short axis to \<10 mm. Disappearance of all non-target lesions. All lymph nodes assigned a non-target lesion must be non-pathological in size (\<10 mm short axis); b) PR = at least a 30% decrease in sum of diameter of all target lesions, taking as reference baseline sum of diameters; c) PD= At least a 20% increase in sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition, sum must also demonstrate an absolute increase of at least 5 mm.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=1 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
DOR: Part II
|
2.1 Months
Only 1 participant was evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From start date of study drug till first documented response (CR or PR) (maximum treatment exposure for Part I was 403.7 weeks)Population: For Part I, FAS consisted of all participants who received at least 1 dose (partial or full) of encorafenib or binimetinib. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure who were responders.
TTR was defined as the time between the start date of study drug in Part I and first documented response (CR or PR). RECIST v1.1: a) CR = disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must had a reduction in short axis to \<10 mm. Disappearance of all non-target lesions. In addition, all lymph nodes assigned a non-target lesion must be non-pathological in size (\<10 mm short axis) and b) PR = at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Kaplan Meier method used for estimation.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=52 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=16 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Time to Response (TTR): Part I
|
1.4 Months
Interval 1.38 to 1.41
|
0.72 Months
Interval 0.72 to 0.82
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From start date of study drug till first documented response (CR or PR) (maximum treatment exposure for Part II was 97.0 weeks)Population: For Part II, FAS consisted of all participants who received at least 1 dose of encorafenib or binimetinib or the assigned third agent following the assignment of the triple combination treatment. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure who were responders.
TTR was defined as the time between the start date of study drug in Part II and first documented response (CR or PR). RECIST v1.1: a) CR = disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must had a reduction in short axis to \<10 mm. Disappearance of all non-target lesions. In addition, all lymph nodes assigned a non-target lesion must be non-pathological in size (\<10 mm short axis) and b) PR = at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Kaplan Meier method used for estimation.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=1 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
TTR: Part II
|
4.1 Months
Only 1 participant was evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From start date of study drug till first documented response (CR or PR or SD) (maximum treatment exposure for Part I was 403.7 weeks)Population: For Part I, FAS consisted of all participants who received at least 1 dose (partial or full) of encorafenib or binimetinib.
DCR was defined as percentage of participants with a best overall response of CR or PR or SD. RECIST v1.1: a) CR = disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must had a reduction in short axis to \<10 mm. Disappearance of all non-target lesions. In addition, all lymph nodes assigned a non-target lesion must be non-pathological in size (\<10 mm short axis); b) PR = at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters and c) SD = neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. PD= At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=75 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=83 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Disease Control Rate (DCR): Part I
|
92.0 Percentage of participants
Interval 83.4 to 97.0
|
42.2 Percentage of participants
Interval 31.4 to 53.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From start date of study drug till first documented response (CR or PR or SD) (maximum treatment exposure for Part II was 97.0 weeks)Population: For Part II, FAS consisted of all participants who received at least 1 dose of encorafenib or binimetinib or the assigned third agent following the assignment of the triple combination treatment.
DCR was defined as percentage of participants with a best overall response of CR or PR or SD. RECIST v1.1: a) CR = disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must had a reduction in short axis to \<10 mm. Disappearance of all non-target lesions. In addition, all lymph nodes assigned a non-target lesion must be non-pathological in size (\<10 mm short axis); b) PR = at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters and c) SD = neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. PD= At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=38 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=1 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=13 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=6 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
DCR: Part II
|
26.3 Percentage of participants
Interval 13.4 to 43.1
|
0 Percentage of participants
Only 1 participant was evaluable.
|
15.4 Percentage of participants
Interval 1.9 to 45.4
|
16.7 Percentage of participants
Interval 0.4 to 64.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From date of start of treatment to date of death due to any cause or censoring date (maximum treatment exposure for Part II was 97.0 weeks)Population: For Part II, FAS consisted of all participants who received at least 1 dose of encorafenib or binimetinib or the assigned third agent following the assignment of the triple combination treatment.
OS was defined as the time from the start date of study treatment (3rd agent combined with encorafenib and binimetinib) to date of death due to any cause. If a participant was not known to have died, survival was censored at the date of last known date participant alive. Kaplan Meier method used for estimation.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=38 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=1 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=13 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=6 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Overall Survival (OS): Part II
|
10.4 Months
Interval 6.0 to 16.7
|
20.8 Months
Only 1 participant was evaluable.
|
5.6 Months
Interval 1.7 to
Upper limit was not estimable due to insufficient number of participants with events.
|
2.5 Months
Interval 0.4 to
Upper limit was not estimable due to insufficient number of participants with events.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to end of treatment (EOT) (maximum treatment exposure for Part I was 403.7 weeks)Population: For Part I, FAS consisted of all participants who received at least 1 dose (partial or full) of encorafenib or binimetinib.
Number of participants with multiple alterations in genomic biomarkers like biomarker BRAF, CCND1, CDK4, EGFR, FGFR1, FGFR4, KRAS, MET, NRAS, PIK3CA, and PTEN were reported and alterations included copy number variant/copy number ratio (CNV/CNR), rearrangement, short variant. It was not necessary that all biomarkers had all alterations. Baseline = last non-missing value prior to the first dose of study treatment.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=75 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=83 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: CNV/CNR at Baseline
|
4 Participants
|
9 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: CNV/CNR at EOT
|
2 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at Baseline chr7:140482508-140482692
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at Baseline chr7:140487121-140487285
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at Baseline chr7:140487916-140488167
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at Baseline chr7:140488878-140489055
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at Baseline cchr7:140489413-140489576
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at Baseline chr7:140490446-140490656
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at Baseline chr7:140491528-140491878
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at Baseline chr7:140491580-140491878
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at Baseline chr7:140492969-140493301
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at EOT chr7:140481691-140482150
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at EOT chr7:140482057-140482467
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at EOT chr7:140482081-140482482
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at EOT chr7:140482088-140482296
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at EOT chr7:140482167-140482382
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at EOT chr7:140482495-140482731
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at EOT chr7:140482644-140482867
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at EOT chr7:140483058-140483257
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at EOT chr7:140486136-140486408
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at EOT chr7:140486274-140486561
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at EOT chr7:140489019-140489575
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at EOT chr7:140489219-140489431
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at EOT chr7:140489830-140490002
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at EOT chr7:140491411-140491879
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at EOT chr7:140492091-140492240
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at EOT chr7:140492379-140492708
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at EOT chr7:140492714-140492997
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at EOT chr7:140493601-140493951
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Rearrangement/Genomic Position at EOT chr7:140493858-140494232
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Short variant/amino acid change at Baseline V600E
|
46 Participants
|
53 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Short variant/amino acid change at Baseline V600G
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Short variant/amino acid change at Baseline V600K
|
4 Participants
|
7 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Short variant/amino acid change at Baseline V600R
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Short variant/amino acid change at EOT V600E
|
18 Participants
|
19 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Short variant/amino acid change at EOT V600K
|
0 Participants
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
BRAF: Short variant/amino acid change at EOT V600R
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
CCND1: CNV/CNR at Baseline
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
CDK4: CNV/CNR at Baseline
|
3 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
EGFR: CNV/CNR at Baseline
|
1 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
EGFR: CNV/CNR at EOT
|
1 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
FGFR1: CNV/CNR at Baseline
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
FGFR1: CNV/CNR at EOT
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
FGFR4: CNV/CNR at Baseline
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
KRAS: CNV/CNR at Baseline
|
2 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
MET: CNV/CNR at Baseline
|
4 Participants
|
6 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
MET: CNV/CNR at EOT
|
3 Participants
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
MET: Rearrangement/Genomic Position at EOT chr7:116321020-116321260
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
NRAS: CNV/CNR at Baseline
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
PIK3CA: CNV/CNR at Baseline
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
PTEN: CNV/CNR at Baseline
|
4 Participants
|
13 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
PTEN: CNV/CNR at EOT
|
5 Participants
|
10 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Summary of Genomic Biomarkers From Tumor Samples: Part I
PTEN: Rearrangement/Genomic Position at EOT chr10:89720538-89720776
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: C1 (1.5 hrs post-dose on D1; pre-dose, 1.5 hrs post-dose on D15); C2 (pre-dose on D8 and D21); C3 pre-dose on D15; C4 pre-dose on D15; C5 pre-dose on D15; EOTPopulation: Pharmacokinetic analysis set (PAS) consisted of all participants who had at least one blood sample providing evaluable pharmacokinetic (PK) data. All participants reported under "Number of Participants Analyzed" contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified time points.
In results reported below, following abbreviation have been used: Cycle 1 (C1), Day 1 (D1), Day 8 (D8), Day 15 (D15), Day 21 (D21), Cycle 2 (C2), Cycle 3 (C3), Cycle 4 (C4), Cycle 5 (C5) and end of treatment (EOT). Maximum treatment exposure for Part I was of 403.7 weeks.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=75 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=78 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Plasma Concentration for Encorafenib (LGX): Part I
C1 D1, 1.5 hr
|
4820 Nanogram per milliliter
Geometric Coefficient of Variation 114.2
|
4480 Nanogram per milliliter
Geometric Coefficient of Variation 124.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Encorafenib (LGX): Part I
C1 D15, Pre-dose
|
10.0 Nanogram per milliliter
Geometric Coefficient of Variation 81.6
|
13.8 Nanogram per milliliter
Geometric Coefficient of Variation 104.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Encorafenib (LGX): Part I
C1 D15, 1.5 hr
|
2470 Nanogram per milliliter
Geometric Coefficient of Variation 116.7
|
2910 Nanogram per milliliter
Geometric Coefficient of Variation 91.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Encorafenib (LGX): Part I
C2 D8, Pre-dose
|
9.96 Nanogram per milliliter
Geometric Coefficient of Variation 81.7
|
14.7 Nanogram per milliliter
Geometric Coefficient of Variation 117.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Encorafenib (LGX): Part I
C2 D21, Pre-dose
|
9.04 Nanogram per milliliter
Geometric Coefficient of Variation 84.2
|
15.6 Nanogram per milliliter
Geometric Coefficient of Variation 156.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Encorafenib (LGX): Part I
C3 D15, Pre-dose
|
8.43 Nanogram per milliliter
Geometric Coefficient of Variation 82.3
|
11.2 Nanogram per milliliter
Geometric Coefficient of Variation 114.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Encorafenib (LGX): Part I
C4 D15, Pre-dose
|
9.21 Nanogram per milliliter
Geometric Coefficient of Variation 100.3
|
12.3 Nanogram per milliliter
Geometric Coefficient of Variation 108.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Encorafenib (LGX): Part I
C5 D15, Pre-dose
|
8.84 Nanogram per milliliter
Geometric Coefficient of Variation 59.4
|
11.9 Nanogram per milliliter
Geometric Coefficient of Variation 72.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Encorafenib (LGX): Part I
EOT
|
19.6 Nanogram per milliliter
Geometric Coefficient of Variation 399.9
|
34.5 Nanogram per milliliter
Geometric Coefficient of Variation 890.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: C1 (1.5, 4 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6, 8 hrs post-dose on D15; 24 hrs post-dose on D16; pre-dose on D21); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; C4 pre-dose on D1; C5 pre-dose on D1; EOTPopulation: PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified time points.
In results reported below, following abbreviation have been used: Cycle 1 (C1), Day 1 (D1), Day 8 (D8), Day 15 (D15), Day 16 (D16), Day 21 (D21), Cycle 2 (C2), Cycle 3 (C3), Cycle 4 (C4), Cycle 5 (C5). Maximum treatment exposure for Part II was of 97.0 weeks.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=3 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=3 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=1 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=5 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
n=5 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=1 Participants
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=3 Participants
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
n=29 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Plasma Concentration for Encorafenib (LGX): Part II
C1 D15: 6 hrs
|
246 Nanogram per milliliter
Geometric Coefficient of Variation 94.6
|
433 Nanogram per milliliter
Geometric Coefficient of Variation 45.0
|
211 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
165 Nanogram per milliliter
Geometric Coefficient of Variation 68.8
|
266 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
317 Nanogram per milliliter
Geometric Coefficient of Variation 26.8
|
209 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
199 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
203 Nanogram per milliliter
Geometric Coefficient of Variation 11.1
|
—
|
567 Nanogram per milliliter
Geometric Coefficient of Variation 51.5
|
—
|
—
|
|
Plasma Concentration for Encorafenib (LGX): Part II
C1 D16: 24 hrs
|
11.3 Nanogram per milliliter
Geometric Coefficient of Variation 45.3
|
25.1 Nanogram per milliliter
Geometric Coefficient of Variation 2066.8
|
6.76 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
8.10 Nanogram per milliliter
Geometric Coefficient of Variation 43.1
|
5.20 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
15.0 Nanogram per milliliter
Geometric Coefficient of Variation 20.9
|
10.7 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
7.85 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
10.8 Nanogram per milliliter
Geometric Coefficient of Variation 106.1
|
—
|
22.8 Nanogram per milliliter
Geometric Coefficient of Variation 199.0
|
—
|
—
|
|
Plasma Concentration for Encorafenib (LGX): Part II
C1 D15: 8 hrs
|
180 Nanogram per milliliter
Geometric Coefficient of Variation 94.5
|
276 Nanogram per milliliter
Geometric Coefficient of Variation 103.8
|
—
|
115 Nanogram per milliliter
Geometric Coefficient of Variation 55.4
|
257 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
217 Nanogram per milliliter
Geometric Coefficient of Variation 34.5
|
142 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
132 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
109 Nanogram per milliliter
Geometric Coefficient of Variation 2.6
|
—
|
412 Nanogram per milliliter
Geometric Coefficient of Variation 62.3
|
—
|
—
|
|
Plasma Concentration for Encorafenib (LGX): Part II
C1 D1: 1.5 hrs
|
—
|
3430 Nanogram per milliliter
Geometric Coefficient of Variation 17.6
|
1860 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1130 Nanogram per milliliter
Geometric Coefficient of Variation 3.8
|
3750 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1770 Nanogram per milliliter
Geometric Coefficient of Variation 62.9
|
878 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
2030 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
847 Nanogram per milliliter
Geometric Coefficient of Variation 28.1
|
—
|
1600 Nanogram per milliliter
Geometric Coefficient of Variation 85.6
|
—
|
—
|
|
Plasma Concentration for Encorafenib (LGX): Part II
C1 D1: 4 hrs
|
—
|
—
|
—
|
—
|
—
|
—
|
238 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
297 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
626 Nanogram per milliliter
Geometric Coefficient of Variation 65.7
|
—
|
596 Nanogram per milliliter
Geometric Coefficient of Variation 51.1
|
—
|
—
|
|
Plasma Concentration for Encorafenib (LGX): Part II
C1 D8: Pre-dose
|
8.97 Nanogram per milliliter
Geometric Coefficient of Variation 89.0
|
21.3 Nanogram per milliliter
Geometric Coefficient of Variation 150.6
|
12.4 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
10.3 Nanogram per milliliter
Geometric Coefficient of Variation 54.4
|
6.21 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
11.7 Nanogram per milliliter
Geometric Coefficient of Variation 56.4
|
12.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
15.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
9.39 Nanogram per milliliter
Geometric Coefficient of Variation 15.9
|
7.15 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
16.2 Nanogram per milliliter
Geometric Coefficient of Variation 116.1
|
—
|
—
|
|
Plasma Concentration for Encorafenib (LGX): Part II
C1 D15: Pre-dose
|
11.2 Nanogram per milliliter
Geometric Coefficient of Variation 106.3
|
18.6 Nanogram per milliliter
Geometric Coefficient of Variation 159.4
|
7.74 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
9.95 Nanogram per milliliter
Geometric Coefficient of Variation 40.1
|
7.95 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
13.5 Nanogram per milliliter
Geometric Coefficient of Variation 35.0
|
9.28 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
10.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
7.75 Nanogram per milliliter
Geometric Coefficient of Variation 37.3
|
—
|
20.9 Nanogram per milliliter
Geometric Coefficient of Variation 188.5
|
—
|
—
|
|
Plasma Concentration for Encorafenib (LGX): Part II
C1 D15: 0.5 hr
|
437 Nanogram per milliliter
Geometric Coefficient of Variation 228.2
|
625 Nanogram per milliliter
Geometric Coefficient of Variation 19.5
|
1690 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
262 Nanogram per milliliter
Geometric Coefficient of Variation 345.5
|
139 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
127 Nanogram per milliliter
Geometric Coefficient of Variation 216.1
|
8.55 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
601 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
473 Nanogram per milliliter
Geometric Coefficient of Variation 1248.5
|
—
|
175 Nanogram per milliliter
Geometric Coefficient of Variation 252.7
|
—
|
—
|
|
Plasma Concentration for Encorafenib (LGX): Part II
C1 D15: 1.5 hrs
|
3050 Nanogram per milliliter
Geometric Coefficient of Variation 59.6
|
2150 Nanogram per milliliter
Geometric Coefficient of Variation 54.6
|
2100 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1550 Nanogram per milliliter
Geometric Coefficient of Variation 62.4
|
2890 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
2500 Nanogram per milliliter
Geometric Coefficient of Variation 27.9
|
366 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1960 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1450 Nanogram per milliliter
Geometric Coefficient of Variation 3.9
|
—
|
1850 Nanogram per milliliter
Geometric Coefficient of Variation 69.7
|
—
|
—
|
|
Plasma Concentration for Encorafenib (LGX): Part II
C1 D15: 2.5 hrs
|
1420 Nanogram per milliliter
Geometric Coefficient of Variation 39.6
|
1320 Nanogram per milliliter
Geometric Coefficient of Variation 30.0
|
1020 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
808 Nanogram per milliliter
Geometric Coefficient of Variation 55.0
|
—
|
1550 Nanogram per milliliter
Geometric Coefficient of Variation 34.4
|
622 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
981 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
686 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
1510 Nanogram per milliliter
Geometric Coefficient of Variation 48.2
|
—
|
—
|
|
Plasma Concentration for Encorafenib (LGX): Part II
C1 D15: 4 hrs
|
649 Nanogram per milliliter
Geometric Coefficient of Variation 37.5
|
770 Nanogram per milliliter
Geometric Coefficient of Variation 6.2
|
397 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
453 Nanogram per milliliter
Geometric Coefficient of Variation 24.3
|
1160 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
667 Nanogram per milliliter
Geometric Coefficient of Variation 20.4
|
389 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
478 Nanogram per milliliter
Geometric Coefficient of Variation 39.6
|
—
|
1020 Nanogram per milliliter
Geometric Coefficient of Variation 34.3
|
—
|
—
|
|
Plasma Concentration for Encorafenib (LGX): Part II
C1 D21: Pre-dose
|
—
|
—
|
10.4 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
13.6 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
13.9 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
12.4 Nanogram per milliliter
Geometric Coefficient of Variation 60.4
|
20.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
17.5 Nanogram per milliliter
Geometric Coefficient of Variation 106.4
|
—
|
—
|
|
Plasma Concentration for Encorafenib (LGX): Part II
C2 D1: Pre-dose
|
13.5 Nanogram per milliliter
Geometric Coefficient of Variation 193.0
|
32.6 Nanogram per milliliter
Geometric Coefficient of Variation 202.9
|
12.7 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
19.9 Nanogram per milliliter
Geometric Coefficient of Variation 210.5
|
2.91 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
14.0 Nanogram per milliliter
Geometric Coefficient of Variation 30.3
|
8.50 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
82.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
8.19 Nanogram per milliliter
Geometric Coefficient of Variation 42.2
|
19.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
11.9 Nanogram per milliliter
Geometric Coefficient of Variation 100.9
|
—
|
—
|
|
Plasma Concentration for Encorafenib (LGX): Part II
C2 D15: Pre-dose
|
41.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
15.6 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
13.9 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
9.68 Nanogram per milliliter
Geometric Coefficient of Variation 36.5
|
—
|
8.49 Nanogram per milliliter
Geometric Coefficient of Variation 70.5
|
11.1 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
16.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
12.3 Nanogram per milliliter
Geometric Coefficient of Variation 24.3
|
8.95 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
21.3 Nanogram per milliliter
Geometric Coefficient of Variation 115.3
|
—
|
—
|
|
Plasma Concentration for Encorafenib (LGX): Part II
C3 D1: Pre-dose
|
13.9 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
20.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
23.2 Nanogram per milliliter
Geometric Coefficient of Variation 33.1
|
—
|
10.1 Nanogram per milliliter
Geometric Coefficient of Variation 72.1
|
—
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Participant had below limit of the quantitation (BLQ) value.
|
—
|
—
|
9.34 Nanogram per milliliter
Geometric Coefficient of Variation 125.7
|
—
|
—
|
|
Plasma Concentration for Encorafenib (LGX): Part II
C4 D1: Pre-dose
|
30.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
12.5 Nanogram per milliliter
Geometric Coefficient of Variation 11.4
|
5.95 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
7.28 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
13.1 Nanogram per milliliter
Geometric Coefficient of Variation 21.8
|
—
|
—
|
|
Plasma Concentration for Encorafenib (LGX): Part II
C5 D1: Pre-dose
|
749 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
10.7 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
9.84 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
9.15 Nanogram per milliliter
Geometric Coefficient of Variation 44.0
|
—
|
—
|
|
Plasma Concentration for Encorafenib (LGX): Part II
EOT
|
1.77 Nanogram per milliliter
Geometric Coefficient of Variation NA
Out of 2, 1 participant had BLQ value.
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Participant had BLQ value.
|
14.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
All participants had BLQ value.
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Participant had BLQ value.
|
13.9 Nanogram per milliliter
Geometric Coefficient of Variation 66.6
|
8.24 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
6.81 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
24.5 Nanogram per milliliter
Geometric Coefficient of Variation 259.8
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Participant had BLQ value.
|
16.6 Nanogram per milliliter
Geometric Coefficient of Variation 265.0
|
—
|
—
|
SECONDARY outcome
Timeframe: C1 (1.5 hrs post-dose on D1; pre-dose, 1.5 hrs post-dose on D15); C2 (pre-dose on D8 and D21); C3 pre-dose on D15; C4 pre-dose on D15; C5 pre-dose on D15; EOTPopulation: PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified time points.
AR00426032 is metabolite of binimetinib. Maximum treatment exposure for Part I was of 403.7 weeks.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=75 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=78 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part I
Binimetinib: C1 D1, 1.5 hr
|
551 Nanogram per milliliter
Geometric Coefficient of Variation 88.8
|
482 Nanogram per milliliter
Geometric Coefficient of Variation 73.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part I
Binimetinib: C1 D15, Pre-dose
|
40.3 Nanogram per milliliter
Geometric Coefficient of Variation 63.5
|
43.3 Nanogram per milliliter
Geometric Coefficient of Variation 72.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part I
Binimetinib: C1 D15, 1.5 hr
|
461 Nanogram per milliliter
Geometric Coefficient of Variation 70.2
|
451 Nanogram per milliliter
Geometric Coefficient of Variation 50.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part I
Binimetinib: C2 D8, Pre-dose
|
39.9 Nanogram per milliliter
Geometric Coefficient of Variation 58.8
|
44.8 Nanogram per milliliter
Geometric Coefficient of Variation 73.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part I
Binimetinib: C2 D21, Pre-dose
|
38.9 Nanogram per milliliter
Geometric Coefficient of Variation 54.9
|
53.1 Nanogram per milliliter
Geometric Coefficient of Variation 78.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part I
Binimetinib: C3 D15, Pre-dose
|
41.9 Nanogram per milliliter
Geometric Coefficient of Variation 60.4
|
38.7 Nanogram per milliliter
Geometric Coefficient of Variation 94.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part I
Binimetinib: C4 D15, Pre-dose
|
36.2 Nanogram per milliliter
Geometric Coefficient of Variation 68.6
|
38.8 Nanogram per milliliter
Geometric Coefficient of Variation 57.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part I
Binimetinib: C5 D15, Pre-dose
|
41.3 Nanogram per milliliter
Geometric Coefficient of Variation 55.7
|
39.2 Nanogram per milliliter
Geometric Coefficient of Variation 76.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part I
Binimetinib: EOT
|
33.2 Nanogram per milliliter
Geometric Coefficient of Variation 179.4
|
52.8 Nanogram per milliliter
Geometric Coefficient of Variation 180.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part I
AR00426032: C1 D1, 1.5 hr
|
57.6 Nanogram per milliliter
Geometric Coefficient of Variation 93.5
|
47.5 Nanogram per milliliter
Geometric Coefficient of Variation 101.6
|
—
|
—
|
—
|
—
|
—
|
—
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—
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—
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—
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—
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—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part I
AR00426032: C1 D15, Pre-dose
|
4.13 Nanogram per milliliter
Geometric Coefficient of Variation 70.8
|
4.50 Nanogram per milliliter
Geometric Coefficient of Variation 64.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part I
AR00426032: C1 D15, 1.5 hr
|
30.6 Nanogram per milliliter
Geometric Coefficient of Variation 110.9
|
31.9 Nanogram per milliliter
Geometric Coefficient of Variation 84.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
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—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part I
AR00426032: C2 D8, Pre-dose
|
3.63 Nanogram per milliliter
Geometric Coefficient of Variation 60.2
|
4.17 Nanogram per milliliter
Geometric Coefficient of Variation 88.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part I
AR00426032: C2 D21, Pre-dose
|
4.11 Nanogram per milliliter
Geometric Coefficient of Variation 61.0
|
4.39 Nanogram per milliliter
Geometric Coefficient of Variation 80.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part I
AR00426032: C3 D15, Pre-dose
|
3.71 Nanogram per milliliter
Geometric Coefficient of Variation 59.5
|
3.90 Nanogram per milliliter
Geometric Coefficient of Variation 60.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part I
AR00426032: C4 D15, Pre-dose
|
3.48 Nanogram per milliliter
Geometric Coefficient of Variation 65.8
|
3.81 Nanogram per milliliter
Geometric Coefficient of Variation 56.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part I
AR00426032: C5 D15, Pre-dose
|
3.77 Nanogram per milliliter
Geometric Coefficient of Variation 66.9
|
3.36 Nanogram per milliliter
Geometric Coefficient of Variation 67.3
|
—
|
—
|
—
|
—
|
—
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—
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—
|
—
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—
|
—
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—
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Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part I
AR00426032: EOT
|
4.09 Nanogram per milliliter
Geometric Coefficient of Variation 90.8
|
5.88 Nanogram per milliliter
Geometric Coefficient of Variation 118.0
|
—
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
|
SECONDARY outcome
Timeframe: C1 (1.5, 4 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6, 8 hrs post-dose on D15; 24 hrs post-dose on D16; pre-dose on D21); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; C4 pre-dose on D1; C5 pre-dose on D1; EOTPopulation: PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table; however, may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified time points.
AR00426032 is metabolite of binimetinib. Maximum treatment exposure for Part II was of 97.0 weeks.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=3 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=3 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=1 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=5 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
n=5 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=1 Participants
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=3 Participants
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
n=29 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=1 Participants
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
n=1 Participants
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
AR00426032, C1 D1: 4 hrs
|
—
|
—
|
—
|
—
|
—
|
—
|
9.40 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
4.09 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
6.71 Nanogram per milliliter
Geometric Coefficient of Variation 145.3
|
—
|
12.3 Nanogram per milliliter
Geometric Coefficient of Variation 75.3
|
4.61 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
AR00426032, C1 D15: 2.5 hrs
|
18.5 Nanogram per milliliter
Geometric Coefficient of Variation 77.0
|
11.3 Nanogram per milliliter
Geometric Coefficient of Variation 447.2
|
7.75 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
18.5 Nanogram per milliliter
Geometric Coefficient of Variation 88.4
|
—
|
34.3 Nanogram per milliliter
Geometric Coefficient of Variation 51.3
|
9.71 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
8.51 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
16.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
18.5 Nanogram per milliliter
Geometric Coefficient of Variation 81.2
|
4.73 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
Binimetinib, C1 D1: 1.5 hrs
|
—
|
410 Nanogram per milliliter
Geometric Coefficient of Variation 48.8
|
416 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
313 Nanogram per milliliter
Geometric Coefficient of Variation 25.6
|
1100 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
508 Nanogram per milliliter
Geometric Coefficient of Variation 130.2
|
396 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
649 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
273 Nanogram per milliliter
Geometric Coefficient of Variation 24.6
|
—
|
446 Nanogram per milliliter
Geometric Coefficient of Variation 59.8
|
522 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1230 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
Binimetinib, C1 D1: 4 hrs
|
—
|
—
|
—
|
—
|
—
|
—
|
152 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
106 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
129 Nanogram per milliliter
Geometric Coefficient of Variation 25.8
|
—
|
215 Nanogram per milliliter
Geometric Coefficient of Variation 44.5
|
99.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
Binimetinib, C1 D8: Pre-dose
|
41.6 Nanogram per milliliter
Geometric Coefficient of Variation 21.7
|
51.1 Nanogram per milliliter
Geometric Coefficient of Variation 9.7
|
46.0 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
74.6 Nanogram per milliliter
Geometric Coefficient of Variation 34.5
|
27.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
67.4 Nanogram per milliliter
Geometric Coefficient of Variation 63.1
|
63.0 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
31.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
25.1 Nanogram per milliliter
Geometric Coefficient of Variation 1.7
|
27.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
51.0 Nanogram per milliliter
Geometric Coefficient of Variation 67.8
|
37.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
Binimetinib, C1 D15: Pre-dose
|
32.0 Nanogram per milliliter
Geometric Coefficient of Variation 17.1
|
39.1 Nanogram per milliliter
Geometric Coefficient of Variation 57.4
|
33.9 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
85.6 Nanogram per milliliter
Geometric Coefficient of Variation 53.7
|
47.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
50.9 Nanogram per milliliter
Geometric Coefficient of Variation 34.4
|
54.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
28.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
21.1 Nanogram per milliliter
Geometric Coefficient of Variation 23.7
|
—
|
48.2 Nanogram per milliliter
Geometric Coefficient of Variation 70.0
|
36.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
Binimetinib, C1 D15: 0.5 hr
|
150 Nanogram per milliliter
Geometric Coefficient of Variation 36.1
|
143 Nanogram per milliliter
Geometric Coefficient of Variation 496.2
|
315 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
430 Nanogram per milliliter
Geometric Coefficient of Variation 26.8
|
401 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
180 Nanogram per milliliter
Geometric Coefficient of Variation 91.5
|
229 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
389 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
161 Nanogram per milliliter
Geometric Coefficient of Variation 54.7
|
—
|
158 Nanogram per milliliter
Geometric Coefficient of Variation 90.1
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
Binimetinib, C1 D15: 1.5 hrs
|
386 Nanogram per milliliter
Geometric Coefficient of Variation 41.1
|
187 Nanogram per milliliter
Geometric Coefficient of Variation 351.0
|
413 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
489 Nanogram per milliliter
Geometric Coefficient of Variation 27.1
|
797 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
734 Nanogram per milliliter
Geometric Coefficient of Variation 45.6
|
261 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
520 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
313 Nanogram per milliliter
Geometric Coefficient of Variation 15.9
|
—
|
437 Nanogram per milliliter
Geometric Coefficient of Variation 46.5
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
Binimetinib, C1 D15: 2.5 hrs
|
250 Nanogram per milliliter
Geometric Coefficient of Variation 17.1
|
143 Nanogram per milliliter
Geometric Coefficient of Variation 172.4
|
235 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
295 Nanogram per milliliter
Geometric Coefficient of Variation 29.7
|
—
|
491 Nanogram per milliliter
Geometric Coefficient of Variation 38.0
|
207 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
331 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
154 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
380 Nanogram per milliliter
Geometric Coefficient of Variation 31.2
|
178 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
Binimetinib, C1 D15: 4 hrs
|
147 Nanogram per milliliter
Geometric Coefficient of Variation 21.4
|
125 Nanogram per milliliter
Geometric Coefficient of Variation 62.1
|
98.0 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
166 Nanogram per milliliter
Geometric Coefficient of Variation 48.9
|
264 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
266 Nanogram per milliliter
Geometric Coefficient of Variation 32.5
|
130 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
98.0 Nanogram per milliliter
Geometric Coefficient of Variation 60.0
|
—
|
241 Nanogram per milliliter
Geometric Coefficient of Variation 28.6
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
Binimetinib, C1 D15: 6 hrs
|
79.0 Nanogram per milliliter
Geometric Coefficient of Variation 36.1
|
97.3 Nanogram per milliliter
Geometric Coefficient of Variation 32.8
|
55.8 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
106 Nanogram per milliliter
Geometric Coefficient of Variation 53.3
|
112 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
141 Nanogram per milliliter
Geometric Coefficient of Variation 15.1
|
167 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
77.4 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
53.3 Nanogram per milliliter
Geometric Coefficient of Variation 36.2
|
—
|
134 Nanogram per milliliter
Geometric Coefficient of Variation 46.5
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
Binimetinib, C1 D15: 8 hrs
|
74.9 Nanogram per milliliter
Geometric Coefficient of Variation 34.7
|
59.7 Nanogram per milliliter
Geometric Coefficient of Variation 12.6
|
—
|
107 Nanogram per milliliter
Geometric Coefficient of Variation 40.9
|
132 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
102 Nanogram per milliliter
Geometric Coefficient of Variation 12.4
|
116 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable
|
65.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable
|
42.2 Nanogram per milliliter
Geometric Coefficient of Variation 39.2
|
—
|
109 Nanogram per milliliter
Geometric Coefficient of Variation 54.8
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
Binimetinib, C1 D16: 24 hrs
|
44.1 Nanogram per milliliter
Geometric Coefficient of Variation 19.1
|
30.2 Nanogram per milliliter
Geometric Coefficient of Variation 59.2
|
42.1 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
63.2 Nanogram per milliliter
Geometric Coefficient of Variation 64.0
|
17.6 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
55.9 Nanogram per milliliter
Geometric Coefficient of Variation 54.0
|
78.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
29.8 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
23.1 Nanogram per milliliter
Geometric Coefficient of Variation 5.2
|
—
|
55.2 Nanogram per milliliter
Geometric Coefficient of Variation 66.0
|
40.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
Binimetinib, C1 D21: Pre-dose
|
—
|
—
|
34.0 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
40.4 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
38.8 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
13.6 Nanogram per milliliter
Geometric Coefficient of Variation 80.7
|
19.6 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
63.2 Nanogram per milliliter
Geometric Coefficient of Variation 51.0
|
35.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
8.91 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
Binimetinib, C2 D1: Pre-dose
|
38.8 Nanogram per milliliter
Geometric Coefficient of Variation 62.5
|
42.7 Nanogram per milliliter
Geometric Coefficient of Variation 27.8
|
40.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
118 Nanogram per milliliter
Geometric Coefficient of Variation 120.1
|
24.6 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
54.2 Nanogram per milliliter
Geometric Coefficient of Variation 32.4
|
58.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
174 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
23.3 Nanogram per milliliter
Geometric Coefficient of Variation 20.2
|
58.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
46.0 Nanogram per milliliter
Geometric Coefficient of Variation 71.2
|
22.4 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
54.1 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
Binimetinib, C2 D15: Pre-dose
|
63.7 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
73.0 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
63.9 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
40.9 Nanogram per milliliter
Geometric Coefficient of Variation 50.8
|
18.9 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
49.8 Nanogram per milliliter
Geometric Coefficient of Variation 21.2
|
63.1 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
19.4 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
15.2 Nanogram per milliliter
Geometric Coefficient of Variation 18.2
|
14.1 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
58.4 Nanogram per milliliter
Geometric Coefficient of Variation 68.3
|
27.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
34.9 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
Binimetinib, C3 D1: Pre-dose
|
50.0 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
47.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
37.8 Nanogram per milliliter
Geometric Coefficient of Variation 189.6
|
—
|
41.9 Nanogram per milliliter
Geometric Coefficient of Variation 49.0
|
53.4 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
4.82 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
45.0 Nanogram per milliliter
Geometric Coefficient of Variation 91.8
|
42.0 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
Binimetinib, C4 D1: Pre-dose
|
46.1 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
53.8 Nanogram per milliliter
Geometric Coefficient of Variation 10.6
|
63.6 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
40.9 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
77.5 Nanogram per milliliter
Geometric Coefficient of Variation 32.1
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
Binimetinib, C5 D1: Pre-dose
|
60.0 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
42.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
28.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
73.8 Nanogram per milliliter
Geometric Coefficient of Variation 25.7
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
Binimetinib, EOT
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
All participants had BLQ value.
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Participant had BLQ value.
|
36.3 Nanogram per milliliter
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
All participants had BLQ value.
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Participant had BLQ value.
|
52.1 Nanogram per milliliter
Geometric Coefficient of Variation 18.3
|
41.0 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
32.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
13.8 Nanogram per milliliter
Geometric Coefficient of Variation 205.5
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Participant had BLQ value.
|
29.0 Nanogram per milliliter
Geometric Coefficient of Variation 179.7
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
AR00426032, C1 D1: 1.5 hrs
|
—
|
22.4 Nanogram per milliliter
Geometric Coefficient of Variation 200.6
|
12.9 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
11.4 Nanogram per milliliter
Geometric Coefficient of Variation 85.7
|
—
|
35.9 Nanogram per milliliter
Geometric Coefficient of Variation 274.1
|
—
|
22.1 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
8.05 Nanogram per milliliter
Geometric Coefficient of Variation 68.9
|
—
|
19.4 Nanogram per milliliter
Geometric Coefficient of Variation 99.3
|
16.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
64.6 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
AR00426032, C1 D8: Pre-dose
|
3.98 Nanogram per milliliter
Geometric Coefficient of Variation 31.9
|
2.95 Nanogram per milliliter
Geometric Coefficient of Variation 165.3
|
1.21 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
7.10 Nanogram per milliliter
Geometric Coefficient of Variation 122.1
|
—
|
6.34 Nanogram per milliliter
Geometric Coefficient of Variation 54.5
|
6.15 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1.10 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1.73 Nanogram per milliliter
Geometric Coefficient of Variation 48.7
|
2.09 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
5.50 Nanogram per milliliter
Geometric Coefficient of Variation 62.6
|
2.14 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
AR00426032, C1 D15: Pre-dose
|
3.14 Nanogram per milliliter
Geometric Coefficient of Variation 74.5
|
3.80 Nanogram per milliliter
Geometric Coefficient of Variation 111.9
|
1.21 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
11.5 Nanogram per milliliter
Geometric Coefficient of Variation 39.5
|
4.36 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
5.45 Nanogram per milliliter
Geometric Coefficient of Variation 42.2
|
4.16 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
3.81 Nanogram per milliliter
Geometric Coefficient of Variation NA
Out of 2, 1 participant had BLQ value.
|
—
|
4.19 Nanogram per milliliter
Geometric Coefficient of Variation 79.2
|
1.09 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
AR00426032, C1 D15: 0.5 hr
|
6.66 Nanogram per milliliter
Geometric Coefficient of Variation 43.2
|
7.43 Nanogram per milliliter
Geometric Coefficient of Variation 455.1
|
8.21 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
13.1 Nanogram per milliliter
Geometric Coefficient of Variation 97.8
|
11.4 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
9.80 Nanogram per milliliter
Geometric Coefficient of Variation 75.7
|
7.31 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
4.35 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
6.16 Nanogram per milliliter
Geometric Coefficient of Variation 490.6
|
—
|
7.81 Nanogram per milliliter
Geometric Coefficient of Variation 119.0
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
AR00426032, C1 D15: 1.5 hrs
|
24.9 Nanogram per milliliter
Geometric Coefficient of Variation 92.2
|
13.2 Nanogram per milliliter
Geometric Coefficient of Variation 1550.1
|
15.8 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
27.9 Nanogram per milliliter
Geometric Coefficient of Variation 85.6
|
—
|
41.1 Nanogram per milliliter
Geometric Coefficient of Variation 25.7
|
12.9 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
12.6 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
16.1 Nanogram per milliliter
Geometric Coefficient of Variation 151.9
|
—
|
18.3 Nanogram per milliliter
Geometric Coefficient of Variation 135.9
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
AR00426032, C1 D15: 4 hrs
|
11.8 Nanogram per milliliter
Geometric Coefficient of Variation 40.3
|
9.98 Nanogram per milliliter
Geometric Coefficient of Variation 142.4
|
3.15 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
9.46 Nanogram per milliliter
Geometric Coefficient of Variation 142.7
|
22.6 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
19.3 Nanogram per milliliter
Geometric Coefficient of Variation 76.9
|
6.76 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
5.21 Nanogram per milliliter
Geometric Coefficient of Variation 81.9
|
—
|
12.2 Nanogram per milliliter
Geometric Coefficient of Variation 78.7
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
AR00426032, C1 D15: 6 hrs
|
6.86 Nanogram per milliliter
Geometric Coefficient of Variation 61.8
|
7.66 Nanogram per milliliter
Geometric Coefficient of Variation 117.7
|
1.82 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
6.90 Nanogram per milliliter
Geometric Coefficient of Variation 142.3
|
8.89 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
9.66 Nanogram per milliliter
Geometric Coefficient of Variation 71.5
|
5.82 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
2.52 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
3.07 Nanogram per milliliter
Geometric Coefficient of Variation 95.0
|
—
|
7.41 Nanogram per milliliter
Geometric Coefficient of Variation 80.2
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
AR00426032b, C1 D15: 8 hrs
|
5.94 Nanogram per milliliter
Geometric Coefficient of Variation 76.7
|
5.24 Nanogram per milliliter
Geometric Coefficient of Variation 70.7
|
—
|
6.49 Nanogram per milliliter
Geometric Coefficient of Variation 124.9
|
8.06 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
8.87 Nanogram per milliliter
Geometric Coefficient of Variation 76.5
|
5.12 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1.95 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
2.67 Nanogram per milliliter
Geometric Coefficient of Variation 72.9
|
—
|
6.73 Nanogram per milliliter
Geometric Coefficient of Variation 75.0
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
AR00426032, C1 D16: 24 hrs
|
3.99 Nanogram per milliliter
Geometric Coefficient of Variation 61.8
|
2.92 Nanogram per milliliter
Geometric Coefficient of Variation 159.3
|
1.27 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
7.79 Nanogram per milliliter
Geometric Coefficient of Variation 87.5
|
1.44 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
4.75 Nanogram per milliliter
Geometric Coefficient of Variation 25.4
|
6.53 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1.08 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
3.19 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
4.70 Nanogram per milliliter
Geometric Coefficient of Variation 80.2
|
1.56 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
AR00426032, C1 D21: Pre-dose
|
—
|
—
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Participant had BLQ value.
|
—
|
—
|
—
|
3.66 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1.47 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
3.18 Nanogram per milliliter
Geometric Coefficient of Variation NA
Out of 2, 1 participant had BLQ value.
|
1.13 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
6.64 Nanogram per milliliter
Geometric Coefficient of Variation 56.1
|
1.65 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
3.11 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
AR00426032, C2 D1: Pre-dose
|
6.23 Nanogram per milliliter
Geometric Coefficient of Variation 82.0
|
3.51 Nanogram per milliliter
Geometric Coefficient of Variation 36.8
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Participant had BLQ value.
|
13.5 Nanogram per milliliter
Geometric Coefficient of Variation 116.8
|
—
|
5.71 Nanogram per milliliter
Geometric Coefficient of Variation 44.2
|
4.32 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
2.06 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
4.09 Nanogram per milliliter
Geometric Coefficient of Variation NA
Out of 2, 1 participant had BLQ value.
|
3.99 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
4.03 Nanogram per milliliter
Geometric Coefficient of Variation 58.1
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Participant had below BLQ value.
|
17.8 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
AR00426032, C2 D15: Pre-dose
|
9.97 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
7.52 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1.07 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
3.27 Nanogram per milliliter
Geometric Coefficient of Variation 65.1
|
1.74 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
4.23 Nanogram per milliliter
Geometric Coefficient of Variation 62.5
|
8.54 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1.63 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1.99 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1.19 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
5.69 Nanogram per milliliter
Geometric Coefficient of Variation 57.0
|
1.33 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
3.74 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
AR00426032 C3 D1: Pre-dose
|
9.74 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Participant had BLQ value.
|
6.15 Nanogram per milliliter
Geometric Coefficient of Variation NA
Out of 2, 1 participant had BLQ value.
|
—
|
4.35 Nanogram per milliliter
Geometric Coefficient of Variation 42.3
|
4.50 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1.09 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
4.46 Nanogram per milliliter
Geometric Coefficient of Variation 70.2
|
1.73 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
AR00426032, C4 D1: Pre-dose
|
7.10 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
5.70 Nanogram per milliliter
Geometric Coefficient of Variation 11.8
|
5.43 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
2.78 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
5.78 Nanogram per milliliter
Geometric Coefficient of Variation 83.0
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
AR00426032, C5 D1: Pre-dose
|
6.05 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
8.89 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1.36 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
6.11 Nanogram per milliliter
Geometric Coefficient of Variation 67.8
|
—
|
—
|
|
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
AR00426032, EOT
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
All participants had BLQ value.
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Participant had BLQ value.
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Participant had BLQ value.
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
All participants had BLQ value.
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Participant had BLQ value.
|
6.68 Nanogram per milliliter
Geometric Coefficient of Variation 80.1
|
3.77 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1.48 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
3.65 Nanogram per milliliter
Geometric Coefficient of Variation NA
Out of 2, 1 participant had BLQ value.
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Participant had BLQ value.
|
4.24 Nanogram per milliliter
Geometric Coefficient of Variation 85.5
|
—
|
—
|
SECONDARY outcome
Timeframe: C1 (1.5, 4 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6, 8 hrs post-dose on D15; 24 hrs post-dose on D16; pre-dose on D21); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; C4 pre-dose on D1; C5 pre-dose on D1; EOTPopulation: PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table; however, may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified time points.
LEQ803 is metabolite of ribociclib. Maximum treatment exposure for Part II was of 97.0 weeks.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=1 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=1 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=3 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=1 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
n=29 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=1 Participants
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
Ribociclib, C1 D15: Pre-dose
|
98.4 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
28.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
30.7 Nanogram per milliliter
Geometric Coefficient of Variation 24.9
|
—
|
104 Nanogram per milliliter
Geometric Coefficient of Variation 54.2
|
64.7 Nanogram per milliliter
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
Ribociclib, C1 D15: 0.5 hr
|
86.1 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
59.7 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
35.4 Nanogram per milliliter
Geometric Coefficient of Variation 66.6
|
—
|
179 Nanogram per milliliter
Geometric Coefficient of Variation 65.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
Ribociclib, C1 D1: 1.5 hrs
|
220 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
117 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
107 Nanogram per milliliter
Geometric Coefficient of Variation 40.6
|
—
|
230 Nanogram per milliliter
Geometric Coefficient of Variation 119.7
|
185 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
784 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
Ribociclib, C1 D1: 4 hrs
|
213 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
84.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
205 Nanogram per milliliter
Geometric Coefficient of Variation 96.0
|
—
|
354 Nanogram per milliliter
Geometric Coefficient of Variation 58.5
|
268 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
Ribociclib, C1 D8: Pre-dose
|
77.4 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
32.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
30.7 Nanogram per milliliter
Geometric Coefficient of Variation 33.5
|
—
|
100 Nanogram per milliliter
Geometric Coefficient of Variation 49.9
|
80.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
127 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
Ribociclib, C1 D15: 1.5 hrs
|
204 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
95.9 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
200 Nanogram per milliliter
Geometric Coefficient of Variation 240.3
|
—
|
508 Nanogram per milliliter
Geometric Coefficient of Variation 95.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
Ribociclib, C1 D15: 2.5 hrs
|
321 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
126 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
718 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
627 Nanogram per milliliter
Geometric Coefficient of Variation 68.3
|
393 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
Ribociclib, C1 D15: 4 hrs
|
368 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
341 Nanogram per milliliter
Geometric Coefficient of Variation 42.9
|
—
|
707 Nanogram per milliliter
Geometric Coefficient of Variation 62.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
Ribociclib, C1 D15: 6 hrs
|
434 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
109 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
239 Nanogram per milliliter
Geometric Coefficient of Variation 37.2
|
—
|
578 Nanogram per milliliter
Geometric Coefficient of Variation 55.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
Ribociclib, C1 D15: 8 hrs
|
311 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
83.6 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
182 Nanogram per milliliter
Geometric Coefficient of Variation 27.1
|
—
|
477 Nanogram per milliliter
Geometric Coefficient of Variation 55.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
Ribociclib, C1 D16: 24 hrs
|
94.0 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
25.6 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
52.7 Nanogram per milliliter
Geometric Coefficient of Variation 90.4
|
—
|
120 Nanogram per milliliter
Geometric Coefficient of Variation 64.9
|
91.8 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
Ribociclib, C1 D21: Pre-dose
|
105 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
102 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
112 Nanogram per milliliter
Geometric Coefficient of Variation 75.8
|
69.9 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
115 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
Ribociclib, C2 D1: Pre-dose
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Participant had BLQ value.
|
19.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1.59 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1.07 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
7.00 Nanogram per milliliter
Geometric Coefficient of Variation 377.8
|
—
|
132 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
Ribociclib, C2 D15: Pre-dose
|
103 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
41.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
53.7 Nanogram per milliliter
Geometric Coefficient of Variation 51.2
|
36.0 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
107 Nanogram per milliliter
Geometric Coefficient of Variation 59.4
|
113 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
102 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
Ribociclib, C3 D1: Pre-dose
|
1.16 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Participant had BLQ value.
|
—
|
—
|
4.06 Nanogram per milliliter
Geometric Coefficient of Variation 172.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
Ribociclib, C4 D1: Pre-dose
|
1.22 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
1.59 Nanogram per milliliter
Geometric Coefficient of Variation 31.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
Ribociclib, C5 D1: Pre-dose
|
—
|
—
|
—
|
—
|
2.16 Nanogram per milliliter
Geometric Coefficient of Variation 35.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
Ribociclib, EOT
|
1.94 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
60.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1.49 Nanogram per milliliter
Geometric Coefficient of Variation NA
One participant had BLQ value.
|
45.8 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
29.0 Nanogram per milliliter
Geometric Coefficient of Variation 292.1
|
—
|
22.8 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
LEQ803, C1 D1: 1.5 hrs
|
57.1 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
70.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
68.2 Nanogram per milliliter
Geometric Coefficient of Variation 2.4
|
—
|
47.5 Nanogram per milliliter
Geometric Coefficient of Variation 97.4
|
59.0 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
63.6 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
LEQ803, C1 D1: 4 hrs
|
65.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
50.8 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
73.5 Nanogram per milliliter
Geometric Coefficient of Variation 20.4
|
—
|
81.1 Nanogram per milliliter
Geometric Coefficient of Variation 55.6
|
63.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
LEQ803, C1 D8: Pre-dose
|
64.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
49.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
38.1 Nanogram per milliliter
Geometric Coefficient of Variation 9.1
|
—
|
53.7 Nanogram per milliliter
Geometric Coefficient of Variation 36.5
|
47.2 Nanogram per milliliter
|
71.2 Nanogram per milliliter
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
LEQ803, C1 D15: Pre-dose
|
76.0 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
37.1 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
32.9 Nanogram per milliliter
Geometric Coefficient of Variation 25.7
|
—
|
55.1 Nanogram per milliliter
Geometric Coefficient of Variation 33.9
|
49.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
LEQ803, C1 D15: 0.5 hr
|
75.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
39.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
32.1 Nanogram per milliliter
Geometric Coefficient of Variation 0.7
|
—
|
60.8 Nanogram per milliliter
Geometric Coefficient of Variation 36.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
LEQ803, C1 D15: 1.5 hrs
|
92.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
72.6 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
82.7 Nanogram per milliliter
Geometric Coefficient of Variation 0.7
|
—
|
112 Nanogram per milliliter
Geometric Coefficient of Variation 46.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
LEQ803, C1 D15: 2.5 hrs
|
130 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
92.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
126 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
133 Nanogram per milliliter
Geometric Coefficient of Variation 45.4
|
137 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
LEQ803, C1 D15: 4 hrs
|
138 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
140 Nanogram per milliliter
Geometric Coefficient of Variation 23.4
|
—
|
152 Nanogram per milliliter
Geometric Coefficient of Variation 31.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
LEQ803, C1 D15: 6 hrs
|
175 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
90.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
111 Nanogram per milliliter
Geometric Coefficient of Variation 27.6
|
—
|
145 Nanogram per milliliter
Geometric Coefficient of Variation 27.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
LEQ803, C1 D15: 8 hrs
|
135 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
79.8 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
95.2 Nanogram per milliliter
Geometric Coefficient of Variation 50.1
|
—
|
128 Nanogram per milliliter
Geometric Coefficient of Variation 27.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
LEQ803, C1 D16: 24 hrs
|
84.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
46.8 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
42.5 Nanogram per milliliter
Geometric Coefficient of Variation 13.8
|
—
|
63.1 Nanogram per milliliter
Geometric Coefficient of Variation 36.1
|
59.6 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
LEQ803, C1 D21: Pre-dose
|
73.8 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
43.7 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
58.1 Nanogram per milliliter
Geometric Coefficient of Variation 39.1
|
52.9 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
80.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
LEQ803, C2 D1: Pre-dose
|
6.68 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
14.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
4.10 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
2.70 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
8.48 Nanogram per milliliter
Geometric Coefficient of Variation 154.5
|
—
|
80.8 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
LEQ803, C2 D15: Pre-dose
|
90.0 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
45.6 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
45.7 Nanogram per milliliter
Geometric Coefficient of Variation 6.8
|
28.0 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
58.3 Nanogram per milliliter
Geometric Coefficient of Variation 42.7
|
66.8 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
61.1 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
LEQ803, C3 D1: Pre-dose
|
7.88 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
2.75 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
7.57 Nanogram per milliliter
Geometric Coefficient of Variation 61.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
LEQ803, C4 D1: Pre-dose
|
7.19 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
5.72 Nanogram per milliliter
Geometric Coefficient of Variation 6.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
LEQ803, C5 D1: Pre-dose
|
—
|
—
|
—
|
—
|
6.07 Nanogram per milliliter
Geometric Coefficient of Variation 28.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
LEQ803, EOT
|
10.4 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
69.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
5.06 Nanogram per milliliter
Geometric Coefficient of Variation 4.6
|
23.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
20.6 Nanogram per milliliter
Geometric Coefficient of Variation 152.2
|
—
|
31.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: C1 (1.5 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6 hrs post-dose on D15; 24 hrs post-dose on D16; pre-dose on D21); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; EOTPopulation: PAS consisted of all participants who had at least one blood sample providing evaluable PK data. Here, "Number Analyzed" signifies number of participants evaluable for specified time points.
BHS697 and CQM157 are metabolites of infigratinib. Maximum treatment exposure for Part II was of 97.0 weeks.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=1 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
CQM157, C1 D15: 6 hrs
|
32.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
CQM157, C1 D21: Pre-dose
|
9.65 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
CQM157, C2 D1: Pre-dose
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Participant had BLQ value.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
CQM157, C2 D15: Pre-dose
|
15.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
CQM157, C3 D1: Pre-dose
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Participant had BLQ value.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
CQM157, EOT
|
11.9 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
Infigratinib, C1 D1: 1.5 hrs
|
15.0 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
Infigratinib, C1 D8: Pre-dose
|
2.67 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
Infigratinib, C1 D15: Pre-dose
|
2.49 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
Infigratinib, C1 D15: 0.5 hr
|
3.39 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
Infigratinib, C1 D15: 1.5 hrs
|
15.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
Infigratinib, C1 D15: 2.5 hrs
|
27.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
Infigratinib, C1 D15: 4 hrs
|
24.7 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
Infigratinib, C1 D15: 6 hrs
|
20.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
Infigratinib, C1 D21: Pre-dose
|
2.05 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
Infigratinib, C2 D1: Pre-dose
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Participant had BLQ value.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
Infigratinib, C2 D15: Pre-dose
|
4.65 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
Infigratinib, C3 D1: Pre-dose
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Participant had BLQ value.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
Infigratinib, EOT
|
2.42 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
BHS697, C1 D1: 1.5 hrs
|
4.83 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
BHS697, C1 D8: Pre-dose
|
2.17 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
BHS697, C1 D15: Pre-dose
|
1.64 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
BHS697, C1 D15: 0.5 hr
|
2.14 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
BHS697, C1 D15: 1.5 hrs
|
6.83 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
BHS697, C1 D15: 2.5 hrs
|
8.53 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
BHS697, C1 D15: 4 hrs
|
6.89 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
BHS697, C1 D15: 6 hrs
|
5.57 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
BHS697, C1 D21: Pre-dose
|
1.37 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
BHS697, C2 D1: Pre-dose
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Participant had BLQ value.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
BHS697, C2 D15: Pre-dose
|
2.83 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
BHS697, C3 D1: Pre-dose
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Participant had BLQ value.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
BHS697, EOT
|
1.69 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
CQM157, C1 D1: 1.5 hrs
|
13.0 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
CQM157, C1 D8: Pre-dose
|
14.1 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
CQM157, C1 D15: Pre-dose
|
11.1 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
CQM157, C1 D15: 0.5 hr
|
12.0 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
CQM157, C1 D15: 1.5 hrs
|
21.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
CQM157, C1 D15: 2.5 hrs
|
28.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
CQM157, C1 D15: 4 hrs
|
25.0 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: C1 (1.5 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6, 8 hrs post-dose on D15; 24 hrs post-dose on D16); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; C4 pre-dose on D1; C5 pre-dose on D1; EOTPopulation: PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table; however, may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified time points.
Maximum treatment exposure for Part II was of 97.0 weeks.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=5 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=1 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=5 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Plasma Concentration for Capmatinib (INC): Part II
C1 D16: 24 hrs
|
79.6 Nanogram per milliliter
Geometric Coefficient of Variation 103.1
|
58.1 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
269 Nanogram per milliliter
Geometric Coefficient of Variation 68.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Capmatinib (INC): Part II
C2 D1: Pre-dose
|
151 Nanogram per milliliter
Geometric Coefficient of Variation 107.6
|
38.7 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
227 Nanogram per milliliter
Geometric Coefficient of Variation 42.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Capmatinib (INC): Part II
C2 D15: Pre-dose
|
65.2 Nanogram per milliliter
Geometric Coefficient of Variation 31.0
|
50.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
166 Nanogram per milliliter
Geometric Coefficient of Variation 80.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Capmatinib (INC): Part II
C3 D1: Pre-dose
|
114 Nanogram per milliliter
Geometric Coefficient of Variation 113.4
|
—
|
96.5 Nanogram per milliliter
Geometric Coefficient of Variation 17.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Capmatinib (INC): Part II
C4 D1: Pre-dose
|
—
|
—
|
175 Nanogram per milliliter
Geometric Coefficient of Variation 44.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Capmatinib (INC): Part II
C5 D1: Pre-dose
|
—
|
41.8 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Capmatinib (INC): Part II
EOT
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
All participants had BLQ values.
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Participant had BLQ value.
|
65.4 Nanogram per milliliter
Geometric Coefficient of Variation 155.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Capmatinib (INC): Part II
C1 D1: 1.5 hrs
|
362 Nanogram per milliliter
Geometric Coefficient of Variation 268.6
|
3600 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
715 Nanogram per milliliter
Geometric Coefficient of Variation 133.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Capmatinib (INC): Part II
C1 D8: Pre-dose
|
74.3 Nanogram per milliliter
Geometric Coefficient of Variation 97.2
|
44.4 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
129 Nanogram per milliliter
Geometric Coefficient of Variation 49.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Capmatinib (INC): Part II
C1 D15: Pre-dose
|
89.3 Nanogram per milliliter
Geometric Coefficient of Variation 35.7
|
71.4 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
173 Nanogram per milliliter
Geometric Coefficient of Variation 41.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Capmatinib (INC): Part II
C1 D15: 0.5 hr
|
196 Nanogram per milliliter
Geometric Coefficient of Variation 103.8
|
1880 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
314 Nanogram per milliliter
Geometric Coefficient of Variation 49.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Capmatinib (INC): Part II
C1 D15: 1.5 hrs
|
636 Nanogram per milliliter
Geometric Coefficient of Variation 78.2
|
3670 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1830 Nanogram per milliliter
Geometric Coefficient of Variation 38.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Capmatinib (INC): Part II
C1 D15: 2.5 hrs
|
545 Nanogram per milliliter
Geometric Coefficient of Variation 81.2
|
—
|
1530 Nanogram per milliliter
Geometric Coefficient of Variation 18.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Capmatinib (INC): Part II
C1 D15: 4 hrs
|
401 Nanogram per milliliter
Geometric Coefficient of Variation 17.3
|
1230 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
950 Nanogram per milliliter
Geometric Coefficient of Variation 39.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Capmatinib (INC): Part II
C1 D15: 6 hrs
|
157 Nanogram per milliliter
Geometric Coefficient of Variation 63.2
|
264 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
487 Nanogram per milliliter
Geometric Coefficient of Variation 23.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Capmatinib (INC): Part II
C1 D15: 8 hrs
|
120 Nanogram per milliliter
Geometric Coefficient of Variation 50.0
|
268 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
390 Nanogram per milliliter
Geometric Coefficient of Variation 10.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: C1 (1.5 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6, 8 hrs post-dose on D15; 24 hrs post-dose on D16); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; C4 pre-dose on D1; C5 pre-dose on D1; EOTPopulation: PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table; however, may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified time points.
Maximum treatment exposure for Part II was of 97.0 weeks.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=3 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=3 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Plasma Concentration for Buparlisib (BKM): Part II
C2 D1: Pre-dose
|
54.7 Nanogram per milliliter
Geometric Coefficient of Variation 134.9
|
110 Nanogram per milliliter
Geometric Coefficient of Variation 51.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Buparlisib (BKM): Part II
C1 D1: 1.5 hrs
|
213 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
213 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Buparlisib (BKM): Part II
C1 D8: Pre-dose
|
45.0 Nanogram per milliliter
Geometric Coefficient of Variation 75.2
|
119 Nanogram per milliliter
Geometric Coefficient of Variation 3.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Buparlisib (BKM): Part II
C1 D15: Pre-dose
|
49.7 Nanogram per milliliter
Geometric Coefficient of Variation 115.9
|
97.3 Nanogram per milliliter
Geometric Coefficient of Variation 16.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Buparlisib (BKM): Part II
C1 D15: 0.5 hr
|
139 Nanogram per milliliter
Geometric Coefficient of Variation 13.4
|
229 Nanogram per milliliter
Geometric Coefficient of Variation 21.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Buparlisib (BKM): Part II
C1 D15: 1.5 hrs
|
266 Nanogram per milliliter
Geometric Coefficient of Variation 51.5
|
312 Nanogram per milliliter
Geometric Coefficient of Variation 10.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Buparlisib (BKM): Part II
C1 D15: 2.5 hrs
|
176 Nanogram per milliliter
Geometric Coefficient of Variation 42.2
|
268 Nanogram per milliliter
Geometric Coefficient of Variation 11.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Buparlisib (BKM): Part II
C1 D15: 4 hrs
|
115 Nanogram per milliliter
Geometric Coefficient of Variation 44.0
|
235 Nanogram per milliliter
Geometric Coefficient of Variation 39.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Buparlisib (BKM): Part II
C1 D15: 6 hrs
|
94.2 Nanogram per milliliter
Geometric Coefficient of Variation 40.0
|
171 Nanogram per milliliter
Geometric Coefficient of Variation 26.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Buparlisib (BKM): Part II
C1 D15: 8 hrs
|
87.4 Nanogram per milliliter
Geometric Coefficient of Variation 63.9
|
111 Nanogram per milliliter
Geometric Coefficient of Variation 25.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Buparlisib (BKM): Part II
C1 D16: 24 hrs
|
41.8 Nanogram per milliliter
Geometric Coefficient of Variation 82.9
|
101 Nanogram per milliliter
Geometric Coefficient of Variation 1.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Buparlisib (BKM): Part II
C2 D15: Pre-dose
|
99.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
138 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Buparlisib (BKM): Part II
C3 D1: Pre-dose
|
81.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Buparlisib (BKM): Part II
C4 D1: Pre-dose
|
73.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Buparlisib (BKM): Part II
C5 D1: Pre-dose
|
122 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Plasma Concentration for Buparlisib (BKM): Part II
EOT
|
1.84 Nanogram per milliliter
Geometric Coefficient of Variation 53.4
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Participant had BLQ value.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: C1 D15: 0.5 hour ± 10 (minutes) min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hourPopulation: PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table; however, may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified study treatment or metabolites for respective arms.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=3 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=3 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=1 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=5 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
n=5 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=1 Participants
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=3 Participants
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
n=29 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=1 Participants
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Encorafenib
|
3060 Nanogram per milliliter
Geometric Coefficient of Variation 58.8
|
2150 Nanogram per milliliter
Geometric Coefficient of Variation 54.6
|
2100 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1600 Nanogram per milliliter
Geometric Coefficient of Variation 62.0
|
2890 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
2570 Nanogram per milliliter
Geometric Coefficient of Variation 23.0
|
622 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1960 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1860 Nanogram per milliliter
Geometric Coefficient of Variation 32.1
|
2010 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
2030 Nanogram per milliliter
Geometric Coefficient of Variation 40.6
|
—
|
—
|
|
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Binimetinib
|
386 Nanogram per milliliter
Geometric Coefficient of Variation 41.1
|
221 Nanogram per milliliter
Geometric Coefficient of Variation 237.6
|
413 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
515 Nanogram per milliliter
Geometric Coefficient of Variation 17.0
|
797 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
858 Nanogram per milliliter
Geometric Coefficient of Variation 13.0
|
261 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
520 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
313 Nanogram per milliliter
Geometric Coefficient of Variation 15.9
|
584 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
489 Nanogram per milliliter
Geometric Coefficient of Variation 31.3
|
291 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Ribociclib
|
—
|
—
|
—
|
—
|
—
|
—
|
434 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
126 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
428 Nanogram per milliliter
Geometric Coefficient of Variation 84.2
|
282 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
753 Nanogram per milliliter
Geometric Coefficient of Variation 70.6
|
597 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Binimetinib metabolite, AR00426032
|
24.9 Nanogram per milliliter
Geometric Coefficient of Variation 92.2
|
18.1 Nanogram per milliliter
Geometric Coefficient of Variation 591.2
|
15.8 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
27.9 Nanogram per milliliter
Geometric Coefficient of Variation 85.6
|
22.6 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
47.1 Nanogram per milliliter
Geometric Coefficient of Variation 29.2
|
12.9 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
12.6 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
16.1 Nanogram per milliliter
Geometric Coefficient of Variation 151.9
|
19.4 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
23.7 Nanogram per milliliter
Geometric Coefficient of Variation 94.1
|
9.04 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Ribociclib metabolite, LEQ803
|
—
|
—
|
—
|
—
|
—
|
—
|
175 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
93.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
144 Nanogram per milliliter
Geometric Coefficient of Variation 19.2
|
67.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
156 Nanogram per milliliter
Geometric Coefficient of Variation 36.2
|
138 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Infigratinib
|
—
|
—
|
27.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Infigratinib metabolite, BHS697
|
—
|
—
|
8.53 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Infigratinib metabolite, CQM157
|
—
|
—
|
32.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Capmatinib
|
—
|
—
|
—
|
722 Nanogram per milliliter
Geometric Coefficient of Variation 85.3
|
3670 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1920 Nanogram per milliliter
Geometric Coefficient of Variation 31.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Buparlisib
|
266 Nanogram per milliliter
Geometric Coefficient of Variation 51.5
|
312 Nanogram per milliliter
Geometric Coefficient of Variation 10.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hourPopulation: PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table; however, may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified study treatment or metabolites for respective arms.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=3 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=3 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=1 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=5 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
n=5 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=1 Participants
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=3 Participants
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
n=29 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=1 Participants
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Time to Reach Cmax at Steady State (Tmax, ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Encorafenib
|
1.33 Hour
Interval 0.58 to 1.5
|
1.54 Hour
Interval 1.5 to 1.58
|
1.50 Hour
Interval 1.5 to 1.5
|
1.50 Hour
Interval 0.5 to 1.53
|
1.50 Hour
Interval 1.5 to 1.5
|
1.50 Hour
Interval 1.5 to 2.5
|
2.37 Hour
Interval 2.37 to 2.37
|
1.47 Hour
Interval 1.47 to 1.47
|
1.00 Hour
Interval 0.5 to 1.5
|
1.50 Hour
Interval 1.5 to 1.5
|
1.58 Hour
Interval 0.63 to 6.17
|
—
|
—
|
|
Time to Reach Cmax at Steady State (Tmax, ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Binimetinib
|
1.50 Hour
Interval 1.33 to 1.67
|
2.75 Hour
Interval 1.5 to 4.0
|
1.50 Hour
Interval 1.5 to 1.5
|
1.50 Hour
Interval 0.5 to 1.58
|
1.50 Hour
Interval 1.5 to 1.5
|
1.50 Hour
Interval 1.5 to 2.5
|
1.38 Hour
Interval 1.38 to 1.38
|
1.47 Hour
Interval 1.47 to 1.47
|
1.50 Hour
Interval 1.5 to 1.5
|
1.50 Hour
Interval 1.5 to 1.5
|
1.58 Hour
Interval 0.5 to 4.08
|
1.08 Hour
Interval 1.08 to 1.08
|
—
|
|
Time to Reach Cmax at Steady State (Tmax, ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Binimetinib metabolite, AR00426032
|
1.50 Hour
Interval 1.33 to 1.67
|
2.75 Hour
Interval 1.5 to 4.0
|
1.50 Hour
Interval 1.5 to 1.5
|
1.50 Hour
Interval 1.5 to 1.58
|
4.00 Hour
Interval 4.0 to 4.0
|
1.92 Hour
Interval 1.5 to 2.5
|
1.38 Hour
Interval 1.38 to 1.38
|
1.47 Hour
Interval 1.47 to 1.47
|
1.50 Hour
Interval 1.5 to 1.5
|
1.50 Hour
Interval 1.5 to 1.5
|
1.65 Hour
Interval 0.67 to 4.08
|
1.08 Hour
Interval 1.08 to 1.08
|
—
|
|
Time to Reach Cmax at Steady State (Tmax, ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Ribociclib
|
—
|
—
|
—
|
—
|
—
|
—
|
5.92 Hour
Interval 5.92 to 5.92
|
2.45 Hour
Interval 2.45 to 2.45
|
3.18 Hour
Interval 2.33 to 4.03
|
1.50 Hour
Interval 1.5 to 1.5
|
3.65 Hour
Interval 1.5 to 6.0
|
0.50 Hour
Interval 0.5 to 0.5
|
—
|
|
Time to Reach Cmax at Steady State (Tmax, ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Ribociclib metabolite, LEQ803
|
—
|
—
|
—
|
—
|
—
|
—
|
5.92 Hour
Interval 5.92 to 5.92
|
4.98 Hour
Interval 4.98 to 4.98
|
3.18 Hour
Interval 2.33 to 4.03
|
1.50 Hour
Interval 1.5 to 1.5
|
4.12 Hour
Interval 1.55 to 7.0
|
1.08 Hour
Interval 1.08 to 1.08
|
—
|
|
Time to Reach Cmax at Steady State (Tmax, ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Infigratinib
|
—
|
—
|
2.50 Hour
Interval 2.5 to 2.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Time to Reach Cmax at Steady State (Tmax, ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Infigratinib metabolite, BHS697
|
—
|
—
|
2.50 Hour
Interval 2.5 to 2.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Time to Reach Cmax at Steady State (Tmax, ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Infigratinib metabolite, CQM157
|
—
|
—
|
5.75 Hour
Interval 5.75 to 5.75
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Time to Reach Cmax at Steady State (Tmax, ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Capmatinib
|
—
|
—
|
—
|
1.53 Hour
Interval 1.5 to 2.58
|
1.50 Hour
Interval 1.5 to 1.5
|
1.50 Hour
Interval 1.5 to 2.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Time to Reach Cmax at Steady State (Tmax, ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Buparlisib
|
1.50 Hour
Interval 1.33 to 1.67
|
1.50 Hour
Interval 1.5 to 1.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hourPopulation: PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table; however, may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified study treatment or metabolites for respective arms.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=3 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=3 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=1 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=5 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
n=5 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=1 Participants
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=3 Participants
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
n=29 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=1 Participants
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Area Under the Concentration-time Curve From Time Zero to Time Tau at Steady-State (AUCtau,ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Capmatinib, and Buparlisib: Part II
Binimetinib
|
1580 Hour*nanogram per milliliter
Geometric Coefficient of Variation 17.0
|
1220 Hour*nanogram per milliliter
Geometric Coefficient of Variation 105.7
|
1260 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
2180 Hour*nanogram per milliliter
Geometric Coefficient of Variation 29.4
|
3040 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
2760 Hour*nanogram per milliliter
Geometric Coefficient of Variation 4.8
|
1700 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1900 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1140 Hour*nanogram per milliliter
Geometric Coefficient of Variation 21.1
|
1740 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
2270 Hour*nanogram per milliliter
Geometric Coefficient of Variation 29.5
|
1470 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Area Under the Concentration-time Curve From Time Zero to Time Tau at Steady-State (AUCtau,ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Capmatinib, and Buparlisib: Part II
Binimetinib metabolite, AR00426032
|
116 Hour*nanogram per milliliter
Geometric Coefficient of Variation 66.8
|
94.4 Hour*nanogram per milliliter
Geometric Coefficient of Variation 222.2
|
42.0 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
124 Hour*nanogram per milliliter
Geometric Coefficient of Variation 113.9
|
135 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
182 Hour*nanogram per milliliter
Geometric Coefficient of Variation 43.1
|
81.5 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
47.0 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
57.9 Hour*nanogram per milliliter
Geometric Coefficient of Variation 128.5
|
66.9 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
115 Hour*nanogram per milliliter
Geometric Coefficient of Variation 92.6
|
41.1 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Area Under the Concentration-time Curve From Time Zero to Time Tau at Steady-State (AUCtau,ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Capmatinib, and Buparlisib: Part II
Ribociclib
|
—
|
—
|
—
|
—
|
—
|
—
|
5630 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1650 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
3730 Hour*nanogram per milliliter
Geometric Coefficient of Variation 62.5
|
2320 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
9230 Hour*nanogram per milliliter
Geometric Coefficient of Variation 60.9
|
5960 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Area Under the Concentration-time Curve From Time Zero to Time Tau at Steady-State (AUCtau,ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Capmatinib, and Buparlisib: Part II
Ribociclib metabolite, LEQ803
|
—
|
—
|
—
|
—
|
—
|
—
|
2770 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1640 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1900 Hour*nanogram per milliliter
Geometric Coefficient of Variation 24.9
|
930 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
2540 Hour*nanogram per milliliter
Geometric Coefficient of Variation 31.3
|
2300 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Area Under the Concentration-time Curve From Time Zero to Time Tau at Steady-State (AUCtau,ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Capmatinib, and Buparlisib: Part II
Capmatinib
|
—
|
—
|
—
|
3070 Hour*nanogram per milliliter
Geometric Coefficient of Variation 52.6
|
12200 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
8420 Hour*nanogram per milliliter
Geometric Coefficient of Variation 22.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Area Under the Concentration-time Curve From Time Zero to Time Tau at Steady-State (AUCtau,ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Capmatinib, and Buparlisib: Part II
Buparlisib
|
2130 Hour*nanogram per milliliter
Geometric Coefficient of Variation 54.6
|
3400 Hour*nanogram per milliliter
Geometric Coefficient of Variation 18.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Area Under the Concentration-time Curve From Time Zero to Time Tau at Steady-State (AUCtau,ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Capmatinib, and Buparlisib: Part II
Encorafenib
|
9080 Hour*nanogram per milliliter
Geometric Coefficient of Variation 42.2
|
10100 Hour*nanogram per milliliter
Geometric Coefficient of Variation 18.4
|
7420 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
4990 Hour*nanogram per milliliter
Geometric Coefficient of Variation 42.6
|
10800 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
8570 Hour*nanogram per milliliter
Geometric Coefficient of Variation 10.6
|
3490 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
6000 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
5740 Hour*nanogram per milliliter
Geometric Coefficient of Variation 7.1
|
6200 Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
11300 Hour*nanogram per milliliter
Geometric Coefficient of Variation 41.1
|
—
|
—
|
SECONDARY outcome
Timeframe: C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hourPopulation: PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table; however, may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified study treatment or metabolites for respective arms.
Elimination half-life means the time required for the plasma concentration to decline by 50% during the elimination phase.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=3 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=3 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=1 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=5 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
n=5 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=1 Participants
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=3 Participants
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
n=29 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=1 Participants
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Elimination Half-life at Steady State (t1/2, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Capmatinib, and Buparlisib: Part II
Encorafenib
|
3.75 Hour
Standard Deviation 0.302
|
5.89 Hour
Standard Deviation 4.32
|
3.57 Hour
Standard Deviation NA
Only 1 participant evaluable.
|
4.18 Hour
Standard Deviation 1.85
|
3.41 Hour
Standard Deviation NA
Only 1 participant evaluable.
|
3.96 Hour
Standard Deviation 0.233
|
4.27 Hour
Standard Deviation NA
Only 1 participant evaluable.
|
3.75 Hour
Standard Deviation NA
Only 1 participant evaluable.
|
4.32 Hour
Standard Deviation 1.62
|
3.83 Hour
Standard Deviation NA
Only 1 participant evaluable.
|
3.60 Hour
Standard Deviation 0.711
|
—
|
—
|
|
Elimination Half-life at Steady State (t1/2, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Capmatinib, and Buparlisib: Part II
Binimetinib
|
8.35 Hour
Standard Deviation 3.52
|
3.48 Hour
Standard Deviation 0.484
|
1.60 Hour
Standard Deviation NA
Only 1 participant evaluable.
|
10.3 Hour
Standard Deviation 6.29
|
—
|
5.88 Hour
Standard Deviation 2.77
|
5.84 Hour
Standard Deviation NA
Only 1 participant evaluable.
|
3.82 Hour
Standard Deviation NA
Only 1 participant evaluable.
|
5.38 Hour
Standard Deviation 3.39
|
10.9 Hour
Standard Deviation NA
Only 1 participant evaluable.
|
4.13 Hour
Standard Deviation 1.42
|
—
|
—
|
|
Elimination Half-life at Steady State (t1/2, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Capmatinib, and Buparlisib: Part II
Binimetinib metabolite, AR00426032
|
6.35 Hour
Standard Deviation 1.21
|
4.14 Hour
Standard Deviation 0.683
|
1.59 Hour
Standard Deviation NA
Only 1 participant evaluable.
|
7.95 Hour
Standard Deviation 4.03
|
2.86 Hour
Standard Deviation NA
Only 1 participant evaluable.
|
5.64 Hour
Standard Deviation 2.49
|
—
|
4.34 Hour
Standard Deviation NA
Only 1 participant evaluable.
|
6.24 Hour
Standard Deviation 4.43
|
—
|
5.91 Hour
Standard Deviation 3.00
|
—
|
—
|
|
Elimination Half-life at Steady State (t1/2, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Capmatinib, and Buparlisib: Part II
Ribociclib
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
9.01 Hour
Standard Deviation NA
Only 1 participant evaluable.
|
8.44 Hour
Standard Deviation 2.21
|
10.7 Hour
Standard Deviation NA
Only 1 participant evaluable.
|
7.77 Hour
Standard Deviation 1.95
|
10.1 Hour
Standard Deviation NA
Only 1 participant evaluable.
|
—
|
|
Elimination Half-life at Steady State (t1/2, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Capmatinib, and Buparlisib: Part II
Ribociclib metabolite, LEQ803
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
19.9 Hour
Standard Deviation NA
Only 1 participant evaluable.
|
14.1 Hour
Standard Deviation 4.04
|
19.2 Hour
Standard Deviation NA
Only 1 participant evaluable.
|
16.0 Hour
Standard Deviation 4.50
|
—
|
—
|
|
Elimination Half-life at Steady State (t1/2, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Capmatinib, and Buparlisib: Part II
Capmatinib
|
—
|
—
|
—
|
2.18 Hour
Standard Deviation 0.0599
|
2.50 Hour
Standard Deviation NA
Only 1 participant evaluable.
|
2.82 Hour
Standard Deviation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Elimination Half-life at Steady State (t1/2, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Capmatinib, and Buparlisib: Part II
Buparlisib
|
15.4 Hour
Standard Deviation 4.62
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hourPopulation: PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table; however, may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified study treatment for respective arms.
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=3 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=3 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=1 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=5 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
n=5 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=1 Participants
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=3 Participants
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
n=29 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=1 Participants
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Apparent Total Plasma Clearance at Steady State (Cl, ss/F) of Encorafenib, Binimetinib, Ribociclib, Capmatinib, and Buparlisib: Part II
Encorafenib
|
49.6 Liter per hour
Geometric Coefficient of Variation 42.1
|
44.7 Liter per hour
Geometric Coefficient of Variation 18.4
|
60.7 Liter per hour
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
40.1 Liter per hour
Geometric Coefficient of Variation 42.6
|
18.6 Liter per hour
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
23.4 Liter per hour
Geometric Coefficient of Variation 10.7
|
28.7 Liter per hour
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
33.3 Liter per hour
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
34.9 Liter per hour
Geometric Coefficient of Variation 6.9
|
32.2 Liter per hour
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
19.5 Liter per hour
Geometric Coefficient of Variation 44.3
|
—
|
—
|
|
Apparent Total Plasma Clearance at Steady State (Cl, ss/F) of Encorafenib, Binimetinib, Ribociclib, Capmatinib, and Buparlisib: Part II
Binimetinib
|
28.5 Liter per hour
Geometric Coefficient of Variation 14.8
|
36.9 Liter per hour
Geometric Coefficient of Variation 105.7
|
35.6 Liter per hour
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
20.8 Liter per hour
Geometric Coefficient of Variation 28.1
|
15.1 Liter per hour
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
16.3 Liter per hour
Geometric Coefficient of Variation 5.0
|
17.4 Liter per hour
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
15.8 Liter per hour
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
26.5 Liter per hour
Geometric Coefficient of Variation 22.6
|
25.9 Liter per hour
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
19.9 Liter per hour
Geometric Coefficient of Variation 29.2
|
—
|
—
|
|
Apparent Total Plasma Clearance at Steady State (Cl, ss/F) of Encorafenib, Binimetinib, Ribociclib, Capmatinib, and Buparlisib: Part II
Ribociclib
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
243 Liter per hour
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
161 Liter per hour
Geometric Coefficient of Variation 61.1
|
173 Liter per hour
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
62.4 Liter per hour
Geometric Coefficient of Variation 58.5
|
99.3 Liter per hour
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Apparent Total Plasma Clearance at Steady State (Cl, ss/F) of Encorafenib, Binimetinib, Ribociclib, Capmatinib, and Buparlisib: Part II
Capmatinib
|
—
|
—
|
—
|
65.9 Liter per hour
Geometric Coefficient of Variation 52.2
|
24.8 Liter per hour
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
45.7 Liter per hour
Geometric Coefficient of Variation 24.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Apparent Total Plasma Clearance at Steady State (Cl, ss/F) of Encorafenib, Binimetinib, Ribociclib, Capmatinib, and Buparlisib: Part II
Buparlisib
|
28.2 Liter per hour
Geometric Coefficient of Variation 53.6
|
23.2 Liter per hour
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hourPopulation: PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table; however, may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified study treatment for respective arms.
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution is the apparent volume of distribution at steady-state.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=3 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=3 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=1 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=5 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
n=5 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=1 Participants
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=3 Participants
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
n=29 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=1 Participants
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Apparent Volume of Distribution at Steady State (Vz, ss/F) of Encorafenib, Binimetinib, Ribociclib, Capmatinib, and Buparlisib: Part II
Encorafenib
|
268 Liter
Geometric Coefficient of Variation 45.4
|
324 Liter
Geometric Coefficient of Variation 69.8
|
313 Liter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
226 Liter
Geometric Coefficient of Variation 92.9
|
91.7 Liter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
133 Liter
Geometric Coefficient of Variation 13.5
|
177 Liter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
180 Liter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
210 Liter
Geometric Coefficient of Variation 32.3
|
178 Liter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
99.3 Liter
Geometric Coefficient of Variation 46.0
|
—
|
—
|
|
Apparent Volume of Distribution at Steady State (Vz, ss/F) of Encorafenib, Binimetinib, Ribociclib, Capmatinib, and Buparlisib: Part II
Binimetinib
|
324 Liter
Geometric Coefficient of Variation 58.3
|
185 Liter
Geometric Coefficient of Variation 83.4
|
82.5 Liter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
244 Liter
Geometric Coefficient of Variation 75.9
|
—
|
125 Liter
Geometric Coefficient of Variation 56.1
|
147 Liter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
86.8 Liter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
184 Liter
Geometric Coefficient of Variation 111.8
|
406 Liter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
113 Liter
Geometric Coefficient of Variation 48.5
|
—
|
—
|
|
Apparent Volume of Distribution at Steady State (Vz, ss/F) of Encorafenib, Binimetinib, Ribociclib, Capmatinib, and Buparlisib: Part II
Ribociclib
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
3160 Liter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1930 Liter
Geometric Coefficient of Variation 30.5
|
2660 Liter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
677 Liter
Geometric Coefficient of Variation 65.0
|
1440 Liter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Apparent Volume of Distribution at Steady State (Vz, ss/F) of Encorafenib, Binimetinib, Ribociclib, Capmatinib, and Buparlisib: Part II
Capmatinib
|
—
|
—
|
—
|
190 Liter
Geometric Coefficient of Variation 30.3
|
89.5 Liter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
233 Liter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Apparent Volume of Distribution at Steady State (Vz, ss/F) of Encorafenib, Binimetinib, Ribociclib, Capmatinib, and Buparlisib: Part II
Buparlisib
|
604 Liter
Geometric Coefficient of Variation 17.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hourPopulation: PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table; however, may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified study treatment or metabolites for respective arms.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=3 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=3 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=1 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=5 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
n=5 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=1 Participants
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=3 Participants
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
n=29 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=1 Participants
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Last Measurable Plasma Concentration at Steady State (Clast, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Binimetinib metabolite, AR00426032
|
3.99 Nanogram per milliliter
Geometric Coefficient of Variation 61.8
|
2.92 Nanogram per milliliter
Geometric Coefficient of Variation 159.3
|
1.82 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
5.57 Nanogram per milliliter
Geometric Coefficient of Variation 130.2
|
1.44 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
4.75 Nanogram per milliliter
Geometric Coefficient of Variation 25.4
|
6.53 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1.08 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
2.31 Nanogram per milliliter
Geometric Coefficient of Variation 47.8
|
3.54 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
4.68 Nanogram per milliliter
Geometric Coefficient of Variation 92.3
|
1.56 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Last Measurable Plasma Concentration at Steady State (Clast, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Ribociclib
|
—
|
—
|
—
|
—
|
—
|
—
|
94.0 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
25.6 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
52.7 Nanogram per milliliter
Geometric Coefficient of Variation 90.4
|
34.9 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
147 Nanogram per milliliter
Geometric Coefficient of Variation 71.8
|
91.8 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Last Measurable Plasma Concentration at Steady State (Clast, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Ribociclib metabolite, LEQ803
|
—
|
—
|
—
|
—
|
—
|
—
|
84.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
46.8 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
42.5 Nanogram per milliliter
Geometric Coefficient of Variation 13.8
|
22.8 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
73.2 Nanogram per milliliter
Geometric Coefficient of Variation 49.6
|
59.6 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Last Measurable Plasma Concentration at Steady State (Clast, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Infigratinib
|
—
|
—
|
20.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Last Measurable Plasma Concentration at Steady State (Clast, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Infigratinib metabolite, BHS697
|
—
|
—
|
5.57 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Last Measurable Plasma Concentration at Steady State (Clast, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Infigratinib metabolite, CQM157
|
—
|
—
|
32.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Last Measurable Plasma Concentration at Steady State (Clast, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Capmatinib
|
—
|
—
|
—
|
79.6 Nanogram per milliliter
Geometric Coefficient of Variation 103.1
|
58.1 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
269 Nanogram per milliliter
Geometric Coefficient of Variation 68.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Last Measurable Plasma Concentration at Steady State (Clast, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Buparlisib
|
41.8 Nanogram per milliliter
Geometric Coefficient of Variation 82.9
|
101 Nanogram per milliliter
Geometric Coefficient of Variation 1.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Last Measurable Plasma Concentration at Steady State (Clast, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Encorafenib
|
11.3 Nanogram per milliliter
Geometric Coefficient of Variation 45.3
|
25.1 Nanogram per milliliter
Geometric Coefficient of Variation 2066.8
|
6.76 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
15.9 Nanogram per milliliter
Geometric Coefficient of Variation 315.9
|
5.20 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
15.0 Nanogram per milliliter
Geometric Coefficient of Variation 20.9
|
10.7 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
7.85 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
10.8 Nanogram per milliliter
Geometric Coefficient of Variation 106.1
|
10.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
33.7 Nanogram per milliliter
Geometric Coefficient of Variation 254.3
|
—
|
—
|
|
Last Measurable Plasma Concentration at Steady State (Clast, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Binimetinib
|
44.1 Nanogram per milliliter
Geometric Coefficient of Variation 19.1
|
30.2 Nanogram per milliliter
Geometric Coefficient of Variation 59.2
|
55.8 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
63.2 Nanogram per milliliter
Geometric Coefficient of Variation 64.0
|
17.6 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
55.9 Nanogram per milliliter
Geometric Coefficient of Variation 54.0
|
78.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
29.8 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
23.1 Nanogram per milliliter
Geometric Coefficient of Variation 5.2
|
47.9 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
58.7 Nanogram per milliliter
Geometric Coefficient of Variation 60.2
|
40.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
SECONDARY outcome
Timeframe: C1 D15: at the end of a dosing interval at steady-state (24 hour ± 2 hour), taken directly before next administrationPopulation: PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table; however, may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified study treatment or metabolites for respective arms.
Outcome measures
| Measure |
Part II: Encorafenib + Binimetinib + Ribociclib
n=3 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=3 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=1 Participants
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=5 Participants
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg
n=5 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day.
|
Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=1 Participants
Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=3 Participants
Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg
n=1 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day.
|
Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg
n=29 Participants
Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day.
|
Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg
n=1 Participants
Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD.
|
Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Measured Concentration at the End of a Dosing Interval at Steady State (Ctrough, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Encorafenib
|
11.2 Nanogram per milliliter
Geometric Coefficient of Variation 106.3
|
18.6 Nanogram per milliliter
Geometric Coefficient of Variation 159.4
|
7.74 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
11.6 Nanogram per milliliter
Geometric Coefficient of Variation 51.3
|
7.95 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
13.5 Nanogram per milliliter
Geometric Coefficient of Variation 35.0
|
9.28 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
10.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
7.75 Nanogram per milliliter
Geometric Coefficient of Variation 37.3
|
10.4 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
21.7 Nanogram per milliliter
Geometric Coefficient of Variation 185.4
|
—
|
—
|
|
Measured Concentration at the End of a Dosing Interval at Steady State (Ctrough, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Binimetinib
|
32.0 Nanogram per milliliter
Geometric Coefficient of Variation 17.1
|
39.1 Nanogram per milliliter
Geometric Coefficient of Variation 57.4
|
33.9 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
81.2 Nanogram per milliliter
Geometric Coefficient of Variation 47.5
|
47.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
50.9 Nanogram per milliliter
Geometric Coefficient of Variation 34.4
|
54.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
28.3 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
21.1 Nanogram per milliliter
Geometric Coefficient of Variation 23.7
|
31.5 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
51.0 Nanogram per milliliter
Geometric Coefficient of Variation 76.1
|
36.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Measured Concentration at the End of a Dosing Interval at Steady State (Ctrough, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Binimetinib metabolite, AR00426032
|
3.14 Nanogram per milliliter
Geometric Coefficient of Variation 74.5
|
3.80 Nanogram per milliliter
Geometric Coefficient of Variation 111.9
|
1.21 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
8.22 Nanogram per milliliter
Geometric Coefficient of Variation 84.6
|
4.36 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
5.45 Nanogram per milliliter
Geometric Coefficient of Variation 42.2
|
4.16 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
3.81 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
1.72 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
4.34 Nanogram per milliliter
Geometric Coefficient of Variation 79.9
|
1.09 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Measured Concentration at the End of a Dosing Interval at Steady State (Ctrough, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Ribociclib
|
—
|
—
|
—
|
—
|
—
|
—
|
98.4 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
28.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
30.7 Nanogram per milliliter
Geometric Coefficient of Variation 24.9
|
36.4 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
104 Nanogram per milliliter
Geometric Coefficient of Variation 54.2
|
64.7 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Measured Concentration at the End of a Dosing Interval at Steady State (Ctrough, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Ribociclib metabolite, LEQ803
|
—
|
—
|
—
|
—
|
—
|
—
|
76.0 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
37.1 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
32.9 Nanogram per milliliter
Geometric Coefficient of Variation 25.7
|
22.8 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
55.1 Nanogram per milliliter
Geometric Coefficient of Variation 33.9
|
49.2 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
|
Measured Concentration at the End of a Dosing Interval at Steady State (Ctrough, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Infigratinib
|
—
|
—
|
2.49 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Measured Concentration at the End of a Dosing Interval at Steady State (Ctrough, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Infigratinib metabolite, BHS697
|
—
|
—
|
1.64 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Measured Concentration at the End of a Dosing Interval at Steady State (Ctrough, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Infigratinib metabolite, CQM157
|
—
|
—
|
11.1 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Measured Concentration at the End of a Dosing Interval at Steady State (Ctrough, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Capmatinib
|
—
|
—
|
—
|
83.9 Nanogram per milliliter
Geometric Coefficient of Variation 34.0
|
71.4 Nanogram per milliliter
Geometric Coefficient of Variation NA
Only 1 participant evaluable.
|
173 Nanogram per milliliter
Geometric Coefficient of Variation 41.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Measured Concentration at the End of a Dosing Interval at Steady State (Ctrough, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Buparlisib
|
49.7 Nanogram per milliliter
Geometric Coefficient of Variation 115.9
|
97.3 Nanogram per milliliter
Geometric Coefficient of Variation 16.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Part I: Encorafenib + Binimetinib (Naive)
Serious events: 47 serious events
Other events: 75 other events
Deaths: 20 deaths
Part I: Encorafenib + Binimetinib (Non-naive)
Serious events: 37 serious events
Other events: 73 other events
Deaths: 29 deaths
Part II: Encorafenib + Binimetinib + Ribociclib
Serious events: 19 serious events
Other events: 33 other events
Deaths: 28 deaths
Part II: Encorafenib + Binimetinib + Infigratinib
Serious events: 0 serious events
Other events: 0 other events
Deaths: 1 deaths
Part II: Encorafenib + Binimetinib + Capmatinib
Serious events: 6 serious events
Other events: 11 other events
Deaths: 8 deaths
Part II: Encorafenib + Binimetinib + Buparlisib
Serious events: 4 serious events
Other events: 5 other events
Deaths: 4 deaths
Serious adverse events
| Measure |
Part I: Encorafenib + Binimetinib (Naive)
n=75 participants at risk
Participants naive to selective V-raf murine sarcoma viral oncogene homolog B1 (BRAF) and mitogen-activated protein kinase (MEK) inhibitors, received encorafenib 450 milligram (mg) once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for encorafenib and binimetinib was defined as 21 days of daily continuous treatment.
|
Part I: Encorafenib + Binimetinib (Non-naive)
n=83 participants at risk
Participants non-naive to selective BRAF and MEK inhibitors, received encorafenib 450 mg once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit and initiation of triple combination treatment. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for both drugs was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Ribociclib
n=38 participants at risk
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=1 participants at risk
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=13 participants at risk
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=6 participants at risk
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
4.0%
3/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
5.3%
2/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.7%
1/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Cardiac disorders
Acute myocardial infarction
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Cardiac disorders
Myocardial infarction
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.7%
1/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.7%
1/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Ear and labyrinth disorders
Vertigo
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Ear and labyrinth disorders
Vertigo positional
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Endocrine disorders
Adrenomegaly
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Endocrine disorders
Adrenocortical insufficiency acute
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Eye disorders
Vision blurred
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Eye disorders
Diplopia
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Eye disorders
Exophthalmos
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Gastrointestinal disorders
Abdominal pain
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.7%
1/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Gastrointestinal disorders
Colitis ulcerative
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Gastrointestinal disorders
Diarrhoea
|
5.3%
4/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Gastrointestinal disorders
Dysphagia
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Gastrointestinal disorders
Gastric ulcer
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.7%
1/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Gastrointestinal disorders
Intestinal mass
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Gastrointestinal disorders
Intussusception
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Gastrointestinal disorders
Intestinal perforation
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.7%
1/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Gastrointestinal disorders
Nausea
|
5.3%
4/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
3.6%
3/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.7%
1/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Gastrointestinal disorders
Subileus
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Gastrointestinal disorders
Terminal ileitis
|
2.7%
2/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Gastrointestinal disorders
Vomiting
|
2.7%
2/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.2%
6/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
General disorders
Asthenia
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
General disorders
Chills
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
General disorders
Disease progression
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
General disorders
Fatigue
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
General disorders
General physical health deterioration
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
4.8%
4/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
General disorders
Non-cardiac chest pain
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
General disorders
Pain
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
General disorders
Pyrexia
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
4.8%
4/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.7%
1/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Infections and infestations
Appendicitis
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Infections and infestations
Arthritis bacterial
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Infections and infestations
Chorioretinitis
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Infections and infestations
Clostridium difficile colitis
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Infections and infestations
Device related infection
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Infections and infestations
Diverticulitis
|
2.7%
2/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Infections and infestations
Erysipelas
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Infections and infestations
Febrile infection
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Infections and infestations
Pneumonia
|
5.3%
4/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Infections and infestations
Pyelonephritis
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Infections and infestations
Sepsis
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
3.6%
3/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Infections and infestations
Streptococcal infection
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Infections and infestations
Urinary tract infection
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.7%
1/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Infections and infestations
Urosepsis
|
2.7%
2/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Infections and infestations
Vestibular neuronitis
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Infections and infestations
Wound infection
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Injury, poisoning and procedural complications
Facial bones fracture
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Injury, poisoning and procedural complications
Osteoradionecrosis
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Injury, poisoning and procedural complications
Periprosthetic fracture
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Injury, poisoning and procedural complications
Procedural pneumothorax
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Injury, poisoning and procedural complications
Seroma
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Injury, poisoning and procedural complications
Wrist fracture
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.7%
1/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Investigations
Blood creatine phosphokinase increased
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Investigations
Ejection fraction decreased
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Investigations
Intraocular pressure increased
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Investigations
Lipase increased
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.4%
2/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Investigations
Troponin T increased
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.4%
2/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
16.7%
1/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Musculoskeletal and connective tissue disorders
Costochondritis
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Musculoskeletal and connective tissue disorders
Fibromyalgia
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Musculoskeletal and connective tissue disorders
Myopathy toxic
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
16.7%
1/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Musculoskeletal and connective tissue disorders
Pathological fracture
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer recurrent
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.7%
1/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to bone
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to spine
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic malignant melanoma
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.4%
2/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour ulceration
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Nervous system disorders
Aphasia
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.7%
1/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Nervous system disorders
Brain oedema
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Nervous system disorders
Cerebral haemorrhage
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Nervous system disorders
Cerebrovascular accident
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Nervous system disorders
Epilepsy
|
4.0%
3/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.4%
2/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Nervous system disorders
Embolic cerebral infarction
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Nervous system disorders
Headache
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Nervous system disorders
Hemiparesis
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Nervous system disorders
Hemiplegia
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Nervous system disorders
Paraesthesia
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Nervous system disorders
Paraparesis
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Nervous system disorders
Paresis
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Nervous system disorders
Partial seizures
|
2.7%
2/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Nervous system disorders
Seizure
|
2.7%
2/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
16.7%
1/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Nervous system disorders
Syncope
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Nervous system disorders
Spinal cord compression
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Psychiatric disorders
Delirium
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
16.7%
1/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Renal and urinary disorders
Haematuria
|
2.7%
2/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Renal and urinary disorders
Nephrolithiasis
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Reproductive system and breast disorders
Pelvic pain
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
16.7%
1/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary alveolar haemorrhage
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
16.7%
1/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Skin and subcutaneous tissue disorders
Drug eruption
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Vascular disorders
Hypotension
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Vascular disorders
Shock
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Vascular disorders
Vasculitis
|
1.3%
1/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
Other adverse events
| Measure |
Part I: Encorafenib + Binimetinib (Naive)
n=75 participants at risk
Participants naive to selective V-raf murine sarcoma viral oncogene homolog B1 (BRAF) and mitogen-activated protein kinase (MEK) inhibitors, received encorafenib 450 milligram (mg) once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for encorafenib and binimetinib was defined as 21 days of daily continuous treatment.
|
Part I: Encorafenib + Binimetinib (Non-naive)
n=83 participants at risk
Participants non-naive to selective BRAF and MEK inhibitors, received encorafenib 450 mg once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit and initiation of triple combination treatment. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for both drugs was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Ribociclib
n=38 participants at risk
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Infigratinib
n=1 participants at risk
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days.
|
Part II: Encorafenib + Binimetinib + Capmatinib
n=13 participants at risk
Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment.
|
Part II: Encorafenib + Binimetinib + Buparlisib
n=6 participants at risk
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment.
|
|---|---|---|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
10.5%
4/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
16.7%
1/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Gastrointestinal disorders
Diarrhoea
|
44.0%
33/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
30.1%
25/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
23.7%
9/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
15.4%
2/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
16.7%
1/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Gastrointestinal disorders
Nausea
|
40.0%
30/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
39.8%
33/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
39.5%
15/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
15.4%
2/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
33.3%
2/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
9.3%
7/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.2%
6/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Skin and subcutaneous tissue disorders
Rash
|
8.0%
6/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
13.3%
11/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Vascular disorders
Hypertension
|
12.0%
9/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
4.8%
4/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.7%
1/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
16.7%
1/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Blood and lymphatic system disorders
Anaemia
|
37.3%
28/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
19.3%
16/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
26.3%
10/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
23.1%
3/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
50.0%
3/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Blood and lymphatic system disorders
Neutropenia
|
8.0%
6/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.4%
2/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
13.2%
5/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Eye disorders
Cataract
|
5.3%
4/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
4.8%
4/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Eye disorders
Dry eye
|
6.7%
5/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
6.0%
5/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Eye disorders
Retinopathy
|
29.3%
22/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
12.0%
10/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Eye disorders
Subretinal fluid
|
12.0%
9/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
9.6%
8/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Eye disorders
Vision blurred
|
14.7%
11/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
9.6%
8/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Eye disorders
Visual field defect
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
15.4%
2/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
16.7%
1/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
General disorders
Asthenia
|
4.0%
3/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.2%
6/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
General disorders
Chills
|
6.7%
5/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
8.4%
7/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Gastrointestinal disorders
Abdominal pain
|
18.7%
14/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
13.3%
11/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
5.3%
2/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
16.7%
1/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Gastrointestinal disorders
Constipation
|
29.3%
22/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
15.7%
13/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
13.2%
5/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.7%
1/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
16.7%
1/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Gastrointestinal disorders
Vomiting
|
20.0%
15/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
26.5%
22/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
26.3%
10/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.7%
1/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
16.7%
1/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Gastrointestinal disorders
Flatulence
|
6.7%
5/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
3.6%
3/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
General disorders
Fatigue
|
41.3%
31/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
32.5%
27/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
15.8%
6/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.7%
1/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
General disorders
Influenza like illness
|
8.0%
6/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
6.0%
5/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
General disorders
Oedema peripheral
|
20.0%
15/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
12.0%
10/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
10.5%
4/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
23.1%
3/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
16.7%
1/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
General disorders
Pyrexia
|
17.3%
13/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
19.3%
16/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
18.4%
7/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
33.3%
2/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Infections and infestations
Conjunctivitis
|
9.3%
7/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
1.2%
1/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Infections and infestations
Nasopharyngitis
|
16.0%
12/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.2%
6/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Infections and infestations
Upper respiratory tract infection
|
14.7%
11/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
3.6%
3/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Infections and infestations
Urinary tract infection
|
9.3%
7/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
3.6%
3/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.9%
3/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
15.4%
2/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Investigations
Alanine aminotransferase increased
|
17.3%
13/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
9.6%
8/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
13.2%
5/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.7%
1/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
16.7%
1/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Investigations
Amylase increased
|
9.3%
7/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.2%
6/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Investigations
Aspartate aminotransferase increased
|
12.0%
9/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.2%
6/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
10.5%
4/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
33.3%
2/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Investigations
Blood alkaline phosphatase increased
|
5.3%
4/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
6.0%
5/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.9%
3/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.7%
1/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Investigations
Blood creatine increased
|
5.3%
4/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
4.8%
4/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
10.5%
4/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
15.4%
2/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Investigations
Blood creatine phosphokinase increased
|
50.7%
38/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
12.0%
10/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
13.2%
5/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
15.4%
2/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Investigations
Blood creatinine increased
|
9.3%
7/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
12.0%
10/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
10.5%
4/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
15.4%
2/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Investigations
Ejection fraction decreased
|
8.0%
6/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.2%
6/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Investigations
Electrocardiogram QT prolonged
|
9.3%
7/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.4%
2/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Investigations
Gamma-glutamyltransferase increased
|
16.0%
12/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
9.6%
8/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
5.3%
2/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
15.4%
2/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
16.7%
1/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Investigations
Lipase increased
|
14.7%
11/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
8.4%
7/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Investigations
Weight increased
|
9.3%
7/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
6.0%
5/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Investigations
White blood cell count decreased
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
10.5%
4/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
6.7%
5/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
16.9%
14/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
23.1%
3/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
34.7%
26/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
18.1%
15/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
5.3%
2/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
16.7%
1/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
21.3%
16/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.2%
6/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
10.5%
4/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
16.7%
1/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
21.3%
16/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
8.4%
7/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.9%
3/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
14.7%
11/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.2%
6/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
10.7%
8/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
10.8%
9/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.6%
1/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.7%
1/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
16.7%
1/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Nervous system disorders
Dizziness
|
10.7%
8/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
6.0%
5/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
10.5%
4/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Nervous system disorders
Headache
|
18.7%
14/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
9.6%
8/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.9%
3/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.9%
3/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.0%
9/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
10.8%
9/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
6.7%
5/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
9.6%
8/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
14.7%
11/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
4.8%
4/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
9.3%
7/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
12.0%
10/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
0.00%
0/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
5.3%
2/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
16.7%
1/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
6.7%
5/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
6.0%
5/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.9%
3/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
7.7%
1/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
|
Skin and subcutaneous tissue disorders
Hyperkeratosis
|
10.7%
8/75 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
2.4%
2/83 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/38 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/1 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/13 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
0.00%
0/6 • Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER