Part B: Pre- and Post-dose H-scores for Individual Participants
Investigate Safety, Pharmacokinetics and Pharmacodynamics of GSK2118436 & GSK1120212 · Source last updated 2019-07-05
Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.
Measure
NUMBER
Unit
scores on a scale
Interval / dispersion
Not reported
Time frame
Screening and at disease progression (up to approximately 8 years)
What was measured
p-ERK and p-AKT, biomarkers in tumor biopsies, were assessed for participants with BRAF mutant colorectal cancer. The H-score, which is a composite score that comprises intensity and percentage of staining, is a method of assessing the amount of protein or phospho-protein present in a biopsy sample. The score is obtained by the formula: (3 \* percentage of strongly staining nuclei) + (2 \* percentage of moderately staining nuclei) + (percentage of weakly staining nuclei). The H-score ranges from 0 to 300, with a score of 0 representing the absence of any of the target protein and an H-score of 300 representing maximum staining and intensity of the target protein.
Analysis population: Biomarker Population: participants with H-score data for pre- and post-biopsy pairs
Groups in this outcome
Part B: Dabrafenib + Trametinib
Melanoma BRAF-positive participants who did not receive prior treatment with BRAF inhibitors received dabrafenib (75 mg or 150 mg) gelatin capsules BID and trametinib (1 mg, 1.5 mg, or 2 mg) tablets QD as continuous daily dosing. Dose escalation decisions were made based on all available pharmacokinetic (PK), safety, and other data from the first 4 evaluable participants, and additional participants were enrolled based on dose-limiting toxicities (DLTs) occurring during the first 3 weeks of treatment.
Group identifiers and denominators belong to this outcome only. They may differ in another outcome or in safety reporting.
Analysis denominator · Participants
Group
Source count
Part B: Dabrafenib + Trametinib
10
Reported measurements
p-ERK: Participant 1, pre-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
135
Not reported
Not reported
Not reported
Not reported
p-ERK: Participant 1, post-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
109
Not reported
Not reported
Not reported
Not reported
p-ERK: Participant 2, pre-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
193
Not reported
Not reported
Not reported
Not reported
p-ERK: Participant 2, post-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
138
Not reported
Not reported
Not reported
Not reported
p-ERK: Participant 3, pre-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
148
Not reported
Not reported
Not reported
Not reported
p-ERK: Participant 3, post-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
65
Not reported
Not reported
Not reported
Not reported
p-ERK: Participant 4, pre-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
80
Not reported
Not reported
Not reported
Not reported
p-ERK: Participant 4, post-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
20
Not reported
Not reported
Not reported
Not reported
p-ERK: Participant 5, pre-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
130
Not reported
Not reported
Not reported
Not reported
p-ERK: Participant 5, post-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
99
Not reported
Not reported
Not reported
Not reported
p-ERK: Participant 6, pre-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
68
Not reported
Not reported
Not reported
Not reported
p-ERK: Participant 6, post-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
7
Not reported
Not reported
Not reported
Not reported
p-ERK: Participant 7, pre-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
128
Not reported
Not reported
Not reported
Not reported
p-ERK: Participant 7, post-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
81
Not reported
Not reported
Not reported
Not reported
p-ERK: Participant 8, pre-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
196
Not reported
Not reported
Not reported
Not reported
p-ERK: Participant 8, post-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
75
Not reported
Not reported
Not reported
Not reported
p-ERK: Participant 9, pre-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
164
Not reported
Not reported
Not reported
Not reported
p-ERK: Participant 9, post-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
109
Not reported
Not reported
Not reported
Not reported
p-ERK: Participant 10, pre-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
239
Not reported
Not reported
Not reported
Not reported
p-ERK: Participant 10, post-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
78
Not reported
Not reported
Not reported
Not reported
p-AKT: Participant 1, pre-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
130
Not reported
Not reported
Not reported
Not reported
p-AKT, Participant 1, post-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
180
Not reported
Not reported
Not reported
Not reported
p-AKT: Participant 2, pre-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
76
Not reported
Not reported
Not reported
Not reported
p-AKT, Participant 2, post-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
50
Not reported
Not reported
Not reported
Not reported
p-AKT: Participant 3, pre-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
192
Not reported
Not reported
Not reported
Not reported
p-AKT, Participant 3, post-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
277
Not reported
Not reported
Not reported
Not reported
p-AKT: Participant 4, pre-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
25
Not reported
Not reported
Not reported
Not reported
p-AKT, Participant 4, post-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
135
Not reported
Not reported
Not reported
Not reported
p-AKT: Participant 5, pre-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
55
Not reported
Not reported
Not reported
Not reported
p-AKT, Participant 5, post-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
2
Not reported
Not reported
Not reported
Not reported
p-AKT: Participant 6, pre-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
145
Not reported
Not reported
Not reported
Not reported
p-AKT, Participant 6, post-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
20
Not reported
Not reported
Not reported
Not reported
p-AKT: Participant 7, pre-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
22
Not reported
Not reported
Not reported
Not reported
p-AKT, Participant 7, post-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
7
Not reported
Not reported
Not reported
Not reported
p-AKT: Participant 8, pre-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
183
Not reported
Not reported
Not reported
Not reported
p-AKT, Participant 8, post-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
123
Not reported
Not reported
Not reported
Not reported
p-AKT: Participant 9, pre-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
278
Not reported
Not reported
Not reported
Not reported
p-AKT, Participant 9, post-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
289
Not reported
Not reported
Not reported
Not reported
p-AKT: Participant 10, pre-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
73
Not reported
Not reported
Not reported
Not reported
p-AKT, Participant 10, post-dose score
Values in scores on a scale · Interval/dispersion: Not reported
Group
Value
Spread
Lower
Upper
Comment
Part B: Dabrafenib + Trametinib
0
Not reported
Not reported
Not reported
Not reported
Complete source fields
classes
categories
measurements
group Id
OG000
value
135
title
p-ERK: Participant 1, pre-dose score
categories
measurements
group Id
OG000
value
109
title
p-ERK: Participant 1, post-dose score
categories
measurements
group Id
OG000
value
193
title
p-ERK: Participant 2, pre-dose score
categories
measurements
group Id
OG000
value
138
title
p-ERK: Participant 2, post-dose score
categories
measurements
group Id
OG000
value
148
title
p-ERK: Participant 3, pre-dose score
categories
measurements
group Id
OG000
value
65
title
p-ERK: Participant 3, post-dose score
categories
measurements
group Id
OG000
value
80
title
p-ERK: Participant 4, pre-dose score
categories
measurements
group Id
OG000
value
20
title
p-ERK: Participant 4, post-dose score
categories
measurements
group Id
OG000
value
130
title
p-ERK: Participant 5, pre-dose score
categories
measurements
group Id
OG000
value
99
title
p-ERK: Participant 5, post-dose score
categories
measurements
group Id
OG000
value
68
title
p-ERK: Participant 6, pre-dose score
categories
measurements
group Id
OG000
value
7
title
p-ERK: Participant 6, post-dose score
denoms
counts
group Id
OG000
value
10
units
Participants
description
p-ERK and p-AKT, biomarkers in tumor biopsies, were assessed for participants with BRAF mutant colorectal cancer. The H-score, which is a composite score that comprises intensity and percentage of staining, is a method of assessing the amount of protein or phospho-protein present in a biopsy sample. The score is obtained by the formula: (3 \* percentage of strongly staining nuclei) + (2 \* percentage of moderately staining nuclei) + (percentage of weakly staining nuclei). The H-score ranges from 0 to 300, with a score of 0 representing the absence of any of the target protein and an H-score of 300 representing maximum staining and intensity of the target protein.
groups
description
Melanoma BRAF-positive participants who did not receive prior treatment with BRAF inhibitors received dabrafenib (75 mg or 150 mg) gelatin capsules BID and trametinib (1 mg, 1.5 mg, or 2 mg) tablets QD as continuous daily dosing. Dose escalation decisions were made based on all available pharmacokinetic (PK), safety, and other data from the first 4 evaluable participants, and additional participants were enrolled based on dose-limiting toxicities (DLTs) occurring during the first 3 weeks of treatment.
id
OG000
title
Part B: Dabrafenib + Trametinib
param Type
NUMBER
population Description
Biomarker Population: participants with H-score data for pre- and post-biopsy pairs
reporting Status
POSTED
time Frame
Screening and at disease progression (up to approximately 8 years)
title
Part B: Pre- and Post-dose H-scores for Individual Participants
Triangle