NCT02124772 · OUTCOME

Incidence of Treatment Emergent Adverse Events in Subjects Treated With Trametinib in Combination With Dabrafenib

Study to Investigate Safety, Pharmacokinetic (PK), Pharmacodynamic (PD) and Clinical Activity of Trametinib in Subjects With Cancer or Plexiform Neurofibromas and Trametinib in Combination With Dabrafenib in Subjects With Cancers Harboring V600 Mutations · Source last updated 2021-07-14

Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.

Measure: COUNT_OF_PARTICIPANTS
Unit: Participants
Interval / dispersion: Not reported
Time frame: From the day of the first dose of the combination up to 30 days after the last dose, up to maximum duration of 53 months

What was measured

Incidence of treatment emergent adverse events is defined as number of participants with adverse events (AEs) and serious adverse events (SAEs), including changes from baseline in vital signs and laboratory results qualifying and reported as AEs. The number of participants in each category is reported in the table.

Analysis population: All subjects who received at least one dose of any component of the combination in Part C and Part D

Groups in this outcome

Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D

Participants treated with a combination therapy of trametinib (0.025 mg/kg/day) plus 50% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (2.63 mg/kg/day for \<12 years old subjects and 2.25 mg/kg/day for ≥12 years old subjects)

Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D

Participants treated with a combination therapy of trametinib (0.025 mg/kg/day) plus 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day for \<12 years old subjects and 4.5 mg/kg/day for ≥12 years old subjects)

Part C - TMT 0.032 mg/kg/Day + 100% DRB RP2D

Participants under 6 years of age treated with a combination therapy of trametinib (0.032 mg/kg/day) with 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day)

Part D - LGG

Participants with low grade glioma (LGG) treated with a combination therapy of trametinib (0.032 mg/kg/day for \< 6 years old subjects and 0.025 mg/kg/day for ≥ 6 years old subjects) plus 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day for \<12 years old subjects and 4.5 mg/kg/day for ≥12 years old subjects)

Part D - LCH

Participants with Langerhans cell histiocytosis (LCH) treated with a combination therapy of trametinib (0.032 mg/kg/day for \< 6 years old subjects and 0.025 mg/kg/day for ≥ 6 years old subjects) plus 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day for \<12 years old subjects and 4.5 mg/kg/day for ≥12 years old subjects)

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 C - TMT 0.025 mg/kg/Day + 50% DRB RP2D	3
Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D	9
Part C - TMT 0.032 mg/kg/Day + 100% DRB RP2D	6
Part D - LGG	20
Part D - LCH	10

Reported measurements

AEs

Values in Participants · Interval/dispersion: Not reported
Group	Value	Spread	Lower	Upper	Comment
Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D	3	Not reported	Not reported	Not reported	Not reported
Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D	9	Not reported	Not reported	Not reported	Not reported
Part C - TMT 0.032 mg/kg/Day + 100% DRB RP2D	6	Not reported	Not reported	Not reported	Not reported
Part D - LGG	20	Not reported	Not reported	Not reported	Not reported
Part D - LCH	10	Not reported	Not reported	Not reported	Not reported

Treatment-related AEs

Values in Participants · Interval/dispersion: Not reported
Group	Value	Spread	Lower	Upper	Comment
Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D	3	Not reported	Not reported	Not reported	Not reported
Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D	9	Not reported	Not reported	Not reported	Not reported
Part C - TMT 0.032 mg/kg/Day + 100% DRB RP2D	6	Not reported	Not reported	Not reported	Not reported
Part D - LGG	20	Not reported	Not reported	Not reported	Not reported
Part D - LCH	10	Not reported	Not reported	Not reported	Not reported

SAEs

Values in Participants · Interval/dispersion: Not reported
Group	Value	Spread	Lower	Upper	Comment
Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D	1	Not reported	Not reported	Not reported	Not reported
Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D	5	Not reported	Not reported	Not reported	Not reported
Part C - TMT 0.032 mg/kg/Day + 100% DRB RP2D	2	Not reported	Not reported	Not reported	Not reported
Part D - LGG	8	Not reported	Not reported	Not reported	Not reported
Part D - LCH	6	Not reported	Not reported	Not reported	Not reported

Treatment-related SAEs

Values in Participants · Interval/dispersion: Not reported
Group	Value	Spread	Lower	Upper	Comment
Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D	0	Not reported	Not reported	Not reported	Not reported
Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D	2	Not reported	Not reported	Not reported	Not reported
Part C - TMT 0.032 mg/kg/Day + 100% DRB RP2D	1	Not reported	Not reported	Not reported	Not reported
Part D - LGG	5	Not reported	Not reported	Not reported	Not reported
Part D - LCH	3	Not reported	Not reported	Not reported	Not reported

Fatal SAEs

Values in Participants · Interval/dispersion: Not reported
Group	Spread	Lower	Upper	Comment
Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D	Not reported	Not reported	Not reported	Not reported
Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D	Not reported	Not reported	Not reported	Not reported
Part C - TMT 0.032 mg/kg/Day + 100% DRB RP2D	Not reported	Not reported	Not reported	Not reported
Part D - LGG	Not reported	Not reported	Not reported	Not reported
Part D - LCH	Not reported	Not reported	Not reported	Not reported

AEs leading to discontinuation

Values in Participants · Interval/dispersion: Not reported
Group	Value	Spread	Lower	Upper	Comment
Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D	0	Not reported	Not reported	Not reported	Not reported
Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D	3	Not reported	Not reported	Not reported	Not reported
Part C - TMT 0.032 mg/kg/Day + 100% DRB RP2D	1	Not reported	Not reported	Not reported	Not reported
Part D - LGG	5	Not reported	Not reported	Not reported	Not reported
Part D - LCH	1	Not reported	Not reported	Not reported	Not reported

AEs requiring dose interruptions

Values in Participants · Interval/dispersion: Not reported
Group	Value	Spread	Lower	Upper	Comment
Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D	1	Not reported	Not reported	Not reported	Not reported
Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D	6	Not reported	Not reported	Not reported	Not reported
Part C - TMT 0.032 mg/kg/Day + 100% DRB RP2D	4	Not reported	Not reported	Not reported	Not reported
Part D - LGG	16	Not reported	Not reported	Not reported	Not reported
Part D - LCH	8	Not reported	Not reported	Not reported	Not reported

AEs requiring dose reductions

Values in Participants · Interval/dispersion: Not reported
Group	Value	Spread	Lower	Upper	Comment
Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D	1	Not reported	Not reported	Not reported	Not reported
Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D	3	Not reported	Not reported	Not reported	Not reported
Part C - TMT 0.032 mg/kg/Day + 100% DRB RP2D	1	Not reported	Not reported	Not reported	Not reported
Part D - LGG	6	Not reported	Not reported	Not reported	Not reported
Part D - LCH	1	Not reported	Not reported	Not reported	Not reported

AEs requiring dose reductions or interruptions

Values in Participants · Interval/dispersion: Not reported
Group	Value	Spread	Lower	Upper	Comment
Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D	1	Not reported	Not reported	Not reported	Not reported
Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D	7	Not reported	Not reported	Not reported	Not reported
Part C - TMT 0.032 mg/kg/Day + 100% DRB RP2D	4	Not reported	Not reported	Not reported	Not reported
Part D - LGG	16	Not reported	Not reported	Not reported	Not reported
Part D - LCH	8	Not reported	Not reported	Not reported	Not reported

Complete source fields

classes

categories
measurements
group Id
OG000
value
3
group Id
OG001
value
9
group Id
OG002
value
6
group Id
OG003
value
20
group Id
OG004
value
10
title
AEs
categories
measurements
group Id
OG000
value
3
group Id
OG001
value
9
group Id
OG002
value
6
group Id
OG003
value
20
group Id
OG004
value
10
title
Treatment-related AEs
categories
measurements
group Id
OG000
value
1
group Id
OG001
value
5
group Id
OG002
value
2
group Id
OG003
value
8
group Id
OG004
value
6
title
SAEs
categories
measurements
group Id
OG000
value
0
group Id
OG001
value
2
group Id
OG002
value
1
group Id
OG003
value
5
group Id
OG004
value
3
title
Treatment-related SAEs
categories
measurements
group Id
OG000
value
0
group Id
OG001
value
0
group Id
OG002
value
0
group Id
OG003
value
0
group Id
OG004
value
0
title
Fatal SAEs
categories
measurements
group Id
OG000
value
0
group Id
OG001
value
3
group Id
OG002
value
1
group Id
OG003
value
5
group Id
OG004
value
1
title
AEs leading to discontinuation
categories
measurements
group Id
OG000
value
1
group Id
OG001
value
6
group Id
OG002
value
4
group Id
OG003
value
16
group Id
OG004
value
8
title
AEs requiring dose interruptions
categories
measurements
group Id
OG000
value
1
group Id
OG001
value
3
group Id
OG002
value
1
group Id
OG003
value
6
group Id
OG004
value
1
title
AEs requiring dose reductions
categories
measurements
group Id
OG000
value
1
group Id
OG001
value
7
group Id
OG002
value
4
group Id
OG003
value
16
group Id
OG004
value
8
title
AEs requiring dose reductions or interruptions

denoms

counts
group Id
OG000
value
3
group Id
OG001
value
9
group Id
OG002
value
6
group Id
OG003
value
20
group Id
OG004
value
10
units
Participants

description

groups

description
Participants treated with a combination therapy of trametinib (0.025 mg/kg/day) plus 50% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (2.63 mg/kg/day for \<12 years old subjects and 2.25 mg/kg/day for ≥12 years old subjects)
id
OG000
title
Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D
description
Participants treated with a combination therapy of trametinib (0.025 mg/kg/day) plus 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day for \<12 years old subjects and 4.5 mg/kg/day for ≥12 years old subjects)
id
OG001
title
Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D
description
Participants under 6 years of age treated with a combination therapy of trametinib (0.032 mg/kg/day) with 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day)
id
OG002
title
Part C - TMT 0.032 mg/kg/Day + 100% DRB RP2D
description
Participants with low grade glioma (LGG) treated with a combination therapy of trametinib (0.032 mg/kg/day for \< 6 years old subjects and 0.025 mg/kg/day for ≥ 6 years old subjects) plus 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day for \<12 years old subjects and 4.5 mg/kg/day for ≥12 years old subjects)
id
OG003
title
Part D - LGG
description
Participants with Langerhans cell histiocytosis (LCH) treated with a combination therapy of trametinib (0.032 mg/kg/day for \< 6 years old subjects and 0.025 mg/kg/day for ≥ 6 years old subjects) plus 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day for \<12 years old subjects and 4.5 mg/kg/day for ≥12 years old subjects)
id
OG004
title
Part D - LCH

param Type

COUNT_OF_PARTICIPANTS

population Description

All subjects who received at least one dose of any component of the combination in Part C and Part D

reporting Status

POSTED

time Frame

From the day of the first dose of the combination up to 30 days after the last dose, up to maximum duration of 53 months

title

Incidence of Treatment Emergent Adverse Events in Subjects Treated With Trametinib in Combination With Dabrafenib

type

SECONDARY

unit Of Measure

Participants

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Preserved source evidence · Independent clinical review pending · Not medical advice