955 / 1266
3.0
mg/kg
3.75
mg/kg
4.5
mg/kg
5.25
mg/kg
COMPLETED
ONGOING
Children or adolescents with BRAF V600-mutant solid tumors
Dabrafenib dose escalation
(modified rolling 6 design)
Eligible patient with
solid tumors
Phase 1 escalation
Phase 2
expansion cohorts
HGG
(n = 10)
Low grade glioma (LGG)
(n = 10)
LCH
(n = 10)
Other solid tumors (eg, PTC, melanoma)
(n = 10)
Dabrafenib
•
RP2D
•
PK
• Safety, tolerability
• Preliminary
antitumor activity
Key inclusion criteria
Key exclusion criteria
RP2D, recommended phase 2 dose.
*AUC
(0-12)
= 4,000-5,500 ng
•
h/mL.
•
Recurrent, refractory, or progressive disease
after at least 1 standard therapy
o
(metastatic melanoma may be first line)
•
BRAF V600 mutation positive
o
(local test with central confirmation)
• Prior treatment with dabrafenib, other RAF or MEK
inhibitor (part 2 only)
• Other malignancy
• MTD
• RP2D
•
Exposure consistent with
adult dose*
109
Registered at clinicaltrials.gov as NCT01677741