BRF116056 is the first clinical experience with GSK2118436, a BRAF inhibitor, in Japan. This study will be designed to assess safety, tolerability, single and repeat dose PK profile and preliminary efficacy of GSK2118436 in Japanese subjects with BRAF V600 mutation positive solid tumors using continuous daily dosing schedule.
BRF116056 is the first clinical experience with GSK2118436, a BRAF inhibitor, in Japan. This study will be designed to assess safety, tolerability, single and repeat dose PK profile and preliminary efficacy of GSK2118436 in Japanese subjects with BRAF V600 mutation positive solid tumors using continuous daily dosing schedule. Dose escalation of GSK2118436 will be performed according to a standard 3+3 dose-escalation design. GSK2118436 is given twice a day. However, to characterize the PK of GSK2118436 and its metabolites after single-dose administration, GSK2118436 will NOT be administrated for a week after the first administration. GSK2118436 continuous dosing will start after the 168-hour PK sample is obtained. Subjects may receive study treatment until disease progression, death or an unacceptable adverse event.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Dose escalation with GSK2118436 may proceed until the overseas recommended phase III dose.
GSK Investigational Site
Shizuoka, Japan
GSK Investigational Site
Tokyo, Japan
Number of participants with adverse events as a measure of safety and tolerability
Adverse Events will be graded by the investigator according to the NCI-CTCAE (version 4.0)
Time frame: First 28 days for Dose-limiting toxicity, Adverse Events for 1 year
Pharmacokinetics (PK) parameters of GSK2118436 and its metabolites including blood concentration, Cmax and AUC
Time frame: For 1 year
Tumor response as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time frame: For 1 year
Serum levels of cytokines
Time frame: For 1 year
Expression levels of pERK and Ki67 in tumor tissues if possible
Time frame: For 1 year
Gene mutation in tumor tissues, including BRAF and KRAS
Time frame: For 1 year
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