A trial to evaluate the impact of liver dysfunction on elimination of encorafenib in combination with binimetinib administered to patients with BRAFV600E-mutant solid tumors
A trial to evaluate the impact of liver dysfunction on elimination of encorafenib in combination with binimetinib administered to patients with BRAFV600E-mutant solid tumors
An open label, multicentre, phase I study to evaluate the impact of moderate and severe hepatic impairments on the pharmacokinetics and safety of encorafenib in combination with binimetinib in adult patients with unresectable or metastatic BRAF V600-mutant solid tumors.
How is the study conducted?
This is an open-label Phase 1 trial with 12 participants.
Participants will be assigned to one of the following 3 study groups :
- Group I : 4 participants with normal hepatic function
- Group II: 4 participants with moderate hepatic impairment
- Group III (*): 4 participants with severe impairment
(*) Before proceeding with Group III, safety and PK data will be analysed to ensure whether it is safe and feasible.
The impact of hepatic impairment on PK will be assessed requiring serial blood samplings on Day 1 (the day of the first treatment administration), and Day 15 (2 weeks after first administration)
After completing the 2-weeks HI assessment phase, participants may continue encorafenib and binimetinib treatments as long as it is beneficial for them. That means as long as the disease does not worsen (disease progression) and the treatment is tolerated.
After treatment discontinuation, participant will perform an End of Treatment visit, followed by a Safety Follow-Up visit (30 days after last treatment dose).
The schema summarizes the information presented above:
Who can take part in the trial ?
To be part of the trial, participant must fulfill several conditions including the following:
• Adults participants with BRAF V600-mutant solid tumors
• Fulfilling hepatic function criteria specific to each trial groups
What are the objectives of the trial and how are they evaluated ?
The primary objective of this study is to evaluate the pharmacokinetic (PK) of encorafenib following a single dose and repeated oral dose of encorafenib in combination with binimetinib.
In addition, the trial will allow:
• to evaluate the PK of binimetinib taken in combination with encorafenib.
• to evaluate the safety of a repeated dose of encorafenib in combination with binimetinib in regard with the number and type of side effects
• to compare the PK profiles between impaired (moderate and severe) and normal hepatic functions
What is the study Medication ?
Dosage of Encorafenib and Binimetinib is adapted for each group of participants as following :
|
Study Treatments |
Pharmaceutical Form and Route of Administration |
Dose |
Frequency |
|
Group I: participants with normal hepatic function |
|||
|
Encorafenib |
6 × 75 mg oral capsule |
450 mg |
QD* |
|
Binimetinib |
3 × 15 mg oral film-coated tablet |
45 mg |
BID** |
|
Group II: participants with moderate hepatic impairment |
|||
|
Encorafenib |
2 × 75 mg oral capsule |
150 mg |
QD* |
|
Binimetinib |
1 × 15 mg oral film-coated tablet |
15 mg |
BID** |
|
Group III: participants with severe hepatic impairment |
|||
|
Encorafeniba |
1 × 75 mg oral capsule |
75 mg |
QD* |
|
Binimetinib |
1 × 15 mg oral film-coated tablet |
15 mg |
BID** |
aEncorafenib Dose for Group III may be adjusted after analysis of PK and safety data of Groups I and II.
(*) QD (Quaque Die) means that treatment is taken once a day
(**) BID (Bis In Die) means that treatment is taken twice a day.