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.

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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
Encorafenib^a	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.

Results

Study primary results :

ClinicalTrials.gov

THE RESULTS

This is a summary of the main results and conclusions of the trial. Please note that:

These are the results from all the participants combined. The individual results of each participant might be different and are not in this summary.

This summary reflects the outcome of one single trial and that other trials may show other results or other outcomes