Hepatic Impairment Study of Encorafenib in Combination With Binimetinib in BRAF Melanoma

Metastatic Melanoma Clinical Trial

Official title: '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'.

Status Withdrawn

Clinical Trial Summary

Encorafenib in combination with binimetinib have been approved in USA, Europe, Australia, Japan and Switzerland for the treatment of adult patients with unresectable or metastatic melanoma with BRAF V600 mutation.

The main objective of this study is to find a safe and effective dose of encorafenib in combination with binimetinib for patients who have BRAF-mutant metastatic or unresectable melanoma with hepatic dysfunction (i.e. moderate or severe impairment).

Clinical Trial Description

This is an open label, multicentre, phase I study to evaluate the impact of moderate and severe hepatic impairment (HI) on the pharmacokinetics and safety of encorafenib in combination with binimetinib, in adult patients with unresectable or metastatic BRAF V600-mutant melanoma.

For each participant, the treatment period will be split in 2 phases:

• a HI assessment phase assessing the impact of hepatic impairment after a single dose (Day 1) and after repeated doses (Day 15).

• a post-HI assessment phase: after completing the HI assessment phase, participants may continue treatment in the post-HI assessment phase until disease progression or unacceptable toxicity.

Participants with hepatic impairment will be enrolled sequentially according to their severity. The study will start first in participants with normal hepatic function and moderate hepatic impairment respectively.

Participants will be assigned to one of the following 3 study groups:

• Group with normal hepatic function: 4 participants

• Group with moderate hepatic impairment (Child-Pugh Class B): 4 participants

• Group with severe impairment (Child-Pugh Class C): 4 participants

An Internal Review Committee (IRC) will review the safety and PK data of encorafenib in combination with binimetinib for group with normal hepatic function and group with moderate hepatic impairment and make a recommendation prior to start group with severe impairment enrolment. The Sponsor will determine whether it is safe and feasible to proceed with group with severe impairment.

Participants will receive treatment doses according to their assigned group. ;

Related Conditions & MeSH terms

• BRAF V600 Mutation
• Hepatic Impairment
• Liver Diseases
• Melanoma
• Metastatic Melanoma
• Unresectable Melanoma

• NCT number: NCT04759846
• Study type: Interventional
• Source: Pierre Fabre Medicament
• Status: Withdrawn
• Phase: Phase 1
• Start date: January 21, 2021
• Completion date: May 2023