An Open-Label, Randomized, Multicentre Trial of Encorafenib + Binimetinib Evaluating a Standard-dose and a High-dose Regimen in Patients With BRAFV600-mutant Melanoma Brain Metastasis

Official Title

A Phase 2, Open-Label, Randomized, Multicentre Trial of Encorafenib + Binimetinib Evaluating a Standard-dose and a High-dose Regimen in Patients With BRAFV600-Mutant Melanoma Brain Metastasis

Summary:

This is a multicentre, randomized open-label Phase 2 study to assess the safety, efficacy and pharmacokinetic (PK) of 2 dosing regimens of encorafenib + binimetinib combination in patients with BRAFV600-mutant melanoma with brain metastasis. Approximately 100 patients will be enrolled, including 9 patients in a Safety Lead-in of the high-dose treatment arm. After a Screening Period, treatment will be administered in 28-day cycles and will continue until disease progression, unacceptable toxicity, withdrawal of consent, start of subsequent anticancer therapy, death.

Trial Description

Primary Outcome:

• Safety Lead-in: Incidence of dose-limiting toxicities (DLTs)
• Safety Lead-in: Incidence and severity of adverse events (AEs)
• Safety Lead-in: Incidence of dose modifications due to AEs
• Safety Lead-in: Incidence of treatment discontinuations due to AEs
• Phase 2: Brain metastasis response rate (BMRR) per modified Response Evaluation Criteria in Solid Tumours version 1.1 (mRECIST v1.1)

• Extracranial response rate per Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1)
• Global response rate (brain metastasis response per mRECIST v1.1 and extracranial response per RECIST v1.1)
• Disease control rate (DCR)
• Duration of Response (DOR)
• Progression-free survival (PFS)
• Brain metastasis response rate (BMRR) per mRECIST v1.1 for Safety Lead-in only
• Overall survival (OS)
• Incidence and severity of adverse events (AEs)
• Pharmacokinetics (PK) of binimetinib and its metabolite
• Pharmacokinetics (PK) of encorafenib and its metabolite

View this trial on ClinicalTrials.gov