Binimetinib and Encorafenib for the Treatment of Metastatic Melanoma and Central Nervous System Metastases

NCT05026983 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2021-0205NCI-2021-08716
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the effects of binimetinib and encorafenib in treating patients with melanoma that has spread to the central nervous system (metastases). Binimetinib and encorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving binimetinib and encorafenib may help control melanoma that has spread to the brain.

Conditions

Clinical Stage IV Cutaneous Melanoma AJCC v8; Metastatic Melanoma; Pathologic Stage IV Cutaneous Melanoma AJCC v8

Outcome Measures

Primary Outcomes (4)

• Progression free survival (PFS) (Cohort A)

  At 3 months

• Incidence of dose-limiting toxicities (DLTs)

  Up to 28 days

• Incidence of adverse events (AEs)

  Graded according to the NCI CTCAE version 4.03 and changes in clinical laboratory parameters, vital signs, ECGs, ECHO/MUGA scans and ophthalmic examinations.

  Up to 30 days after last dose

• Incidence of dose interruptions, dose modifications and discontinuations due to AEs

  Up to 3 years

Secondary Outcomes (6)

• Progression free survival

  From the date of first dose of study drug to the time of the first documented progression or death, whichever occurs first, assessed up to 3 years

• Extracranial response rate

  Up to 3 years

• Intracranial response rate

  Up to 3 years

• Disease control rate

  Up to 3 years

• Duration of response (DOR)

  From first documented response of CR or PR per Investigator assessment until first documented progression or death due to any cause, whichever occurs first, assessed up to 3 years

Study Arms (1)

Treatment (encorafenib, binimetinib)

EXPERIMENTAL

Patients receive encorafenib PO QD and binimetinib PO BID on day 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Binimetinib; Drug: Encorafenib; Other: Questionnaire Administration

Interventions

Binimetinib DRUG

Given PO

Also known as: ARRY-162, ARRY-438162, MEK162, Mektovi

Treatment (encorafenib, binimetinib)

Encorafenib DRUG

Given PO

Also known as: Braftovi, LGX 818, LGX-818, LGX818

Treatment (encorafenib, binimetinib)

Questionnaire Administration OTHER

Ancillary studies

Treatment (encorafenib, binimetinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide written informed consent.
• Age \>= 18 years at the time of informed consent
• Histologically confirmed diagnosis of melanoma
• Presence of BRAFV600 mutation in tumor tissue previously determined by a local assay (including immunohistochemistry \[IHC\]) at any time prior to Screening or during Screening
• Cohort A: BRAF V600 mutant melanoma patients with progressive central nervous system (CNS) metastases. This includes patients with parenchymal brain metastases and/or LMD
• Cohort A: Prior therapy with Food and Drug Administration (FDA)-approved BRAF inhibitors (+/- MEK inhibitors) is required
• No washout period is required
• Cohort A: Prior therapy with immunotherapy or other investigational agents is allowed
• Washout period of 14 days since last dose
• Cohort B: BRAF V600 mutant melanoma patients who are treatment naive to BRAF/MEK inhibitors with CNS metastases, including LMD. Prior treatment with immunotherapy is permitted
• For patients with parenchymal brain metastases (mets) without LMD
• Metastatic disease to the brain with at least 1 progressing parenchymal brain lesion \>= 0.5 cm and =\< 3 cm, defined as a magnetic resonance imaging (MRI) contrast-enhancing lesion that may be accurately measured in at least 1 dimension
• For patients with LMD
• Patients must have investigator assessed radiographic and/or CSF cytological evidence of LMD
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of =\< 2

You may not qualify if:

• Evidence of active infection =\< 7 days prior to initiation of study drug therapy (does not apply to viral infections that are presumed to be associated with the underlying tumor type required for study entry)
• Use of non-oncology vaccines containing live virus for prevention of infectious diseases within 30 days of prior to study drug. Dead virus vaccines (e.g Flu) are allowed, even during treatment with study drug
• Inability to swallow and retain study treatment
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) even if fully immunocompetent on antiretroviral therapy (ART)
• Impaired cardiovascular function or clinically significant cardiovascular disease including, but not limited to, the following:
• History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) \< 6 months prior to screening
• Congestive heart failure requiring treatment (New York Heart Association grade \>= 2)
• A left ventricular ejection fraction (LVEF) \< 50% as determined by multigated acquisition (MUGA) or echocardiogram (ECHO)
• History or presence of clinically significant cardiac arrhythmias (including resting bradycardia, uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia)
• Baseline Fridericia's correction formula (QTcF) interval \>= 480 msec. Can be repeated up to three times to confirm
• Concurrent neuromuscular disorder (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
• Impairment of gastrointestinal function or disease which may significantly alter the absorption of study treatment (e.g., uncontrolled nausea, vomiting or diarrhea; malabsorption syndrome; small bowel resection). Known history of acute or chronic pancreatitis
• History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes); history of retinal degenerative disease
• Use of herbal supplements, medications or foods that are moderate or strong inhibitors or inducers of cytochrome P450 (CYP) 3A4/5 =\< 1 week prior to the start of study treatment
• History of a thromboembolic event \< 12 weeks prior to starting study treatment. Examples of thromboembolic events include transient ischemia attack, cerebrovascular accident, deep vein thrombosis or pulmonary embolism. Catheter-related venous thrombosis is not considered a thromboembolic event for this trial even if \< 12 weeks prior to starting study treatment. Note: Patients with either deep vein thrombosis or pulmonary emboli that do not result in hemodynamic instability are allowed to enroll as long as they are stable, asymptomatic and on stable anticoagulants for at least 2 weeks. Additionally, patients with thromboembolic events related to indwelling catheters or other procedures may be enrolled

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Publications (1)

• Corradi G, De Martino S, Rinaldi A, Siepe G, Marchese PV, Melotti B, Comito F. Rapid radiological response of leptomeningeal carcinosis and prolonged survival to encorafenib and binimetinib in BRAF-mutated melanoma. Anticancer Drugs. 2025 Sep 1;36(8):691-693. doi: 10.1097/CAD.0000000000001737. Epub 2025 May 30.

  PMID: 40439484 DERIVED

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Melanoma

Interventions

binimetinib; encorafenib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Isabella C Glitza

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Isabella C Glitza, MD,PHD

CONTACT

713-792-2921; icglitza@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2021
• First Posted: August 30, 2021
• Study Start: December 27, 2021
• Primary Completion (Estimated): February 2, 2027
• Study Completion (Estimated): February 2, 2027
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

US (1)