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Kinase Inhibitor

Binimetinib + Encorafenib for Melanoma

Phase 2
Recruiting
Led By Isabella C Glitza
Research Sponsored by M.D. Anderson Cancer Center
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Age >= 18 years at the time of informed consent
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
Must not have
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 Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection NOTE: Patients with laboratory evidence of cleared HBV or HCV infection may be enrolled NOTE: Patients with no prior history of HBV infection who have been vaccinated against HBV and who have a positive antibody against hepatitis B surface antigen as the only evidence of prior exposure may enroll Pregnancy or breastfeeding or patients who plan to become pregnant during the duration of the study Other severe, acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study treatment administration or that may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient an inappropriate candidate for the study
Timeline
Screening 3 weeks
Treatment Varies
Follow Up up to 3 years
Awards & highlights

Summary

This trial tests whether binimetinib and encorafenib can help control melanoma that has spread to the brain.

Who is the study for?
Adults with metastatic melanoma that has spread to the brain, including those who have previously received FDA-approved BRAF inhibitors. Participants must have a specific BRAFV600 mutation and be in good enough health as determined by certain lab parameters. Pregnant or breastfeeding individuals are excluded, as well as those with significant heart conditions, infections, gastrointestinal impairments, or a history of certain blood clots.Check my eligibility
What is being tested?
The trial is testing binimetinib and encorafenib's effectiveness on melanoma that has reached the central nervous system. These drugs aim to halt tumor growth by inhibiting key enzymes. The study includes patients who've had prior treatments and those new to these medications.See study design
What are the potential side effects?
Potential side effects may include fatigue, skin reactions, vision changes due to eye problems like retinal vein occlusion (RVO), liver enzyme elevations indicating potential liver damage, muscle pain or weakness from neuromuscular issues, high blood pressure, bleeding events and clotting disorders.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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I am 18 years old or older.
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My tumor has the BRAFV600 mutation.
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Your blood tests need to show specific levels for things like white blood cells, hemoglobin, and platelets. Your liver and kidney function also need to be within certain limits. If you can become pregnant, you need to have a negative pregnancy test and agree to use birth control during the study. You also need to be able to keep up with your doctor visits and treatment plan.
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I have brain metastases but no leptomeningeal disease.
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I can take care of myself but might not be able to do heavy physical work.
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I have a brain tumor between 0.5 and 3 cm that is getting worse.
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My cancer has spread to the lining of my brain or spinal cord, confirmed by scans or tests.
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My diagnosis of melanoma is confirmed through tissue examination.
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I am taking 4 mg or less of dexamethasone daily for LMD, or just enough for adrenal insufficiency.
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I have melanoma with a BRAF V600 mutation and it has spread to my brain.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
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I do not have significant heart issues, recent serious heart events, uncontrolled heart rhythm problems, severe eye conditions, recent major blood clots, certain infections like active hepatitis B or C, and I am not pregnant or planning to become pregnant during the study.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~up to 3 years
This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3 years for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.
Primary outcome measures
Incidence of adverse events (AEs)
Incidence of dose interruptions, dose modifications and discontinuations due to AEs
Incidence of dose-limiting toxicities (DLTs)
+1 more
Secondary outcome measures
Disease control rate
Duration of response (DOR)
Extracranial response rate
+3 more

Side effects data

From 2022 Phase 3 trial • 702 Patients • NCT02928224
78%
Diarrhoea
68%
Dermatitis acneiform
59%
Nausea
54%
Fatigue
51%
Vomiting
51%
Dry Skin
43%
Pyrexia
43%
Anaemia
41%
Decreased appetite
38%
Abdominal pain
38%
Constipation
35%
Dyspnoea
32%
Vision blurred
30%
Blood creatine increased
30%
Blood creatine phosphokinase increased
24%
Arthralgia
24%
Myalgia
24%
Skin fissures
22%
Back Pain
22%
Dizziness
19%
Malaise
19%
Urinary tract infection
19%
Headache
19%
Aspartate aminotransferase increased
16%
Oedema peripheral
16%
Stomatitis
16%
Asthenia
16%
PPE syndrome
16%
Hypomagnesaemia
16%
Rash maculo-papular
16%
Palmar-planar erythrodysaesthesia
16%
Chills
16%
Paronychia
16%
Rash pustular
16%
Alanine aminotransferase increased
16%
Dysgeusia
16%
Peripheral sensory neuropathy
14%
Cough
14%
Abdominal pain upper
14%
Infusion-related reaction
14%
Ejection fraction decreased
14%
Dry eye
11%
Trichiasis
11%
Vitreous floaters
11%
Pollakiuria
11%
Dyspepsia
11%
Hypoalbuminaemia
11%
Hypertension
11%
Tumour Pain
8%
Weight decreased
8%
Macular oedema
8%
Hypokalaemia
8%
Iron deficiency
8%
Rhinitis allergic
8%
Visual impairment
8%
Hypertrichosis
8%
Nasopharyngitis
8%
Proteinuria
8%
Infusion related reaction
8%
Flank pain
8%
Rash
8%
Pruritus
8%
Pain in extremity
8%
Blood bilirubin increased
8%
Rhinnorrhoea
8%
Hypotension
5%
Musculoskeletal chest pain
5%
Wound
5%
Pleural effusion
5%
Ascites
5%
Rectal haemorrhage
5%
Trichomegaly
5%
Hypocalcaemia
5%
Nail disorder
5%
Hypophosphataemia
5%
Colitis
5%
Chorioretinopathy
5%
Abdominal pain lower
5%
Musculoskeletal pain
5%
Pruritus generalised
5%
Urinary incontinence
5%
Infection
5%
Bone pain
5%
Anal haemorrhage
5%
Restless legs syndrome
5%
Nervous system disorder
5%
Insomnia
5%
Gastroesophageal reflux disease
5%
Abdominal distension
5%
Eczema
5%
Cystitis
5%
Renal failure
5%
Conjunctivitis
5%
Syncope
5%
Dehydration
5%
Dry Mouth
5%
Skin hyperpigmentation
5%
Muscle spasms
5%
Erythema
5%
Retinal detachment
5%
Pulmonary embolism
5%
Dysphonia
5%
Haematuria
5%
Blood creatinine increased
5%
Depression
5%
Palpitations
3%
Upper respiratory tract infection
3%
Urinary tract infection bacterial
3%
Epistaxis
3%
Large intestine perforation
3%
Back pain
3%
Confusional state
3%
Device occlusion
3%
Streptococcal infection
3%
Large intestinal ulcer
3%
Cholangitis
3%
Large intestinal ulcer hemorrhage
3%
Kidney infection
3%
Bacterial sepsis
3%
Hyperkeratosis
3%
Rhabdomyolysis
3%
Rectal hemorrhage
3%
Skin papilloma
3%
Alopecia
3%
Tumour pain
3%
Melanocytic naevus
3%
Urinary tract obstruction
3%
Colon cancer
3%
Sepsis
3%
Acute kidney injury
3%
Large intestine ulcer
3%
Neutropenia
3%
Bacteria sepsis
3%
Hydronephrosis
3%
Neuropathy peripheral
3%
Abdominal abscess
3%
Hyperglycaemia
100%
80%
60%
40%
20%
0%
Study treatment Arm
Combined Safety Lead-in
Phase 3: Triplet Arm
Phase 3: Doublet Arm
Phase 3: Control Arm

Trial Design

1Treatment groups
Experimental Treatment
Group I: Treatment (encorafenib, binimetinib)Experimental Treatment3 Interventions
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.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Encorafenib
2022
Completed Phase 3
~970
Binimetinib
2018
Completed Phase 3
~1100

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.
Mechanism Of Action
Side Effect Profile
Prior Approvals
Other Research
The most common treatments for melanoma, particularly those involving enzyme inhibition, include BRAF and MEK inhibitors like binimetinib and encorafenib. These drugs work by targeting specific enzymes that are involved in the growth and proliferation of melanoma cells. BRAF inhibitors block the activity of the mutated BRAF protein, which is present in about half of melanomas and drives tumor growth. MEK inhibitors, on the other hand, target the MEK enzyme, which is part of the same signaling pathway as BRAF. By inhibiting these enzymes, these treatments can effectively slow down or stop the growth of melanoma cells. This is crucial for melanoma patients as it can lead to better control of the disease, potentially prolonging survival and improving quality of life.
Involution of eruptive melanocytic nevi on combination BRAF and MEK inhibitor therapy.

Find a Location

Who is running the clinical trial?

M.D. Anderson Cancer CenterLead Sponsor
3,002 Previous Clinical Trials
1,794,244 Total Patients Enrolled
104 Trials studying Melanoma
25,627 Patients Enrolled for Melanoma
Isabella C GlitzaPrincipal InvestigatorM.D. Anderson Cancer Center
2 Previous Clinical Trials
76 Total Patients Enrolled
2 Trials studying Melanoma
76 Patients Enrolled for Melanoma

Media Library

Binimetinib (Kinase Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT05026983 — Phase 2
Melanoma Research Study Groups: Treatment (encorafenib, binimetinib)
Melanoma Clinical Trial 2023: Binimetinib Highlights & Side Effects. Trial Name: NCT05026983 — Phase 2
Binimetinib (Kinase Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT05026983 — Phase 2
~8 spots leftby May 2025