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Kinase Inhibitor

Encorafenib/Binimetinib/Nivolumab vs Ipilimumab/Nivolumab for Melanoma

Phase 2

Recruiting

Led By Zeynep Eroglu

Research Sponsored by SWOG Cancer Research Network

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participants with a known history of hepatitis C virus (HCV) infection must have been treated and cured

Participants must be able to swallow and retain pills

Must not have

Participants must not have had grade 3 or 4 immune-related adverse events on ipilimumab or nivolumab that required more than 12 weeks of immune suppression with corticosteroids

Participants must not have had adverse events related to encorafenib and/or binimetinib specifically, that required discontinuation of one or both drugs

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years after randomization

Awards & highlights

No Placebo-Only Group

Summary

This trial compares the effect of two different drug combinations in treating patients with melanoma that has spread to the brain. One combination is encorafenib and binimetinib, which may stop the growth of tumor cells. The other combination is ipilimumab and nivolumab, which are monoclonal antibodies that may interfere with the ability of tumor cells to grow and spread. This trial aims to find out which approach is more effective in shrinking and controlling brain metastases from melanoma.

Who is the study for?

This trial is for adults with BRAF-V600 mutant melanoma that has spread to the brain. They must be able to take pills, have a certain level of physical fitness (Zubrod status <=2), and their major organs need to function within specific limits. People with HIV can join if they're on effective therapy. Those who've had other cancers may qualify if it doesn't affect this study's safety or results.

What is being tested?

The trial compares two treatments for melanoma in the brain: one group receives Encorafenib + Binimetinib + Nivolumab, while the other gets Ipilimumab + Nivolumab. The goal is to see which combination better controls or shrinks brain metastases from melanoma.

What are the potential side effects?

Possible side effects include liver problems, fatigue, skin reactions, digestive issues, changes in blood pressure and heart rhythm, immune system reactions like inflammation in various organs or tissues, and an increased risk of infections.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I had hepatitis C but have been treated and cured.

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I can swallow and keep down pills.

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My melanoma has a BRAF-V600 mutation, confirmed by a certified lab.

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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 scan showing a tumor larger than 0.5 cm.

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My melanoma 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 haven't had severe side effects from ipilimumab or nivolumab that needed long-term steroids.

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I have not stopped taking encorafenib or binimetinib due to side effects.

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I will not seek other cancer treatments while in this study.

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I haven't been treated for an autoimmune disease with biologic agents in the last 6 months.

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I have not had any drug treatments for cancer that has spread.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from date of registration to date of death due to any cause, assessed up to 3 years after randomization

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from date of registration to date of death due to any cause, assessed up to 3 years after randomization

This trial's timeline: 3 weeks for screening, Varies for treatment, and from date of registration to date of death due to any cause, assessed up to 3 years after randomization for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Progression-free survival

Secondary study objectives

Intracranial response rate (ICRR)

Objective response rate

Overall survival (OS)

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%

Asthenia

16%

Stomatitis

16%

Oedema peripheral

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%

Pollakiuria

11%

Vitreous floaters

11%

Dyspepsia

11%

Hypoalbuminaemia

11%

Hypertension

11%

Tumour Pain

Rhinitis allergic

Infusion related reaction

Hypokalaemia

Visual impairment

Macular oedema

Hypertrichosis

Iron deficiency

Nasopharyngitis

Weight decreased

Flank pain

Proteinuria

Rash

Pruritus

Pain in extremity

Blood bilirubin increased

Rhinnorrhoea

Hypotension

Pleural effusion

Wound

Trichomegaly

Restless legs syndrome

Musculoskeletal pain

Nervous system disorder

Infection

Hypocalcaemia

Hypophosphataemia

Rectal haemorrhage

Anal haemorrhage

Ascites

Colitis

Abdominal pain lower

Nail disorder

Pruritus generalised

Bone pain

Musculoskeletal chest pain

Chorioretinopathy

Urinary incontinence

Insomnia

Gastroesophageal reflux disease

Abdominal distension

Eczema

Cystitis

Renal failure

Conjunctivitis

Syncope

Dehydration

Dry Mouth

Skin hyperpigmentation

Muscle spasms

Erythema

Retinal detachment

Pulmonary embolism

Dysphonia

Haematuria

Blood creatinine increased

Depression

Palpitations

Melanocytic naevus

Tumour pain

Large intestinal ulcer hemorrhage

Rectal hemorrhage

Large intestinal ulcer

Skin papilloma

Upper respiratory tract infection

Urinary tract infection bacterial

Kidney infection

Epistaxis

Hyperkeratosis

Alopecia

Streptococcal infection

Large intestine perforation

Bacterial sepsis

Cholangitis

Urinary tract obstruction

Confusional state

Device occlusion

Back pain

Rhabdomyolysis

Colon cancer

Sepsis

Acute kidney injury

Large intestine ulcer

Neutropenia

Bacteria sepsis

Hydronephrosis

Neuropathy peripheral

Abdominal abscess

Hyperglycaemia

100%

80%

60%

40%

20%

Study treatment Arm

Combined Safety Lead-in

Phase 3: Triplet Arm

Phase 3: Doublet Arm

Phase 3: Control Arm

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm II (nivolumab, ipilimumab)Experimental Treatment2 Interventions

Patients receive nivolumab IV on day 1 of all cycles and ipilimumab IV over 30 minutes on day 1 of cycles 1-4. Cycles repeat every 21 days for 4 cycles and then every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (encorafenib, binimetinib, nivolumab)Experimental Treatment3 Interventions

Patients receive encorafenib PO QD on days 1-28, binimetinib PO BID on days 1-28, and nivolumab IV on day 1. 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

~1250