NCT04511013|RecruitingPhase 2DMCFDA Drug

A Study to Compare the Administration of Encorafenib + Binimetinib + Nivolumab Versus Ipilimumab + Nivolumab in BRAF-V600 Mutant Melanoma With Brain Metastases

A Randomized Phase 2 Trial of Encorafenib + Binimetinib + Nivolumab vs Ipilimumab + Nivolumab in BRAF-V600 Mutant Melanoma With Brain Metastases

SWOG Cancer Research Network ClinicalTrials.gov

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3 other identifiers

S2000NCI-2020-05496U10CA180888

Study Type

interventional

Target

112

Locations

1 country

Sites

331

Timeline

RegisteredAug 2020

StartedJan 2021

CompletionJun 2027

Brief Summary

This phase II trial compares the effect of encorafenib, binimetinib, and nivolumab versus ipilimumab and nivolumab in treating patients with BRAF- V600 mutant melanoma that has spread to the brain (brain metastases). Encorafenib and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Ipilimumab and nivolumab 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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

112

participants targeted

Target at P50-P75 for phase_2

Timeline

14mo left

Started Jan 2021

Longer than P75 for phase_2

Geographic Reach

1 country

331 active sites

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

6.5 years study duration

Study Progress82%

Jan 2021Jun 2027

First Submitted

Initial submission to the registry

August 10, 2020

Completed

2 days until next milestone

First Posted

Study publicly available on registry

August 12, 2020

Completed

5 months until next milestone

Study Start

First participant enrolled

January 6, 2021

Completed

6.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2027

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2027

Last Updated

September 11, 2025

Status Verified

September 1, 2025

Enrollment Period

6.5 years

First QC Date

August 10, 2020

Last Update Submit

September 4, 2025

Conditions

Acral Lentiginous Melanoma Clinical Stage IV Cutaneous Melanoma AJCC v8 Metastatic Cutaneous Melanoma Metastatic Malignant Neoplasm in the Brain Metastatic Melanoma Metastatic Mucosal Melanoma Pathologic Stage IV Cutaneous Melanoma AJCC v8

Outcome Measures

Primary Outcomes (1)

Progression-free survival
Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
From date of registration to date of first documentation of progression, or symptomatic deterioration, or death due to any cause, assessed up to 3 years after randomization

Secondary Outcomes (4)

Overall survival (OS)
From date of registration to date of death due to any cause, assessed up to 3 years after randomization
Intracranial response rate (ICRR)
Up to 3 years after randomization
Objective response rate
Up to 3 years after randomization
Duration of response
Up to 3 years after randomization

Study Arms (2)

Arm I (encorafenib, binimetinib, nivolumab)

EXPERIMENTAL

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.

Drug: BinimetinibDrug: EncorafenibBiological: Nivolumab

Arm II (nivolumab, ipilimumab)

EXPERIMENTAL

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.

Biological: IpilimumabBiological: Nivolumab

Interventions

BinimetinibDRUG

Given PO

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

Arm I (encorafenib, binimetinib, nivolumab)

EncorafenibDRUG

Given PO

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

Arm I (encorafenib, binimetinib, nivolumab)

IpilimumabBIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy

Arm II (nivolumab, ipilimumab)

NivolumabBIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Arm I (encorafenib, binimetinib, nivolumab)Arm II (nivolumab, ipilimumab)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Participants must have histologically and pathologically confirmed melanoma that has metastasized to the brain
Any primary (cutaneous, acral/mucosal, etc) or unknown origin are permitted, except that participants with uveal primary are not eligible
Participants must have BRAF-V600 mutant melanoma documented by a Clinical Laboratory Improvement Act (CLIA)-certified laboratory
All participants must have an magnetic resonance imaging (MRI) of the brain within 28 days prior to registration and must have central nervous system metastases with at least one measurable brain metastasis \>= 0.5 cm in size (per modified RECIST 1.1) that has not been irradiated, or progressed (in the opinion of the treating physician) after prior radiation therapy. Participating sites MUST use MRI slice thickness of =\< 1.5 mm and are recommended to adhere to the 'minimum' Brain Tumor Imaging Protocol for Clinical Trials in Brain Metastases (BTIP-BM) compliant MRI acquisition protocol. Computed tomography (CT) of the head cannot substitute for brain MRI. (NOTE: All central nervous system \[CNS\] disease must be documented on BOTH the Brain Metastases Baseline Tumor Assessment Form, using modified RECIST, and the Baseline Tumor Assessment Form \[RECIST 1.1\] using RECIST 1.1.)
Participants may have measurable or non-measurable extracranial disease. All measurable disease must be assessed within 28 days prior to randomization; all non-measurable disease must be assessed within 42 days prior to randomization. Please note, while any extracranial disease will also be assessed and followed, participants are NOT required to have extracranial disease for randomization. NOTE: All disease must be assessed and documented on the Baseline Tumor Assessment Form (RECIST 1.1). CNS disease must be documented on BOTH the Brain Metastases Baseline Tumor Assessment Form, using modified RECIST, and the Baseline Tumor Assessment Form (RECIST 1.1) using RECIST 1.1
Participants may have leptomeningeal disease
Participants may be receiving corticosteroids for brain metastases at a dose of up to 8 mg of dexamethasone per day. The dose must not have exceeded 8 mg per day for at least 7 days prior to randomization
Participants must have Zubrod performance status =\< 2
Participants must have complete history and physical examination within 28 days prior to randomization
Participants must be able to swallow and retain pills
Hemoglobin \>= 8.0 g/dL (within 28 days prior to randomization)
Absolute neutrophil count \>= 1,500/mcL (within 28 days prior to randomization)
Platelets \>= 75,000/mcL (within 28 days prior to randomization)
Total bilirubin =\< 1.5 institutional upper limit of normal (ULN) (within 28 days prior to randomization)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x institutional ULN (in participants with liver metastases =\< 5 x ULN) (within 28 days prior to randomization)
+9 more criteria

You may not qualify if:

Participants must not have received prior systemic therapy for metastatic disease. Prior systemic therapy received only in the neoadjuvant and/or adjuvant setting (e.g., BRAF/MEK inhibitor therapy, anti-PD-1 therapy or anti-CTLA4 therapy, alfa-interferon, etc.) is permitted. If patients received prior neoadjuvant/adjuvant therapy, they must have had eventual disease relapse prior to randomization
Participants must not have had prior radiation therapy within 7 days prior to randomization
Participants must not be planning to require any additional form of systemic anti-tumor therapy for melanoma while on protocol treatment
Participants must not be planning to use hormonal contraceptives
Participants must not have a serious active infection requiring systemic therapy at time of randomization in the opinion of the treating physician
Participants must not have active autoimmune disease that has required treatment in the past 6 months with use of biologic disease modifying agents (.e.g. infliximab, adalimumab). Patients on non-biologic disease modifying agents (e.g. methotrexate) or patients on corticosteroids =\< 10 mg prednisone daily or equivalent (to treat auto-immune disease), or on replacement therapy (e.g., thyroxine, insulin) are eligible if deemed in the best interest of the patient by treating physician
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. (Please note this does not apply to other BRAF/MEK inhibitor drugs.)
Participants must not be pregnant or nursing. Women/men of reproductive potential must have agreed to use an effective method of contraception. (NOTE: Patients must agree to not use hormonal contraceptives, as encorafenib can result in decreased concentration and loss of efficacy.) A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate participant chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures

Contact the study team to confirm eligibility.

Sponsors & Collaborators

SWOG Cancer Research Networklead
National Cancer Institute (NCI)collaborator

Study Sites (331)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

RECRUITING

Thomas Hospital

Fairhope, Alabama, 36532, United States

RECRUITING

Mobile Infirmary Medical Center

Mobile, Alabama, 36607, United States

RECRUITING

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

RECRUITING

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

RECRUITING

Alaska Breast Care and Surgery LLC