Binimetinib Encorafenib Pembrolizumab +/- Stereotactic Radiosurgery in BRAFV600 Melanoma With Brain Metastasis
BEPCOME-MB
Randomised Phase 2 Trial Testing the Addition of Upfront Stereotactic Radiosurgery to Binimetinib Encorafenib Pembrolizumab Compared to Binimetinib Encorafenib Pembrolizumab Alone in BRAFV600 Mutation-positive Melanoma With Brain Metastasis
2 other identifiers
interventional
10
1 country
21
Brief Summary
This study evaluates the addition of stereotactic radiosurgery (SRS) to the combination of binimetinib + encorafenib + pembrolizumab in the treatment of BRAFⱽ⁶⁰⁰ mutation-positive melanoma with brain metastases (MBM).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Sep 2022
Typical duration for phase_2
21 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 26, 2019
CompletedFirst Posted
Study publicly available on registry
August 29, 2019
CompletedStudy Start
First participant enrolled
September 5, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 27, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
March 27, 2026
CompletedMarch 25, 2026
October 1, 2025
3.6 years
August 26, 2019
March 24, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Intracranial (IC) progression-free survival (PFS)
Time from randomisation until IC-progressive disease (PD) as evaluated by centralized assessment using modified response evaluation criteria in solid tumours version 1.1 (RECIST v1.1), or death, whichever occurs first.
From randomisation until IC-PD, or death, whichever occurs first, up to 12 months.
Secondary Outcomes (13)
Intracranial-response rate (RR)
From randomisation until IC-CR or IC-PR, up to 60 months.
Intracranial disease control (DC)
From randomisation until IC-CR or IC-PR or stable intracranial disease, up to 60 months.
Extracranial (EC) response rate
From randomisation until confirmed EC-CR or EC-PR, up to 60 months.
Overall response rate (ORR)
From randomisation until confirmed CR or PR, up to 60 months.
Duration of intracranial, extracranial, and overall response
Time from first observation of, IC-, EC-, or overall response respectively (i.e. CR or PR), until disease progression (PD), up to 60 months.
- +8 more secondary outcomes
Study Arms (2)
Encorafenib + binimetinib + pembrolizumab
EXPERIMENTALEncorafenib 450 mg oral route (PO) once daily (QD) + binimetinib 45 mg PO twice daily (BID) + pembrolizumab 200 mg intravenous (IV) every 3 weeks (Q3W).
SRS followed by encorafenib + binimetinib + pembrolizumab
EXPERIMENTALUpfront SRS of all lesions ≥5 mm in diameter (or ≥3 mm if other cerebral metastases \>5 mm); followed by encorafenib 450 mg PO QD + binimetinib 45 mg PO BID + pembrolizumab 200 mg IV Q3W. The treatment should be started more than 24 hours and less than 8 days (excluded) after the SRS
Interventions
All patients: binimetinib 45 mg PO BID.
All patients: encorafenib 450 mg PO QD
All patients: pembrolizumab 200 mg IV Q3W
For patients randomised to arm B only: Upfront SRS of all lesions ≥5 mm in diameter (or ≥3 mm if other cerebral metastases \>5 mm).
Eligibility Criteria
You may qualify if:
- Provided written informed consent prior to any trial specific procedures.
- Aged ≥18 years old.
- An Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
- Histologically confirmed Stage IV M1d cutaneous melanoma or unknown primary melanoma that is metastatic to the brain.
- Presence of BRAFV600E/K/D/R mutation according to a locally validated BRAF Assay.
- Candidacy for SRS therapy validated by the radiation oncologist and/or neurosurgeon at the investigative centre. This should be documented in the patient file.
- Absence of previous systemic treatment with BRAF inhibitors, MEK inhibitors or anti-PD-1 for distant metastatic melanoma. Patients having received such treatments as adjuvant therapy are allowed provided adjuvant treatment has been stopped for 6 months or more.
- No more than one previous local intracranial therapy for one lesion (e.g. craniotomy, SRS).
- Note: Treatment with stereotactic radiosurgery must have been completed ≥14 days prior to randomisation and this lesion cannot be target lesion for radiosurgery.
- Able to undergo gadolinium-enhanced MRI.
- At least one measurable intracranial lesion for which all of the following criteria have to be met:
- Previously untreated (no local therapy including local radiotherapy, resection, radiosurgery) or progressive after previous local therapy.
- Longest diameter ≥5 mm as determined by contrast-enhanced MRI. Longest diameter ≥3 mm is acceptable for other IC lesions provided there is at least one lesion ≥5 mm.
- Cumulative Intracranial Target Volume ≤12 cmᵌ as determined by contrast-enhanced MRI.
- All prior anti-cancer treatment-related toxicities (except alopecia and laboratory values) must be resolved or Grade 1 according to NCI-CTCAE v5.0.
- +14 more criteria
You may not qualify if:
- More than 10 intracranial metastases.
- Presence of neurological symptoms related to intracranial metastases which induce alteration of the ECOG performance status to 2 or more or require immediate radiation treatment.
- Ocular melanoma.
- Brain metastases which necessitate immediate neurosurgery.
- Any previous treatment with whole-brain radiation.
- Presence of leptomeningeal disease or any parenchymal brain metastasis \>30 mm in longest diameter.
- Note: On MRI, the most common finding of leptomeningeal disease is pial enhancement and nodularity, typically over the cerebral convexities, in the basal cisterns, on the tentorium, or in the ventricular ependymal surfaces.
- Current or expected use of a strong inhibitor of CYP3A4.
- History of malignancy other than disease under study occurring within 3 years of study enrolment with the exception of: completely resected non-melanoma skin cancer or indolent second malignancies.
- Any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that, in the opinion of the investigator, could interfere with the patient's safety, obtaining informed consent, or compliance with study procedures.
- Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (patients with laboratory evidence of cured HBV and/or HCV will be permitted).
- A history or evidence of cardiovascular risk including any of the following:
- Left ventricular ejection fraction \< local LLN as determined by a MUGA scan or echocardiogram;
- A QT interval corrected for heart rate QTc \> 480 ms according to local standard formula;
- A history or evidence of current clinically significant uncontrolled arrhythmias.
- +19 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pierre Fabre Medicamentcollaborator
- Merck Sharp & Dohme LLCcollaborator
- UNICANCERlead
- European Association of Dermato Oncologycollaborator
Study Sites (21)
APHP - Hôpital Avicenne
Bobigny, France
CHU de Bordeaux - Hôpital Saint André
Bordeaux, France
GH Sud CHU Bordeaux - Hôpital Levêque
Bordeaux, France
APHP - Hôpital Ambroise Paré
Boulogne-Billancourt, France
CHU de Caen
Caen, France
CLCC - Centre Jean François Baclesse
Caen, France
APHP - Hôpital Henri Mondor
Créteil, France
CHU de Dijon - Hopital Du Bocage
Dijon, France
CLCC - Centre Georges François Leclerc
Dijon, France
CLCC - Centre Léon Bérard
Lyon, France
APHM - Hopital De La Timone
Marseille, France
CHU De Montpellier - Hopital Saint Eloi
Montpellier, France
CLCC - Institut de Cancerologie de Montpellier
Montpellier, France
CHU Nice - Hôpital de l'Archet
Nice, France
CLCC - Centre Antoine Lacassagne
Nice, France
APHP - L'hôpital de la Pitié-Salpêtrière
Paris, France
CHU de Nantes - Hôtel Dieu
Saint-Herblain, France
CLCC - Institut de Cancerologie de l'Ouest - Nantes
Saint-Herblain, France
CLCC - IUCT-0 / Institut Claudius Regaud
Toulouse, France
CHU de TOURS - Hôpital Bretonneau
Tours, France
CLCC - Gustave Roussy
Villejuif, France
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Philippe Saiag, Prof
APHP - CHU Ambroise Paré
- PRINCIPAL INVESTIGATOR
Marie Charissoux, MD
Institut Régional du Cancer
- PRINCIPAL INVESTIGATOR
Jean Regis, Prof
APHM - Hôpital de la Timone
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 26, 2019
First Posted
August 29, 2019
Study Start
September 5, 2022
Primary Completion
March 27, 2026
Study Completion
March 27, 2026
Last Updated
March 25, 2026
Record last verified: 2025-10
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.
- Access Criteria
- Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.
Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.