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Malignant MelanomaPhase 2BEPCOME-MBNCT04074096

Binimetinib Encorafenib Pembrolizumab +/- Stereotactic Radiosurgery in BRAFV600 Melanoma With Brain Metastasis

A Phase 2 study testing Stereotaxic radiosurgery (SRS), Binimetinib Oral Tablet and Encorafenib Oral Capsule in people with Malignant Melanoma and BRAF V600 Mutation, run by UNICANCER at 21 sites in France.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Stereotaxic radiosurgery (SRS), Binimetinib Oral Tablet and Encorafenib Oral Capsule
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
21 sitesFrance
Study dates
5 Sep 2022to 27 Mar 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • Able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption (malabsorption syndrome, major resection of the stomach or bowels).
  • Adequate bone marrow, organ function, and laboratory parameters defined as the following (all criteria must be met):
  • Absolute neutrophil count (ANC) ≥1.5 x 10⁹/L;
  • Haemoglobin ≥9 g/dL without transfusions;
  • Platelets ≥100 x 10⁹/L without transfusions;
  • Aspartate aminotransferase and alanine aminotransferase ≤2.5 × upper limit of normal (ULN); ≤5 x ULN is acceptable for patient with liver metastases;
  • Total bilirubin ≤2 x ULN;
  • Creatinine ≤1.5 mg/dL, or calculated creatinine clearance ≥50 mL/min (as determined using the MDRD method).
  • Adequate cardiac function, defined as the following (all criteria must be met):
  • Left ventricular ejection fraction (LVEF) ≥ local lower normal limit (LLN) as determined by a multigated acquisition (MUGA) scan or echocardiogram;
  • Baseline QT interval corrected for heart rate QTc ≤ 480 ms according to local standard formula.
  • Women of childbearing potential (WOCBP) or men must agree to refrain from sexual activity or use adequate contraception for the duration of study treatment and for 120 days after completing treatment. Male participants must agree to refrain from donating sperm during this period.
  • Patient affiliated to or a beneficiary of the local social security system or equivalent.
  • Patient is willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up.

Who cannot join

  • 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.
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  • 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.
  • Note: Patients with atrial fibrillation controlled for >30 days prior to randomisation are eligible.
  • A history or evidence of current >Class II congestive heart failure as defined by the New York Heart Association guidelines;
  • Treatment refractory hypertension defined as a systolic blood pressure of >140 mmHg and/or diastolic blood pressure >90 mmHg, which cannot be controlled by antihypertensive therapy;
  • Patients with intra-cardiac defibrillators;
  • A history of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting less than 6 months prior to enrolment.
  • A history or current evidence of retinal vein occlusion.
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatments, and their excipients.
  • Hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption
  • Participation in another therapeutic trial within the 30 days prior to randomization
  • Pregnant or breastfeeding female. Note: WOCBP must have a negative serum pregnancy test within 14 days prior to enrolment.
  • History of, or active interstitial lung disease or (non-infectious) pneumonitis.
  • Active, known or suspected autoimmune disease or a documented history of autoimmune disease, including ulcerative colitis and Crohn's disease (Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll).
  • Diagnosis of immunodeficiency or systemic chronic steroid therapy (≥ 10mg/day prednisone or equivalent) or any immunosuppressive therapy 7 days prior to planned date for first dose of study treatment. Topical, inhaled, nasal and ophthalmic steroids are allowed.
  • Has received a live vaccine within 30 days prior to the first dose of study drug.
  • Active infection requiring systemic therapy.
  • Known history of active TB (Bacillus Tuberculosis).
  • Allogenic tissue/solid organ transplant.
  • Person deprived of their liberty or under protective custody or guardianship.
  • Patient unwilling or unable to comply with the medical follow-up required by the trial because of geographic, social or psychological reasons

Trial locations and contacts

21 sites in 1 country.

21 sites in 1 country

France21 sites

  • APHP - Hôpital Avicenne

    Bobigny

  • CHU de Bordeaux - Hôpital Saint André

    Bordeaux

  • GH Sud CHU Bordeaux - Hôpital Levêque

    Bordeaux

  • APHP - Hôpital Ambroise Paré

    Boulogne-Billancourt

  • CHU de Caen

    Caen

  • CLCC - Centre Jean François Baclesse

    Caen

  • APHP - Hôpital Henri Mondor

    Créteil

  • CHU de Dijon - Hopital Du Bocage

    Dijon

  • CLCC - Centre Georges François Leclerc

    Dijon

  • CLCC - Centre Léon Bérard

    Lyon

  • APHM - Hopital De La Timone

    Marseille

  • CHU De Montpellier - Hopital Saint Eloi

    Montpellier

  • CLCC - Institut de Cancerologie de Montpellier

    Montpellier

  • CHU Nice - Hôpital de l'Archet

    Nice

  • CLCC - Centre Antoine Lacassagne

    Nice

  • APHP - L'hôpital de la Pitié-Salpêtrière

    Paris

  • CHU de Nantes - Hôtel Dieu

    Saint-Herblain

  • CLCC - Institut de Cancerologie de l'Ouest - Nantes

    Saint-Herblain

  • CLCC - IUCT-0 / Institut Claudius Regaud

    Toulouse

  • CHU de TOURS - Hôpital Bretonneau

    Tours

  • CLCC - Gustave Roussy

    Villejuif

Other trials in France

About this study

Official title: 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

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).

Read the detailed description

This is a Phase 2, randomised, controlled, open-label, multicentric, parallel trial with a safety lead-in phase, to assess the efficacy and safety of adding upfront SRS to binimetinib-encorafenib-pembrolizumab combination therapy in the treatment of BRAFⱽ⁶⁰⁰ mutation-positive MBM.

The study will incorporate a safety lead-in (SLI) phase to assess the tolerability of binimetinib-encorafenib-pembrolizumab combination therapy +/- SRS in the first six patients enrolled. Safety will be assessed by the occurrence of predefined dose limiting toxicity (DLT) events. The safety data will be reviewed by an independent data monitoring committee (IDMC).

The trial plans to enrol 150 patients who will be randomly assigned (1:1) to receive treatment with either:

  • Arm A: Encorafenib + binimetinib + pembrolizumab
  • Arm B: Upfront stereotactic radiosurgery of all lesions ≥5 mm in diameter (or ≥3 mm if other cerebral metastases >5 mm); followed by encorafenib + binimetinib + pembrolizumab . The treatment should be started more than 24 hours and less than 8 days (excluded) after the SRS.

Patients will be treated until disease progression. Pembrolizumab will be discontinued after a maximum of 35 administrations. Treatment may also be terminated early at the initiative of either the patient or the investigator for any reason that would be beneficial to the patient

All patients will be followed for a total of 5 years post-randomisation.

Being tested
Stereotaxic radiosurgery (SRS), Binimetinib Oral Tablet, Encorafenib Oral Capsule, Pembrolizumab
Keywords
Melanoma, BRAF V600, Brain metastases, Encorafenib, Binimetinib, Pembrolizumab, Stereotaxic, SRS
Medical subject headings
Melanoma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Stereotaxic radiosurgery (SRS)Radiation

    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).

  • Binimetinib Oral TabletDrug

    Also called Mektovi

    All patients: binimetinib 45 mg PO BID.

  • Encorafenib Oral CapsuleDrug

    Also called Braftovi

    All patients: encorafenib 450 mg PO QD

  • PembrolizumabDrug

    Also called Keytruda

    All patients: pembrolizumab 200 mg IV Q3W

Study groups in NCT04074096
Study groupRoleWhat they receive
Encorafenib + binimetinib + pembrolizumabExperimentalEncorafenib 450 mg oral route (PO) once daily (QD) + binimetinib 45 mg PO twice daily (BID) + pembrolizumab 200 mg intravenous (IV) every 3 weeks (Q3W).
Receives: Drug: Binimetinib Oral Tablet; Drug: Encorafenib Oral Capsule; Drug: Pembrolizumab
SRS followed by encorafenib + binimetinib + pembrolizumabExperimentalUpfront 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
Receives: Radiation: Stereotaxic radiosurgery (SRS); Drug: Binimetinib Oral Tablet; Drug: Encorafenib Oral Capsule; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: From randomisation until IC-PD, or death, whichever occurs first, up to 12 months.

Secondary outcomes (13)

  1. Intracranial-response rate (RR)

    Percentage of patients with a confirmed IC-complete response (CR) or IC-partial response (PR) as assessed by the investigator using modified RECIST v1.1.

    Measured: From randomisation until IC-CR or IC-PR, up to 60 months.

  2. Intracranial disease control (DC)

    Percentage of patients with an IC-CR or IC-PR or stable intracranial disease as assessed by the investigator using modified RECIST v1.1.

    Measured: From randomisation until IC-CR or IC-PR or stable intracranial disease, up to 60 months.

  3. Extracranial (EC) response rate

    Percentage of patients with a confirmed EC-CR or EC-PR as assessed by the investigator using modified RECIST v1.1.

    Measured: From randomisation until confirmed EC-CR or EC-PR, up to 60 months.

  4. Overall response rate (ORR)

    Percentage of patients with a confirmed CR or PR as assessed by the investigator using modified RECIST v1.1 to assess IC-response and RECIST v1.1 for EC-response.

    Measured: From randomisation until confirmed CR or PR, up to 60 months.

  5. 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) according to modified RECIST v1.1 (intracranial disease) or RECIST v1.1 (extracranial disease) or death, whichever occurs first.

    Measured: Time from first observation of, IC-, EC-, or overall response respectively (i.e. CR or PR), until disease progression (PD), up to 60 months.

  6. Duration of response of treated target lesions

    Time from first documented response (i.e. CR or PR) until PD of treated target lesions or death, whichever occurs first.

    Measured: From first documented response (i.e. CR or PR) until PD of treated target lesions or death, whichever occurs first, up to 60 months.

  7. Progression-free survival (PFS)

    Time from randomisation until IC-PD according to modified RECIST v1.1, EC-PD according to RECIST v1.1, or death, whichever occurs first.

    Measured: From randomisation until IC-PD, EC-PD or death, whichever occurs first, up to 60 months.

  8. Overall survival (OS)

    Time from randomisation until death due to any cause.

    Measured: From randomisation until death due to any cause, up to 60 months.

  9. Global Quality of Life (HRQOL) - QLQ-C30

    This self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials.

    The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease.

    All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

    Measured: From randomisation until end of treatment, up to 60 months.

  10. Quality of Life (HRQOL) in patients with brain metastases - QLQ-BN20

    This EORTC brain cancer specific questionnaire is intended to supplement the QLQ-C30 questionaire.

    The QLQ-BN20 contains 20 items organized into four scales (three items each: future uncertainty, visual disorder, motor dysfunction, and communication deficit), and seven single items (headaches, seizures, drowsiness, hair loss, itchy skin, weakness of legs, and bladder control). All items are rated on a four-point Likert-type scale (1 = "not at all," 2 = "a little," 3 = "quite a bit," and 4 = "very much"), and are linearly transformed to a 0-100 scale, with higher scores indicating more severe symptoms.

    Measured: From randomisation until end of treatment, up to 60 months.

  11. Cognitive performance

    Assessed using the Montreal Cognitive Assessment (MoCA).

    Measured: From randomisation until end of treatment, up to 60 months.

  12. Incidence of dose-limiting toxicities

    Occurrence of adverse events predefined as dose-limiting toxicities in any patient during the safety lead-in phase of the trial

    Measured: From randomisation until completion of 2 cycles of treatment

  13. Frequency and severity of adverse events

    Assessed according to National Cancer Institute - Common terminology criteria for adverse events version 5.0 (NCI-CTCAE v5.0).

    Measured: From randomisation until end of treatment, up to 60 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Aug 2019
  2. Study start5 Sep 2022
  3. Primary completion7 May 2026
  4. Study completion27 Mar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04074096
Sponsor's protocol ID
RAD06 - UC-0107/1810
Other IDs
2021-006331-26
Acronym
BEPCOME-MB
Status last verified
Oct 2025
First submitted
26 Aug 2019
Last updated
5 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Stereotaxic radiosurgery (SRS), Binimetinib Oral Tablet and Encorafenib Oral Capsule in people with Malignant Melanoma and BRAF V600 Mutation, run by UNICANCER at 21 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 5 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Intracranial (IC) progression-free survival (PFS) (time frame: From randomisation until IC-PD, or death, whichever occurs first, up to 12 months.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04074096.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2026.

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