Actively Recruiting
Encorafenib and biNimetinib Followed by CEmiplimab and FiAnLimab in Patients With BRAF Mutant melanOma and Symptomatic Brain Metastases
Led by Grupo Español Multidisciplinar de Melanoma · Updated on 2025-10-01
33
Participants Needed
18
Research Sites
135 weeks
Total Duration
On this page
Sponsors
G
Grupo Español Multidisciplinar de Melanoma
Lead Sponsor
R
Regeneron Pharmaceuticals
Collaborating Sponsor
AI-Summary
What this Trial Is About
Brain metastases in patients with advanced and metastatic melanoma are a frequent complication and a significant cause of morbidity and mortality in this patient population. As the incidence of brain metastases continues to increase in patients with metastatic melanoma, it is urgent that the investigators identify effective therapies. ENCEFALO is a Phase II, single arm, multicentre clinical trial designed to evaluate the activity of encorafenib plus binimetinib followed by cemiplimab and fianlimab in patients with BRAF mutated melanoma and symptomatic brain metastases, following the simon design Two-stage minimax. The objective main is to evaluate the 6 month intracranial progression-free survival (icPFS) proportion of Encorafenib plus Binimetinib followed by Cemiplimab plus Fianlimab in patients with BRAF-mutated melanoma and symptomatic brain metastases according RECIST criteria The trial hypothesis is: For patients with BRAF-mutated melanoma and symptomatic brain metastases, an induction treatment with encorafenib and binimetinib (EB) for about two months (i.e. 8 weeks) followed by cemiplimab plus fianlimab (CF) would allow a 6 month icPFS rate of 40% in comparison to historical control of 20% based on CM204 symptomatic arm (Tawbi et al 2021).
CONDITIONS
Official Title
Encorafenib and biNimetinib Followed by CEmiplimab and FiAnLimab in Patients With BRAF Mutant melanOma and Symptomatic Brain Metastases
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Provide written informed consent approved by the ethics committee before any study activities.
- Have histologically confirmed unresectable metastatic BRAF-mutated melanoma (stage IV) with one or more brain metastases sized 5 to 50 mm.
- Have symptomatic brain metastases related to intracranial hypertension, focal neurological deficits, or epilepsy.
- Confirmed BRAF-V600 mutation in tumor tissue.
- Modified Barthel Index score greater than 10.
- Be 18 years of age or older.
- ECOG performance status between 0 and 2.
- Able to swallow oral medication.
- Adequate blood counts: hemoglobin ≥ 9 g/dL, platelet count ≥ 75 x 10^9/L, neutrophil count ≥ 1.5 x 10^9/L.
- Adequate liver function with bilirubin ≤ 2x upper normal limit and AST/ALT ≤ 2.5x upper normal limit (or ≤ 5x if liver metastases present).
- Serum creatinine ≤ 2x upper normal limit or creatinine clearance ≥ 30 mL/min.
- Prior immunotherapy allowed only in adjuvant/neoadjuvant setting with resolved severe toxicities.
- Women of childbearing potential must have a negative pregnancy test and agree to use effective contraception during and for 6 months after treatment.
- Male participants with partners of childbearing potential must use condoms during the study and for 6 months after treatment.
- Willing and able to attend scheduled visits and follow the study procedures.
You will not qualify if you...
- Diagnosis of uveal melanoma.
- History of leptomeningeal metastases unless not causing main neurological symptoms.
- Other non-cured cancers within the last 2 years except certain treated localized cancers.
- History of allogeneic organ transplant.
- History or current retinal diseases such as central serous retinopathy, retinal vein occlusion, or retinal degeneration.
- History of interstitial lung disease.
- Prior systemic immunotherapy containing anti LAG-3 or brain metastases before adjuvant/neoadjuvant immunotherapy.
- Prior targeted therapy against BRAF and/or MEK in any setting.
- Prior chemotherapy in any setting.
- Need for urgent brain surgery before study entry.
- Prior brain radiotherapy before study entry.
- Significant infections requiring treatment within 2 weeks before study.
- Active infections needing therapy.
- Recent or ongoing autoimmune disease requiring systemic immunosuppressive treatment.
- Uncontrolled HIV, HBV, or HCV infections or related immunodeficiency.
- Significant cardiovascular disease or impaired heart function.
- Elevated troponin levels above specified limits.
- Uncontrolled high blood pressure despite treatment.
- Moderate to severe liver impairment.
- Inability to swallow tablets or capsules.
- Neuromuscular disorders with high creatine kinase levels.
- Recent immunosuppressive therapy except steroids for brain metastasis symptoms.
- History of pneumonitis within 5 years.
- Active inflammatory bowel disease.
- Conditions interfering with consent or study compliance.
- Known allergies to study drugs or their ingredients.
- Persistent toxicity from prior therapy above certain grades.
- Live vaccination within 30 days before starting treatment.
- Pregnancy or breastfeeding or unwillingness to use effective contraception.
- Known alcohol or drug abuse.
- Participation in other interventional studies within 30 days.
- Lactase deficiency or glucose-galactose malabsorption.
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 18 locations
1
Complejo Hospitalario Universitario A Coruña
A Coruña, A Coruña, Spain, 15006
Actively Recruiting
2
Quiron Dexeus - IOR
Barcelona, Barcelona, Spain, 08028
Actively Recruiting
3
Hospital Universitario Vall d´Hebron
Barcelona, Barcelona, Spain, 08035
Actively Recruiting
4
Hospital Clínic de Barcelona
Barcelona, Barcelona, Spain, 08036
Actively Recruiting
5
Instituto Catalán de Oncología - Hospital Duran i Reynals
Barcelona, Barcelona, Spain, 08908
Actively Recruiting
6
Hospital Universitario de Burgos
Burgos, Burgos, Spain, 09006
Actively Recruiting
7
Hospital Universitario Marqués de Valdecilla
Santander, Cantabria, Spain, 39008
Actively Recruiting
8
Hospital Universitario San Pedro de Alcántara
Cáceres, Cáceres, Spain, 10003
Actively Recruiting
9
Onkologikoa (Donostia)
Donostia / San Sebastian, Donostia, Spain, 20014
Actively Recruiting
10
Hospital Universitario Gregorio Marañon
Madrid, Madrid, Spain, 28007
Not Yet Recruiting
11
Hospital Universitario Ramón y Cajal
Madrid, Madrid, Spain, 28034
Actively Recruiting
12
Hospital Clinico San Carlos
Madrid, Madrid, Spain, 28040
Actively Recruiting
13
Hospital Universitario Puerta del Hierro
Majadahonda, Madrid, Spain, 28222
Actively Recruiting
14
Clinico Universitario Virgen de la Arrixaca
Murcia, Murcia, Spain, 30120
Actively Recruiting
15
Hospital Regional Universitario de Málaga
Málaga, Málaga, Spain, 29010
Actively Recruiting
16
Hospital Virgen de la Macarena (Sevilla)
Seville, Sevilla, Spain, 41009
Actively Recruiting
17
Hospital Clínico Universitario Valencia.
Valencia, Valencia, Spain, 46010
Actively Recruiting
18
Hospital General Universitario de Valencia
Valencia, Valencia, Spain, 46014
Actively Recruiting
Research Team
A
A responsible person Designated by the sponsor, M.D., PhD.
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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