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).
Written informed consent approved by the Independent Ethics Committee (IEC), prior to the performance of any trial activities.
Histologically confirmed diagnosis of unresectable metastatic BRAF-mutated melanoma (stage IV, AJCC v9), with one or more brain metastases with a diameter of 5 to 50 mm, measured by contrast enhanced MRI.
Any symptom related with intracranial hypertension, providing the patient has an Eastern cooperative Oncology Group performance status (ECOG PS) 0-2 and the other inclusion and
Any symptom related to focal neurologic deficit.
Epilepsy Note: Patients could have or not these symptoms controlled with corticosteroids at the inclusion of the clinical trial.
A documented mutation in BRAF-V600 in the tumor tissue.
Modified Barthel Index of Activities of Daily Living > 10 (see Appendix 5).
Single group
Encorafenib + Binimetinib
DrugInduction treatment with oral encorafenib 450 mg once daily (QD) + binimetinib 45 mg twice daily (BID)(combination: EB) for approximately two months (i.e. 8 weeks)
cemiplimab+fianlimab
Drugcemiplimab 350 mg + fianlimab 1600 mg combination every 3 weeks (Q3W)(Combination: CF) administered to patients intravenously (IV) for up to two years.
intracranial progression-free survival (icPFS) follow-up
Contrast enhanced brain MRI and/or color digital photography will be performed baseline and every 8 weeks (+/-1 week) up to 12 months and according to standard practice thereafter until disease progression, independently of the end of treatment (except for documentation of disease progression).
Extracraneal PFS (ecPFS) follow-up
Body CT-scan and/or color digital photography will be performed baseline and every 8 weeks (+/-1 week) up to 12 months and according to standard practice thereafter until disease progression, independently of the end of treatment (except for documentation of disease progression).
Overall survival (OS)
Follow up at least every 4 weeks until end of study, patient withdrawal or death, whichever occurs first.
Barthel index follow-up
Barthel index will be monitored at baseline and at every other cycle (every 3 weeks during cemiplimab fianlimab and 4 weeks during encorafenib binimetinib) until progression. The Barthel Index for Activities of Daily Living is an ordinal scale which measures a person's ability to complete activities of daily living (ADL). The Barthel Index assesses the functional situation of the elderly person within a range of 0 to 100 pointss. A menor puntuación, más dependencia; y a mayor puntuación, más independencia. The lower the score, the greater thedependency; and the higher the score, the greater the independence: * 0-20 Total dependence * 21-60 Severe dependence * 61-90 Moderate dependence * 91-99 Mild dependence * 100 Independence
Adverse events (AE)
Adverse events (AE) assessment: type, frequency, grade, outcome, relation with study treatment (TRAE)
Click on the lead sponsor to view all of their trials.
Grupo Español Multidisciplinar de Melanoma
Lead sponsor
Regeneron Pharmaceuticals
Collaborator
MFAR
Collaborator
Pierre Fabre Laboratories
Collaborator
