OncoMatch/Clinical Trials/NCT06887088
Encorafenib and biNimetinib Followed by CEmiplimab and FiAnLimab in Patients With BRAF Mutant melanOma and Symptomatic Brain Metastases
Is NCT06887088 recruiting? Yes, currently enrolling (May 2026). This Phase 2 trial studies multiple treatments including Encorafenib + Binimetinib and cemiplimab+fianlimab for melanoma braf v600e/k mutated.
Treatment: Encorafenib + Binimetinib · cemiplimab+fianlimab — 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).
Check if I qualifyExtracted eligibility criteria
Cancer type
Melanoma
Biomarker criteria
Required: BRAF V600E
A documented mutation in BRAF-V600 in the tumor tissue.
Required: BRAF V600K
A documented mutation in BRAF-V600 in the tumor tissue.
Disease stage
Required: Stage IV
Metastatic disease required
Performance status
ECOG 0–2(Ambulatory, capable of self-care)
Prior therapy
Cannot have received: targeted therapy against BRAF and/or MEK
Targeted therapy against BRAF and/or MEK will not be allowed in any setting, including adjuvant.
Cannot have received: chemotherapy
Chemotherapy will not be allowed in any setting.
Cannot have received: systemic immunotherapy
Exception: Allowed only in adjuvant/neoadjuvant setting if ALL: regimen did not contain anti LAG-3; no brain metastases prior; at least 6 months duration; no other treatments before symptomatic brain metastases; not discontinued due to adverse events.
Systemic immunotherapy treatment for melanoma would be allowed only in the adjuvant/neoadjuvant setting (regardless if the brain relapse was during or after that) providing that ALL the following criteria are met: 1. The immunotherapy regimen did not contain anti LAG-3 treatment. 2. Patient did not have brain metastases (whether they were symptomatic or asymptomatic) prior to this adjuvant/neoadjuvant immunotherapy setting. 3. Patient was treated with adjuvant/neoadjuvant for at least 6 months. 4. No other treatments different than the one in adjuvant/neoadjuvant before symptomatic brain metastases were applied. 5. Patient did not discontinue immunotherapy due to related adverse events.
Cannot have received: brain radiotherapy
Exception: Allowed during trial only if: received at least TWO doses of cemiplimab and fianlimab AND intracranial progression occurs during cemiplimab/fianlimab AND encorafenib/binimetinib rechallenge; not allowed before trial entry.
Brain radiotherapy will not be allowed before entering the clinical trial. Patients can receive brain radiotherapy during the clinical trial, if they progress into the brain, as per institutional guidelines ONLY if (must fulfill the three): 1. They have received at least TWO doses of cemiplimab and fianlimab AND 2. The event of an intracranial progressive disease happens during cemiplimab and fianlimab AND 3. They comply to receive encorafenib and binimetinib as rechallenge. Encorafenib and binimetinib should be stopped 24h before, during and 24h after radiotherapy.
Lab requirements
Blood counts
Haemoglobin ≥ 9 g/dL (may have been transfused); Platelet count ≥ 75 × 10^9/L; Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L
Kidney function
Serum Creatinine ≤ 2.0 x ULN or estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
Liver function
total bilirubin level ≤ 2.0 × ULN and AST and ALT levels ≤ 2.5 × ULN; or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver)
Cardiac function
LVEF ≥ 50% evaluated as per institutional guidelines; no significant (CTCAE grade ≥2) cardiovascular disease; no cerebrovascular accident/stroke < 6 months prior to enrolment, myocardial infarction < 6 months prior to enrolment, unstable angina, congestive heart failure (≥ NYHA Class II), serious cardiac arrhythmia requiring medication, or triplicate average baseline QTc interval > 500 ms, history of myocarditis; TnT or troponin I TnI > 2x institutional ULN at baseline (exceptions for repeat testing as described)
Adequate hematologic function: Haemoglobin ≥ 9 g/dL (may have been transfused). Platelet count ≥ 75 × 10^9/L. Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L. Adequate hepatic function defined by a total bilirubin level ≤ 2.0 × the upper limit of normality (ULN) and AST and ALT levels ≤ 2.5 × ULN; or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver). Serum Creatinine ≤ 2.0 x ULN or estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method). Impaired cardiovascular function or clinically significant (i.e., active) cardiovascular diseases such as: cerebrovascular accident/stroke (< 6 months prior to enrolment), myocardial infarction (< 6 months prior to enrolment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), a LVEF < 50% evaluated as per institutional guidelines, or serious cardiac arrhythmia requiring medication or a triplicate average baseline QTc interval > 500 ms, history of myocarditis. TnT or troponin I TnI > 2x institutional ULN at baseline.
Structured fields extracted by AI. May contain errors — verify against the official protocol.
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