Encorafenib and biNimetinib Followed by CEmiplimab and FiAnLimab in Patients With BRAF Mutant melanOma and Symptomatic Brain Metastases

Conditions

• Melanoma BRAF V600E/K Mutated
• Melanoma and Brain Metastases

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Encorafenib + Binimetinib — DRUG
  Induction 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 — DRUG
  cemiplimab 350 mg + fianlimab 1600 mg combination every 3 weeks (Q3W)(Combination: CF) administered to patients intravenously (IV) for up to two years.

Study Details

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).

Key Dates

Start date

May 29, 2025

Status verified

Sep 2025

Primary completion

Jan 31, 2028

Completion

Jan 31, 2028

Study Design

Enrollment

33 participants (estimated)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: Encorafenib+biNimetinib followed Cemiplimab+Fianlimab in BRAF mutated melanoma and brain metastses
  Patients with BRAF mutant melanoma and symptomatic brain metastases will treatment with encorafenib plus binimetinib followed by cemiplimab and fianlimab Induction 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) followed by cemiplimab 350 mg + fianlimab 1600 mg combination every 3 weeks (Q3W)(Combination: CF) administered to patients intravenously (IV) for up to two years. Treatment may be discontinued due to death, PD or non-acceptable toxicity. Encorafenib plus binimetinib should be discontinued at least 72 hours prior to the first dose of cemiplimab plus fianlimab. Rechallenge with encorafenib 450mg QD + binimetinib 45 mg BID will be mandatory for those patients that progress under CF, with the exception of patients with intracranial response or stabilization and only extracranial PD in which case CF could be continued at the physician criteria. In the case of continuing treat

Primary Outcome Measure

intracranial progression-free survival (icPFS) follow-up [ Time Frame: Throughout the study period, at 12 months from the start of treatment ]

Central Contacts

• A responsible person Designated by the sponsor, M.D., PhD.
  +34 93 434 44 12
  [email protected]