Adaptive BRAF-MEK Inhibitor Therapy for Advanced BRAF Mutant Melanoma

Study Purpose

This pilot early phase I trial studies how well encorafenib, binimetinib, and nivolumab work in treating patients with BRAF mutant stage IIIC-IV melanoma. Encorafenib and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with nivolumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving encorafenib, binimetinib, and nivolumab may kill more tumor cells.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.

An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.

Searching Both is inclusive of interventional and observational studies.

Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Patients must be 18 years of age or above.
  • - Subjects must have cytologically or histologically-confirmed unresectable melanoma that harbors a BRAF V600E mutation determined by pyrosequencing assay or equivalent genotyping assay in a Clinical Laboratory Improvement Act (CLIA) certified laboratory, meeting one of the following American Joint Committee on Cancer (AJCC) (8th edition) staging criteria: - AJCC stage IV.
  • - AJCC stage IIIC or IIID with unresectable nodal/locoregional involvement.
  • - Subjects must have baseline plasma ctDNA >= 0.5 copy/ul at time of study enrollment.
  • - Hemoglobin >= 8.0 g/dL.
  • - Absolute neutrophil count >= 1,500/mcL.
  • - Platelets >= 75,000/mcL.
  • - Total bilirubin =< 2 institutional upper limit of normal (ULN), unless suspected Gilbert's syndrome.
  • - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x institutional ULN (in participants with liver metastases =< 5 x ULN) - Creatinine =< 2.0 institutional ULN.
  • - Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2.
  • - Negative serum pregnancy test within 7 days prior to commencement of dosing in premenopausal women.
Women of non-childbearing potential may be included without serum pregnancy test if they are either surgically sterile or have been postmenopausal for >= 1 year.
  • - Fertile men and women must use an effective method of contraception during treatment and for at least 6 months after completion of treatment as directed by their physician.
(NOTE: Patients must agree to not use hormonal contraceptives, as encorafenib can result in decreased concentration and loss of efficacy.)
  • - Patients on non-biologic disease modifying agents (e.g. methotrexate) or patients on corticosteroids =< 10 mg prednisone daily or equivalent are permitted to enroll.
  • - Patients must not have had grade 3 or 4 immune-related adverse events on nivolumab that required more than 12 weeks of immune suppression with corticosteroids.
  • - No anti-PD-1/PD-L1 or BRAF/MEK inhibitor therapy in the metastatic setting is allowed; these treatments are allowed if given in neoaduvant or adjuvant setting > 24 weeks ago.
Prior radiation therapy is permitted. All adverse events associated with prior systemic therapy or radiation therapy must have resolved to =< grade 1 prior to start of study.
  • - Subjects must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

Exclusion Criteria:

  • - Female subjects who are pregnant, intend to become pregnant or are nursing.
  • - Patients previously treated with BRAF/MEK inhibitor or anti-PD-1/PD-L1 therapy in the metastatic setting.
  • - Uncontrolled intercurrent illness including, but not limited to, serious infection.
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better.
  • - Patients with known human immunodeficiency virus (HIV)-infection are eligible providing they are on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test and within 90 days prior to randomization.
  • - Patients with untreated or uncontrolled brain metastases.
Patients with asymptomatic brain metastases which have been previously treated (with locoregional treatment such as radiation or surgery) and are clinically stable (i.e. not requiring corticosteroids) at the time of study start will be eligible. - Previous malignancy is not an exclusion provided that the other malignancy is considered under control, patient is not on concomitant anti-cancer drug therapy, and target lesions from melanoma are clearly defined for response assessment

Trial Details

Trial ID:

This trial id was obtained from, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.


Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Early Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

H. Lee Moffitt Cancer Center and Research Institute
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Zeynep Eroglu, M.D.
Principal Investigator Affiliation H. Lee Moffitt Cancer Center and Research Institute
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Overall Status Recruiting
Countries United States

The disease, disorder, syndrome, illness, or injury that is being studied.

Melanoma (Skin), Skin Cancer, Skin Melanoma, Skin Carcinoma
Study Website: View Trial Website
Arms & Interventions


Experimental: Arm A: BRAF-MEK Inhibitor Therapy

Participants will receive 450 mg Encorafenib daily, along with 45 mg Binimetinib twice daily and 240 mg Nivolumab IV every 2 weeks.

Active Comparator: Arm B

Participants will receive 240 mg Nivolumab IV every 2 weeks


Drug: - Encorafenib

450 mg encorafenib daily by mouth

Drug: - Binimetinib

45 mg binimetinib daily by mouth

Drug: - Nivolumab

240 mg Nivolumab IV every 2 weeks

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Tampa, Florida




H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612

Site Contact

Malik Hall


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