Adaptive BRAF-MEK Inhibitor Therapy for Advanced BRAF Mutant Melanoma

NCT03543969 | Active Not Recruiting Early Phase 1 FDA Drug

• 1 other identifier: MCC-19441
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Skin Cancer; Skin Melanoma; Skin Carcinoma; Melanoma (Skin)

Outcome Measures

Primary Outcomes (1)

• 8 Week Completion Rate

  Number of participants who reach 8 weeks with the prescribed on/off schedule without progression of disease. Progression as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

  At the end of the first 8 week treatment period

Secondary Outcomes (2)

• Time to Treatment Failure

  Up to 5 years

• Objective Tumor Response Rate

  Up to 5 years

Study Arms (2)

Arm A: BRAF-MEK Inhibitor Therapy

EXPERIMENTAL

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

Drug: Encorafenib; Drug: Binimetinib; Drug: Nivolumab

Arm B

ACTIVE COMPARATOR

Participants will receive 240 mg Nivolumab IV every 2 weeks

Drug: Nivolumab

Interventions

Encorafenib DRUG

450 mg encorafenib daily by mouth

Also known as: BRAFTOVI, BRAF/MEK-inhibitor

Arm A: BRAF-MEK Inhibitor Therapy

Binimetinib DRUG

45 mg binimetinib daily by mouth

Also known as: MEKTOVI, BRAF/MEK-inhibitor

Arm A: BRAF-MEK Inhibitor Therapy

Nivolumab DRUG

240 mg Nivolumab IV every 2 weeks

Also known as: Opdivo

Arm A: BRAF-MEK Inhibitor Therapy; Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Melanoma; Skin Neoplasms

Interventions

encorafenib; binimetinib; Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Zeynep Eroglu, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2018
• First Posted: June 1, 2018
• Study Start: June 14, 2018
• Primary Completion: December 27, 2024
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 5, 2026

Record last verified: 2026-02

Locations

US (1)