Inclusion Criteria:

1. Histologically confirmed diagnosis of melanoma.
2. Unresectable Stage III or stage IV melanoma.
3. Evidence of disease progression according to RECIST 1.1 on prior regimen.
4. Subjects with brain metastases will be eligible if they have undergone complete surgical excision and are more then 1 month post surgery with no radiographic evidence of disease recurrence in the brain or have undergone stereotactic radio surgery (gamma knife procedure) and are more then 1 month post procedure and with no radiographic evidence of disease progression in the brain; and are asymptomatic, and discontinued corticosteroid treatment at least 30 days prior starting treatment.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
6. Adequately controlled blood pressure
7. Adequate renal function
8. Adequate bone marrow function
9. Adequate blood coagulation function
10. Adequate liver function
11. Males or females greater than or equal to 18 years of age at the time of informed consent.
12. Negative serum or urine pregnancy test
13. Voluntary agreement to provide written informed consent

Exclusion Criteria:

1. Melanoma of intraocular origin
2. Leptomeningeal metastases or brain metastases except as for subjects with brain metastases will be eligible if they have undergone complete surgical excision and are more then 1 month post surgery with no radiographic evidence of disease recurrence in the brain or have undergone stereotactic radio surgery (gamma knife procedure) and are more then 1 month post procedure and with no radiographic evidence of disease progression in the brain; and are asymptomatic, and discontinued corticosteroid treatment at least 30 days prior starting treatment
3. More than 2 prior systemic anticancer regimen treatments including immunotherapies for unresectable stage III or stage IV disease (if BRAF V600E mutation negative) or not previously treated with BRAF V600E-targeted therapy or received in the past more than two prior systemic anticancer regimen treatments, including immunotherapies, in addition to a BRAF-V600E-targeted therapy (if BRAF V600E mutation positive)
4. Any anti-cancer treatment within 21 days or any investigational agent within 30 days prior to the first dose of study drug
5. Inability to take oral medication, gastrointestinal malabsorption, or any other condition that might affect the absorption of E7080.
6. Major surgery within 3 weeks prior to the first dose of study drug.
7. Significant cardiovascular impairment
8. Bleeding disorder or a thrombotic disorder requiring anticoagulant therapy
9. Active malignancy (except for melanoma, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 24 months.
10. Females who are pregnant or breastfeeding.
11. Known intolerance to the study drug (or any of the excipients).
12. Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial.