An Open-Label, 2-Cohort, Multicenter, Phase 2 Study of E7080 in Previously Treated Subjects With Unresectable Stage III or Stage IV Melanoma

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.

13. prolongation of QTc interval > 480 msec

14. 24 hour urine protein >/= 1 gm

15. Active hemoptysis within 3 wks prior to the first dose of study drug.