Efficacy and Safety Study of GSK1120212, a MEK Inhibitor, in Subjects With Uveal Melanoma

A Single-Arm, Open-Label, Multi-Center Study to Investigate the Objective Response Rate, Safety, and Pharmacokinetics of GSK1120212, a MEK Inhibitor, in Subjects With Metastatic Uveal Melanoma or With Mutation-Positive GNAQ or GNA11 Metastatic Melanoma

The purpose of this study is to determine whether GSK1120212, a MEK inhibitor, is an effective and safe treatment for cancer subjects with metastatic uveal melanoma and mutation-positive GNAQ or GNA11 metastatic melanoma.

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of metastatic uveal melanoma or previously documented mutation-positive GNAQ or GNA11 metastatic melanoma not previously treated with a MEK inhibitor.
• Provide archival tumor tissue or, if tissue blocks are not available, undergo fresh tumor biopsy prior to enrollment.
• The patient has a radiographically measurable tumor.
• ECOG performance status 0, 1, or 2.
• The patient is able to swallow and retain oral medication.
• Life expectancy of at least 4 months.
• Toxicities from previous anti-cancer therapy (except alopecia) are recovered (Grade 1 or less) at the time of enrollment.
• The patient has adequate organ and bone marrow function.
• Sexually active patients must use medically acceptable methods of contraception during the course of the study.
• Female patients of childbearing potential must have a negative serum pregnancy test at screening.

Exclusion Criteria:

• The patient has had any of the following within 21 days of starting study drug or anticipates the need for any of the following during the course of study treatment: chemotherapy, immunotherapy, biologic therapy, hormone therapy, major surgery, or tumor embolization.
• The patient has received experimental therapy within 21 days of starting study drug.
• The patient has received nitrosourea or mitomycin C within 42 days of starting study drug.
• The patient has received any herbal medications or palliative radiotherapy within 14 days of starting study drug.
• The patient is currently receiving anticoagulation therapy that is not well controlled.
• Ongoing or newly diagnosed eye abnormality other than symptoms due to uveal melanoma.
• History of retinal vein occlusion or central serous retinopathy.
• Current severe, uncontrolled systemic disease.
• History of leptomeningeal disease or spinal cord compression secondary to metastasis.
• Brain metastasis, unless previously treated with surgery, whole-brain radiation or stereotactic radiosurgery and the disease has been stable for at least 3 months without steroid use or on a stable dose of steroids for at least 1 month prior to starting study drug. Stability of brain metastases must be confirmed with imaging.
• The patient has a concurrent, active hematological malignancy or other solid tumor malignancy.
• History of clinically significant cardiac or pulmonary dysfunction.
• Allergy or hypersensitivity to components of the GSK1120212 formulation.
• The patient is pregnant or breastfeeding.