Table 3 Key patient selection criteria

• Clinical diagnosis of metastatic uveal melanoma

• Any prior systemic anticancer therapy, including for the treatment of this current diagnosis

• Histological or cytological confirmation of melanoma

• An investigational drug within 30 days of starting treatment, or has not recovered from side effects of an investigational drug

• Male or female aged ≥18 years

• Suitable for treatment with dacarbazine chemotherapy

• Any non-systemic anticancer therapy that has not been cleared from the body by the time of starting study treatment

• ≥1 lesion that can be accurately measured at baseline as ≥10 mm in the longest diameter, which is suitable for accurate repeated measurements

• Radiation therapy within 4 weeks prior to starting study treatment

• Major surgery within 4 weeks prior to entry into the study that would prevent administration of study treatment

• ECOG performance status 0–1

• Life expectancy >12 weeks

• Normal organ and marrow function

• Any prior investigational therapy comprising inhibitors of RAS, RAF or MEK at any time

• Negative urinary or serum pregnancy test for women with childbearing potential

• Previous treatment with dacarbazine

• Able to swallow selumetinib/placebo capsules

• Any unresolved toxicity > CTCAE grade 2 from previous anticancer therapy, excluding alopecia

• Signed informed consent document

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib or dacarbazine

• Symptomatic brain metastases or spinal cord compression

• Cardiac conditions, such as uncontrolled hypertension, acute coronary syndrome, uncontrolled angina or heart failure

• Severe concomitant systemic disorder, active infection, active bleeding diatheses or renal transplant

• Refractory nausea and vomiting, chronic gastrointestinal diseases or significant bowel resection that would preclude adequate absorption

• History of another primary malignancy within 5 years prior to starting study treatment

• Current or past history of retinal pigmented epithelial detachment/central serous retinopathy; retinal vein occlusion; intraocular pressure >21 mmHg; uncontrolled glaucoma

• Female patients who are breast-feeding and male or female patients of reproductive potential who are not employing an effective method of birth control

• Judgement by the investigator that the patient should not participate in the study