A Pharmacokinetic/Pharmacodynamic Study of RO5185426 in Previously Treated Patients With Metastatic Melanoma

A Phase I, Randomized, Open-label, Multi-center, Multiple Dose Study to Investigate the Pharmacokinetics and Pharmacodynamics of RO5185426 Administered as 240 mg Tablets to Previously Treated BRAF V600E Positive Metastatic Melanoma Patients

This open-label study will assess the pharmacokinetics, efficacy and safety of RO5185426 administered as 240mg tablets in previously treated patients with metastatic melanoma. Patients will be randomized to receive one of four dose-levels of RO5185426 [RG7204; PLEXXIKON; PLX4032] orally twice daily on days 1 to 15 (morning dose). Starting on day 22, treatment with RO5185426 may be resumed at a dose of 960 mg twice daily and continued until disease progression. Target sample size is <100 patients.

Inclusion Criteria:

• adult patients, >/=18 years of age
• histologically confirmed metastatic melanoma, stage IIIc or IV (AJCC)
• failure of at least one prior standard of care regimen
• positive for BRAF V600E mutation (by Roche CoDx BRAF mutation assay)
• ECOG performance status 0 or 1
• adequate hematologic, renal and liver function

Exclusion Criteria:

• active CNS lesions on CT/MRI within 28 days prior to enrollment
• history of spinal cord compression o carcinomatous meningitis
• anticipated or ongoing anti-cancer therapies other than those administered in this study
• previous treatment with BRAF inhibitor (sorafenib allowed) or MEK inhibitor
• severe cardiovascular disease within 6 months prior to study
• previous malignancy within the past 5 years except for basal or squamous cell carcinoma of the skin, melanoma in-situ and carcinoma in-situ of the cervix