A Phase II Study of Single Agent MEK162 in Patients With Advanced Melanoma

• Progression Free SUurvival (PFS) [ Time Frame: every 8 weeks up to end of study ] [ Designated as safety issue: No ]
  The key secondary efficacy objective is estimation of progression free survival (PFS) distribution by study arm. PFS is defined as the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause, as per RECIST.
• Overall Survival, Duration of response (DoR) and Time to Response [ Time Frame: every 8-12 weeks up to end of study ] [ Designated as safety issue: No ]
  These endpoints will allow further analysis of the efficacy of MEK162
• Frequency and severity of adverse events and changes in laboratory values [ Time Frame: every 30 days after last dose ] [ Designated as safety issue: Yes ]
  To characterize safety and tolerability of MEK162
• Change in pharmacodynamics pre- and post-dose [ Time Frame: After 15 days of dosing ] [ Designated as safety issue: No ]
  To measure the changes in molecular markers of cell proliferation/survival pre-vs. post-dose tumor tissues and potential correlation with clinical outcomes

• estimation of progression free survival (PFS) distribution by study arm. PFS is defined as the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause, as per RECIST. [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]
• To characterize safety and tolerability as measured by the frequency and severity of adverse events and changes in laboratory values [ Time Frame: until 30 days after last dose ] [ Designated as safety issue: Yes ]
• Changes in molecular markers of cell proliferation/survival pre- vs. post-dose tumor tissues and potential correlation with clinical outcomes [ Time Frame: After 15 days of dosing ] [ Designated as safety issue: No ]

The study will assess the safety and efficacy of single-agent MEK162 in adult patients with locally advanced and unresectable or metastatic malignant cutaneous melanoma, harboring BRAFV600E or NRAS mutations.

• Experimental: Arm 1
  Intervention: Drug: MEK162
• Experimental: NRAS mutant, 45mg bid
  45mg bid
  Intervention: Drug: MEK162
• Experimental: BRAFV600 mutant, 60mg bid
  60mg bid
  Intervention: Drug: MEK162

Inclusion Criteria:

• Locally advanced or metastatic cutaneous melanoma AJCC Stage IIIB to IV, not potentially curable with surgery
• BRAF or NRAS mutation in tumor tissue
• All patients enrolled should provide sufficient fresh or archival tumor sample at baseline to enable confirmation of BRAF or NRAS mutations and the additional analyses described in the protocol
• Evidence of measurable tumor disease as per RECIST
• WHO performance status of 0-2
• Adequate organ function and laboratory parameters

Exclusion Criteria:

• History or evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or any eye condition that would be considered a risk factor for CSR or RVO
• Patients with unstable CNS metastasis
• Prior treatment with a MEK- inhibitor
• Impaired cardiovascular function
• HIV, active Hepatitis B, and/or active Hepatitis C infection
• Pregnant or nursing (lactating) women
• Women of child-bearing potential UNLESS they comply with protocol contraceptive requirements

Other protocol-defined inclusion/exclusion criteria may apply.