Access Study of Trametinib for Subjects With Advanced Unresectable (Stage IIIc) or Distant Metastatic (Stage IV) BRAF V600E/K Mutation Positive Cutaneous Melanoma

Who cannot join

• Subjects who have received prior therapy with a MEK or BRAF inhibitor. NOTE: However subjects may be eligible in the following cases: Subjects whose tumor has not progressed based on radiographic and clinical assessments. Such subjects may receive therapy with: trametinib in combination with dabrafenib (in case of an adverse event related to a previous BRAF or MEK inhibitor other than trametinib or dabrafenib and without cross-reaction anticipated, or if clinically indicated according to investigator judgement). Prior treatment (except trametinib and dabrafenib) should have been stopped for a period of 5 half lives or 28 days (whichever is shorter) before starting treatment of this study; trametinib monotherapy if the subject has benefited from a treatment with a BRAF-inhibitor without progression but cannot receive it anymore due to tolerability reason. Subjects who have met the criteria for disease progression may receive trametinib in combination with dabrafenib if: the disease progression was confirmed after a period of at least 6 months of clinical benefit (Response or Stable Disease) on monotherapy and if the progression was characterized by a limited radiographic progression in the absence of clinical signs and symptoms of progression. no treatment-related grade 4 AEs or any SAEs occurred during the last 4 weeks of treatment.
• Concurrent treatment with other systemic anti-cancer therapies is not allowed (except dabrafenib in combination with trametinib). Subjects who are currently being treated with another systemic anti-cancer therapy (e.g. chemo, immune, biologic, or targeted therapy) must discontinue use prior to initiation of treatment in this open label access study for a period of 5 half lives or 28 days (whichever is shorter).
• Presence of malignancy other than melanoma within 1 year of enrolment into this program or any malignancy with confirmed activating RAS mutation. Subject with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. Note: Prospective RAS testing is not required. However, if the results of previous RAS testing are known, they must be used in assessing eligibility.
• Has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trametinib or dabrafenib, or excipients or to dimethyl sulfoxide (DMSO).
• Current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
• Current evidence of cardiovascular risk including any of the following: Left Ventricular Ejection Fraction (LVEF) < lower limit of normal (LLN); A QT interval corrected for heart rate using the Bazett's formula >=480 millisecond (msec); Clinically significant uncontrolled arrhythmias; Acute coronary syndromes (including myocardial infarction and unstable angina); Congestive heart failure >=Class II as defined by New York Heart Association.