Dabrafenib With Trametinib in the Adjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma (COMBI-AD).

Inclusion Criteria

• At least 18 years of age
• Completely resected histologically confirmed high-risk (Stage IIIa [lymph node metastasis > 1 mm], IIIb or IIIc) cutaneous melanoma determined to be V600E/K mutation positive using the bioMerieux (bMX) THxID BRAF Assay by a central laboratory. Patients presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma were eligible
• Must be surgically rendered free of disease (defined as the date of the most recent surgery) no more than 12 weeks before randomization
• Recovered from definitive surgery (e.g., no uncontrolled wound infections or indwelling drains)
• ECOG Performance Status of 0-1
• Had adequate hematologic, hepatic, renal and cardiac function. Key

Exclusion Criteria

• Known mucosal or ocular melanoma or the presence of unresectable in-transit metastases
• Evidence of distant metastatic disease on Screening evaluation
• Prior anti-cancer treatment (chemotherapy, immunotherapy, biologic therapy, vaccine therapy, or investigational treatment) including radiotherapy for melanoma. Prior surgery for melanoma was allowed
• History of another malignancy including melanoma or a concurrent malignancy. Patients who previously had Stage III melanoma or any malignancy with confirmed activating RAS mutation at any time were not eligible. Exceptions to this include:
• Patients with a history of any malignancy that had been disease-free for at least 5 years were eligible except those with confirmed activating RAS mutations
• Patients with a history of completely resected non-melanoma skin cancer (e.g., basal cell carcinoma, squamous cell carcinoma) were eligible irrespective of the time since the resection
• Patients with successfully treated in situ carcinoma were eligible
• Patients presenting with multiple primary melanomas were eligible only if the lesions were concurrent. Patients who had concurrent multiple primary melanomas that were "distant" were eligible provided each lesion was considered local disease or resectable regional disease.