COLUMBUS-AD: This phase III study is evaluating how safe and effective combination targeted therapy (Encorafenib and Binimetinib), compared to a targeted therapy combined with a placebo (Binimetinib and placebo), is in people with melanoma who have had prior surgeryAdjuvant Encorafenib & Binimetinib vs. Placebo in Fully Resected Stage IIB/C BRAF V600E/K Mutated Melanoma: a Randomized Triple-blind Phase III Study in Collaboration With the EORTC Melanoma Group

Inclusion

Pre-Screening

• Male or female ≥ 18 years of age;
• Surgically resected, with tumour free margins, and histologically/pathologically confirmed new diagnosis of stage II (pT3b-pT4bN0) cutaneous melanomaa;
• Sentinel node (SN) biopsy within 14 weeks from initial diagnosis of melanoma.
• Sentinel node (SN) staged node negative (pN0);
• Available tumour sample for central determination of the BRAF V600E/K mutation.

Screening

• Melanoma confirmed centrally to be BRAF V600E/K mutation-positive;
• Participant still free of disease as evidenced by the required baseline imaging and physical/dermatological assessments performed respectively within 6 weeks and 2 weeks before randomization (Day 1);
• No more than 12 weeks elapsed between full surgical resection (including SLNB) and randomization;
• Recovered from definitive surgery (e.g., complete wound healing, no uncontrolled wound infections or indwelling drains);
• ECOG performance status of 0 or 1;

• Adequate haematological function as defined as Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L and Hemoglobin

  ≥ 9.0 g/dL;

• Adequate renal function as defined as Serum creatinine ≤ 1.5 × ULN; or calculated creatinine clearance ≥ 50 mL/min;
• Adequate electrolytes, defined as serum potassium and magnesium levels within institutional normal limits;
• Adequate hepatic function as defined as Serum total bilirubin ≤ 1.5 x ULN and < 2 mg/dL, Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 2.5 x ULN;
• Adequate cardiac function as defined as LVEF ≥ 50% as determined by MUGA scan or echocardiogram and Mean triplicate QTcF value ≤ 480 msec and no history of QT syndrome;
• Adequate coagulation function, defined as INR ≤1.5× ULN unless the patient is receiving anticoagulant therapy as long as PT or aPTT is within the therapeutic range;
• Negative serum β-HCG test (female patient of childbearing potential only) performed within 3 days prior to Day 1;
• Female patients of child-bearing potential and male patients must agree to follow the protocol's contraception guidance during the treatment period and for ≥30 days after last administration.