Phase III study of adjuvant encorafenib plus binimetinib versus placebo in fully resected stage IIB/C BRAFV600-mutated melanoma: COLUMBUS-AD study design.

Abstract

TPS9601 Background: Significant progress has been made in the treatment of advanced BRAFV600-mutant melanoma. Encorafenib in combination with binimetinib is a well-tolerated and effective treatment option, providing sustained progression-free and overall survival benefit in unresectable or metastatic setting. The focus has shifted to early-stage disease in order to prevent recurrence. 18% of stage IIB and 25% stage IIC patients die due to melanoma within 10 years from the diagnosis [Gershenwald and al 2017], indicating an unmet medical need. Currently only immunotherapy has been approved in first countries across the world in this setting. There is a need for more treatment options for BRAF-mutated stage II disease. We report here the rationale and design of COLUMBUS-AD (NCT05270044). Methods: COLUMBUS-AD study is an international randomized, placebo-controlled, triple-blind, multicenter Phase III trial evaluating adjuvant encorafenib + binimetinib against placebo in patients with fully resected stage IIB/C BRAF V600-mutant melanoma. Approximately 815 patients will be enrolled. More than 170 sites in up to 26 countries worldwide will participate in the study conducted in collaboration with the European Organisation for Research and Treatment of Cancer (EORTC). Patients will receive encorafenib + binimetinib or placebo for 12 months, or until disease recurrence and will be followed monthly during treatment period, then every 3 months up to year 3, and then at regular intervals. The participants will be followed for a total of 10 years. Patients included in the study must have undergone resection of a stage IIB/C cutaneous melanoma with a BRAFV600E/K mutation, confirmed on resected tumor sample by a central laboratory, and a negative result on sentinel node biopsy. Patients must have recovered from surgery, have an ECOG 0/1, and adequate hematologic, hepatic, cardiac, coagulation and renal functions. Eligible patients will be randomized 1:1 to receive either encorafenib 450 mg once daily plus binimetinib 45 mg twice daily or matching placebos. The primary objective of the study is to evaluate the efficacy of the combination of encorafenib+ binimetinib for prolonging recurrence-free survival (RFS). The secondary objectives are to compare distant metastasis-free survival (DMFS), overall survival (OS), health-related quality of life (QoL), and safety and tolerability between the two arms and to provide additional pharmacokinetic data. Conclusion: COLUMBUS-AD is the first phase 3 randomised trial to evaluate adjuvant BRAFi/MEKi in stage IIB/C melanoma. This study will evaluate whether the combination of encorafenib and binimetinib can decrease the risk for recurrence and improve distant metastasis-free survival and overall survival versus placebo in completely resected IIB/C BRAFV600E/K-mutant cutaneous melanoma. Clinical trial information: NCT05270044 .