Phase III study of adjuvant encorafenib plus binimetinib vs placebo in fully resected stage IIB/C BRAFV600-mutated melanoma: COLUMBUS-AD study design
Van Akkooi, A. C. J. Hauschild, A. Long, G. V. Mandala, M. Kicinski, M. Govaerts, A. S. Klauck, I. Ouali, M. Lorigan, Paul C Eggermont, A. M. M.
Van Akkooi, A. C. J.
Hauschild, A.
Long, G. V.
Mandala, M.
Kicinski, M.
Govaerts, A. S.
Klauck, I.
Ouali, M.
Lorigan, Paul C
Eggermont, A. M. M.
Citations
Altmetric:
Abstract
Background: Melanoma treatment has radically changed during the past decade. This
is due to the discovery that BRAFV600-mutant directed targeted therapy, next to
immune checkpoint blockade. In the Columbus study, encorafenib in combination
with binimetinib has shown safety and efficacy in BRAF V600E/K mutant advanced /
metastatic stage IV melanoma. Standard of care for stage II melanoma was surveil lance follow-up after full resection. Considering that stage IIB/IIC melanoma has an
equal or higher risk of recurrence and mortality compared to stage IIIA/B, there is an
unmet medical need for stage IIB/C melanoma.
Trial design: COLUMBUS-AD (NCT05270044) trial is a placebo-controlled, randomized,
triple-blind Phase 3 study evaluating 1 year of adjuvant encorafenib + binimetinib
against placebo in patients with fully resected stage IIB/C BRAF V600-mutant mela noma. 2200 will be screened to enroll 815 patients. Patients will receive encorafenib +
binimetinib or placebo for up to a maximum of 12 months, or until disease recur rence, unacceptable toxicity, death or withdrawal of consent. Patients will be followed
up routinely with periodic imaging assessments up to a maximum of 10 years. In clusion criteria include adult patients ( 18 years of age), fully resected stage IIB/cutaneous melanoma, mandatorily within 12 weeks of negative sentinel lymph node
biopsy (SLNB) staging, no other signs of metastases (including no (micro-)satellites or
in-transit metastases), fully recovered from surgery, ECOG 0/1 with adequate he matologic, hepatic, cardiac, coagulation and renal functions. The primary endpoint of
this trial is recurrence-free survival (RFS), with the hypothesis that the combination of
encorafenib + binimetinib will prolong RFS. Secondary endpoints include 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.
The exploratory objectives include evaluation of the role of circulating tumor DNA
(ctDNA) as a biomarker. The first patient was screened in May 2022 and first ran domized in June 2022. Anticipated accrual completion mid 2025
Description
Date
2022
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Van Akkooi ACJ, Hauschild A, Long GV, Mandala M, Kicinski M, Govaerts AS, et al. Phase III study of adjuvant encorafenib plus binimetinib vs placebo in fully resected stage IIB/C BRAFV600-mutated melanoma: COLUMBUS-AD study design. Annals of Oncology. 2022 Nov;33:S1617-S8. PubMed PMID: WOS:000897943700465.