primary analysis of the RANDOMIZED eortc-2139/columbus-ad trial: Adjuvant encorafenib and binimetinib versus placebo in high-risk stage II BRAF-V600E/K melanoma

Alexander Cj van Akkooi; Michal Kicinski; Anne-Sophie Govaerts; Axel Hauschild; Piotr Rutkowski; Petr Arenberger; Paolo A Ascierto; Piotr Tomczak; Gaëlle Quereux; Federica De Galitiis; Caroline Dutriaux; Christoffer Gebhardt; Ellen Kapiteijn; Laurent Machet; Miguel Ga Berciano; Michele Del Vecchio; Mathilde Jalving; Thomas Jouary; Ivana Krajsova; Suzana Matkovic; Barbara Merelli; Laurent Mortier; Pages-LaurentCecile Pagès-Laurent; Giuseppe Palmieri; Marc Pracht; Yvetta Vantuchova; Daniela Massi; Nathalie Elaut; Gaetan de Schaetzen; Sarah Nuyens; Nitish Jha; Isabelle Klauck; Benoît Sansas; Jean Claude Vedovato; Paul C Lorigan; Georgina V Long; Alexander Mm Eggermont; Mario Mandala

doi:10.1016/j.ejca.2026.116951

primary analysis of the RANDOMIZED eortc-2139/columbus-ad trial: Adjuvant encorafenib and binimetinib versus placebo in high-risk stage II BRAF-V600E/K melanoma

Alexander Cj van Akkooi^*
, Michal Kicinski
, Anne-Sophie Govaerts
, Axel Hauschild
, Piotr Rutkowski
, Petr Arenberger
, Paolo A Ascierto
, Piotr Tomczak
, Gaëlle Quereux
, Federica De Galitiis
, Caroline Dutriaux
, Christoffer Gebhardt
, Ellen Kapiteijn
, Laurent Machet
, Miguel Ga Berciano
, Michele Del Vecchio
, Mathilde Jalving
, Thomas Jouary
, Ivana Krajsova
, Suzana Matkovic

Barbara Merelli, Laurent Mortier, Pages-LaurentCecile Pagès-Laurent, Giuseppe Palmieri, Marc Pracht, Yvetta Vantuchova, Daniela Massi, Nathalie Elaut, Gaetan de Schaetzen, Sarah Nuyens, Nitish Jha, Isabelle Klauck, Benoît Sansas, Jean Claude Vedovato, Paul C Lorigan, Georgina V Long, Alexander Mm Eggermont, Mario Mandala

^*Corresponding author for this work

Department of Hematology

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

PURPOSE: Stage IIB/IIC melanoma has a high risk of recurrence after resection. Combined BRAF/MEK inhibitor therapy showed benefit in resected high-risk stage III and advanced melanoma. The objective of this study was to investigate its role in stage IIB/IIC.

METHODS: Adult patients with resected stage IIB/IIC cutaneous melanoma which had a BRAF V600E/K mutation were randomized 1:1 to receive encorafenib (enco) 450 mg QD + binimetinib (bini) 45 mg BID orally for one year or placebo. The study planned to randomize 815 patients and was designed to demonstrate superiority regarding recurrence-free survival (RFS). Following a premature termination of accrual, the study was amended with safety as the primary endpoint and RFS as secondary endpoint.

RESULTS: Between June 9, 2022, and October 9, 2023, 339 patients were screened for a BRAF mutation and 110 randomized. Data cutoff was 19 Nov. 2024, after the last patient discontinued study participation. Among randomized patients, 87 (79%) had a BRAF V600E mutation, and 39 (35%) AJCC8 stage IIC. Median follow-up was 12 and 7 months for enco/bini and placebo arms, respectively. Among 54 patients who initiated enco + bini, grade ≥ 3 treatment-related adverse events (AE) occurred in 13 (24%) patients, and 18 (33%) patients had an AE leading to permanent treatment discontinuation. RFS at 12 months was 86% (95% CI: 65-95%) in the enco + bini and 70% (95% CI: 46-85%) in the placebo arm, distant metastasis-free survival at 12 months was 92% (95% CI: 77-97%) for enco + bini and 82% (95% CI: 55-93%) for placebo.

CONCLUSION: EORTC 2139 - Columbus-AD demonstrated a consistent and manageable safety profile and encouraging efficacy results for the combination of enco and bini in resected stage IIB/C BRAF V600E/K-mutated cutaneous melanomas.

Original language	English
Article number	116951
Journal	European Journal of Cancer
Volume	245
Early online date	21 Jul 2026
DOIs	https://doi.org/10.1016/j.ejca.2026.116951
Publication status	E-pub ahead of print - 21 Jul 2026

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10.1016/j.ejca.2026.116951

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van Akkooi, A. C., Kicinski, M., Govaerts, A.-S., Hauschild, A., Rutkowski, P., Arenberger, P., Ascierto, P. A., Tomczak, P., Quereux, G., De Galitiis, F., Dutriaux, C., Gebhardt, C., Kapiteijn, E., Machet, L., Berciano, M. G., Del Vecchio, M., Jalving, M., Jouary, T., Krajsova, I., ... Mandala, M. (2026). primary analysis of the RANDOMIZED eortc-2139/columbus-ad trial: Adjuvant encorafenib and binimetinib versus placebo in high-risk stage II BRAF-V600E/K melanoma. European Journal of Cancer, 245, Article 116951. Advance online publication. https://doi.org/10.1016/j.ejca.2026.116951

@article{e0c057211a514091a6397b7e16fc92e1,

title = "primary analysis of the RANDOMIZED eortc-2139/columbus-ad trial: Adjuvant encorafenib and binimetinib versus placebo in high-risk stage II BRAF-V600E/K melanoma",

abstract = "PURPOSE: Stage IIB/IIC melanoma has a high risk of recurrence after resection. Combined BRAF/MEK inhibitor therapy showed benefit in resected high-risk stage III and advanced melanoma. The objective of this study was to investigate its role in stage IIB/IIC.METHODS: Adult patients with resected stage IIB/IIC cutaneous melanoma which had a BRAF V600E/K mutation were randomized 1:1 to receive encorafenib (enco) 450 mg QD + binimetinib (bini) 45 mg BID orally for one year or placebo. The study planned to randomize 815 patients and was designed to demonstrate superiority regarding recurrence-free survival (RFS). Following a premature termination of accrual, the study was amended with safety as the primary endpoint and RFS as secondary endpoint.RESULTS: Between June 9, 2022, and October 9, 2023, 339 patients were screened for a BRAF mutation and 110 randomized. Data cutoff was 19 Nov. 2024, after the last patient discontinued study participation. Among randomized patients, 87 (79\%) had a BRAF V600E mutation, and 39 (35\%) AJCC8 stage IIC. Median follow-up was 12 and 7 months for enco/bini and placebo arms, respectively. Among 54 patients who initiated enco + bini, grade ≥ 3 treatment-related adverse events (AE) occurred in 13 (24\%) patients, and 18 (33\%) patients had an AE leading to permanent treatment discontinuation. RFS at 12 months was 86\% (95\% CI: 65-95\%) in the enco + bini and 70\% (95\% CI: 46-85\%) in the placebo arm, distant metastasis-free survival at 12 months was 92\% (95\% CI: 77-97\%) for enco + bini and 82\% (95\% CI: 55-93\%) for placebo.CONCLUSION: EORTC 2139 - Columbus-AD demonstrated a consistent and manageable safety profile and encouraging efficacy results for the combination of enco and bini in resected stage IIB/C BRAF V600E/K-mutated cutaneous melanomas.",

author = "\{van Akkooi\}, \{Alexander Cj\} and Michal Kicinski and Anne-Sophie Govaerts and Axel Hauschild and Piotr Rutkowski and Petr Arenberger and Ascierto, \{Paolo A\} and Piotr Tomczak and Ga{\"e}lle Quereux and \{De Galitiis\}, Federica and Caroline Dutriaux and Christoffer Gebhardt and Ellen Kapiteijn and Laurent Machet and Berciano, \{Miguel Ga\} and \{Del Vecchio\}, Michele and Mathilde Jalving and Thomas Jouary and Ivana Krajsova and Suzana Matkovic and Barbara Merelli and Laurent Mortier and Pages-LaurentCecile Pag{\`e}s-Laurent and Giuseppe Palmieri and Marc Pracht and Yvetta Vantuchova and Daniela Massi and Nathalie Elaut and \{de Schaetzen\}, Gaetan and Sarah Nuyens and Nitish Jha and Isabelle Klauck and Beno{\^i}t Sansas and Vedovato, \{Jean Claude\} and Lorigan, \{Paul C\} and Long, \{Georgina V\} and Eggermont, \{Alexander Mm\} and Mario Mandala",

note = "Publisher Copyright: Copyright {\textcopyright} 2026. Published by Elsevier Ltd.",

year = "2026",

month = jul,

day = "21",

doi = "10.1016/j.ejca.2026.116951",

language = "English",

volume = "245",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Elsevier Limited",

}

van Akkooi, AC, Kicinski, M, Govaerts, A-S, Hauschild, A, Rutkowski, P, Arenberger, P, Ascierto, PA, Tomczak, P, Quereux, G, De Galitiis, F, Dutriaux, C, Gebhardt, C, Kapiteijn, E, Machet, L, Berciano, MG, Del Vecchio, M, Jalving, M, Jouary, T, Krajsova, I, Matkovic, S, Merelli, B, Mortier, L, Pagès-Laurent, P-L, Palmieri, G, Pracht, M, Vantuchova, Y, Massi, D, Elaut, N, de Schaetzen, G, Nuyens, S, Jha, N, Klauck, I, Sansas, B, Vedovato, JC, Lorigan, PC, Long, GV, Eggermont, AM & Mandala, M 2026, 'primary analysis of the RANDOMIZED eortc-2139/columbus-ad trial: Adjuvant encorafenib and binimetinib versus placebo in high-risk stage II BRAF-V600E/K melanoma', European Journal of Cancer, vol. 245, 116951. https://doi.org/10.1016/j.ejca.2026.116951

primary analysis of the RANDOMIZED eortc-2139/columbus-ad trial: Adjuvant encorafenib and binimetinib versus placebo in high-risk stage II BRAF-V600E/K melanoma. / van Akkooi, Alexander Cj; Kicinski, Michal; Govaerts, Anne-Sophie et al.
In: European Journal of Cancer, Vol. 245, 116951, 09.09.2026.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - primary analysis of the RANDOMIZED eortc-2139/columbus-ad trial

T2 - Adjuvant encorafenib and binimetinib versus placebo in high-risk stage II BRAF-V600E/K melanoma

AU - van Akkooi, Alexander Cj

AU - Kicinski, Michal

AU - Govaerts, Anne-Sophie

AU - Hauschild, Axel

AU - Rutkowski, Piotr

AU - Arenberger, Petr

AU - Ascierto, Paolo A

AU - Tomczak, Piotr

AU - Quereux, Gaëlle

AU - De Galitiis, Federica

AU - Dutriaux, Caroline

AU - Gebhardt, Christoffer

AU - Kapiteijn, Ellen

AU - Machet, Laurent

AU - Berciano, Miguel Ga

AU - Del Vecchio, Michele

AU - Jalving, Mathilde

AU - Jouary, Thomas

AU - Krajsova, Ivana

AU - Matkovic, Suzana

AU - Merelli, Barbara

AU - Mortier, Laurent

AU - Pagès-Laurent, Pages-LaurentCecile

AU - Palmieri, Giuseppe

AU - Pracht, Marc

AU - Vantuchova, Yvetta

AU - Massi, Daniela

AU - Elaut, Nathalie

AU - de Schaetzen, Gaetan

AU - Nuyens, Sarah

AU - Jha, Nitish

AU - Klauck, Isabelle

AU - Sansas, Benoît

AU - Vedovato, Jean Claude

AU - Lorigan, Paul C

AU - Long, Georgina V

AU - Eggermont, Alexander Mm

AU - Mandala, Mario

PY - 2026/7/21

Y1 - 2026/7/21

N2 - PURPOSE: Stage IIB/IIC melanoma has a high risk of recurrence after resection. Combined BRAF/MEK inhibitor therapy showed benefit in resected high-risk stage III and advanced melanoma. The objective of this study was to investigate its role in stage IIB/IIC.METHODS: Adult patients with resected stage IIB/IIC cutaneous melanoma which had a BRAF V600E/K mutation were randomized 1:1 to receive encorafenib (enco) 450 mg QD + binimetinib (bini) 45 mg BID orally for one year or placebo. The study planned to randomize 815 patients and was designed to demonstrate superiority regarding recurrence-free survival (RFS). Following a premature termination of accrual, the study was amended with safety as the primary endpoint and RFS as secondary endpoint.RESULTS: Between June 9, 2022, and October 9, 2023, 339 patients were screened for a BRAF mutation and 110 randomized. Data cutoff was 19 Nov. 2024, after the last patient discontinued study participation. Among randomized patients, 87 (79%) had a BRAF V600E mutation, and 39 (35%) AJCC8 stage IIC. Median follow-up was 12 and 7 months for enco/bini and placebo arms, respectively. Among 54 patients who initiated enco + bini, grade ≥ 3 treatment-related adverse events (AE) occurred in 13 (24%) patients, and 18 (33%) patients had an AE leading to permanent treatment discontinuation. RFS at 12 months was 86% (95% CI: 65-95%) in the enco + bini and 70% (95% CI: 46-85%) in the placebo arm, distant metastasis-free survival at 12 months was 92% (95% CI: 77-97%) for enco + bini and 82% (95% CI: 55-93%) for placebo.CONCLUSION: EORTC 2139 - Columbus-AD demonstrated a consistent and manageable safety profile and encouraging efficacy results for the combination of enco and bini in resected stage IIB/C BRAF V600E/K-mutated cutaneous melanomas.

AB - PURPOSE: Stage IIB/IIC melanoma has a high risk of recurrence after resection. Combined BRAF/MEK inhibitor therapy showed benefit in resected high-risk stage III and advanced melanoma. The objective of this study was to investigate its role in stage IIB/IIC.METHODS: Adult patients with resected stage IIB/IIC cutaneous melanoma which had a BRAF V600E/K mutation were randomized 1:1 to receive encorafenib (enco) 450 mg QD + binimetinib (bini) 45 mg BID orally for one year or placebo. The study planned to randomize 815 patients and was designed to demonstrate superiority regarding recurrence-free survival (RFS). Following a premature termination of accrual, the study was amended with safety as the primary endpoint and RFS as secondary endpoint.RESULTS: Between June 9, 2022, and October 9, 2023, 339 patients were screened for a BRAF mutation and 110 randomized. Data cutoff was 19 Nov. 2024, after the last patient discontinued study participation. Among randomized patients, 87 (79%) had a BRAF V600E mutation, and 39 (35%) AJCC8 stage IIC. Median follow-up was 12 and 7 months for enco/bini and placebo arms, respectively. Among 54 patients who initiated enco + bini, grade ≥ 3 treatment-related adverse events (AE) occurred in 13 (24%) patients, and 18 (33%) patients had an AE leading to permanent treatment discontinuation. RFS at 12 months was 86% (95% CI: 65-95%) in the enco + bini and 70% (95% CI: 46-85%) in the placebo arm, distant metastasis-free survival at 12 months was 92% (95% CI: 77-97%) for enco + bini and 82% (95% CI: 55-93%) for placebo.CONCLUSION: EORTC 2139 - Columbus-AD demonstrated a consistent and manageable safety profile and encouraging efficacy results for the combination of enco and bini in resected stage IIB/C BRAF V600E/K-mutated cutaneous melanomas.

U2 - 10.1016/j.ejca.2026.116951

DO - 10.1016/j.ejca.2026.116951

M3 - Article

C2 - 42501621

SN - 0959-8049

VL - 245

JO - European Journal of Cancer

JF - European Journal of Cancer

M1 - 116951

ER -

primary analysis of the RANDOMIZED eortc-2139/columbus-ad trial: Adjuvant encorafenib and binimetinib versus placebo in high-risk stage II BRAF-V600E/K melanoma

Abstract

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