# COLUMBUS

Source: https://onco.cc/trials/columbus/  
OnCo record `columbus` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

COLUMBUS tested encorafenib-binimetinib, the third BRAF/MEK doublet, which has the longest median survival of the class and less fever than dabrafenib-trametinib.

## Summary

COLUMBUS, trial NCT01909453 sponsored by Array, now Pfizer, and reported in 2018, tested encorafenib plus binimetinib, the third BRAF and MEK doublet, in advanced BRAF V600 melanoma against vemurafenib and against encorafenib alone. It randomised 577 patients, met its primary progression-free survival endpoint against vemurafenib with a large effect, and its seven-year update showed the longest median survival of the class, with less fever and photosensitivity than dabrafenib plus trametinib, attributed to encorafenib's longer dissociation half-life on BRAF; approval followed in June 2018. OnCo links it to BRAF as a target, the MAPK pathway, encorafenib, binimetinib, vemurafenib, Paolo A. Ascierto and Reinhard Dummer, and the class effect was replicated in coBRIM and COMBI-d and COMBI-v. Whether the tolerability difference changes which doublet clinicians choose is the open question.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-07
- Registry id: NCT01909453
- Phase: 3
- Setting: Advanced BRAF V600 melanoma: encorafenib + binimetinib vs vemurafenib vs encorafenib
- Sponsor: Array / Pfizer
- Enrolled: 577
- Result: PFS 14.9 vs 7.3 months (HR 0.54); median OS 33.6 months.
- Outcomes: Progression-free survival: Encorafenib + binimetinib 14.9 months vs Vemurafenib 7.3 months, HR 0.54
- Replication: Class effect replicated across coBRIM (vemurafenib-cobimetinib) and COMBI-d/v (dabrafenib-trametinib).

## Sources

- ClinicalTrials.gov NCT01909453: https://clinicaltrials.gov/study/NCT01909453
- Lancet Oncology 2018: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30142-6/fulltext

## Connected records

- cancers: [Advanced melanoma (unresectable stage III and stage IV)](https://onco.cc/cancers/advanced-melanoma/), [BRAF V600-mutant melanoma](https://onco.cc/cancers/braf-v600-melanoma/), [Melanoma](https://onco.cc/cancers/melanoma/)
- technologies: [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [BRAF](https://onco.cc/targets/braf/)
- drugs: [Binimetinib](https://onco.cc/drugs/binimetinib/), [Encorafenib](https://onco.cc/drugs/encorafenib/), [Vemurafenib](https://onco.cc/drugs/vemurafenib/)
- companies: [Pfizer (incl. Seagen)](https://onco.cc/companies/pfizer/)
- pathways: [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- people: [Paolo A. Ascierto](https://onco.cc/people/paolo-ascierto/), [Reinhard Dummer](https://onco.cc/people/reinhard-dummer/)
- key papers: [COLUMBUS: encorafenib plus binimetinib versus vemurafenib or encorafenib in BRAF-mutant melanoma](https://onco.cc/key-papers/paper-columbus-lancet-oncol-2018/), [Overall survival in patients with BRAF-mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or encorafenib (COLUMBUS): a multicentre, open-label, randomised, phase 3 trial](https://onco.cc/key-papers/paper-columbus-lancet-oncol-2018-update/)
- ideas: [Test intermittent dosing of targeted drugs to delay resistance, with honest priors](https://onco.cc/ideas/idea-tr1-intermittent-dosing-to-delay-resistance/)

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