Pharmacokinetics & Pharmacodynamics

Explore BRAFTOVI^® + MEKTOVI^® PK-PD properties

BRAFTOVI^® (encorafenib) is a potent and highly selective ATP-competitive small molecule RAF kinase inhibitor¹. MEKTOVI^® (binimetinib) is an ATP-uncompetitive, reversible inhibitor of the kinase activity of the MEK kinase 1 & 2.²

When BRAFTOVI^® is used in combination with MEKTOVI^® it shows a greater antiproliferative activity compared with monotherapy¹¹.

Allow powerful and sustained target suppression^10,11

No direct link between pharmacological properties of molecules and their clinical efficacy can be established

a Allows a prolonged inhibition of pERK due to its long dissociation half-life.¹¹

AE, adverse event; ATP, adenosine triphosphate; MEK, mitogen-activated extracellular signal regulated kinase; pERK, protein kinase RNA-like ER kinase.

EU healthcare professionals

This is an international website for BRAFTOVI® + MEKTOVI® dedicated to EU healthcare professionals (outside the UK and ROI).

IMPORTANT: the information on this website is based on the EU Summaries of Product Characteristics. Prescribing Information and indication may vary per country. You must refer to your country prescribing information. Please be aware we do not take responsibility for accessing such information which may not comply with the regulation or usage in your country.

I certify that:

I am a Healthcare Professional in the EU (outside the UK and ROI) and I have read the information above.

Patients/ Non EU healthcare professionals

This is an international website for BRAFTOVI^® + MEKTOVI^® dedicated to EU healthcare professionals (outside the UK and ROI).

I am a patient or a healthcare professional outside the EU.

https://www.pierre-fabre.com/en

REFERENCES

1. BRAFTOVI^® Summary of Product Characteristics. Pierre Fabre Médicament.
2. MEKTOVI^® Summary of Product Characteristics. Pierre Fabre Médicament.
3. Schadendorf D, Dummer R, Flaherty KT, et al. COLUMBUS 7-year update: A randomized, open-label, phase III trial of encorafenib plus
binimetinib versus vemurafenib or encorafenib in patients with BRAF V600E/K-mutant melanoma. Eur J Cancer 2024;204:114073.
4. Dummer R, Flaherty KT, Robert C, et al. COLUMBUS 5-Year Update: A Randomized, Open-Label, Phase III Trial of Encorafenib Plus
Binimetinib Versus Vemurafenib or Encorafenib in Patients With BRAF V600-Mutant Melanoma [published correction appears in J Clin Oncol
2023;41(12):2301.]. J Clin Oncol 2022;40(36):4178–4188.
5. Dummer R, Ascierto PA, Gogas HJ, et al. Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant
melanoma (COLUMBUS): a multicentre, open-label, randomised Phase 3 trial. Lancet Oncol 2018;19(5):603–615.
6. Dummer R, Ascierto PA, Gogas HJ, et al. 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. Lancet Oncol 2018;19(10):1315–1327.
7. Schadendorf D, Dummer R, Flaherty KT, et al. COLUMBUS 7-year update: a randomized, open-label, phase III trial of encorafenib plus
binimetinib versus vemurafenib or encorafenib in patients with BRAFV600E/K-mutant melanoma. Eur J Cancer 2024;204:114073.
[Supplementary appendix].
8. Ascierto PA, Dummer R, Gogas HJ, et al. Update on tolerability and overall survival in COLUMBUS: landmark analysis of a randomised
Phase 3 trial of encorafenib plus binimetinib vs vemurafenib or encorafenib in patients with BRAFV600-mutant melanoma. Eur J Cancer
2020;126:33–44.
9. Gogas HJ, Flaherty KT, Dummer R, et al. Adverse events associated with encorafenib plus binimetinib in the COLUMBUS study:
incidence, course and management. Eur J Cancer 2019;119:97–106.
10. Heinzerling L, Elgentler TK, Fluck M, et al. Tolerability of BRAF/MEK inhibitor combinations: adverse event evaluation and
management. ESMO Open 2019;4(3):e000491.
11. Trojaniello C, Festino L, Vanella V, et al. Encorafenib in combination with binimetinib for unresectable metastatic melanoma
with BRAF mutation. Expert Rev Clin Pharmacol 2019;12(3):259–266.
12. Delord JP, Robert C, Nyakas M, et al. Phase I Dose-Escalation and -Expansion Study of the BRAF Inhibitor Encorafenib (LGX818)
in Metastatic BRAF-Mutant Melanoma. Clin Cancer Res 2017;23(18):5339–5348.
13. Stuart DD, Li N, Poon DJ, et al. Preclinical profile of LGX818: A potent and selective RAF kinase inhibitor. Cancer Res 2012;72:Abstract 3790.
14. Smith DA, Beaumont K, Maurer TS, Di L. Relevance of Half-Life in Drug Design. J Med Chem 2018;61(10):4273–4282.
15. Vauquelin G, Charlton SJ. Long-lasting target binding and rebinding as mechanisms to prolong in vivo drug action. Br J Pharmacol
2010;161(3):488-508.
16. Gogas HJ, Dummer R, Ascierto PA, et al. Quality of life in patients with BRAF-mutant melanoma receiving the combination encorafenib plus
binimetinib: results from a multicentre, open-label, randomised, Phase III study (COLUMBUS). Eur J Cancer 2021 ;152:116–128.
17. Musoro JZ, Bottomley A, Coens C, et al. Interpreting European Organisation for Research and Treatment for Cancer Quality of life
Questionnaire core 30 scores as minimally importantly different for patients with malignant melanoma. Eur J Cancer 2021;104:169–181.
18. Gogas HJ, Dummer R, Ascierto PA, et al. Updated Quality of Life (QoL) of encorafenib + binimetinib (COMBO450) versus (vs) vemurafenib
(VEM) from COLUMBUS Part 1 Phase III study in BRAF-mutant melanoma. Presented at: 16th International Congress of the Society for
Melanoma Research (SMR); 20–23 November 2019; Salt Lake City, Utah, USA

This is an international website for BRAFTOVI®+MEKTOVI®. IMPORTANT: the information on this website is based on the European Summaries of Product Characteristics . Prescribing Information and indication may vary per country. You must refer to your country prescribing information. Please be aware we do not take responsibility for accessing such information which may not comply with the regulation or usage in your country.

HQ-MEK-09-23-2300001 V2.0 Last update: October 2025

BRAFTOVI® is a trademark of Array BioPharma Inc., a wholly owned subsidiary of Pfizer Inc. MEKTOVI® is a trademark of Array BioPharma Inc. a wholly owned subsidiary of Pfizer Inc. © 2023, Pierre Fabre all rights reserved

Pharmacokinetics & Pharmacodynamics

Explore BRAFTOVI® + MEKTOVI® PK-PD properties

Allow powerful and sustained target suppression10,11

EU healthcare professionals​

Patients/ Non EU healthcare professionals​

Explore BRAFTOVI^® + MEKTOVI^® PK-PD properties

Allow powerful and sustained target suppression^10,11

EU healthcare professionals

Patients/ Non EU healthcare professionals