PKPD illustration

Pharmacokinetics & Pharmacodynamics

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

MAP pathway

BRAFTOVI^® (encorafenib) is a potent and highly selective ATP-competitive small molecule RAF kinase inhibitor. MEKTOVI^® (binimetinib) is an ATP-uncompetitive, reversible inhibitor of the kinase activity of the MEK kinase 1 & 2.^1,2

When BRAFTOVI^® is used in combination with MEKTOVI^® it shows a greater antiproliferative activity compared with monotherapy⁹.

Watch the video to learn more on the combination PK-PD profile

Allow powerful and sustained target suppression^9,10

PKPD characteristics

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

PD, pharmacodynamic; PK, pharmacokinetic; MEK, Mitogen-activated Extracellular signal regulated kinase; RAF, Rapidly Accelerated Fibrosarcoma.

^aAllows a prolonged inhibition of pERK due to its long dissociation half-life.^{9 b}Allows for increased doses of BRAFTOVI due to its ameliorative effect on toxicity.¹¹

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 European Summaries of Product Characteristics of BRAFTOVI® and MEKTOVI®. 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. Dummer R, et Al. COLUMBUS 5-Year Update: A randomized, open-label, phase III trial of encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAFV600–mutant melanoma. J. Clin. Oncol. (2022). DOI: 10.1200/JCO.21.026595-year publication.
4. 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.
5. 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 BRAF^V600-mutant melanoma. Eur J Cancer 2020;126:33–44.
6. 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.
7. 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.
8. 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.
9. 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.
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. 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.
12. Lebbe C, Lorigan P, Ascierto PA et al. Treatment patterns and outcomes among patients diagnosed with unresectable stage III or IV melanoma in Europe: a retrospective, longitudinal survey (MELODY study). Eur J Cancer 2012;48(17):3205–3214.
13. Gogas HJ, 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 the 16th International Congress of the Society for Melanoma Research (SMR). November 20–23, 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 Last update: September 2023

Pierre Fabre

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