Study of Encorafenib, Binimetinib, and Pembrolizumab for Patients with Advanced Melanoma with BRAF V600E/K Mutation

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What is this study about?

This clinical trial is focused on studying a type of skin cancer called melanoma, specifically when it has spread to other parts of the body or cannot be removed by surgery. The study is looking at patients with a specific genetic change known as the BRAF V600E/K mutation. The trial will test the effectiveness of a combination of medications: Encorafenib, Binimetinib, and Pembrolizumab. Encorafenib is taken as a capsule, Binimetinib as a tablet, and Pembrolizumab is given through an infusion, which means it is delivered directly into the bloodstream through a vein.

The purpose of the study is to compare the effects of the combination of Encorafenib, Binimetinib, and Pembrolizumab against a placebo combined with Pembrolizumab. Participants will be randomly assigned to receive either the combination of the three medications or the placebo with Pembrolizumab. The study will last for up to 24 months, during which participants will receive regular treatments and check-ups to monitor their health and the progress of the melanoma.

This trial aims to determine if the combination of these medications can improve outcomes for patients with this specific type of melanoma. The study will also assess the safety of the medication combination and monitor any side effects that may occur. Participants will be closely observed by healthcare professionals throughout the study to ensure their well-being and to gather important information about the treatment’s effectiveness.

1 joining the study

Upon joining the study, eligibility is confirmed based on specific criteria, including age, type of melanoma, and genetic mutation status.

Adequate tumor tissue must be submitted for laboratory testing to confirm the presence of the BRAF V600E or V600K mutation.

2 safety lead-in phase

During this phase, the main goal is to determine the recommended dose of encorafenib and binimetinib when combined with pembrolizumab.

Participants may receive encorafenib and binimetinib orally, along with pembrolizumab administered intravenously.

3 randomized phase 3

Participants are randomly assigned to one of two groups: the triplet arm or the control arm.

The triplet arm receives encorafenib, binimetinib, and pembrolizumab, while the control arm receives a placebo with pembrolizumab.

The effectiveness of the treatment is compared between the two groups.

4 treatment administration

Encorafenib and binimetinib are taken orally, while pembrolizumab is given as an intravenous infusion.

The dosage and frequency of administration are determined based on the safety lead-in phase results.

5 monitoring and assessments

Regular monitoring of health status, including vital signs and laboratory tests, is conducted to assess safety and effectiveness.

Imaging tests are performed to evaluate the response of the melanoma to the treatment.

6 end of study participation

Participation in the study concludes upon completion of the treatment period or if the disease progresses.

Final assessments are conducted to gather data on the overall outcomes of the treatment.

Who Can Join the Study?

  • Participants must be male or female and at least 18 years old.
  • Participants must have a type of skin cancer called melanoma that is either not removable by surgery or has spread to other parts of the body. This must be confirmed by a test called a histological test.
  • Participants must have a specific change in their cancer cells called a BRAF V600E or V600K mutation.
  • Participants need to provide a sample of their tumor for testing to confirm the presence of the BRAF V600E/K mutation.
  • For the Safety Lead-In part of the study, participants should not have received more than one previous treatment for their melanoma that has spread or cannot be removed by surgery.
  • For the Phase 3 part of the study, participants should not have received any previous treatment for their melanoma that has spread or cannot be removed by surgery.
  • Participants must have at least one tumor that can be measured using a specific guideline called RECIST v1.1.
  • Participants must have a good general health status, which is measured by a scale called ECOG Performance Status, and should have a score of 0 or 1. They must also have healthy organs and heart function, with a heart test showing a Left Ventricular Ejection Fraction (LVEF) of 50% or higher.

Who Cannot Join the Study?

  • Patients with other types of cancer that are not the specific type being studied.
  • Patients who have had a different treatment for their cancer recently.
  • Patients with serious heart problems.
  • Patients with serious liver or kidney problems.
  • Patients who are pregnant or breastfeeding.
  • Patients who have an infection that is not well controlled.
  • Patients who have a history of another serious illness that could affect the study.
  • Patients who are unable to follow the study procedures.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name City Country Status
Universitaetsklinikum Heidelberg AöR Heidelberg Germany
Universitaet Leipzig Leipzig Germany
Technische Universitaet Dresden Dresden Germany

Other Sites

Site Name City Country Status
Istituto Oncologico Veneto Padua Italy
Orszagos Onkologiai Intezet Budapest Hungary
Hautklinik, Klinikum Nürnberg, Universitätsklinik der Paracelsus Medizinischen Privatuniversität Nürnberg Germany
Medical Center Nadezhda Clinical EOOD Sofia Bulgaria
Istituto Di Candiolo Fondazione Del Piemonte Per Loncologia IRCCS Candiolo Italy
Charite Universitaetsmedizin Berlin KöR Berlin Germany
IRCCS Ospedale Policlinico San Martino Genoa Italy
University Clinical Hospital Virgen De La Arrixaca Murcia Spain
Uniwersytecki Szpital Kliniczny W Poznaniu Poznan Poland
Istituto Europeo Di Oncologia S.r.l. Milan Italy
IRCCS Istituto Nazionale Tumori Fondazione Pascale Naples Italy
Universitaetsklinikum Schleswig-Holstein AöR Kiel Germany
Azienda Sanitaria Universitaria Friuli Centrale Udine Italy
HELIOS Klinikum Erfurt GmbH Erfurt Germany
Hospital Universitario Puerta De Hierro De Majadahonda Majadahonda Spain
Hospital Santa Maria Della Misericordia Perugia Italy
Fundacion Instituto Valenciano De Oncologia Valencia Spain
Johannes Wesling Klinikum Minden Minden Germany
Jasz-Nagykun-Szolnok Varmegyei Hetenyi Geza Korhaz-Rendelointezet Szolnok Hungary
Vychodoslovensky Onkologicky Ustav a.s. Kosice Slovakia
Rheinische Friedrich-Wilhelms-Universitaet Bonn Bonn Germany
University Of Debrecen Debrecen Hungary
Semmelweis University Budapest Hungary
University Of Pecs Pecs Hungary
University Of Szeged Szeged Hungary
Fachklinik Hornheide e.V. Munster Germany
Fakultni nemocnice Olomouc Olomouc Czechia
Czwsypmiw Uezfswqidacqda Secxwvhhv Woluwe-Saint-Lambert Belgium
Phll Pnljfq svkrna Poprad Slovakia
Nokttipe Ojzpgalt Iolbkbkdo Bratislava Slovakia
Mti Hanover Germany
Hcryrjdn Upxfmyqgmd Cbgehja Hlytcvys Helsinki Finland
Awapkuf Okxqbbvteeo Uudqfxnfmemjp Saqktv Siena Italy
Kuzgwqbr dsk Uyfwpzwpexqg Misdydpt Anj Munich Germany
Ufwvkcxtvhghffyseixxi Eaurm Agc Essen Germany
Ingxzt Iptbfpwo Flogwsjcreoxv Oracwrfernf Rome Italy
Hnzrbprp Utnviidozlbvo Mcibqwr Db Vpvgkdgwwx Santander Spain
Myknajiyxxugvcucfjqixkgfhw Hpoaltrbemcyewjz Halle (Saale) Germany
Ltqok Ghskypi Hawolrgw Ov Ajnwbg Athens Greece
Ncazzbza Ilcilwos Oavglvgkk Igo Mjmlj Sdpwjczzxnmxzutyhcutnhotbhvh Ibqgyzpd Bpmmvvtl Cracow Poland
Hmvoermo Uevpouelkvnhb Hditcgyi Trhyg y Pzzpei Ifhzflyn Cfzziq dghryxuiwsdosviqj (wutp Badalona Spain
Hrmkrzon Uimhpbjnnhekh dy A Cqdmwn A Coruna Galicia Spain
Uznqtmyhfz Szekweozvvj Hesescnk Fmu Avjwul Tdkqiynzo Iu Oozltjku Evo Sofia Bulgaria

Want to learn more about this study or check if you can participate? Contact us.

Trial status

Country Status Recruitment Start
Belgium Belgium
Not recruiting
15.01.2021
Bulgaria Bulgaria
Not recruiting
15.01.2021
Czechia Czechia
Not recruiting
15.01.2021
Finland Finland
Not recruiting
15.01.2021
Germany Germany
Not recruiting
15.01.2021
Greece Greece
Not recruiting
15.01.2021
Hungary Hungary
Not recruiting
15.01.2021
Italy Italy
Not recruiting
15.01.2021
Poland Poland
Not recruiting
15.01.2021
Slovakia Slovakia
Not recruiting
15.01.2021
Spain Spain
Not recruiting
15.01.2021

Trial locations

Encorafenib is a medication used in this trial to target specific cancer cells with a mutation known as BRAF V600E/K. It works by blocking the activity of a protein that promotes cancer cell growth, helping to slow down or stop the progression of the melanoma.

Binimetinib is another medication used in combination with encorafenib. It targets a different protein in the cancer cell growth pathway, which helps to enhance the effect of encorafenib and further inhibit the growth of melanoma cells.

Pembrolizumab is an immunotherapy drug used in this trial. It works by helping the immune system recognize and attack cancer cells. Pembrolizumab blocks a specific protein that prevents the immune system from attacking the cancer, thereby boosting the body’s natural defenses against the melanoma.

Metastatic or unresectable locally advanced BRAF V600E/K mutation positive melanoma – This is a type of skin cancer that has spread to other parts of the body or cannot be surgically removed. It is characterized by a specific mutation in the BRAF gene, known as V600E or V600K. This mutation leads to uncontrolled cell growth and division, contributing to the progression of melanoma. The disease often begins as a change in the appearance of a mole or a new skin growth. Over time, it can invade nearby tissues and spread to distant organs. The progression of this melanoma can vary, but it typically involves the development of new tumors in other parts of the body.

Trial ID:
2024-512038-13-00
Protocol code:
C4221016
NCT ID:
NCT04657991
Trial Phase:
Therapeutic confirmatory (Phase III)

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