Study of Encorafenib, Binimetinib, and Pembrolizumab for Patients with BRAF V600E/K Mutation-Positive Melanoma After Anti-PD-1 Therapy

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What is this study about?

This clinical trial is focused on studying a type of skin cancer called melanoma, specifically in patients who have a mutation known as BRAF V600E/K. This mutation can make the cancer more aggressive and harder to treat. The study is looking at patients whose melanoma has either spread to other parts of the body or cannot be removed by surgery. These patients have already been treated with a type of therapy called anti-PD-1 therapy, which helps the immune system fight cancer, but their cancer has continued to grow.

The purpose of the study is to compare two different treatment combinations to see which is more effective. One group of participants will receive a combination of three medications: encorafenib, binimetinib, and pembrolizumab. The other group will receive a combination of two medications: nivolumab and ipilimumab. These medications are given to help the immune system target and destroy cancer cells. Encorafenib and binimetinib are taken as tablets, while pembrolizumab, nivolumab, and ipilimumab are given through an infusion into a vein.

Participants in the study will be randomly assigned to one of the two treatment groups. The study will last for a period of time, during which participants will receive their assigned treatment and be monitored regularly by the study team. The goal is to see which treatment combination works better in controlling the cancer and improving the participants’ health. The study will also look at the safety of the treatments and any side effects that may occur. Participants will have regular check-ups and tests to track their progress and the effects of the treatment.

1 randomization

Upon joining the study, participants are randomly assigned to one of two groups: the triplet arm or the control arm.

The triplet arm involves treatment with encorafenib, binimetinib, and pembrolizumab. The control arm involves treatment with nivolumab and ipilimumab.

2 treatment administration

Participants in the triplet arm receive encorafenib and binimetinib orally, and pembrolizumab intravenously.

Participants in the control arm receive nivolumab and ipilimumab intravenously.

The specific dosage and frequency of administration are determined by the study protocol and medical team.

3 monitoring and assessments

Regular monitoring is conducted to assess the response to treatment. This includes imaging tests to evaluate tumor size and progression.

Participants undergo routine blood tests and other assessments to monitor health and detect any side effects.

4 response evaluation

The primary goal is to measure the overall response rate (ORR), which is the proportion of participants with a significant reduction in tumor size.

Secondary evaluations include progression-free survival (PFS), overall survival (OS), and duration of response (DOR).

5 completion of study

The study is estimated to conclude by May 23, 2027.

Participants will continue to be monitored for health outcomes and any long-term effects 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 histology test.
Participants must have a specific change in their cancer cells called a BRAF V600E or V600K mutation.
Participants must provide a sample of their tumor for testing in a lab during the screening period.
Participants must have received only one previous treatment for melanoma, which could be either a supportive treatment after surgery or a first treatment using a type of medicine called anti-PD-1 monotherapy, such as nivolumab or pembrolizumab.
Participants must have melanoma that is resistant to anti-PD-1 treatment, meaning the cancer did not respond or stopped responding to this treatment. This must be confirmed by a specific method of measuring disease progression.
Participants must have at least one tumor that can be measured using a specific method called RECIST v1.1.
Participants must have a good general health status, as measured by a scale called ECOG PS, and must have healthy organs and heart function, including a heart test showing a left ventricular ejection fraction (LVEF) of at least 50%.

Who Cannot Join the Study?

Where you can join this trial?

Verified and Recommended Sites

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Verified Sites

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Other Sites

Site Name	City	Country
Istituto Oncologico Veneto	Padua	Italy
F D Roosevelt University General Hospital Of Banska Bystrica	Banska Bystrica	Slovakia
Istituto Europeo Di Oncologia S.r.l.	Milan	Italy
Hospital Universitario 12 De Octubre	Madrid	Spain
Szpital Kliniczny Ministerstwa Spraw Wewnetrznych I Administracji Z Warminsko-Mazurskim Centrum Onkologii W Olsztynie	Olsztyn	Poland
Nemocnica Na Okraji Mesta N.O.	Partizanske	Slovakia
Universitaetsklinikum Tuebingen AöR	Tuebingen	Germany
Istituto Di Candiolo Fondazione Del Piemonte Per Loncologia IRCCS	Candiolo	Italy
Pratia S.A.	Skorzewo	Poland
Uniwersytecki Szpital Kliniczny W Poznaniu	Poznan	Poland
Fondazione I.R.C.C.S. Istituto Neurologico Besta	Milan	Italy
Fachklinik Hornheide e.V.	Munster	Germany
Ptjp Ptqeei sxrxwi	Poprad	Slovakia
Ngvgtqrb Otoqyuiq Izjaptqjw	Bratislava	Slovakia
Ihllxqzf Cmrzwn Dtkabvtaausvbjfap	L'hospitalet De Llobregat	Spain
Nzwgnrgr Iojyhylc Oglaeajzw Irk Mobww Sdaudzmqsyiwbanhfujqnofbhypq Iayjrpyt Bzrqdvnr	Cracow	Poland
Utflbstetnxxnr Cbfnxbl Ktjlcwvrg	Gdansk	Poland

Trial status

Country	Status	Recruitment Start
Germany	Not recruiting	13.06.2023
Italy	Not recruiting	13.06.2023
Poland	Not recruiting	13.06.2023
Slovakia	Not recruiting	13.06.2023
Spain	Not recruiting	13.06.2023

Trial locations

Investigated drugs:

Encorafenib is a medication used to treat melanoma, a type of skin cancer. It works by targeting and inhibiting a specific protein in cancer cells, which helps to slow down or stop the growth of the cancer.

Binimetinib is another medication used in combination with encorafenib to treat melanoma. It targets a different protein in the cancer cells, and when used together with encorafenib, it can enhance the effectiveness of the treatment.

Pembrolizumab is an immunotherapy drug that helps the immune system recognize and attack cancer cells. It is used in combination with encorafenib and binimetinib to treat melanoma, aiming to improve the body’s natural defense against the cancer.

Nivolumab is an immunotherapy medication that also helps the immune system fight cancer. It is used in this trial as part of a combination treatment to compare its effectiveness against other therapies in treating melanoma.

Ipilimumab is another immunotherapy drug used in combination with nivolumab. It works by activating the immune system to attack cancer cells, and is being tested in this trial to see how well it works in treating melanoma compared to other treatments.

Investigated diseases:

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, which leads to uncontrolled cell growth. The disease often begins as a mole or pigmented spot on the skin that changes in size, shape, or color. As it progresses, it can invade nearby tissues and spread to distant organs, such as the lungs, liver, or brain. The presence of the BRAF mutation can influence the behavior of the melanoma and its response to certain treatments. The progression of this melanoma can vary, but it typically involves the growth and spread of cancerous cells beyond the original site.

Trial ID:

2023-509471-17-00

Protocol code:

C4221023

Trial Phase:

Therapeutic exploratory (Phase II)

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Study of Encorafenib, Binimetinib, and Pembrolizumab for Patients with BRAF V600E/K Mutation-Positive Melanoma After Anti-PD-1 Therapy

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