Skip to content
Clinical Trials – home

Rare diseases

Investigational molecules

Locations

Our offerNewsroom

Not recruiting

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

Fast replyRegistered drugNo placebo
Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

What is this trial about?

A plain-language summary of the goals, design and what participants do

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.

The research process

The trial runs in 5 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 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. Step 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. Step 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. Step 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. Step 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 trial?

8 criteria

  • 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%.
Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

Tell us about your condition – we search every trial in Europe and connect you with the right site.

We usually reply within a few days

Verified sites

All sites with verified contact details – recruitment status may not be available; ask directly

Trial locations

Where you can join this trial

Countries are shaded by recruitment status. Click a recruiting country to ask about joining there.

Not recruiting
Not finding your country?

Not sure what to do next?

Joining a clinical trial can seem overwhelming. We guide you step by step, so you know exactly what to expect and how we support you through the process.

See the full process and FAQ

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.

What is already known about the treatment

  • Encorafenib

    This medication is administered orally and is currently being studied in clinical trials for its effectiveness in treating melanoma with specific genetic mutations. It is primarily used for patients with BRAF V600E/K mutation-positive melanoma that is either metastatic or cannot be surgically removed. Encorafenib works by inhibiting the BRAF protein, which is involved in cell growth, thereby slowing down or stopping the growth of cancer cells. It is classified as a BRAF inhibitor.

  • Binimetinib

    Administered orally, binimetinib is under investigation in clinical trials for its role in treating certain types of melanoma. It is used in combination with other medications for patients with BRAF V600E/K mutation-positive melanoma. Binimetinib functions by inhibiting the MEK proteins, which are part of a pathway that promotes cell division and survival, thus helping to control cancer growth. It belongs to the class of MEK inhibitors.

  • Pembrolizumab

    This medication is given through intravenous infusion and is being evaluated in clinical trials for its use in melanoma treatment. It is indicated for patients with BRAF V600E/K mutation-positive melanoma, particularly those who have not responded to previous treatments. Pembrolizumab works by blocking the PD-1 pathway, enhancing the immune system's ability to detect and fight cancer cells. It is classified as an immune checkpoint inhibitor.

  • Nivolumab

    Administered via intravenous infusion, nivolumab is part of ongoing clinical trials for its application in melanoma therapy. It is used for patients with BRAF V600E/K mutation-positive melanoma, especially after other treatments have failed. Nivolumab acts by inhibiting the PD-1 protein on immune cells, boosting the body's immune response against cancer cells. It is categorized as an immune checkpoint inhibitor.

  • Ipilimumab

    This medication is delivered through intravenous infusion and is being studied in clinical trials for its effectiveness in treating melanoma. It is used in combination with other drugs for patients with BRAF V600E/K mutation-positive melanoma. Ipilimumab works by targeting the CTLA-4 protein on T-cells, enhancing the immune system's ability to attack cancer cells. It is classified as an immune checkpoint inhibitor.

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 detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IITrial ID2023-509471-17-00Protocol codeC4221023Estimated enrolment141 patientsSponsorPfizer Inc.

sourced from the EU Clinical Trials Register and site verification

Want to learn more about this trial or check if you can participate?

Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

Tell us about your condition – we search every trial in Europe and connect you with the right site.