Skip to content
Clinical Trials – home

Rare diseases

Investigational molecules

Locations

Our offerNewsroom

Not recruiting

Study Comparing Naporafenib and Trametinib Combination to Other Therapies for Patients with Previously Treated Unresectable or Metastatic NRAS Mutant Melanoma

Fast replyRegistered drug
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 treatments for unresectable or metastatic NRAS mutant cutaneous melanoma, a type of skin cancer that cannot be removed by surgery and has spread to other parts of the body. The study will explore the effectiveness of a combination of two medications: naporafenib and trametinib. Naporafenib, also known by its code name LXH254, is a medication that targets specific proteins involved in cancer cell growth. Trametinib is another medication that works by inhibiting certain proteins that help cancer cells grow and divide.

The purpose of the study is to compare the combination of naporafenib and trametinib with other treatments chosen by doctors, which may include dacarbazine, temozolomide, or trametinib alone. Dacarbazine and temozolomide are chemotherapy medications that work by damaging the DNA of cancer cells, preventing them from growing. The study will begin with a phase to determine the best dose of the naporafenib and trametinib combination. After this, the main part of the study will compare how well patients do on the combination treatment versus the other treatment options.

Participants in the study will receive their assigned treatment and be monitored over a period of time to assess the effects on their cancer. The study will look at how long patients live without their cancer getting worse and their overall survival. The trial will also monitor the safety of the treatments and any side effects that may occur. This research aims to find the most effective treatment option for patients with this specific type of melanoma.

The research process

The trial runs in 6 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Joining the study

    Upon joining the study, the patient will be informed about the trial's purpose and procedures. Written consent is required to participate.

    Eligibility criteria include being 18 years or older, having a confirmed diagnosis of unresectable or metastatic NRAS mutant cutaneous melanoma, and having previously received an anti-PD-1/L1 based treatment.

  2. Step 2

    Stage 1: dose optimization

    The initial phase involves determining the optimal dose of the combination of naporafenib and trametinib.

    Patients will receive these medications orally. The specific dosage will be adjusted based on safety and effectiveness data collected during this stage.

  3. Step 3

    Stage 2: treatment assignment

    Patients will be randomly assigned to receive either the combination of naporafenib and trametinib or a treatment chosen by the physician, which could be dacarbazine, temozolomide, or trametinib alone.

    The choice of therapy will depend on the patient's specific condition and previous treatments.

  4. Step 4

    Medication administration

    The combination of naporafenib and trametinib is administered orally. Dacarbazine is given intravenously, while temozolomide is taken orally.

    The frequency and duration of administration will be determined by the study protocol and the patient's response to treatment.

  5. Step 5

    Monitoring and assessments

    Regular monitoring will occur to assess the treatment's effectiveness and any side effects. This includes blood tests, imaging studies, and physical examinations.

    Patients will be evaluated for progression-free survival and overall survival, as well as any adverse effects from the medications.

  6. Step 6

    End of study participation

    The study is expected to conclude by July 2028. Participation may end earlier if the patient experiences significant side effects or if the disease progresses.

    Upon completion, patients will receive information about their treatment outcomes and any further steps if necessary.

Who can join the trial?

9 criteria

  • The patient must agree to participate by signing a written consent form.
  • The patient must be at least 18 years old.
  • The patient must have a type of skin cancer called **unresectable or metastatic cutaneous melanoma**, confirmed by a lab test.
  • The patient must have a specific change in their cancer called an **NRAS mutation**, confirmed by a test on tumor tissue or blood.
  • The patient must have a sample of their tumor collected within the last 5 years available for further analysis.
  • The patient must have previously received a treatment called **anti-PD-1/L1 therapy** and shown disease progression during or shortly after this treatment.
  • The patient must have an **ECOG performance status** of 0, 1, or 2, which is a scale that measures how well they can perform daily activities.
  • The patient must have at least one tumor that can be measured by doctors using a standard method called **RECIST v1.1**.
  • The patient must be able to swallow pills.

Who cannot join the trial?

5 criteria

  • Patients who have a type of skin cancer called NRAS mutant cutaneous melanoma that cannot be removed by surgery or has spread to other parts of the body.
  • Patients who are not within the specified age range for the study.
  • Patients who are not part of the specified clinical trial groups.
  • Patients who are not male or female, as both genders are included in the study.
  • Patients who are considered part of a vulnerable population, which means they might need special protection or care.
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

  • Naporafenib

    is an investigational medication being studied for its potential to treat patients with a specific type of skin cancer known as NRAS mutant cutaneous melanoma. It is being tested in combination with another medication to see if it can help improve outcomes for patients whose cancer cannot be surgically removed or has spread to other parts of the body.

  • Trametinib

    is a medication used to treat certain types of skin cancer. In this trial, it is being used both in combination with naporafenib and as a standalone treatment option. The study aims to determine the effectiveness of trametinib when used alone or in combination with naporafenib.

  • Dacarbazine

    is a chemotherapy drug that is used to treat melanoma. In this trial, it is one of the treatment options that doctors can choose for patients. The study is comparing the effectiveness of dacarbazine to other treatments to see which works best for patients with this type of skin cancer.

  • Temozolomide

    is another chemotherapy medication that is used to treat melanoma. It is included in the trial as one of the treatment options available to doctors. The trial is evaluating how well temozolomide works compared to other treatments for patients with NRAS mutant cutaneous melanoma.

What is already known about the treatment

  • Naporafenib

    Naporafenib is administered orally and is currently being studied in clinical trials for its effectiveness in treating unresectable or metastatic NRAS mutant cutaneous melanoma. It is not yet widely used in standard medical practice, as it is still under investigation. The main therapeutic indication for naporafenib is its potential to treat specific types of skin cancer that have a mutation in the NRAS gene. At the molecular level, naporafenib works by inhibiting certain proteins involved in cell growth and division, which may help slow down or stop the growth of cancer cells. It is classified as a kinase inhibitor in pharmacology.

  • Trametinib

    Trametinib is taken orally and is approved for use in treating certain types of melanoma, including unresectable or metastatic NRAS mutant cutaneous melanoma. It is well-documented in medical literature and is used both in combination with other drugs and as a monotherapy. The main therapeutic indication for trametinib is its ability to treat melanoma by targeting and inhibiting MEK proteins, which are part of a pathway that promotes cancer cell growth. This action helps to slow down or stop the progression of the cancer. Trametinib is classified as a MEK inhibitor in pharmacological terms.

Investigated diseases

Unresectable or Metastatic NRAS Mutant Cutaneous Melanoma – This is a type of skin cancer that occurs when melanocytes, the cells responsible for skin pigment, grow uncontrollably. It is characterized by a mutation in the NRAS gene, which can lead to aggressive tumor growth. The term "unresectable" indicates that the cancer cannot be removed completely through surgery. When the disease is metastatic, it means that the cancer has spread from its original site to other parts of the body. The progression of this melanoma can vary, but it often involves the development of new tumors in distant organs. The condition is typically monitored through imaging and clinical evaluations to assess the spread and growth of the cancer.
Trial detailsLast updated 2 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2024-511404-17-00Protocol codeERAS-254-02Estimated enrolment472 patientsSponsorErasca 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.

ClinicalTrials.eu

Every clinical trial in Europe, in plain language.

Explore the full ecosystem of clinical research in Europe.

Search trials

Legal notice · Published by CTIN POLAND sp. z o.o., ul. rtm. Witolda Pileckiego 67/109, 02-781 Warsaw, Poland · KRS 0001111334 · REGON 528919042 · NIP 9512598637

© 2026 Clinical Trials EU – European Clinical Trials Information Network

GDPR compliance, ISO 9001 and ISO 27001 certified (LL-C Certification)

On this site, “treatment” means an investigational medicine being studied in a clinical trial. Its safety and efficacy for the use being studied have not yet been confirmed, some participants may receive a placebo or a comparator medicine, and taking part does not guarantee any health benefit. The decision to take part is made by the doctor at the research site. This site is for information only and does not replace medical advice.

This service is not affiliated with the European Commission, the EMA, or the official CTIS system. Most information comes from publicly available international clinical-trial registries, supplemented by data from academic sites, national regulators and commercial sponsors. On this site, “treatment” and “therapy” mean a medicine being tested in a clinical trial. Its safety and effectiveness in the use being studied are not yet confirmed, some participants may receive a placebo or a comparator, and taking part does not guarantee a health benefit. The doctor at the research site decides who can take part. This site provides information, not medical advice. Certain content and visual elements on this website have been generated or enhanced using artificial intelligence (AI).