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Study on the Effectiveness and Safety of Naporafenib Combinations in Patients with Previously Treated Unresectable or Metastatic Melanoma

Verified siteInvestigationalNo placebo
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What is this trial about?

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

This clinical trial is focused on studying the effectiveness and safety of different combinations of treatments for patients with a type of skin cancer called melanoma. Specifically, it involves patients who have previously been treated for melanoma that cannot be surgically removed or has spread to other parts of the body. The study is looking at cases where the melanoma has specific genetic changes known as BRAFV600 or NRAS mutations. The treatments being tested in this study include combinations of medications such as ribociclib (also known as LEE011), trametinib dimethyl sulfoxide (TMT212), naporafenib (LXH254), and rineterkib (LTT462). These medications are taken orally in the form of tablets or capsules.

The purpose of the study is to evaluate how well these treatment combinations work in shrinking the tumors and to assess their safety. Participants in the study will receive one of the treatment combinations or a placebo. The study will monitor the response of the cancer to the treatment and any side effects that may occur. The study is divided into two parts and will involve regular check-ups and assessments to track the progress of the treatment.

Throughout the study, participants will undergo various tests and evaluations to measure the effectiveness of the treatment. This includes imaging tests to see how the cancer is responding and regular health check-ups to monitor for any side effects. The study aims to provide valuable information on the potential benefits and risks of these treatment combinations for patients with advanced melanoma.

The research process

The trial runs in 4 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, eligibility is confirmed based on specific criteria, including age, weight, and previous treatment history for melanoma.

    A new tumor biopsy is required at the start and during the treatment phase, following the institution's guidelines.

  2. Step 2

    Treatment phase

    The study involves multiple treatment combinations, each administered orally in the form of tablets or capsules.

    Medications include ribociclib, trametinib dimethyl sulfoxide, naporafenib, and rineterkib, provided in film-coated tablets or hard capsules.

    The specific dosage and frequency of each medication depend on the assigned treatment arm.

  3. Step 3

    Monitoring and assessments

    Regular assessments are conducted to evaluate the response to treatment, using criteria such as the Objective Response Rate (ORR) and RECIST 1.1 guidelines.

    Safety is monitored through the incidence and severity of any adverse events, including changes in laboratory values and vital signs.

  4. Step 4

    Follow-up

    The study aims to assess the duration of response, progression-free survival, and overall survival.

    Participants continue to be monitored for any long-term effects or outcomes related to the treatment.

Who can join the trial?

8 criteria

  • Must be a male or female who is at least 12 years old.
  • If you are between 12 and 17 years old, you must weigh more than 40 kg (about 88 pounds).
  • Must have a type of skin cancer called unresectable or metastatic cutaneous melanoma, which means the cancer cannot be removed by surgery or has spread to other parts of the body.
  • Must have a specific change in the cancer cells called a BRAFV600 or NRAS mutation, confirmed by a test on the tumor tissue.
  • Must have been previously treated for unresectable or metastatic melanoma:
  • If you have the NRAS mutation, you must have received treatment with medicines called checkpoint inhibitors (CPI), which help the immune system fight cancer. These could be anti-PD-1/PD-L1 drugs, either alone or with other treatments like anti-CTLA-4, experimental drugs, chemotherapy, or local treatments.
  • If you have the BRAFV600 mutation, you must have received treatment with checkpoint inhibitors and also a type of treatment called targeted therapy with a drug known as RAFi, either alone or with another drug called MEKi.
  • Must have a place in the body where the disease can be safely biopsied multiple times, and be willing to have a new tumor biopsy before starting the study and during the study.

Who cannot join the trial?

5 criteria

  • Patients who have already received treatment for their melanoma that cannot be removed by surgery or has spread to other parts of the body.
  • Patients with a specific type of melanoma that has a change in the genes called BRAFV600 or NRAS.
  • Patients who are not within the specified age range for the study.
  • Patients who belong to a group that is not included in the study.
  • Patients who are considered part of a vulnerable population, which means they might need special protection or care.
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Investigated drugs

  • LXH254

    is an investigational medication being studied for its potential to treat melanoma, a type of skin cancer. It is being tested in combination with other treatments to see if it can help shrink tumors in patients who have specific genetic mutations in their cancer cells.

  • BRAFV600

    and NRAS are genetic mutations found in some melanoma patients. The study is exploring treatments that target these mutations to see if they can improve outcomes for patients whose cancer has these specific changes.

What is already known about the treatment

LXH254 – This medication is administered orally and is currently being studied in clinical trials for its effectiveness in treating previously treated unresectable or metastatic melanoma with specific genetic mutations (BRAFV600 or NRAS). It is not yet widely used in standard medical practice, as it is still under investigation. The main therapeutic indication is for melanoma that has not responded to other treatments. LXH254 works by targeting specific pathways in cancer cells that are involved in cell growth and survival, aiming to inhibit tumor progression. It is classified as a targeted therapy, focusing on molecular changes in cancer cells.

Investigated diseases

Melanoma – Melanoma is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. It often appears as a new or unusual growth or a change in an existing mole. Melanoma can spread to other parts of the body if not detected early. The disease progresses by invading nearby tissues and potentially spreading to distant organs through the lymphatic system or bloodstream. It is more likely to occur in individuals with fair skin, a history of sunburns, or a family history of the disease. Early detection and monitoring of skin changes are crucial in managing melanoma.
Trial detailsLast updated 2 Oct 2026
Age18+ yearsPhasePhase IITrial ID2024-511934-11-00Protocol codeCLXH254C12201Estimated enrolment251 patientsSponsorNovartis Pharma AG

sourced from the EU Clinical Trials Register and site verification

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