Ongoing Clinical Trials for Malignant Melanoma Stage IV
There are currently 9 clinical trials investigating new treatments for patients with Stage IV melanoma across Europe. These trials are testing various combinations of targeted therapies, immunotherapies, and personalized treatments to improve outcomes for patients with advanced melanoma.
Clinical trial locations
- Austria
- Belgium
- Study of Encorafenib, Binimetinib, and Pembrolizumab for Patients with Advanced Melanoma with BRAF V600E/K Mutation
- Study of Nivolumab and Relatlimab for Patients with Stage III-IV Melanoma After Surgery
- Study of Regorafenib with BRAF/MEK-Inhibitor Combination for Patients with Advanced Melanoma After Previous Treatment
- Bulgaria
- Czechia
- Denmark
- Finland
- France
- Germany
- Study of Encorafenib, Binimetinib, and Pembrolizumab for Patients with Advanced Melanoma with BRAF V600E/K Mutation
- Study of Encorafenib, Binimetinib, and Pembrolizumab for Patients with BRAF V600E/K Mutation-Positive Melanoma After Anti-PD-1 Therapy
- Study of Nivolumab and Relatlimab for Patients with Stage III-IV Melanoma After Surgery
- Study on the Effectiveness and Safety of RO7198457 and Pembrolizumab for Patients with Untreated Advanced Melanoma
- Greece
- Hungary
- Italy
- Study of Encorafenib, Binimetinib, and Pembrolizumab for Patients with Advanced Melanoma with BRAF V600E/K Mutation
- Study of Encorafenib, Binimetinib, and Pembrolizumab for Patients with BRAF V600E/K Mutation-Positive Melanoma After Anti-PD-1 Therapy
- Study of Nivolumab and Relatlimab for Patients with Stage III-IV Melanoma After Surgery
- Netherlands
- Norway
- Poland
- Romania
- Slovakia
- Study of Encorafenib, Binimetinib, and Pembrolizumab for Patients with Advanced Melanoma with BRAF V600E/K Mutation
- Study of Encorafenib, Binimetinib, and Pembrolizumab for Patients with BRAF V600E/K Mutation-Positive Melanoma After Anti-PD-1 Therapy
- Study of INCB099280 and Ipilimumab for Patients with Advanced Solid Tumors
- Spain
- Study of Encorafenib, Binimetinib, and Pembrolizumab for Patients with Advanced Melanoma with BRAF V600E/K Mutation
- Study of Encorafenib, Binimetinib, and Pembrolizumab for Patients with BRAF V600E/K Mutation-Positive Melanoma After Anti-PD-1 Therapy
- Study of Nivolumab and Relatlimab for Patients with Stage III-IV Melanoma After Surgery
- Study on the Effectiveness and Safety of RO7198457 and Pembrolizumab for Patients with Untreated Advanced Melanoma
- Study on the Safety and Effects of ATL001 and Nivolumab for Adults with Metastatic or Recurrent Melanoma
- Sweden
Study of Regorafenib with BRAF/MEK-Inhibitor Combination for Patients with Advanced Melanoma After Previous Treatment
This trial is taking place in Belgium and focuses on patients with advanced melanoma who have a specific genetic mutation called BRAF V600. The study examines whether adding regorafenib to existing BRAF and MEK inhibitor treatments can improve outcomes for patients who have already received prior therapy.
Main inclusion criteria: Participants must be at least 18 years old with advanced melanoma that cannot be removed by surgery. They need to have tried and not fully responded to previous treatments with immunotherapy and, if they have the BRAF V600 mutation, targeted therapy. Women of childbearing age must use effective contraception, and all participants must have adequate organ function and be able to swallow pills.
Main exclusion criteria: Patients who have not been diagnosed with melanoma or have not experienced disease progression while on BRAF-MEK inhibitor therapy are excluded. Those who stopped these treatments more than 12 weeks ago or who belong to vulnerable populations also cannot participate.
Focus of the trial: The study aims to determine if adding regorafenib to BRAF/MEK inhibitor combinations can slow disease progression and improve survival rates. Researchers will track how tumors respond to treatment, monitor side effects, and measure how long patients live without their disease worsening.
Investigational drugs: Regorafenib is an oral medication that blocks multiple proteins involved in tumor growth. It is being tested alongside BRAF inhibitors, which target the BRAF protein that drives cancer cell growth, and MEK inhibitors, which block another protein in the same cancer growth pathway.
Study to Evaluate IOpener-Melanoma Test for Predicting Response to Immunotherapy in Stage III or IV Skin Melanoma Patients
This trial, conducted in the Netherlands, evaluates a diagnostic test called IOpener-melanoma that helps predict which patients with advanced melanoma will respond better to immunotherapy treatments. Based on test results, patients receive either combination immunotherapy or single-agent treatment.
Main inclusion criteria: Participants must be 18 years or older with unresectable stage III or stage IV cutaneous melanoma and have a life expectancy of more than three months. Patients with treated or symptom-free brain metastases may participate. All participants must provide sufficient tumor tissue for testing and give written informed consent.
Main exclusion criteria: Patients with uveal melanoma or mucosal melanoma cannot participate. Those who have already received treatment for advanced melanoma, are unable to provide adequate tumor tissue, have serious medical conditions affecting safety, are pregnant or breastfeeding, or have a history of other cancers that could interfere with results are excluded.
Focus of the trial: The primary goal is to determine whether the IOpener-melanoma test can accurately predict treatment response and guide therapy selection. Researchers will measure progression-free survival, overall survival, disease control rates, and quality of life to assess whether personalized treatment selection improves outcomes.
Investigational drugs: The IOpener-melanoma test itself is the main investigational component, helping doctors choose between combination immunotherapy (such as nivolumab plus ipilimumab) or single-agent therapy (pembrolizumab or nivolumab alone). These immunotherapies help the immune system recognize and attack cancer cells.
Study of Encorafenib, Binimetinib, and Pembrolizumab for Patients with Advanced Melanoma with BRAF V600E/K Mutation
This large international trial spans 11 countries including Belgium, Bulgaria, Czechia, Finland, Germany, Greece, Hungary, Italy, Poland, Slovakia, and Spain. It tests a three-drug combination of encorafenib, binimetinib, and pembrolizumab against a control group receiving pembrolizumab with placebo.
Main inclusion criteria: Participants must be at least 18 years old with histologically confirmed metastatic or unresectable melanoma that has a BRAF V600E or V600K mutation. They should not have received more than one previous treatment (for the Phase 3 part, no previous treatment is allowed). Patients must have at least one measurable tumor and good general health with an ECOG performance status of 0 or 1.
Main exclusion criteria: Patients with cancer types other than the specific melanoma being studied, serious heart, liver, or kidney problems, uncontrolled infections, pregnancy, breastfeeding, or those unable to follow study procedures are excluded.
Focus of the trial: The study evaluates whether the triple combination of encorafenib, binimetinib, and pembrolizumab is more effective than pembrolizumab alone in treating previously untreated advanced melanoma with BRAF mutations. The trial will measure tumor response, progression-free survival, and overall survival over up to 24 months.
Investigational drugs: Encorafenib and binimetinib are oral medications that block proteins driving cancer growth in BRAF-mutated melanoma. Pembrolizumab is an immunotherapy given by infusion that helps the immune system detect and fight cancer cells by blocking the PD-1 protein.
Study of Encorafenib, Binimetinib, and Pembrolizumab for Patients with BRAF V600E/K Mutation-Positive Melanoma After Anti-PD-1 Therapy
This trial takes place in Germany, Italy, Poland, Slovakia, and Spain, specifically targeting patients whose melanoma continued to grow despite previous anti-PD-1 immunotherapy treatment.
Main inclusion criteria: Participants must be at least 18 years old with metastatic or unresectable melanoma confirmed by histology and possessing a BRAF V600E or V600K mutation. They must have received only one prior treatment with anti-PD-1 therapy (such as nivolumab or pembrolizumab) and have melanoma that is resistant to this treatment. Patients must have good organ function and an ECOG performance status of 0 or 1.
Main exclusion criteria: The trial excludes patients without the appropriate melanoma diagnosis or BRAF mutation, those who have received more than one previous treatment line, and individuals unable to provide informed consent.
Focus of the trial: The study compares the effectiveness of combining encorafenib, binimetinib, and pembrolizumab against the combination of nivolumab and ipilimumab in patients whose cancer has become resistant to anti-PD-1 therapy. The primary goal is to measure overall response rate, with secondary evaluations including progression-free survival and overall survival.
Investigational drugs: Encorafenib and binimetinib are targeted therapies taken orally that inhibit the BRAF and MEK proteins involved in cancer cell growth. Pembrolizumab, nivolumab, and ipilimumab are all immunotherapy medications given by infusion that work by enhancing the immune system’s ability to recognize and destroy cancer cells through different mechanisms.
Study of INCB099280 and Ipilimumab for Patients with Advanced Solid Tumors
This trial is conducted in Norway, Slovakia, and Sweden and studies the combination of an experimental medication called INCB099280 with ipilimumab for patients with various types of advanced solid tumors, including melanoma.
Main inclusion criteria: Participants must be 18 years or older, able to understand and sign informed consent, and have a confirmed diagnosis of solid tumors that can be measured. They must have an ECOG performance score of 0 or 1, a life expectancy of more than three months, and be willing to use contraception to avoid pregnancy during the study and for a specified period afterward.
Main exclusion criteria: Patients who are not within the specified age range, do not meet safety and tolerability requirements, or belong to certain vulnerable populations may be excluded.
Focus of the trial: The primary aim is to assess the safety and tolerability of combining INCB099280 with ipilimumab in treating advanced solid tumors. Researchers will monitor for side effects, determine the appropriate dosage, and evaluate the treatment’s effectiveness in controlling tumor growth.
Investigational drugs: INCB099280 is an experimental immunotherapy medication taken as a film-coated tablet that aims to enhance the body’s immune response against cancer. Ipilimumab is an established immunotherapy given by infusion that works by blocking a protein on immune cells, allowing them to better attack cancer cells.
Study of INCB099280 for Patients with Advanced Solid Tumors Who Have Not Received Immunotherapy
This trial is being conducted in Greece, Hungary, and Romania and focuses on testing INCB099280 in patients with advanced solid tumors who have not previously received immunotherapy treatment.
Main inclusion criteria: Participants must be at least 18 years old with measurable disease according to specific guidelines and must not have received immunotherapy before. They need an ECOG performance status of 0 or 1 (up to 2 for certain cancer types), a life expectancy exceeding three months, and willingness to use contraception during the study.
Main exclusion criteria: Patients who have already received immunotherapy, have medical conditions not designed to be treated in this study, are outside the specified age range, or belong to vulnerable populations not included in the study design are excluded.
Focus of the trial: The study evaluates how safe and tolerable INCB099280 is for immunotherapy-naive patients with advanced solid tumors. It also assesses preliminary effectiveness by measuring objective response rates, disease control, duration of response, progression-free survival, and overall survival over a treatment period of up to 24 weeks.
Investigational drugs: INCB099280 is an oral medication in the form of film-coated tablets, taken twice daily at doses of 400 mg, 600 mg, or 800 mg. It is an immune checkpoint inhibitor that works by modulating the immune system to enhance its ability to fight cancer cells.
Study of Nivolumab and Relatlimab for Patients with Stage III-IV Melanoma After Surgery
This extensive trial is being conducted across 13 countries: Austria, Belgium, Czechia, Denmark, Finland, France, Germany, Greece, Italy, Norway, Romania, Spain, and Sweden. It examines whether combining nivolumab with relatlimab after complete surgical removal of melanoma can better prevent recurrence compared to nivolumab alone.
Main inclusion criteria: Participants must be at least 12 years old (or 18 where local regulations require) with Stage IIIA (with tumor larger than 1 mm in lymph node), IIIB, IIIC, IIID, or Stage IV melanoma that has been completely removed by surgery. All melanoma types are allowed except uveal melanoma, though conjunctival melanoma is permitted. Patients must have no signs of remaining disease confirmed by physical examination and imaging studies within 35 days before starting treatment.
Main exclusion criteria: Patients who have not had their melanoma completely removed by surgery cannot participate.
Focus of the trial: The study measures how effective the combination of nivolumab and relatlimab is compared to nivolumab alone in preventing melanoma from returning after surgery. The primary outcome is the time until recurrence or death, with additional measures including overall survival and quality of life assessments over the course of the trial, which extends until November 2029.
Investigational drugs: Nivolumab is an established immunotherapy given by infusion that blocks the PD-1 protein on immune cells, helping them attack cancer cells. Relatlimab is a newer immunotherapy also given by infusion that targets the LAG-3 protein, providing an additional boost to the immune system’s cancer-fighting ability when combined with nivolumab.
Study on the Effectiveness and Safety of RO7198457 and Pembrolizumab for Patients with Untreated Advanced Melanoma
This trial is being conducted in Germany and Spain and evaluates a novel gene therapy approach using mRNA technology combined with standard immunotherapy for patients who have not yet received treatment for their advanced melanoma.
Main inclusion criteria: Participants must have confirmed advanced melanoma that is either metastatic or unresectable, including recurrent, newly diagnosed Stage IV, or locally advanced Stage IIIC or IIID disease. They must have an ECOG performance status of 0 or 1, a life expectancy of at least 12 weeks, adequate blood and organ function, and measurable disease according to specific guidelines. Patients must not have received prior systemic anti-cancer therapy for advanced melanoma.
Main exclusion criteria: Patients with other types of cancer, those outside the specified age range, vulnerable populations, individuals with medical conditions or taking medications that could interfere with treatment, those who have received certain previous treatments, those with other serious health conditions, and those unable to follow study procedures are excluded.
Focus of the trial: The study compares the combination of RO7198457 and pembrolizumab against pembrolizumab alone in previously untreated advanced melanoma patients. The primary measure is progression-free survival, with additional evaluations of overall survival, response rates, quality of life, and safety over a 24-month period.
Investigational drugs: RO7198457 (Autogene Cevumeran) is an experimental gene therapy product using mRNA technology, given by intravenous infusion, designed to stimulate the immune system to recognize and attack cancer cells. Pembrolizumab (Keytruda) is an established immunotherapy also administered intravenously that blocks the PD-1 pathway, enhancing the immune system’s natural defenses against cancer.
Study on the Safety and Effects of ATL001 and Nivolumab for Adults with Metastatic or Recurrent Melanoma
This trial is taking place in Spain and represents a highly personalized approach to treatment, using a patient’s own modified immune cells to fight melanoma that has spread or returned after previous treatment.
Main inclusion criteria: Participants must be at least 18 years old with metastatic or recurrent melanoma and a life expectancy of at least six months at tissue collection. They must have measurable disease and be medically fit to undergo all study procedures, including tissue collection and receiving lymphodepleting medications. Patients must have an ECOG performance status of 0 or 1, adequate organ function, and must have previously received anti-PD-1/PD-L1 therapy with either disease progression or stable disease after at least four doses. Those with BRAF V600 mutations must have received targeted therapy unless contraindicated.
Main exclusion criteria: Patients with cancer types other than metastatic or recurrent melanoma, those unable to give informed consent, pregnant or breastfeeding women, those with medical conditions that might interfere with the study, participants in other clinical trials, those recovering from major surgery, individuals with severe allergic reactions to similar treatments, those with active infections requiring treatment, and those with substance abuse histories are excluded.
Focus of the trial: The study evaluates the safety and effectiveness of ATL001, a personalized T cell therapy targeting specific cancer mutations, used alone or in combination with nivolumab. Researchers will monitor how well the treatment controls cancer, assess side effects, measure tumor response, and track overall survival until July 2027.
Investigational drugs: ATL001 is a personalized cell therapy created from the patient’s own T cells, which are modified to recognize and attack specific mutations in their cancer cells, then administered by infusion. Nivolumab is an established immunotherapy given intravenously that blocks the PD-1 protein, helping the immune system better recognize and fight cancer cells.
Summary
The nine ongoing clinical trials for Stage IV melanoma reflect several important trends in advanced melanoma treatment. A notable concentration of trials is taking place in Western and Central European countries, with Germany and Spain participating in the most studies. Many trials focus on combination approaches, particularly pairing targeted therapies with immunotherapies for patients with BRAF mutations, or combining different immunotherapy agents to enhance effectiveness.
Several trials specifically target patients whose disease has progressed despite previous immunotherapy, addressing an important unmet need. The studies also showcase innovation in treatment approaches, from diagnostic tests that predict treatment response to personalized cell therapies tailored to individual patients’ tumors. Pembrolizumab and nivolumab are the most frequently studied immunotherapy medications across these trials, often combined with various targeted therapies or other immunotherapy agents.
The trials vary in scope from large international studies spanning more than ten countries to smaller regional investigations. Treatment duration ranges from several months to multiple years, with some follow-up periods extending to 2029. These studies collectively aim to improve outcomes for patients with advanced melanoma through personalized treatment selection, novel drug combinations, and innovative therapeutic approaches.
