In short
Currently, there are 2 clinical trials ongoing for gastrointestinal melanoma. These studies are investigating combination treatments for patients with advanced melanoma that carries a specific genetic mutation called BRAF V600E/K. The trials are testing combinations of targeted therapies and immunotherapies across multiple European countries, including Germany, Italy, Spain, Poland, and Slovakia.
Clinical trial locations
- Belgium
- Bulgaria
- Czechia
- Finland
- Germany
- Greece
- Hungary
- Italy
- Poland
- Slovakia
- Spain
Study of Encorafenib, Binimetinib, and Pembrolizumab for Patients with Advanced Melanoma with BRAF V600E/K Mutation
This trial is investigating a combination treatment approach for patients with advanced melanoma that has spread to other parts of the body or cannot be removed through surgery. The study specifically focuses on melanoma that has a genetic change known as the BRAF V600E/K mutation, which makes the cancer more aggressive.
Main inclusion criteria:
- Patients must be at least 18 years old
- Must have melanoma that cannot be surgically removed or has spread to other parts of the body, confirmed by laboratory testing
- Must have the BRAF V600E or V600K mutation in their cancer cells
- Must provide a tumor tissue sample for laboratory confirmation of the mutation
- Must have at least one measurable tumor
- Must have good overall health with a performance status score of 0 or 1 and healthy organ function, including a heart function test showing at least 50% effectiveness
- For the safety phase: no more than one previous treatment for advanced melanoma
- For the main phase: no previous treatment for advanced melanoma
Main exclusion criteria:
- Other types of cancer not being studied
- Recent treatment with different cancer therapies
- Serious heart, liver, or kidney problems
- Pregnancy or breastfeeding
- Uncontrolled infections
- History of other serious illnesses that could affect the study
- Inability to follow study procedures
Study focus and goal: The trial compares the effectiveness of a three-drug combination (encorafenib, binimetinib, and pembrolizumab) against a control treatment (placebo with pembrolizumab). Participants are randomly assigned to one of these two groups. The study will last up to 24 months and aims to determine whether the three-drug combination improves outcomes for patients with this specific type of melanoma. Regular monitoring and assessments will track both the effectiveness of the treatment and any side effects that occur.
Investigational drugs: Encorafenib is taken as a capsule and works by blocking a protein that promotes cancer cell growth in tumors with the BRAF V600E/K mutation. Binimetinib is taken as a tablet and targets a different protein in the cancer growth pathway, enhancing the effect of encorafenib. Pembrolizumab is given through an infusion into a vein and is an immunotherapy that helps the immune system recognize and attack cancer cells by blocking a protein that prevents the immune system from working effectively against cancer.
Study of Encorafenib, Binimetinib, and Pembrolizumab for Patients with BRAF V600E/K Mutation-Positive Melanoma After Anti-PD-1 Therapy
This trial is designed for patients with melanoma carrying the BRAF V600E/K mutation whose cancer has continued to grow despite previous treatment with anti-PD-1 therapy, a type of immunotherapy. The study is comparing two different treatment combinations to determine which is more effective for patients whose cancer has become resistant to their previous treatment.
Main inclusion criteria:
- Patients must be at least 18 years old
- Must have melanoma that cannot be surgically removed or has spread to other parts of the body, confirmed by laboratory testing
- Must have the BRAF V600E or V600K mutation in their cancer cells
- Must provide a tumor sample for laboratory testing during the screening period
- Must have received only one previous treatment for advanced melanoma, which was either supportive treatment after surgery or anti-PD-1 therapy such as nivolumab or pembrolizumab
- Must have melanoma that is resistant to anti-PD-1 treatment, meaning the cancer did not respond or stopped responding to this therapy
- Must have at least one measurable tumor
- Must have good overall health with healthy organ and heart function, including a heart test showing at least 50% effectiveness
Main exclusion criteria: The trial excludes patients with other types of cancer not being studied, those who have had recent different cancer treatments, those with serious heart, liver, or kidney problems, pregnant or breastfeeding women, patients with uncontrolled infections, those with a history of other serious illnesses that could affect the study, and patients unable to follow study procedures.
Study focus and goal: The trial compares two treatment approaches. One group receives a three-drug combination of encorafenib, binimetinib, and pembrolizumab, while the other receives a two-drug combination of nivolumab and ipilimumab. Participants are randomly assigned to one of these groups. The main goal is to measure the overall response rate, which is the proportion of participants whose tumors shrink significantly. Secondary goals include measuring how long patients live without their disease getting worse, overall survival, and how long the treatment response lasts. The study is expected to conclude by May 2027.
Investigational drugs: Encorafenib and binimetinib are taken as tablets and work by inhibiting specific proteins involved in cancer cell growth in tumors with the BRAF mutation. Pembrolizumab is an immunotherapy given through a vein infusion that helps the immune system fight cancer by blocking the PD-1 pathway. Nivolumab and ipilimumab are also immunotherapy drugs given through vein infusions. Nivolumab works by blocking the PD-1 protein on immune cells, while ipilimumab targets the CTLA-4 protein on T-cells, both enhancing the immune system's ability to attack cancer cells.
Summary
Both ongoing clinical trials for gastrointestinal melanoma focus specifically on advanced disease with the BRAF V600E/K mutation. The trials are concentrated primarily in Central and Southern European countries, with Germany, Italy, Spain, Poland, and Slovakia hosting both studies, while several other countries participate in the first trial only.
A notable feature of these trials is their focus on combination therapies. The first trial tests whether adding targeted therapies (encorafenib and binimetinib) to immunotherapy (pembrolizumab) provides better results than immunotherapy alone for patients who have not yet received treatment for their advanced disease. The second trial addresses a more specific situation, comparing different treatment combinations for patients whose cancer has become resistant to anti-PD-1 immunotherapy.
The investigational drugs appear consistently across both trials, with encorafenib, binimetinib, and pembrolizumab being central to both studies. These medications represent two main treatment approaches: targeted therapy that blocks specific proteins in cancer cells with the BRAF mutation, and immunotherapy that helps the immune system recognize and attack cancer cells. The second trial also includes nivolumab and ipilimumab as an alternative combination treatment option.
Both trials require participants to have laboratory-confirmed BRAF V600E/K mutations and measurable tumors, emphasizing the importance of genetic testing in determining treatment eligibility. The studies also maintain strict health requirements, ensuring participants have adequate organ function and overall health to participate safely in the research.
