Superficial spreading melanoma stage III Trials in Disease

Study on the Effectiveness of L19IL2 and L19TNF Injections with Surgery for Patients with Stage IIIB/C Melanoma

This trial is testing a treatment called Daromun for patients with Stage IIIB or IIIC melanoma that can be completely removed by surgery. Daromun combines two medications, Darleukin and Fibromun, which are injected directly into the tumor to help the body's immune system fight cancer cells.

Who can join this study:

• Adults aged 18 or older with Stage IIIB or IIIC melanoma that can be surgically removed
• Must have at least one tumor that is 10 mm or larger that can be injected
• Life expectancy of more than 24 months
• Able to carry out light work or activities (performance status of 1 or less)
• Adequate blood counts: neutrophils greater than 1.5 x 10⁹/L, hemoglobin greater than 9.0 g/dL, platelets greater than 100 x 10⁹/L
• Liver enzymes (ALT and AST) at or below 2.5 times the normal limit
• Kidney function (serum creatinine) less than 1.5 times the normal limit
• LDH at or below 1.5 times the normal limit
• Total bilirubin at or below 30 μmol/L
• Negative tests for HIV, Hepatitis B, and Hepatitis C
• Women of childbearing potential must have a negative pregnancy test and use highly effective birth control during the study and for three months after treatment
• Men with partners who can have children must use two forms of birth control during the study and for three months after treatment

Who cannot join this study:

• Patients with any other type of cancer besides melanoma
• Those who have not fully recovered from previous cancer treatments
• Patients with autoimmune diseases, where the immune system attacks the body
• Those with active infections that are not controlled or treated
• Pregnant or breastfeeding women
• Patients with a history of severe allergic reactions to similar treatments
• Those with significant heart problems or uncontrolled high blood pressure
• Patients with severe liver or kidney disease
• Those participating in another clinical trial

What the study involves: The main goal is to see if using Daromun before surgery can improve the time patients remain free from cancer recurrence compared to surgery alone. Participants are randomly assigned to receive either Daromun injections directly into their tumors followed by surgery, or just surgery alone. Both groups receive standard post-surgery treatments to help prevent the cancer from returning. Throughout the study, patients attend regular follow-up visits for physical exams, imaging tests, and laboratory tests to monitor their health and treatment effectiveness.

The investigational drug Daromun contains special proteins called bifikafusp alfa and onfekafusp alfa, which are designed to help the immune system recognize and destroy cancer cells. It is given as an injection directly into the tumor site.

Study on the Safety and Effects of ATL001 and Nivolumab for Adults with Metastatic or Recurrent Melanoma

This trial is testing a personalized cell therapy called ATL001, either alone or in combination with nivolumab (brand name OPDIVO), for patients with metastatic or recurrent melanoma. ATL001 uses the patient's own immune cells, specifically T cells, which are modified to better recognize and attack cancer cells.

Who can join this study:

• Adults at least 18 years old
• Confirmed diagnosis of metastatic or recurrent melanoma through a tissue sample
• Life expectancy of at least 6 months at the time of tissue collection
• Measurable disease according to specific criteria
• Performance status of 0-1, meaning fully active or having some symptoms but able to care for themselves
• Must have previously received a PD-1/PD-L1 inhibitor and experienced disease progression or stable disease after at least 4 doses
• Patients with BRAF V600 mutation must have received targeted therapy for this mutation
• Adequate organ function shown by specific blood test results
• Medically fit to undergo all study procedures including blood and tumor tissue collection
• Women of childbearing potential must use very effective birth control during the study and for at least 12 months after receiving ATL001
• Male patients must use acceptable birth control for at least 6 months after receiving ATL001
• Women in certain groups receiving nivolumab must use effective birth control for at least 5 months after the last dose

Who cannot join this study:

• Patients with other types of cancer besides metastatic or recurrent melanoma
• Those unable to give informed consent
• Pregnant or breastfeeding women
• Patients with certain medical conditions that might interfere with the study or be worsened by treatment
• Those currently participating in another clinical trial
• Patients who recently had major surgery or are still recovering from surgery
• Those with a history of severe allergic reactions to similar treatments
• Patients with active infections requiring treatment
• Those with a history of substance abuse that might interfere with the study

What the study involves: The purpose is to evaluate the safety and effectiveness of ATL001 alone and in combination with nivolumab. After an initial assessment, a procedure is performed to collect tumor tissue, which is used to manufacture the personalized ATL001 treatment. Before receiving ATL001, patients undergo a process called lymphodepletion using medications (fludarabine and cyclophosphamide) to reduce the number of immune cells in the body. ATL001 is then administered as an infusion directly into the bloodstream. Some patients also receive nivolumab, which helps the immune system fight cancer by blocking a protein that prevents the immune system from attacking cancer cells. Regular follow-up visits include physical examinations, imaging tests, and laboratory tests to monitor response and side effects.

The investigational drug ATL001 is a personalized therapy that activates T cells specifically reactive to neoantigens, which are unique markers found on cancer cells. Nivolumab is a checkpoint inhibitor that blocks the PD-1 protein on T cells, enhancing the immune response against cancer cells. Both are administered intravenously in a clinical setting.

Summary

Both ongoing clinical trials for Stage III melanoma are being conducted in Spain, reflecting a concentration of research activity in this country for advanced melanoma treatments. The trials focus on different immunotherapy approaches: one uses direct tumor injections with Daromun to stimulate local immune response before surgery, while the other employs personalized T cell therapy with ATL001, sometimes combined with nivolumab, for patients whose cancer has spread or returned after previous treatment.

These studies represent the evolving landscape of melanoma treatment, moving toward personalized and immune-based therapies. Both trials require careful patient selection based on disease stage, previous treatments, and overall health status. Patients interested in participating should discuss eligibility criteria with their healthcare providers to determine if either trial might be appropriate for their specific situation.