Efficacy of Daromun Neoadjuvant Intratumoral Treatment in Clinical Stage IIIB/C Melanoma Patients (Neo-DREAM)

This clinical study is being conducted for research purposes. The study medication, the combination of the two drugs L19IL2 and L19TNF ("Daromun"), is being investigated for the treatment of metastatic melanoma (skin cancer). The purpose of this clinical study is to test if Daromun neoadjuvant (before surgery) treatment followed by surgery and adjuvant (after surgery) therapy prolongs the time to disease relapse (recurrence-free survival, RFS) of compared to the standard of care (surgery and adjuvant therapy) for melanoma patients.

The study medication, Daromun, is a new, investigational substance that has not yet been licensed by the regulatory authorities. The term “investigational” means that it has not been approved by the U.S. Food and Drug Administration (FDA) and it must be tested to see if it is a safe and effective treatment for the disease or condition being studied. Daromun belongs to the immunocytokine (i.e., cytokines attached to an antibody) class of drugs. These drugs have been developed in the past few years and function by allowing a specific accumulation of the cytokines IL2 and TNF (which stimulate the immune system and have tumor killing activity) in the melanoma, thanks to the binding ability of the antibody (the L19).

The study treatment consists of the study medication, which will be administered prior to complete surgery of all melanoma metastases and its efficacy will be compared to that of surgery alone. You will receive either the test drug Daromun followed by surgery and adjuvant therapy, or surgery and adjuvant therapy. Whether you receive the study drug plus surgery and adjuvant therapy or surgery and adjuvant therapy will be determined randomly, that is, by chance. In this study, 1 out of every 2 participants will receive surgery and adjuvant therapy. If you will be assigned to the group of participants who receive surgery and adjuvant therapy only, you'll be receiving the standard of care for melanoma at this stage of disease progression.

If you agree to participate in this study, your participation may last up to 72 months. If you take part in the clinical study and are assigned to Arm 1, your treatment will begin soon after end of the initial examination. The study is expected to last for a maximum of nine weeks (four weeks treatment, followed by a safety visit at week 5 and surgery within a maximum of additional 4 weeks), during which time you will make 5 or 6 visits to the study center. Visits to receive study treatment will be scheduled approximately once per week. Follow-up visits will occur every three months after randomization, up to a maximum of 36 months, then every six months from 36 to 60 months and through a dedicated survey via a phone call every six months up to 72 months.

If you take part in the clinical study and are assigned to Arm 2, you will receive surgery to remove all your melanoma metastases within a maximum of four weeks from the date of randomization. Follow-up visits will occur every three months after randomization, up to a maximum of 36 months, every six months from 36 to 60 months and through a dedicated survey via a phone call every six months up to 72 months.

In order to participate you must meet the following criteria:

• Diagnosis of clinical stage IIIB and IIIC (AJCC v7) metastatic melanoma, eligible for complete surgical resection of all metastases (surgically resectable).
• Eligible subjects must have measurable disease and must be candidate for intralesional therapy with at least one injectable cutaneous, subcutaneous, or nodal melanoma lesion (≥ 10 mm in longest diameter) or with multiple injectable lesions that in aggregate have a longest diameter of ≥ 10 mm.
• Males or females, age ≥ 18 years with ECOG Performance Status/WHO Performance Status ≤ 1

You will be excluded from the study if any of the following criteria apply to you:

• Uveal melanoma or mucosal melanoma
• Evidence of distant metastases at screening

This is a partial list of eligibility requirements.