Study to Evaluate Impact® As Support to Anti PD1 Treatment in Patients with Inoperable Locally Advanced or Metastatic Melanoma

This is a monocentric, prospective study evaluating the effectiveness in reducing immune-related adverse events, and translational study conducted on 20 patients with inoperable locally advanced or metastatic melanoma.

The patients will be treated with Oral Impact® administered at the dose of two bricks/day for 21 days + one brick/day for 14 days, starting exactly one week before Anti PD-1 treatment (nivolumab) as per clinical practice, administered up to two years.

The comparison will be done with historical literature data on patients matched by age, sex, disease stage, and therapy dosage, not treated with Impact.


Eligibility Criteria:
Inclusion Criteria:

1. Age \> 18 years;
2. Histologically confirmed stage III (unresectable) or stage IV Cutaneous Melanoma;
3. PD-L1 expression in the medium-high range;
4. Nivolumab planned as per standard clinical practice and decision by the treating oncologist;
5. Measurable disease by computed tomography (CT) or Magnetic Resonance Imaging (MRI) per RECIST 1.1 criteria;
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1;
7. Screening laboratory values must meet the following criteria before starting the treatment:

   1. WBCs ≥2000/μL
   2. Neutrophils ≥1500/μL
   3. Platelets ≥100 x 10³/μL
   4. Hemoglobin ≥9.0 g/dL
   5. Serum creatinine of ≤1.5 times the upper normal limits or creatinine clearance \>40 mL/minute
   6. AST ≤ 3 times the upper normal limits
   7. ALT ≤ 3 times the upper normal limits
   8. Total bilirubin ≤1.5 times the upper normal limits (except patients with Gilbert Syndrome who must have total bilirubin \<3.0 mg/dL)
8. Prior palliative radiotherapy must have been completed at least 2 weeks prior to study drug administration;
9. Patients of reproductive potential, must use adequate contraception methods;
10. Signed written consent form;

Exclusion Criteria:

1. Active brain metastases;
2. Low PD-L1 expression;
3. Patients with previous malignancies unless a complete remission was achieved at least 2 years prior to study entry;
4. Patients with prior systemic anticancer therapy for unresectable or metastatic melanoma;
5. Any serious or uncontrolled medical disorder or active infection that, in the opinion of the investigator, may increase the risk associated with study participation, study drug administration, or would impair the ability of the patient to receive protocol therapy;
6. Presence of active, known, or suspected autoimmune disease;
7. Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of treatment;
8. Participation in any interventional drug or medical device study within 30 days prior to treatment start;
9. Patients with active hepatitis B (defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) or active C hepatitis;
10. History of severe hypersensitivity reactions to other monoclonal antibodies;
11. Pregnant and breast-feeding women;
12. Patients of reproductive who refuse to use effective methods of contraception.