Combination Therapy With Nivolumab and PD-L1/IDO Peptide Vaccine to Patients With Metastatic Melanoma

Inclusion Criteria

• Age ≥ 18
• The patient has unrespectable or metastatic melanoma with progressive, persistent or recurrent disease on or following treatment with standard of care agents
• Patients belonging to one of the following patient groups will be enrolled:

Cohort A: Anti PD-1/PD-L1 naïve patients (30 patients). The patient is a candidate for Nivolumab monotherapy. Prior anti-PD-1/anti-PD-L1 antibody treatment is not allowed.

OR Cohort B: Extension cohort (10 patients). Progressive disease ON anti-PD-1 monotherapy.Subjects should not have experienced serious and/or life-threatening toxicity to antibody therapy.

OR Cohort C: Extension cohort (10 patients). Progressive disease during follow up OFF anti-PD-1 after clinical benefit (SD/PR/CR) on anti-PD-1 therapy. Subjects should not have discontinued antibody therapy due to serious and/or lifethreatening toxicity

• At least one measurable parameter according to RECIST 1.1.
• The patient has an ECOG performance status of 0 or 1
• The patient is a female of childbearing potential with negative pregnancy test
• For women: Agreement to use contraceptive methods with a failure rate of 1,5 ULN
• Serum creatinine ≤1,5 X ULN
• ANC (Absolute Neutrophil Count) ≥1,000/mcL
• Platelets ≥ 75,000 /mcL
• Hemoglobin ≥ 9 g/dL eller ≥ 5.6 mmol/L
• Signed declaration of content after oral and written information about the protocol.

Exclusion Criteria

• The patient has not recovered to grade 0-1 from adverse events due to prior chemotherapy, radioactive or biological cancer therapy
• The patient has not recovered from surgery or is less than 4 weeks from major surgery
• The patient has a history of life-threatening or severe immune related adverse events on treatment with another immunotherapy and is considered to be at risk of not recovering
• The patient is expected to require any other form of systemic antineoplastic therapy while receiving the treatment
• The patient has a history of severe clinical autoimmune disease
• The patient has a history of pneumonitis, organ transplant, human immunodeficiency virus positive, active hepatitis B or hepatitis C
• The patient requires systemic steroids for management of immune-related adverse events experienced on another immunotherapy
• The patient has active CNS metastases and/or carcinomatous meningitis. However, patients with subclinical brain metastases < 1 cm can be included (maximum of 4 metastases < 1 cm). (Patients with previously treated brain metastases may participate provided they are clinically stable. Patients with untreated brain metastasis will be excluded)
• The patient has any condition that will interfere with patient compliance or safety (including but not limited to psychiatric or substance abuse disorders)
• The patient is pregnant or breastfeeding
• The patient is unable to voluntarily agree to participate by signed informed consent or assent
• The patient has an active infection requiring systemic therapy
• The patient has received a live virus vaccine within 30 days of planned start of therapy
• Known side effects to Montanide ISA-51
• Significant medical disorder according to investigator; e.g. severe asthma or chronic obstructive lung disease, dysregulated heart disease or dysregulated diabetes mellitus
• Concurrent treatment with other experimental drugs
• Any active autoimmune diseases e.g. autoimmune neutropenia, thrombocytopenia or hemolytic anemia, systemic lupus erythematosus, scleroderma, myasthenia gravis, autoimmune glomerulonephritis, autoimmune adrenal deficiency, autoimmune thyroiditis etc.
• Severe allergy or anaphylactic reactions earlier in life