Phase II Study to Assess the Safety and Immunogenicity of recMAGE-A3+AS15 ASCI With or Without Poly IC:LC

A Randomized Phase II Study to Assess the Safety and Immunogenicity of recMAGE-A3+AS15 ASCI With or Without Poly IC:LC in Patients With Resected MAGE-A3 Positive, Stage IV Melanoma

The overall purpose of this research study is to find a better way to treat melanoma.

The goals of this study are:

1. To measure the side effects of and find out how well patients tolerate the recMAGE-A3 + AS15 ASCI (MAGE-A3 ASCI) treatment with or without the Poly IC:LC
2. To see how well the patient's immune system responds to the MAGE-A3 ASCI treatment with or without the Poly IC:LC
3. To measure the rate of return of the patient's tumor after the MAGE-A3 ASCI treatment with or without the Poly IC:LC
4. To measure the rate of return of the patient's tumor in two groups of patients: one group positive for the gene signature, and the other group not positive for the gene signature in their tumor after the MAGE-A3 ASCI treatment with or without the Poly IC:LC.

In the first year, participants may receive up to 8 injections given in the following order:

1. 5 ASCI injections with or without Poly IC:LC with a 3-week interval between each.

2. 3 ASCI injections with or without Poly IC:LC with a 3-month interval between each.

   During years 2 through 3, participants may receive up to 5 ASCI injections with or without Poly IC:LC given in the following order:

3. During year 2, ASCI injections with or without Poly IC:LC will be given every 3 months for a total of up to 3 injections.

4. During year 3, ASCI injections with or without Poly IC:LC will continue to be given every 3 months for a total of up to 2 more injections.

Inclusion Criteria:

• Written informed consent for the study will be obtained prior to the performance of MAGE-A3 expression screening on resected tumor tissue or any other protocol-specific procedure.
• Male or female patient with histologically proven and completely resected stage IV cutaneous or mucosal melanoma. In terms of the American Joint Committee on Cancer (AJCC) classification [AJCC, 2009], this means that patients with resected M1a-b-c (stage IV) disease may be enrolled.
• The patient must have been surgically rendered free of disease no more than 12 weeks before the randomization.
• Patient is equal to or greater than 18 years old at the time of signing the informed consent form.
• The patient's tumor shows expression of the MAGE-A3 gene, as determined by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) analysis on paraffin imbedded tumor tissue (FFPE). In all patients in whom it can be obtained, a frozen portion of the resected tumor will be analyzed for gene profiling.
• The patient has fully recovered from surgery.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at the time of randomization.
• The patient must have adequate bone-marrow reserve, adequate renal function and adequate hepatic function as assessed by standard laboratory criteria: Absolute neutrophil count (ANC) equal to or greater than 1.5 x 10^9/L, Platelet count equal to or greater than 75 x 10^9/L, Serum creatinine equal to or less than 1.5 times the Upper Limit of Normal (ULN), Total bilirubin equal to or less than 1.5 times the ULN, Transaminase (ALT - AST) equal to or less than 2.5 times the ULN
• If the patient is female, she must be of non-childbearing potential, i.e. have a current tubal ligation, hysterectomy, ovariectomy or be post menopausal, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to randomization, have a negative pregnancy test and continue such precautions during the entire study treatment period and for 2 months after completion of the injection series.
• Men must also agree to use an adequate method of contraception.
• In the opinion of the investigator, the patient can and will comply with all the requirements of the protocol.

Exclusion Criteria:

• The patient has an ocular melanoma.
• The patient has in-transit metastases.
• The patient has been treated or is scheduled to be treated with an adjuvant anticancer therapy after the metastasectomy that qualifies the patient for inclusion in the present trial.
• One prior systemic treatment with an immunomodulator (i.e., interferon, vaccine and/or anti-CTLA-4) after a previous surgery is permitted, provided that the last dose has been administered at least 45 days before randomization in the present trial.
• Previous radiotherapy is permitted, provided that the treatment has been completed before the surgery that qualifies the patient for participation in the present trial.
• The patient requires concomitant chronic treatment (more than 7 consecutive days) with systemic corticosteroids or any other immunosuppressive agents. The use of prednisone, or equivalent, at a dose of < 0.125 mg/kg/day (absolute maximum 10 mg/day) or topical steroids is permitted.
• Use of any investigational or non-registered product (drug or vaccine) other than the study treatment within 30 days preceding the randomization or planned use during the study period.
• The patient has a history of autoimmune disease such as, but not limited to, multiple sclerosis, lupus, and inflammatory bowel disease. Patients with vitiligo are not excluded.
• The patient has a family history of congenital or hereditary immunodeficiency.
• The patient is known to be positive for Human Immunodeficiency Virus (HIV) or has another confirmed or suspected immunosuppressive or immunodeficient condition.
• History of allergic disease or reactions likely to be exacerbated by any component of the treatments.
• The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the trial procedures.
• The patient has concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
• The patient has previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers or carcinoma in situ of the cervix or effectively treated malignancy that has been in remission for over 5 years and is highly likely to have been cured.
• The patient has an uncontrolled bleeding disorder.
• For female patients: the patient is pregnant or lactating.