A Study to Test the Benefit of a New Anti-cancer Treatment in Patients With Unresectable Advanced Melanoma

GSK2132231A Antigen-Specific Cancer Immunotherapeutic as First-line Treatment of Patients With Unresectable Metastatic Melanoma

The objective of this study is to evaluate the clinical activity of the GSK2132231A immunotherapeutic in patients with MAGE-A3 positive unresectable metastatic melanoma presenting with the predictive gene signature.

In this study, patients were to receive a maximum of 24 doses of recMAGE-A3 + AS15 according four cycles over a period of four years. An active follow-phase (up to five years after registration into the study) was planned for all patients.

As of Amendment 2, there will no longer be an active follow-up of patients after discontinuation or completion of the treatment. The study will end approximately 30 days after the last dose will be administered.

In addition, no more biological samples will be collected for protocol research purposes. For each biological sample already collected in the scope of this study and not tested yet, testing will not be performed by default, except if a scientific rationale remains relevant.

Blood sampling for safety monitoring as per protocol will continue.

Inclusion Criteria:

• Male or female patients with histologically proven metastatic cutaneous melanoma that is measurable.
• Patients with regional or distant cutaneous, subcutaneous or lymph-node metastasis can be included in the study, provided the disease is not amenable to curative treatment with surgery. In terms of the AJCC 2002 classification, this includes patients with unresectable stage III melanoma including in-transit metastases or patient with stage IV M1a melanoma.
• Written informed consent obtained from the patient prior to performance of any study specific procedure.
• Patient is >= 18 years at the time of signature of the informed consent form.
• The patient's tumor shows expression of MAGE-A3, as determined by RT-PCR analysis on a fresh tumor tissue sample obtained during the screening phase.
• Fresh tissue from the same lesion as used for MAGE-A3 expression testing must be available for the testing of the predictive gene signature.
• Formalin-fixed paraffin-embedded (FFPE) tissue must be available for complementary MAGE-A3 and gene signature testing.
• Patient fully recovered from any previous intervention (i.e., biopsy).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate bone-marrow reserve, adequate renal function and adequate hepatic function as assessed by standard laboratory criteria
• If the patient is female, she must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for at least 30 days prior to registration in the trial, 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.
• In the opinion of the investigator, the patient can and will comply with the protocol requirements.

Exclusion Criteria:

• Patients with unresectable stage IV M1b,c melanoma and patients with ocular and mucosal melanoma.
• The patient has at any time received any systemic anticancer treatment.
• Prior systemic treatment with an immunomodulator or loco-regional radiotherapy is permitted as prior adjuvant treatment provided that the last dose was administered at least 30 days before the registration into this trial;
• Previous adjuvant treatment with a cancer vaccine containing a tumor antigen other than MAGE-A3 is allowed if the last administration took place at least 8 weeks before registration into the trial.
• Prior isolated limb perfusion is permitted provided that the last dose was administered at least 30 days before registration into this trial
• The patient is scheduled to receive any anti-cancer specific treatment, including radiotherapy, other immunotherapy, chemotherapy and immunomodulating agents.
• The patient requires concomitant chronic treatment (more than 7 consecutive days) with systemic corticosteroids, or any other immunosuppressive agents.
• 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).
• History of allergic disease or reactions likely to be exacerbated by any component of the ASCI treatment.
• The patient has previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancer or carcinoma in situ of the cervix and effectively treated malignancy that has been in remission for over 5 years and is highly likely to have been cured.
• The patient has psychiatric or addictive disorders
• The patient has an uncontrolled bleeding disorder.
• 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.
• Use of any investigational or non-registered product (drug or vaccine) other than the study medication within the 30 days preceding the first investigational treatment injection or planned use during the study period.
• Concurrently participating in another clinical study, at any time during the study period, in which the patient has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device). For female patients: the patient is pregnant or lactating.