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

Cancer staging (characteristics and categories) as by the categorization by the American Joint Committee on Cancer (AJCC) Staging Manual 2002: "Stage IIIA patients have up to three microscopic nodal metastases arising from a non-ulcerating primary melanoma and have an ' intermediate risk' for distant metastases and melanom-specific survival. Stage IIIB patients have up to three microscopic nodal metastases arising from a non-ulcerating melanoma or have up to three microscopic nodal metastases arising from an ulcerating melanoma, or have intralymphatic metastases without nodal metastases. They constitute a 'high-risk' group prognostically." The remaining patients with regional melanoma are Stage IIIC patients are at 'very high risk' for distant metastases and melanoma-specific mortality. Stage IV melanoma patients have metastasis at any distant site and constitute the group with the worst prognosis. Stage MC patients are those with confirmed missing cancer.

From study start (Month 0) to Month 24, each patient was censored out of the analysis at 1st report of disease progression or death. PFS was defined and calculated as the time from first treatment to either the first progression of the disease or the date of death, whichever occurred first. In case a patient went off protocol treatment, the date of first documented progression (if applicable) was to be used as date of progression. Patients still alive with no evidence of disease progression at the time of their last visit or for whom date of first documented progression was not applicable, were censored at the time of the last examination. PFS analysis was performed using the non-parametric Kaplan-Meier method.

PFS was defined as the time from the date of registration of the patient to either the date of disease progression or the date of death, whichever comes first. Patients alive and without disease progression were censored at the date of their last tumor evaluation. The PFS estimates were assessed by the Kaplan-Meier method and expressed as the percentage of patients who did not progress and were alive at a given time.

OS was defined as the time from registration of the patient until death, with patients alive at the time of analysis censored at the time of the last contact.

The TTF was defined as the time from registration of the patient until the date of the last treatment administration, irrespective of the reason for study treatment discontinuation.

The BOR was the best response recorded from the start of the treatment until disease progression/ recurrence, except for confirmed objective response, which was reported as BOR independently of its time of occurrence. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions without any new lesions and/or progression of existing non-target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (PD) without any new lesions and/or progression of existing non-target lesions; PD, >=20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; NE = Non-evaluable response.

Duration of response was measured from the time when the measurement criteria for CR/ PR (whichever was recorded first) were met until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded since the treatment started). Note: As there was only one patient analysed in the GSK2132231A GS- Group, the median duration of response was not calculated for this latter group.

The duration of stable disease (SD), or TTP, was tabulated for patients whose best response was SD. The minimal time interval required between 2 measurements for determination of SD was 12 weeks.

Seropositive patients were those patients with anti-MAGE-A3 antibody concentrations ≥ 27 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).

Anti-MAGE-A3 antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in EL.U/mL.

Seropositive patients were those patients with anti-PD antibody concentrations ≥ 100 EL.U/mL.

Anti-PD antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in EL.U/mL.

Anti-MAGE-A3 antibody response defined as: For initially seronegative patients: post-vaccination antibody concentration ≥ 27 EL.U/mL; For initially seropositive patients: post-vaccination antibody concentration ≥ 2 fold the pre-vaccination antibody concentration.

Anti-PD antibody response defined as: For initially seronegative patients: post-vaccination antibody concentration ≥ 100 EL.U/mL; For initially seropositive patients: post-vaccination antibody concentration ≥ 2 fold the pre-vaccination antibody concentration.

The status of each patient as regards ALT laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3 and Unknown (UNK).

The status of each patient as regards AST laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1 and Unknown (UNK).

The status of each patient as regards ALK laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1 and Unknown (UNK).

The status of each patient as regards BIL laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0), G1 and G2. CTC grade statuses reported at SE were G0, G1, G2 and Unknown (UNK).

The status of each patient as regards CREA laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0), G1 and G2. CTC grade statuses reported at SE were G0, G1, G2 and Unknown (UNK).

The status of each patient as regards HGB laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0), G1 and G2. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).

The status of each patient as regards LEU laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0), G1 and G2. CTC grade statuses reported at SE were G0, G1, G2, G4, and Unknown (UNK).

The status of each patient as regards LYM laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0), G1, G2 and G3. CTC grade statuses reported at SE were G0, G1, G2, G3 and Unknown (UNK).

The status of each patient as regards NEU laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0), G1 and G2. CTC grade statuses reported at SE were G0, G1, G2, G3 and Unknown (UNK).

The status of each patient as regards PLT laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G4, and Unknown (UNK).

Auto-immune diseases or immune-mediated inflammatory disorders were tabulated during the whole duration of the study (up to 30 days after the last administration of the study treatment). The results were tabulated as Any event(s) reported.

The assessed AEs were ASCI-related adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE; Grade 5 = Death due to AE. An unsolicited AE covers any untoward medical occurrence in a clinical investigation patient temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.

An unsolicited AE covers any untoward medical occurrence in a clinical investigation patient temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.