A Phase III Study to Test the Benefit of a New Kind of Anti-cancer Treatment in Patients With Melanoma, After Surgical Removal of Their Tumor

DFS = time to event from randomization to the date of first disease recurrence (as assessed by investigator) or the date of death (whatever cause), whichever occurred first. DFS was expressed as the person-year rate i.e. the number of patients with at least one event (n) over the sum of the follow-up periods in years (T), until the first occurrence of a recurrence/death. Types of recurrence to be considered as an event included loco-regional and distant metastases. Any death occurring without prior documentation of tumor recurrence was considered as an event (not censored in the stat. analysis) as this approach was less prone to introduce bias. If no event occurred by the time of analysis, then the time to event was censored at the last assessment date (tumor assessment/visit) of the patient. Any new primary cancer at another site, including second primary melanoma, was not considered as a recurrence and had to be reported as a Serious Adverse Event (SAE).

Time frame: At follow-up analysis (up to Year 5)

Population: The analysis was performed on the Total Treated population - as randomized, which included patients in the treatment groups as allocated by the randomization system at the start of the study. Between the final and follow-up analyses, 1 patient was found to have an invalid ICF and was not included in the follow-up analysis.

DFS = time to event from randomization to the date of first disease recurrence (as assessed by investigator) or the date of death (whatever cause), whichever occurred first. DFS was expressed as the person-year rate i.e. the number of patients with at least one event (n) over the sum of the follow-up periods in years (T), until the first occurrence of a recurrence/death. Types of recurrence to be considered as an event included loco-regional and distant metastases. Any death occurring without prior documentation of tumor recurrence was considered as an event (not censored in the stat. analysis) as this approach was less prone to introduce bias. If no event occurred by the time of analysis, then the time to event was censored at the last assessment date (tumor assessment/visit) of the patient. Any new primary cancer at another site, including second primary melanoma, was not considered as a recurrence and had to be reported as a Serious Adverse Event (SAE).

Time frame: At Final analysis (Month 30 = Year 2.5)

Population: The analysis was performed on the Total Treated population - as randomized, which included patients in the treatment groups as allocated by the randomization system at the start of the study.

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

Time frame: At Weeks 0, 6, 12, 36, 48 72, 120 (Concluding visit) and at Month 120 + 6 months

Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all eligible subjects who have received at least the first 4 MAGE-A3 ASCI study treatment doses and have provided a result for immunogenicity measurement within the time schedule for study product administration and blood sample draw.

Disease Free Specific Survival (DFSS) was defined as the time to event from randomization to the date of first recurrence of disease or date of death due to melanoma (cause as assessed by investigator), whichever occurred first. DFSS was expressed as the person-year rate i.e. the number of patients with at least one event (n) over the sum of the follow-up periods in years (T), until the first occurrence of a recurrence/death. Patients who died due to a cause other than the disease under study and patients alive at the time of analysis were censored on the date of last assessment (visit or tumor assessment).

Time frame: At Final analysis (Month 30 = Year 2.5)

Population: The analysis was performed on the Total Treated population - as randomized, which included patients in the treatment groups as allocated by the randomization system at the start of the study.

Distant Metastasis Free Survival (DMFS) was defined as the time to event from randomization to the date of first distant metastasis or date of death, whichever occurred first. DMFS was expressed as the person-year rate i.e. the number of patients with at least one event (n) over the sum of the follow-up periods in years (T), until the first occurrence of distant metastasis/death. Patients alive and without distant metastases were censored at the date of last assessment (visit or tumor assessment, or date of last tumor assessment as documented during the yearly contact follow-up period).

Time frame: At Final analysis (Month 30 = Year 2.5)

Population: The analysis was performed on the Total Treated population - as randomized, which included patients in the treatment groups as allocated by the randomization system at the start of the study.

The assessment of health-related quality of life was restricted to patients who consented to study participation after Protocol Amendment 1 became effective at their study site, and for whom a validated version of the Euro Quality of Life-5D (EQ-5D) questionnaire was available in their native language. The EQ-5D comprises a 5-dimensional descriptive system (mobility, self-care, usual activities, pain/discomfort and anxiety/depression), where each item has 3 levels and together they define 243 possible health states. For each health state, a value (utility) was determined by using an additive algorithm. These utility scores were calculated for each patient at each timepoint at which an EQ-5D questionnaire was completed. The score had a maximum value of 1.0 corresponding to full health level, while lower scores, down to a minimum value of 0.0 reflected degradation in the health-related quality of life.

Time frame: At Weeks 0, 6, 12 [on the day of and the day after treatment administration (TA)], at Month 6, 9, 12, 24, at the Concluding visit (Month 30) + 6 months and +12 Months and at disease recurrence

Population: The analysis was performed on subjects with valid EQ-5D data from the Total Treated population - as randomized, which included patients in the treatment groups as allocated by the randomization system at the start of the study.

Laboratory abnormalities belong to hematological and biochemical parameters such as: alanine aminotransferase \[ALT\], asparatate aminostransferase \[AST\], alkaline phoshatase \[AP\], bilirubin \[BIL\], creatinine \[CREA\], hemoglobin \[HGB\], leukocytes \[LEU\], lymphopenia \[LYMPH\], neutrophils \[NEU\], platelets \[PLA\]. Parameter grades (Grade \[G\] 0, 1, 2, 3, 4, Unknown) were compared to each baseline parameter grade (G Unknown, 0, 1, 2, 3), as defined by the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 of August 9, 2006.

Time frame: Within the 31-day (Days 0-30) post-treatment period

Population: The analysis was performed on the Total Treated population - as treated, which included patients in the treatment group as per treatment actually received.

The cut-off value was 27 Enzyme-Linked Immunosorbent Assay (ELISA) units per milliliter (EL.U/mL).

Time frame: At Weeks 0, 6, 12, 36, 48 72, 120 (Concluding visit) and at Week 120 + 6 months

Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all eligible subjects who have received at least the first 4 MAGE-A3 ASCI study treatment doses and have provided a result for immunogenicity measurement within the time schedule for study product administration and blood sample draw.

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

Time frame: At Weeks 6, 12, 36, 48 72, 120 (Concluding visit) and at Month 120 + 6 months

Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all eligible subjects who have received at least the first 4 MAGE-A3 ASCI study treatment doses and have provided a result for immunogenicity measurement within the time schedule for study product administration and blood sample draw.

An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject 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. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.

Time frame: Within the 31-day (Days 0-30) follow-up period after treatment

Population: The analysis was performed on the Total Treated population - as treated, which included patients in the treatment group as per treatment actually received.

Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

Time frame: From Day 0 up to study end (up to 5 years)

Population: The analysis was performed on the Total Treated population - as treated, which included patients in the treatment group as per treatment actually received.

Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.

Time frame: From Day 0 up to study end (up to 5 years)

Population: The analysis was performed on the Total Treated population - as treated, which included patients in the treatment group as per treatment actually received.

Overall Survival (OS) was defined as the time to event from randomization to the date of death, irrespective of the cause of death. OS was expressed as the person-year rate i.e. the number of patients with death (n) over the sum of the follow-up periods in years (T). Patients alive at the time of the analysis were censored on the date last known to be alive.

Time frame: At Final analysis (Month 30 = Year 2.5) and at follow-up analysis (up to Year 5)

Population: The analysis was performed on the Total Treated population - as randomized, which included patients in the treatment groups as allocated by the randomization system at the start of the study. Between the final and follow-up analyses, 1 patient was found to have an invalid ICF and was not included in the follow-up analysis.