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

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00796445
• Collaborator: (none)
• Enrollment: 1,351
• Locations: 257
• Arms: 2
• Actual Duration (Months): 85.8
• Patients Per Site: 5.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this clinical trial is to evaluate the benefit of the immunotherapeutic product GSK 2132231A in preventing disease relapse when given to melanoma patients, after surgical removal of their tumor.

This Protocol Posting has been updated following Amendments 1 of the Protocol, March 2010. The impacted sections are outcome measures and entry criteria.

Condition or Disease	Intervention/Treatment	Phase
Melanoma	Drug: GSK 2132231A; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1351 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: GSK 2132231A Antigen-Specific Cancer Immunotherapeutic as Adjuvant Therapy in Patients With Resected Melanoma
• Actual Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: Jan 27, 2016
• Actual Study Completion Date: Jan 27, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MAGE-A3 Group Patients who received up to 13 doses of recMAGE-A3 + AS15 ASCI. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Drug: GSK 2132231A; IM solution, a course of 13 injections administered over 27 months
Placebo Comparator: Placebo Group Patients who received up to 13 doses of placebo. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.	Drug: Placebo; IM solution, a course of 13 injections administered over 27 months

Outcome Measures

Primary Outcome Measures

1. Disease Free Survival (DFS) [At Final analysis (Month 30 = Year 2.5)]

   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).

2. Disease Free Survival (DFS) [At follow-up analysis (up to Year 5)]

   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).

Secondary Outcome Measures

1. Overall Survival (OS) [At Final analysis (Month 30 = Year 2.5) and at follow-up analysis (up to Year 5)]

   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.

2. Disease-free Specific Survival (DFSS) [At Final analysis (Month 30 = Year 2.5)]

   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).

3. Distant Metastasis-free Survival (DMFS) [At Final analysis (Month 30 = Year 2.5)]

   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).

4. Health-related Quality of Life [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]

   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.

5. Number of Subjects With Anti-MAGE-A3 Antibody Concentrations Above the Cut-off Value [At Weeks 0, 6, 12, 36, 48 72, 120 (Concluding visit) and at Week 120 + 6 months]

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

6. Anti-MAGE-A3 Antibody Geometric Mean Concentrations [At Weeks 0, 6, 12, 36, 48 72, 120 (Concluding visit) and at Month 120 + 6 months]

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

7. Number of Subjects With Anti-MAGE-A3 Antibody Response [At Weeks 6, 12, 36, 48 72, 120 (Concluding visit) and at Month 120 + 6 months]

   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.

8. Number of Subjects With Abnormal Haematological and Biochemical Parameters [Within the 31-day (Days 0-30) post-treatment period]

   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.

9. Number of Subjects With Any Adverse Events (AEs) [Within the 31-day (Days 0-30) follow-up period after treatment]

   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.

10. Number of Subjects With Any Serious Adverse Events (SAEs) [From Day 0 up to study end (up to 5 years)]

    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.

11. Number of Subjects With Potential Immune-mediated Diseases (pIMDs) [From Day 0 up to study end (up to 5 years)]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Written informed consent signed.

• Male or female patient with histologically proven stage IIIB or IIIC cutaneous melanoma presenting with macroscopic lymph node involvement suitable for surgery.

• The patient must have been surgically rendered free of disease before the randomization.

• Patient is ≥ 18 years old at the time of signing the informed consent form.

• The patient's lymph node tumor shows expression of the MAGE-A3 gene.

• The patient has fully recovered from surgery.

• ECOG performance status of 0 or 1 at the time of randomization.

• The patient must have adequate organ functions as assessed by standard laboratory criteria.

• If the patient is female, she must be of non-childbearing potential, or practice adequate contraception.

• In the opinion of the investigator, the patient can and will comply with all the requirements of the protocol.

Exclusion Criteria:

• The patient suffers from a mucosal or ocular melanoma.

• The patient has or has had any history of in-transit metastases

• The patient has been treated or is scheduled to be treated with an adjuvant anticancer therapy after the surgery that qualifies the patient for inclusion in the present trial.

• The patient requires concomitant chronic treatment with systemic corticosteroids or any other immunosuppressive agents.

• Use of any investigational or non-registered product (drug or vaccine) other than the study treatment.

• The patient has a history of autoimmune disease.

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Birmingham	Alabama	United States	35243
2	GSK Investigational Site	Tucson	Arizona	United States	85724-5024
3	GSK Investigational Site	Little Rock	Arkansas	United States	72205
4	GSK Investigational Site	La Jolla	California	United States	92093-0987
5	GSK Investigational Site	Los Angeles	California	United States	90025
6	GSK Investigational Site	Los Angeles	California	United States	90095
7	GSK Investigational Site	Orange	California	United States	92868
8	GSK Investigational Site	Riverside	California	United States	92505
9	GSK Investigational Site	San Francisco	California	United States	94117-1079
10	GSK Investigational Site	Santa Rosa	California	United States	95403-1757
11	GSK Investigational Site	Aurora	Colorado	United States	80045
12	GSK Investigational Site	Jacksonville	Florida	United States	32204
13	GSK Investigational Site	Jacksonville	Florida	United States	32207
14	GSK Investigational Site	Miami	Florida	United States	33136-1002
15	GSK Investigational Site	Orange Park	Florida	United States	32073
16	GSK Investigational Site	Orlando	Florida	United States	32806
17	GSK Investigational Site	Stuart	Florida	United States	34994
18	GSK Investigational Site	Atlanta	Georgia	United States	30309
19	GSK Investigational Site	Atlanta	Georgia	United States	30322
20	GSK Investigational Site	Chicago	Illinois	United States	60611-2906
21	GSK Investigational Site	Chicago	Illinois	United States	60612-7323
22	GSK Investigational Site	Chicago	Illinois	United States	60612
23	GSK Investigational Site	Chicago	Illinois	United States	60637
24	GSK Investigational Site	Indianapolis	Indiana	United States	46202
25	GSK Investigational Site	Louisville	Kentucky	United States	40202
26	GSK Investigational Site	Metairie	Louisiana	United States	70006
27	GSK Investigational Site	Baltimore	Maryland	United States	21231
28	GSK Investigational Site	Baltimore	Maryland	United States	21237
29	GSK Investigational Site	Boston	Massachusetts	United States	02118
30	GSK Investigational Site	Boston	Massachusetts	United States	02215
31	GSK Investigational Site	Ann Arbor	Michigan	United States	48019
32	GSK Investigational Site	Grand Rapids	Michigan	United States	49503
33	GSK Investigational Site	Fridley	Minnesota	United States	55432
34	GSK Investigational Site	Minneapolis	Minnesota	United States	55455
35	GSK Investigational Site	Saint Louis Park	Minnesota	United States	55426
36	GSK Investigational Site	Saint Louis	Missouri	United States	63110
37	GSK Investigational Site	Las Vegas	Nevada	United States	89169
38	GSK Investigational Site	Hackensack	New Jersey	United States	07601
39	GSK Investigational Site	Morristown	New Jersey	United States	07962-1956
40	GSK Investigational Site	Albany	New York	United States	12206
41	GSK Investigational Site	Latham	New York	United States	12110
42	GSK Investigational Site	New York	New York	United States	10016
43	GSK Investigational Site	Chapel Hill	North Carolina	United States	27599-7305
44	GSK Investigational Site	Charlotte	North Carolina	United States	28204
45	GSK Investigational Site	Durham	North Carolina	United States	27710
46	GSK Investigational Site	Winston-Salem	North Carolina	United States	27157
47	GSK Investigational Site	Cincinnati	Ohio	United States	45219
48	GSK Investigational Site	Cleveland	Ohio	United States	44106
49	GSK Investigational Site	Portland	Oregon	United States	97213
50	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19104
51	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19107
52	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19111
53	GSK Investigational Site	Pittsburgh	Pennsylvania	United States	15213-2584
54	GSK Investigational Site	Sayre	Pennsylvania	United States	18840
55	GSK Investigational Site	Charleston	South Carolina	United States	29406
56	GSK Investigational Site	Charleston	South Carolina	United States	29425
57	GSK Investigational Site	Memphis	Tennessee	United States	38104
58	GSK Investigational Site	Nashville	Tennessee	United States	37232-6307
59	GSK Investigational Site	Amarillo	Texas	United States	79106
60	GSK Investigational Site	Austin	Texas	United States	78759
61	GSK Investigational Site	Bedford	Texas	United States	76022
62	GSK Investigational Site	Dallas	Texas	United States	75230
63	GSK Investigational Site	Dallas	Texas	United States	75246
64	GSK Investigational Site	Fort Worth	Texas	United States	76104
65	GSK Investigational Site	Houston	Texas	United States	77030
66	GSK Investigational Site	Lubbock	Texas	United States	79410
67	GSK Investigational Site	Plano	Texas	United States	75093
68	GSK Investigational Site	Tyler	Texas	United States	75702
69	GSK Investigational Site	Murray	Utah	United States	84107
70	GSK Investigational Site	Charlottesville	Virginia	United States	22903
71	GSK Investigational Site	Seattle	Washington	United States	98109
72	GSK Investigational Site	Vancouver	Washington	United States	98684
73	GSK Investigational Site	Morgantown	West Virginia	United States	26506
74	GSK Investigational Site	Milwaukee	Wisconsin	United States	53215
75	GSK Investigational Site	Ciudad Autónoma de Buenos Aires	Buenos Aires	Argentina	C1050AAK
76	GSK Investigational Site	Cipolletti	Río Negro	Argentina	R8324EMB
77	GSK Investigational Site	Rosario	Santa Fe	Argentina	S2000KZE
78	GSK Investigational Site	Ciudad Autónoma de Buenos Aires		Argentina	C1121ABE
79	GSK Investigational Site	Camperdown	New South Wales	Australia	2060
80	GSK Investigational Site	North Sydney	New South Wales	Australia	2060
81	GSK Investigational Site	Waratah	New South Wales	Australia	2298
82	GSK Investigational Site	Westmead	New South Wales	Australia	2145
83	GSK Investigational Site	Brisbane	Queensland	Australia	4102
84	GSK Investigational Site	Adelaide	South Australia	Australia	5000
85	GSK Investigational Site	Hobart	Tasmania	Australia	7000
86	GSK Investigational Site	East Melbourne	Victoria	Australia	3002
87	GSK Investigational Site	Heidelberg	Victoria	Australia	3084
88	GSK Investigational Site	Feldkirch		Austria	A-6800
89	GSK Investigational Site	Graz		Austria	A-8036
90	GSK Investigational Site	Linz		Austria	A-4010
91	GSK Investigational Site	Salzburg		Austria	A-5020
92	GSK Investigational Site	Wels		Austria	A-4600
93	GSK Investigational Site	Wien		Austria	A-1030
94	GSK Investigational Site	Wien		Austria	A-1090
95	GSK Investigational Site	Wien		Austria	A-1220
96	GSK Investigational Site	Bruxelles		Belgium	1070
97	GSK Investigational Site	Bruxelles		Belgium	1180
98	GSK Investigational Site	Bruxelles		Belgium	1200
99	GSK Investigational Site	Liège		Belgium	4000
100	GSK Investigational Site	Wilrijk		Belgium	2610
101	GSK Investigational Site	Belo Horizonte	Minas Gerais	Brazil	30.140-001
102	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul	Brazil	90610-000
103	GSK Investigational Site	São Paulo		Brazil	03102-002
104	GSK Investigational Site	Plovdiv		Bulgaria	4000
105	GSK Investigational Site	Sofia		Bulgaria	1756
106	GSK Investigational Site	Winnipeg	Manitoba	Canada	R3E 0V9
107	GSK Investigational Site	Ottawa	Ontario	Canada	K1H 8L6
108	GSK Investigational Site	Brno		Czechia	656 53
109	GSK Investigational Site	Hradec Kralove		Czechia	500 05
110	GSK Investigational Site	Ostrava		Czechia	708 52
111	GSK Investigational Site	Praha 10		Czechia	100 34
112	GSK Investigational Site	Praha 2		Czechia	128 08
113	GSK Investigational Site	Tallinn		Estonia	13419
114	GSK Investigational Site	Tartu		Estonia	51014
115	GSK Investigational Site	Besançon cedex		France	25030
116	GSK Investigational Site	Bordeaux		France	33075
117	GSK Investigational Site	Boulogne		France	92104
118	GSK Investigational Site	Brest		France	29609
119	GSK Investigational Site	Dijon		France	21079
120	GSK Investigational Site	Grenoble		France	38043
121	GSK Investigational Site	Le Mans		France	72000
122	GSK Investigational Site	Lille		France	59037
123	GSK Investigational Site	Limoges cedex		France	87042
124	GSK Investigational Site	Marseille Cedex 5		France	13385
125	GSK Investigational Site	Montpellier		France	34295
126	GSK Investigational Site	Nantes		France	44093
127	GSK Investigational Site	Nice		France	06202
128	GSK Investigational Site	Paris Cedex 10		France	75475
129	GSK Investigational Site	Paris		France	75006
130	GSK Investigational Site	Paris		France	75018
131	GSK Investigational Site	Pierre-Bénite cedex		France	69495
132	GSK Investigational Site	Poitiers		France	86021
133	GSK Investigational Site	Reims		France	51092
134	GSK Investigational Site	Rennes		France	35042
135	GSK Investigational Site	Rouen		France	76031
136	GSK Investigational Site	Saint-Etienne		France	42055
137	GSK Investigational Site	Toulouse cedex 9		France	31059
138	GSK Investigational Site	Tours		France	37044
139	GSK Investigational Site	Villejuif		France	94805
140	GSK Investigational Site	Freiburg	Baden-Wuerttemberg	Germany	79104
141	GSK Investigational Site	Heidelberg	Baden-Wuerttemberg	Germany	69120
142	GSK Investigational Site	Mannheim	Baden-Wuerttemberg	Germany	68167
143	GSK Investigational Site	Tuebingen	Baden-Wuerttemberg	Germany	72076
144	GSK Investigational Site	Ulm	Baden-Wuerttemberg	Germany	89081
145	GSK Investigational Site	Muenchen	Bayern	Germany	80337
146	GSK Investigational Site	Muenchen	Bayern	Germany	80802
147	GSK Investigational Site	Nuernberg	Bayern	Germany	90419
148	GSK Investigational Site	Regensburg	Bayern	Germany	93053
149	GSK Investigational Site	Wuerzburg	Bayern	Germany	97080
150	GSK Investigational Site	Frankfurt	Hessen	Germany	60590
151	GSK Investigational Site	Kassel	Hessen	Germany	34125
152	GSK Investigational Site	Marburg	Hessen	Germany	35033
153	GSK Investigational Site	Wiesbaden	Hessen	Germany	65191
154	GSK Investigational Site	Greifswald	Mecklenburg-Vorpommern	Germany	17475
155	GSK Investigational Site	Buxtehude	Niedersachsen	Germany	21614
156	GSK Investigational Site	Hannover	Niedersachsen	Germany	30625
157	GSK Investigational Site	Oldenburg	Niedersachsen	Germany	26133
158	GSK Investigational Site	Bonn	Nordrhein-Westfalen	Germany	53127
159	GSK Investigational Site	Essen	Nordrhein-Westfalen	Germany	45122
160	GSK Investigational Site	Koeln	Nordrhein-Westfalen	Germany	50937
161	GSK Investigational Site	Minden	Nordrhein-Westfalen	Germany	32429
162	GSK Investigational Site	Muenster	Nordrhein-Westfalen	Germany	48149
163	GSK Investigational Site	Ludwigshafen	Rheinland-Pfalz	Germany	67063
164	GSK Investigational Site	Mainz	Rheinland-Pfalz	Germany	55131
165	GSK Investigational Site	Homburg	Saarland	Germany	66421
166	GSK Investigational Site	Magdeburg	Sachsen-Anhalt	Germany	39120
167	GSK Investigational Site	Quedlinburg	Sachsen-Anhalt	Germany	06484
168	GSK Investigational Site	Dresden	Sachsen	Germany	01307
169	GSK Investigational Site	Leipzig	Sachsen	Germany	04103
170	GSK Investigational Site	Kiel	Schleswig-Holstein	Germany	24105
171	GSK Investigational Site	Luebeck	Schleswig-Holstein	Germany	23538
172	GSK Investigational Site	Erfurt	Thueringen	Germany	99089
173	GSK Investigational Site	Jena	Thueringen	Germany	07740
174	GSK Investigational Site	Berlin		Germany	10117
175	GSK Investigational Site	Berlin		Germany	10249
176	GSK Investigational Site	Berlin		Germany	13585
177	GSK Investigational Site	Athens		Greece	11527
178	GSK Investigational Site	Athens		Greece	185 47
179	GSK Investigational Site	Cork		Ireland
180	GSK Investigational Site	Dublin		Ireland	4
181	GSK Investigational Site	Dublin		Ireland	7
182	GSK Investigational Site	Dublin		Ireland	8
183	GSK Investigational Site	Dublin		Ireland	9
184	GSK Investigational Site	Galway		Ireland	Co Galway
185	GSK Investigational Site	Haifa		Israel	31096
186	GSK Investigational Site	Petach Tikva		Israel	49100
187	GSK Investigational Site	Ramat Gan		Israel	52621
188	GSK Investigational Site	Napoli	Campania	Italy	80131
189	GSK Investigational Site	Meldola (FC)	Emilia-Romagna	Italy	47014
190	GSK Investigational Site	Modena	Emilia-Romagna	Italy	41124
191	GSK Investigational Site	Aviano (PN)	Friuli-Venezia-Giulia	Italy	33081
192	GSK Investigational Site	Roma	Lazio	Italy	00144
193	GSK Investigational Site	Genova	Liguria	Italy	16132
194	GSK Investigational Site	Milano	Lombardia	Italy	20133
195	GSK Investigational Site	Milano	Lombardia	Italy	20141
196	GSK Investigational Site	Bari	Puglia	Italy	70124
197	GSK Investigational Site	Pisa	Toscana	Italy	56125
198	GSK Investigational Site	Siena	Toscana	Italy	53100
199	GSK Investigational Site	Padova	Veneto	Italy	35128
200	GSK Investigational Site	Shizuoka		Japan	411-8777
201	GSK Investigational Site	Tokyo		Japan	104-0045
202	GSK Investigational Site	Seoul		Korea, Republic of	05505
203	GSK Investigational Site	Seoul		Korea, Republic of	06351
204	GSK Investigational Site	Monterrey	Nuevo León	Mexico	64710
205	GSK Investigational Site	Nijmegen		Netherlands	6525 GA
206	GSK Investigational Site	Rotterdam		Netherlands	3075 EA
207	GSK Investigational Site	Auckland		New Zealand	0622
208	GSK Investigational Site	Christchurch		New Zealand	8011
209	GSK Investigational Site	Wellington		New Zealand	6021
210	GSK Investigational Site	Oslo		Norway	0310
211	GSK Investigational Site	Bydgoszcz		Poland	85-796
212	GSK Investigational Site	Gdansk		Poland	80-215
213	GSK Investigational Site	Kraków		Poland	31-108
214	GSK Investigational Site	Olsztyn		Poland	10-228
215	GSK Investigational Site	Poznan		Poland	61-866
216	GSK Investigational Site	Slupsk		Poland	76-200
217	GSK Investigational Site	Warszawa		Poland	02-781
218	GSK Investigational Site	Warszawa		Poland	04-125
219	GSK Investigational Site	Baia Mare		Romania	430031
220	GSK Investigational Site	Cluj-Napoca		Romania
221	GSK Investigational Site	Craiova, Dolj		Romania	200535
222	GSK Investigational Site	Chelyabinsk		Russian Federation	454087
223	GSK Investigational Site	Kursk		Russian Federation	305035
224	GSK Investigational Site	Moscow		Russian Federation	115478
225	GSK Investigational Site	Omsk		Russian Federation	644013
226	GSK Investigational Site	St. Petersburg		Russian Federation	197758
227	GSK Investigational Site	St. Petersburg		Russian Federation	198255
228	GSK Investigational Site	Stavropol		Russian Federation	355047
229	GSK Investigational Site	Belgrad		Serbia	11 000
230	GSK Investigational Site	Belgrad		Serbia
231	GSK Investigational Site	Sremska Kamenica		Serbia	21204
232	GSK Investigational Site	Barcelona		Spain	08036
233	GSK Investigational Site	Madrid		Spain	28040
234	GSK Investigational Site	Pamplona		Spain	31008
235	GSK Investigational Site	Sevilla		Spain	41009
236	GSK Investigational Site	Valencia		Spain	46014
237	GSK Investigational Site	Göteborg		Sweden	SE-413 45
238	GSK Investigational Site	Malmö		Sweden	SE-205 20
239	GSK Investigational Site	Uppsala		Sweden	SE-751 85
240	GSK Investigational Site	Basel		Switzerland	4031
241	GSK Investigational Site	Zürich		Switzerland	8091
242	GSK Investigational Site	Kaohsiung		Taiwan	807
243	GSK Investigational Site	Taipei		Taiwan	112
244	GSK Investigational Site	Taoyuan Hsien		Taiwan	333
245	GSK Investigational Site	Dnipropetrovsk		Ukraine	49100
246	GSK Investigational Site	Dnipropetrovsk		Ukraine	49102
247	GSK Investigational Site	Donetsk		Ukraine	83092
248	GSK Investigational Site	Krivoy Rog		Ukraine	50048
249	GSK Investigational Site	Kyiv		Ukraine	03022
250	GSK Investigational Site	Lviv		Ukraine	79031
251	GSK Investigational Site	Chelmsford	Essex	United Kingdom	CM1 7ET
252	GSK Investigational Site	Belfast, Northern Ireland		United Kingdom	BT9 7AB
253	GSK Investigational Site	Colchester		United Kingdom	CO3 3NB
254	GSK Investigational Site	Dundee		United Kingdom	DD1 9SY
255	GSK Investigational Site	London		United Kingdom	SW17 0RE
256	GSK Investigational Site	Poole, Dorset		United Kingdom	BH15 2JB
257	GSK Investigational Site	Salisbury		United Kingdom	SP2 8BJ

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• IPD for this study will be made available via the Clinical Study Data Request site.

Publications

• Dizier B, Callegaro A, Debois M, Dreno B, Hersey P, Gogas HJ, Kirkwood JM, Vansteenkiste JF, Sequist LV, Atanackovic D, Goeman J, van Houwelingen H, Salceda S, Wang F, Therasse P, Debruyne C, Spiessens B, Brichard VG, Louahed J, Ulloa-Montoya F. A Th1/IFNγ Gene Signature Is Prognostic in the Adjuvant Setting of Resectable High-Risk Melanoma but Not in Non-Small Cell Lung Cancer. Clin Cancer Res. 2020 Apr 1;26(7):1725-1735. doi: 10.1158/1078-0432.CCR-18-3717. Epub 2019 Nov 15.
• Dreno B, Thompson JF, Smithers BM, Santinami M, Jouary T, Gutzmer R, Levchenko E, Rutkowski P, Grob JJ, Korovin S, Drucis K, Grange F, Machet L, Hersey P, Krajsova I, Testori A, Conry R, Guillot B, Kruit WHJ, Demidov L, Thompson JA, Bondarenko I, Jaroszek J, Puig S, Cinat G, Hauschild A, Goeman JJ, van Houwelingen HC, Ulloa-Montoya F, Callegaro A, Dizier B, Spiessens B, Debois M, Brichard VG, Louahed J, Therasse P, Debruyne C, Kirkwood JM. MAGE-A3 immunotherapeutic as adjuvant therapy for patients with resected, MAGE-A3-positive, stage III melanoma (DERMA): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Jul;19(7):916-929. doi: 10.1016/S1470-2045(18)30254-7. Epub 2018 Jun 13.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00796445
• Other Study ID Numbers: 111482; 2008-002447-16
• First Posted: Nov 24, 2008
• Last Update Posted: Mar 5, 2021
• Last Verified: Feb 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: DERMA; Tumor antigen; Immunotherapeutic; Adjuvant cancer therapy; Melanoma; ASCI
• Additional relevant MeSH terms: Melanoma

Study Results

Participant Flow

Pre-assignment Detail

Out of 1351 patients enrolled in the study, 6 patients did not receive treatment and were excluded from study start, hence 1345 patients were included in the Total treated population-as treated (895 in the MAGE-A3 Group and 450 in the Placebo Group). 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, which included 1344 patients: 894 in the MAGE-A3 Group and 450 in the Placebo Group.

Arm/Group Title	MAGE-A3 Group	Placebo Group
Arm/Group Description	Patients who received up to 13 doses of recMAGE-A3 + AS15 ASCI. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Patients who received up to 13 doses of placebo. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.
Period Title: Overall Study
STARTED	895	450
COMPLETED	310	158
NOT COMPLETED	585	292

Baseline Characteristics

Arm/Group Title	MAGE-A3 Group	Placebo Group	Total
Arm/Group Description	Patients who received up to 13 doses of recMAGE-A3 + AS15 ASCIStudy products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Patients who received up to 13 doses of placebo. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.	Total of all reporting groups
Overall Participants	895	450	1345
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56.0 (13.51)	56.2 (13.66)	56.1 (13.59)
Sex: Female, Male (Count of Participants)
Female	345 38.5%	188 41.8%	533 39.6%
Male	550 61.5%	262 58.2%	812 60.4%
Race/Ethnicity, Customized (Count of Participants)
Asian - Japanese Heritage	4 0.4%	3 0.7%	7 0.5%
White - Arabic/North African Heritage	4 0.4%	1 0.2%	5 0.4%
White - Caucasian/European Heritage	880 98.3%	443 98.4%	1323 98.4%
Other - Mixed origin	7 0.8%	3 0.7%	10 0.7%

Outcome Measures

1. Primary Outcome

Title	Disease Free Survival (DFS)
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MAGE-A3 Group	Placebo Group	GS+ Mage-A3 Sub-Group	GS+ Placebo Sub-Group	GS- Mage-A3 Sub-Group	GS- Placebo Sub-Group
Arm/Group Description	Patients who received up to 13 doses of recMAGE-A3 + AS15 ASCI. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Patients who received up to 13 doses of placebo. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.	Subset of patients with the pre-specified gene signature (GS+), receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Subset of patients with the pre-specified gene signature, receiving placebo. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.	Subset of patients without the pre-specified gene signature (GS-), receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Subset of patients without the pre-specified gene signature, receiving placebo. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.
Measure Participants	893	452	200	116	255	126
Number [First events per person-year]	0.505	0.478	0.500	0.460	0.437	0.442

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MAGE-A3 Group, Placebo Group
	Comments	At Final analysis (Month 30)
	Type of Statistical Test	Non-Inferiority
	Comments	The aim of this analysis was to demonstrate the clinical efficacy in terms of disease-free survival (DFS) of recMAGE-A3 + AS15 ASCI compared to placebo in the overall study population of patients with completely resected stage III cutaneous melanoma with macroscopic lymph node involvement.
Statistical Test of Hypothesis	p-Value	0.8566
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.013
	Confidence Interval	(2-Sided) 95%; 0.879 to 1.169
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GS+ Mage-A3 Sub-Group, GS+ Placebo Sub-Group
	Comments	At Final analysis (Month 30)
	Type of Statistical Test	Non-Inferiority
	Comments	The aim of this analysis was to demonstrate the clinical efficacy in terms of DFS of the recMAGE-A3 + AS15 ASCI compared to placebo in the population presenting the potentially favorable gene expression signature.
Statistical Test of Hypothesis	p-Value	0.4821
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.111
	Confidence Interval	(2-Sided) 95%; 0.828 to 1.491
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	GS- Mage-A3 Sub-Group, GS- Placebo Sub-Group
	Comments	At Final analysis (Month 30)
	Type of Statistical Test	Non-Inferiority
	Comments	The aim of this analysis was to demonstrate the clinical efficacy in terms of DFS of the recMAGE-A3 + AS15 ASCI compared to placebo in the population without the potentially favorable gene expression signature
Statistical Test of Hypothesis	p-Value	0.5375
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.915
	Confidence Interval	(2-Sided) 95%; 0.691 to 1.212
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Disease Free Survival (DFS)
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MAGE-A3 Group	Placebo Group	GS+ Mage-A3 Sub-Group	GS+ Placebo Sub-Group	GS- Mage-A3 Sub-Group	GS- Placebo Sub-Group
Arm/Group Description	Patients who received up to 13 doses of recMAGE-A3 + AS15 ASCI. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Patients who received up to 13 doses of placebo. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.	Subset of patients with the pre-specified gene signature (GS+), receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Subset of patients with the pre-specified gene signature, receiving placebo. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.	Subset of patients without the pre-specified gene signature (GS-), receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Subset of patients without the pre-specified gene signature, receiving placebo. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.
Measure Participants	892	452	200	116	255	126
Number [First events per person-year]	0.366	0.345	0.345	0.335	0.316	0.319

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MAGE-A3 Group, Placebo Group
	Comments	At Follow-up analysis (up to Year 5)
	Type of Statistical Test	Non-Inferiority
	Comments	The aim of this analysis was to demonstrate the clinical efficacy in terms of disease-free survival (DFS) of recMAGE-A3 + AS15 ASCI compared to placebo in the overall study population of patients with completely resected stage III cutaneous melanoma with macroscopic lymph node involvement
Statistical Test of Hypothesis	p-Value	0.7534
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.023
	Confidence Interval	(2-Sided) 95%; 0.890 to 1.175
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GS+ Mage-A3 Sub-Group, GS+ Placebo Sub-Group
	Comments	At Follow-up analysis (up to Year 5)
	Type of Statistical Test	Non-Inferiority
	Comments	The aim of this analysis was to demonstrate the clinical efficacy in terms of DFS of the recMAGE-A3 + AS15 ASCI compared to placebo in the population presenting the potentially favorable gene expression signature.
Statistical Test of Hypothesis	p-Value	0.5385
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.094
	Confidence Interval	(2-Sided) 95%; 0.821 to 1.457
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	GS- Mage-A3 Sub-Group, GS- Placebo Sub-Group
	Comments	At Follow-up analysis (up to Year 5)
	Type of Statistical Test	Non-Inferiority
	Comments	The aim of this analysis was to demonstrate the clinical efficacy in terms of DFS of the recMAGE-A3 + AS15 ASCI compared to placebo in the population without the potentially favorable gene expression signature.
Statistical Test of Hypothesis	p-Value	0.5419
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.918
	Confidence Interval	(2-Sided) 95%; 0.698 to 1.207
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Overall Survival (OS)
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MAGE-A3 Group	Placebo Group	GS+ Mage-A3 Sub-Group	GS+ Placebo Sub-Group	GS- Mage-A3 Sub-Group	GS- Placebo Sub-Group
Arm/Group Description	Patients who received up to 13 doses of recMAGE-A3 + AS15 ASCI. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Patients who received up to 13 doses of placebo. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.	Subset of patients with the pre-specified gene signature, receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Subset of patients with the pre-specified gene signature, receiving placebo. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.	Subset of patients without the pre-specified gene signature, receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Subset of patients without the pre-specified gene signature, receiving placebo. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.
Measure Participants	893	452	200	116	255	126
OS, Final analysis	0.177	0.165	0.172	0.188	0.165	0.151
OS, Follow-up analysis	0.146	0.140	0.146	0.153	0.132	0.120

4. Secondary Outcome

Title	Disease-free Specific Survival (DFSS)
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MAGE-A3 Group	Placebo Group	GS+ Mage-A3 Sub-Group	GS- Mage-A3 Sub-Group	GS+ Placebo Sub-Group	GS- Placebo Sub-Group
Arm/Group Description	Patients who received up to 13 doses of recMAGE-A3 + AS15 ASCI. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Patients who received up to 13 doses of placebo. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.	Subset of patients with the pre-specified gene signature, receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Subset of patients without the pre-specified gene signature, receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Subset of patients with the pre-specified gene signature, receiving placebo. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.	Subset of patients without the pre-specified gene signature, receiving placebo. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.
Measure Participants	893	452	200	116	255	126
Number [First events per person-year]	0.499	0.478	0.500	0.460	0.434	0.442

5. Secondary Outcome

Title	Distant Metastasis-free Survival (DMFS)
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MAGE-A3 Group	Placebo Group	GS+ Mage-A3 Sub-Group	GS+ Placebo Sub-Group	GS- Mage-A3 Sub-Group	GS- Placebo Sub-Group
Arm/Group Description	Patients who received up to 13 doses of recMAGE-A3 + AS15 ASCI. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Patients who received up to 13 doses of placebo. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.	Subset of patients with the pre-specified gene signature, receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Subset of patients with the pre-specified gene signature, receiving placebo. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.	Subset of patients without the pre-specified gene signature, receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Subset of patients without the pre-specified gene signature, receiving placebo. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.
Measure Participants	893	452	200	116	255	126
Number [First events per person-year]	0.387	0.342	0.388	0.337	0.334	0.307

6. Secondary Outcome

Title	Health-related Quality of Life
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MAGE-A3 Group	Placebo Group
Arm/Group Description	Patients who received up to 13 doses of recMAGE-A3 + AS15 ASCI. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Patients who received up to 13 doses of placebo. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.
Measure Participants	245	118
EQ-5D, Week 0 (day of TA)	0.842 (0.182)	0.861 (0.159)
EQ-5D, Week 0 (day after TA)	0.773 (0.182)	0.873 (0.141)
EQ-5D, Week 6 (day of TA)	0.853 (0.183)	0.865 (0.173)
EQ-5D, Week 6 (day after TA)	0.722 (0.245)	0.867 (0.174)
EQ-5D, Week 12 (day of TA)	0.873 (0.158)	0.887 (0.138)
EQ-5D, Week 12 (day after TA)	0.788 (0.170)	0.888 (0.126)
EQ-5D, Month 6	0.879 (0.146)	0.900 (0.156)
EQ-5D, Month 9	0.891 (0.134)	0.876 (0.194)
EQ-5D, Month 12	0.891 (0.157)	0.899 (0.149)
EQ-5D, Month 24	0.894 (0.132)	0.881 (0.150)
EQ-5D, Month 30 + 6 months	0.727 (0.000)	0.568 (0.074)
EQ-5D, Month 30 + 12 months	0.791 (0.264)	0.648 (0.344)
EQ-5D, Disease recurrence	0.752 (0.261)	0.815 (0.197)

7. Secondary Outcome

Title	Number of Subjects With Anti-MAGE-A3 Antibody Concentrations Above the Cut-off Value
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MAGE-A3 Group	Placebo Group
Arm/Group Description	Patients who received up to 13 doses of recMAGE-A3 + AS15 ASCI. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Patients who received up to 13 doses of placebo. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.
Measure Participants	629	316
Anti-MAGE-A3, Week 0	25 2.8%	19 4.2%
Anti-MAGE-A3, Week 6	478 53.4%	22 4.9%
Anti-MAGE-A3, Week 12	424 47.4%	13 2.9%
Anti-MAGE-A3, Week 36	259 28.9%	6 1.3%
Anti-MAGE-A3, Week 48	224 25%	5 1.1%
Anti-MAGE-A3, Week 72	178 19.9%	4 0.9%
Anti-MAGE-A3, Week 120	257 28.7%	10 2.2%
Anti-MAGE-A3, Week 120+6 months	70 7.8%	1 0.2%

8. Secondary Outcome

Title	Anti-MAGE-A3 Antibody Geometric Mean Concentrations
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MAGE-A3 Group	Placebo Group
Arm/Group Description	Patients who received up to 13 doses of recMAGE-A3 + AS15 ASCI. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Patients who received up to 13 doses of placebo. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.
Measure Participants	629	316
Anti-MAGE-A3, Week 0	11.0	11.4
Anti-MAGE-A3, Week 6	1451.6	11.9
Anti-MAGE-A3, Week 12	4031.6	11.3
Anti-MAGE-A3, Week 36	2189.6	11.4
Anti-MAGE-A3, Week 48	2243.4	11.3
Anti-MAGE-A3, Week 72	2489.4	11.2
Anti-MAGE-A3, Week 120	3109.7	12.7
Anti-MAGE-A3, Week 120+6 months	1293.4	10.8

9. Secondary Outcome

Title	Number of Subjects With Anti-MAGE-A3 Antibody Response
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MAGE-A3 Group	Placebo Group
Arm/Group Description	Patients who received up to 13 doses of recMAGE-A3 + AS15 ASCI. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Patients who received up to 13 doses of placebo. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.
Measure Participants	482	271
Anti-MAGE-A3, Week 6	476 53.2%	9 2%
Anti-MAGE-A3, Week 12	424 47.4%	4 0.9%
Anti-MAGE-A3, Week 36	259 28.9%	2 0.4%
Anti-MAGE-A3, Week 48	224 25%	2 0.4%
Anti-MAGE-A3, Week 72	178 19.9%	2 0.4%
Anti-MAGE-A3, Week 120	257 28.7%	6 1.3%
Anti-MAGE-A3, Week 120+6 months	70 7.8%	1 0.2%

10. Secondary Outcome

Title	Number of Subjects With Abnormal Haematological and Biochemical Parameters
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	MAGE-A3 Group	Placebo Group
Arm/Group Description	Patients who received up to 13 doses of recMAGE-A3 + AS15 ASCI. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Patients who received up to 13 doses of placebo. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.
Measure Participants	894	450
ALT, Unknown - G0	3 0.3%	2 0.4%
ALT, Unknown - G1	1 0.1%	0 0%
ALT, Unknown - G2	0 0%	0 0%
ALT, Unknown - G3	0 0%	0 0%
ALT, Unknown - G4	0 0%	0 0%
ALT, Unknown - Unknown	2 0.2%	0 0%
ALT, G0 - G0	625 69.8%	337 74.9%
ALT, G0 - G1	98 10.9%	30 6.7%
ALT, G0 - G2	10 1.1%	4 0.9%
ALT, G0 - G3	3 0.3%	4 0.9%
ALT, G0 - G4	0 0%	0 0%
ALT, G0 - Unknown	36 4%	18 4%
ALT, G1 - G0	45 5%	22 4.9%
ALT, G1 - G1	49 5.5%	25 5.6%
ALT, G1 - G2	14 1.6%	4 0.9%
ALT, G1 - G3	1 0.1%	2 0.4%
ALT, G1 - G4	0 0%	0 0%
ALT, G1 - Unknown	2 0.2%	1 0.2%
ALT, G2 - G0	1 0.1%	1 0.2%
ALT, G2 - G1	2 0.2%	0 0%
ALT, G2 - G2	1 0.1%	0 0%
ALT, G2 - G3	0 0%	0 0%
ALT, G2 - G4	0 0%	0 0%
ALT, G2 - Unknown	0 0%	0 0%
ALT, G3 - G0	0 0%	0 0%
ALT, G3 - G1	0 0%	0 0%
ALT, G3 - G2	0 0%	0 0%
ALT, G3 - G3	0 0%	0 0%
ALT, G3 - G4	0 0%	0 0%
ALT, G3 - Unknown	1 0.1%	0 0%
ALT, Total - G0	674 75.3%	362 80.4%
ALT, Total - G1	150 16.8%	55 12.2%
ALT, Total - G2	25 2.8%	8 1.8%
ALT, Total - G3	4 0.4%	6 1.3%
ALT, Total - G4	0 0%	0 0%
ALT, Total - Unknown	41 4.6%	19 4.2%
AST, Unknown - G0	3 0.3%	3 0.7%
AST, Unknown - G1	1 0.1%	0 0%
AST, Unknown - G2	0 0%	0 0%
AST, Unknown - G3	0 0%	0 0%
AST, Unknown - G4	0 0%	0 0%
AST, Unknown - Unknown	3 0.3%	0 0%
AST, G0 - G0	701 78.3%	356 79.1%
AST, G0 - G1	88 9.8%	37 8.2%
AST, G0 - G2	5 0.6%	3 0.7%
AST, G0 - G3	3 0.3%	4 0.9%
AST, G0 - G4	0 0%	0 0%
AST, G0 - Unknown	40 4.5%	19 4.2%
AST, G1 - G0	24 2.7%	15 3.3%
AST, G1 - G1	18 2%	11 2.4%
AST, G1 - G2	3 0.3%	1 0.2%
AST, G1 - G3	2 0.2%	0 0%
AST, G1 - G4	0 0%	0 0%
AST, G1 - Unknown	1 0.1%	1 0.2%
AST, G2 - G0	0 0%	0 0%
AST, G2 - G1	0 0%	0 0%
AST, G2 - G2	1 0.1%	0 0%
AST, G2 - G3	0 0%	0 0%
AST, G2 - G4	0 0%	0 0%
AST, G2 - Unknown	1 0.1%	0 0%
AST, Total - G0	728 81.3%	374 83.1%
AST, Total - G1	107 12%	48 10.7%
AST, Total - G2	9 1%	4 0.9%
AST, Total - G3	5 0.6%	4 0.9%
AST, Total - G4	0 0%	0 0%
AST, Total - Unknown	45 5%	20 4.4%
AP, Unknown - G0	9 1%	6 1.3%
AP, Unknown - G1	0 0%	1 0.2%
AP, Unknown - G2	1 0.1%	0 0%
AP, Unknown - G3	0 0%	0 0%
AP, Unknown - G4	0 0%	0 0%
AP, Unknown - Unknown	2 0.2%	0 0%
AP, G0 - G0	749 83.7%	378 84%
AP, G0 - G1	56 6.3%	18 4%
AP, G0 - G2	3 0.3%	4 0.9%
AP, G0 - G3	2 0.2%	1 0.2%
AP, G0 - G4	0 0%	0 0%
AP, G0 - Unknown	38 4.2%	18 4%
AP, G1 - G0	18 2%	13 2.9%
AP, G1 - G1	14 1.6%	9 2%
AP, G1 - G2	0 0%	0 0%
AP, G1 - G3	0 0%	0 0%
AP, G1 - G4	0 0%	0 0%
AP, G1 - Unknown	2 0.2%	2 0.4%
AP, Total - G0	776 86.7%	397 88.2%
AP, Total - G1	70 7.8%	28 6.2%
AP, Total - G2	4 0.4%	4 0.9%
AP, Total - G3	2 0.2%	1 0.2%
AP, Total - G4	0 0%	0 0%
AP, Total - Unknown	42 4.7%	20 4.4%
BIL, Unknown - G0	7 0.8%	5 1.1%
BIL, Unknown - G1	1 0.1%	0 0%
BIL, Unknown - G2	0 0%	0 0%
BIL, Unknown - G3	0 0%	0 0%
BIL, Unknown - G4	0 0%	0 0%
BIL, Unknown - Unknown	1 0.1%	1 0.2%
BIL, G0 - G0	771 86.1%	383 85.1%
BIL, G0 - G1	33 3.7%	21 4.7%
BIL, G0 - G2	3 0.3%	2 0.4%
BIL, G0 - G3	0 0%	1 0.2%
BIL, G0 - G4	0 0%	0 0%
BIL,G 0 - Unknown	44 4.9%	19 4.2%
BIL, G1 -G 0	11 1.2%	3 0.7%
BIL, G1 - G1	10 1.1%	5 1.1%
BIL, G1 -G 2	9 1%	4 0.9%
BIL, G1 - G3	0 0%	0 0%
BIL, G1 - G4	0 0%	0 0%
BIL, G1 - Unknown	3 0.3%	2 0.4%
BIL, G2 - G0	0 0%	0 0%
BIL, G2 - G1	0 0%	2 0.4%
BIL, G2 - G2	0 0%	2 0.4%
BIL, G2 - G3	0 0%	0 0%
BIL, G2 - G4	0 0%	0 0%
BIL, G2 - Unknown	1 0.1%	0 0%
BIL, Total - G0	789 88.2%	391 86.9%
BIL, Total - G1	44 4.9%	28 6.2%
BIL, Total - G2	12 1.3%	8 1.8%
BIL, Total - G3	0 0%	1 0.2%
BIL, Total - G4	0 0%	0 0%
BIL, Total - Unknown	49 5.5%	22 4.9%
CREA, Unknown - G0	2 0.2%	1 0.2%
CREA, Unknown - G1	0 0%	0 0%
CREA, Unknown - G2	0 0%	0 0%
CREA, Unknown - G3	0 0%	0 0%
CREA, Unknown - G4	0 0%	0 0%
CREA, Unknown - Unknown	1 0.1%	0 0%
CREA, G0 - G0	789 88.2%	391 86.9%
CREA, G0 - G1	31 3.5%	19 4.2%
CREA, G0 - G2	0 0%	1 0.2%
CREA, G0 - G3	0 0%	1 0.2%
CREA, G0 - G4	0 0%	0 0%
CREA, G0 - Unknown	36 4%	19 4.2%
CREA, G1 - G0	8 0.9%	6 1.3%
CREA, G1 - G1	19 2.1%	12 2.7%
CREA, G1 - G2	3 0.3%	0 0%
CREA, G1 - G3	0 0%	0 0%
CREA, G1 - G4	0 0%	0 0%
CREA, G1 - Unknown	4 0.4%	0 0%
CREA, G2 - G0	0 0%	0 0%
CREA, G2 - G1	0 0%	0 0%
CREA, G2 - G2	1 0.1%	0 0%
CREA, G2 - G3	0 0%	0 0%
CREA, G2 - G4	0 0%	0 0%
CREA, G2 - Unknown	0 0%	0 0%
CREA, Total - G0	799 89.3%	398 88.4%
CREA, Total - G1	50 5.6%	31 6.9%
CREA, Total - G2	4 0.4%	1 0.2%
CREA, Total - G3	0 0%	1 0.2%
CREA, Total - G4	0 0%	0 0%
CREA, Total - Unknown	41 4.6%	19 4.2%
HGB, Unknown - G0	2 0.2%	1 0.2%
HGB, Unknown - G1	1 0.1%	0 0%
HGB, Unknown - G2	0 0%	0 0%
HGB, Unknown - G3	0 0%	0 0%
HGB, Unknown - G4	0 0%	0 0%
HGB, Unknown - Unknown	0 0%	0 0%
HGB, G0 - G0	636 71.1%	326 72.4%
HGB, G0 - G1	78 8.7%	28 6.2%
HGB, G0 - G2	7 0.8%	3 0.7%
HGB, G0 - G3	2 0.2%	1 0.2%
HGB, G0 - G4	0 0%	0 0%
HGB, G0 - Unknown	35 3.9%	17 3.8%
HGB, G1 - G0	39 4.4%	27 6%
HGB, G1 - G1	77 8.6%	41 9.1%
HGB, G1 - G2	7 0.8%	2 0.4%
HGB, G1 - G3	1 0.1%	0 0%
HGB, G1 - G4	1 0.1%	0 0%
HGB, G1 - Unknown	4 0.4%	3 0.7%
HGB, G2 - G0	1 0.1%	1 0.2%
HGB, G2 - G1	1 0.1%	0 0%
HGB, G2 - G2	2 0.2%	0 0%
HGB, G2 - G3	0 0%	0 0%
HGB, G2 - G4	0 0%	0 0%
HGB, G2 - Unknown	0 0%	0 0%
HGB, Total - G0	678 75.8%	355 78.9%
HGB, Total - G1	157 17.5%	69 15.3%
HGB, Total - G2	16 1.8%	5 1.1%
HGB, Total - G3	3 0.3%	1 0.2%
HGB, Total - G4	1 0.1%	0 0%
HGB, Total - Unknown	39 4.4%	20 4.4%
LEU, Unknown - G0	2 0.2%	1 0.2%
LEU, Unknown - G1	1 0.1%	0 0%
LEU, Unknown - G2	0 0%	0 0%
LEU, Unknown - G3	0 0%	0 0%
LEU, Unknown - G4	0 0%	0 0%
LEU, Unknown - Unknown	0 0%	0 0%
LEU, G0 - G0	762 85.1%	382 84.9%
LEU, G0 - G1	53 5.9%	31 6.9%
LEU, G0 - G2	4 0.4%	2 0.4%
LEU, G0 - G3	0 0%	0 0%
LEU, G0 - G4	2 0.2%	0 0%
LEU, G0 - Unknown	39 4.4%	18 4%
LEU, G1 - G0	13 1.5%	8 1.8%
LEU, G1 - G1	15 1.7%	6 1.3%
LEU, G1 - G2	1 0.1%	1 0.2%
LEU, G1 - G3	0 0%	0 0%
LEU, G1 - G4	0 0%	0 0%
LEU, G1 - Unknown	0 0%	1 0.2%
LEU, G2 - G0	0 0%	0 0%
LEU, G2 - G1	1 0.1%	0 0%
LEU, G2 - G2	0 0%	0 0%
LEU, G2 - G3	1 0.1%	0 0%
LEU, G2 - G4	0 0%	0 0%
LEU, G2 - Unknown	0 0%	0 0%
LEU, Total - G0	777 86.8%	391 86.9%
LEU, Total - G1	70 7.8%	37 8.2%
LEU, Total - G2	5 0.6%	3 0.7%
LEU, Total - G3	1 0.1%	0 0%
LEU, Total - G4	2 0.2%	0 0%
LEU, Total - Unknown	39 4.4%	19 4.2%
LYMPH, Unknown - G0	8 0.9%	1 0.2%
LYMPH, Unknown - G1	2 0.2%	2 0.4%
LYMPH, Unknown - G2	0 0%	0 0%
LYMPH, Unknown - G3	0 0%	0 0%
LYMPH, Unknown - G4	0 0%	0 0%
LYMPH, Unknown - Unknown	0 0%	0 0%
LYMPH, G0 - G0	633 70.7%	303 67.3%
LYMPH, G0 - G1	93 10.4%	57 12.7%
LYMPH, G0 - G2	17 1.9%	8 1.8%
LYMPH, G0 - G3	4 0.4%	0 0%
LYMPH, G0 - G4	0 0%	0 0%
LYMPH, G0 - Unknown	38 4.2%	22 4.9%
LYMPH, G1 - G0	29 3.2%	9 2%
LYMPH, G1 - G1	49 5.5%	37 8.2%
LYMPH, G1 - G2	4 0.4%	6 1.3%
LYMPH, G1 - G3	4 0.4%	0 0%
LYMPH, G1 - G4	0 0%	0 0%
LYMPH, G1 - Unknown	4 0.4%	0 0%
LYMPH, G2 - G0	1 0.1%	1 0.2%
LYMPH, G2 - G1	4 0.4%	1 0.2%
LYMPH, G2 - G2	2 0.2%	2 0.4%
LYMPH, G2 - G3	2 0.2%	0 0%
LYMPH, G2 - G4	0 0%	0 0%
LYMPH, G2 - Unknown	0 0%	0 0%
LYMPH, G3 - G0	0 0%	0 0%
LYMPH, G3 - G1	0 0%	1 0.2%
LYMPH, G3 - G2	0 0%	0 0%
LYMPH, G3 - G3	0 0%	0 0%
LYMPH, G3 - G4	0 0%	0 0%
LYMPH, G3 - Unknown	0 0%	0 0%
LYMPH, Total - G0	671 75%	314 69.8%
LYMPH, Total - G1	148 16.5%	98 21.8%
LYMPH, Total - G2	23 2.6%	16 3.6%
LYMPH, Total - G3	10 1.1%	0 0%
LYMPH, Total - G4	0 0%	0 0%
LYMPH, Total - Unknown	42 4.7%	22 4.9%
NEU, Unknown - G0	6 0.7%	1 0.2%
NEU, Unknown - G1	0 0%	1 0.2%
NEU, Unknown - G2	0 0%	0 0%
NEU, Unknown - G3	0 0%	0 0%
NEU, Unknown - G4	0 0%	0 0%
NEU, Unknown - Unknown	0 0%	0 0%
NEU, G0 - G0	781 87.3%	393 87.3%
NEU, G0 - G1	39 4.4%	16 3.6%
NEU, G0 - G2	9 1%	2 0.4%
NEU, G0 - G3	0 0%	0 0%
NEU, G0 - G4	1 0.1%	0 0%
NEU, G0 - Unknown	43 4.8%	22 4.9%
NEU, G1 - G0	7 0.8%	10 2.2%
NEU, G1 - G1	6 0.7%	3 0.7%
NEU, G1 - G2	1 0.1%	2 0.4%
NEU, G1 - G3	0 0%	0 0%
NEU, G1 - G4	0 0%	0 0%
NEU, G1 - Unknown	0 0%	0 0%
NEU, G2 - G0	0 0%	0 0%
NEU, G2 - G1	1 0.1%	0 0%
NEU, G2 - G2	0 0%	0 0%
NEU, G2 - G3	0 0%	0 0%
NEU, G2 - G4	0 0%	0 0%
NEU, G2 - Unknown	0 0%	0 0%
NEU, Total - G0	794 88.7%	404 89.8%
NEU, Total - G1	46 5.1%	20 4.4%
NEU, Total - G2	10 1.1%	4 0.9%
NEU, Total - G3	0 0%	0 0%
NEU, Total - G4	1 0.1%	0 0%
NEU, Total - Unknown	43 4.8%	22 4.9%
PLA, Unknown - G0	4 0.4%	1 0.2%
PLA, Unknown - G1	0 0%	0 0%
PLA, Unknown - G2	0 0%	0 0%
PLA, Unknown - G3	0 0%	0 0%
PLA, Unknown - G4	0 0%	0 0%
PLA, Unknown - Unknown	0 0%	0 0%
PLA, G0 - G0	796 88.9%	390 86.7%
PLA, G0 - G1	34 3.8%	25 5.6%
PLA, G0 - G2	0 0%	1 0.2%
PLA, G0 - G3	0 0%	0 0%
PLA, G0 - G4	1 0.1%	3 0.7%
PLA, G0 - Unknown	36 4%	17 3.8%
PLA, G1 - G0	4 0.4%	1 0.2%
PLA, G1 - G1	15 1.7%	10 2.2%
PLA, G1 - G2	1 0.1%	0 0%
PLA, G1 - G3	0 0%	0 0%
PLA, G1 - G4	0 0%	0 0%
PLA, G1 - Unknown	3 0.3%	2 0.4%
PLA, Total - G0	804 89.8%	392 87.1%
PLA, Total - G1	49 5.5%	35 7.8%
PLA, Total - G2	1 0.1%	1 0.2%
PLA, Total - G3	0 0%	0 0%
PLA, Total - G4	1 0.1%	3 0.7%
PLA, Total - Unknown	39 4.4%	19 4.2%

11. Secondary Outcome

Title	Number of Subjects With Any Adverse Events (AEs)
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	MAGE-A3 Group	Placebo Group
Arm/Group Description	Patients who received up to 13 doses of recMAGE-A3 + AS15 ASCI. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Patients who received up to 13 doses of placebo. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.
Measure Participants	895	450
Count of Participants [Participants]	822 91.8%	333 74%

12. Secondary Outcome

Title	Number of Subjects With Any Serious Adverse Events (SAEs)
Description	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	MAGE-A3 Group	Placebo Group
Arm/Group Description	Patients who received up to 13 doses of recMAGE-A3 + AS15 ASCI. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Patients who received up to 13 doses of placebo. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.
Measure Participants	895	450
Count of Participants [Participants]	129 14.4%	64 14.2%

13. Secondary Outcome

Title	Number of Subjects With Potential Immune-mediated Diseases (pIMDs)
Description	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	MAGE-A3 Group	Placebo Group
Arm/Group Description	Patients who received up to 13 doses of recMAGE-A3 + AS15 ASCI. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.	Patients who received up to 13 doses of placebo. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.
Measure Participants	895	450
Count of Participants [Participants]	33 3.7%	23 5.1%

Adverse Events

Time Frame	Adverse events (AEs): Within the 31-day (Days 0-30) follow-up period after treatment. Serious Adverse Events: from Day 0 up to study end (up to 5 years).
Arm/Group Title	MAGE-A3 Group		Placebo Group
Arm/Group Description	Patients who received up to 13 doses of recMAGE-A3 + AS15 ASCI. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.		Patients who received up to 13 doses of placebo. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.
All Cause Mortality
	MAGE-A3 Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/895 (0.6%)		1/450 (0.2%)
Serious Adverse Events
	MAGE-A3 Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	129/895 (14.4%)		64/450 (14.2%)
Blood and lymphatic system disorders
Anaemia	1/895 (0.1%)	1	0/450 (0%)	0
Disseminated intravascular coagulation	0/895 (0%)	0	1/450 (0.2%)	1
Haemolytic uraemic syndrome	0/895 (0%)	0	1/450 (0.2%)	1
Leukopenia	1/895 (0.1%)	1	0/450 (0%)	0
Lymphadenitis	1/895 (0.1%)	1	0/450 (0%)	0
Lymphadenopathy	1/895 (0.1%)	1	0/450 (0%)	0
Neutropenia	1/895 (0.1%)	1	0/450 (0%)	0
Thrombocytopenia	1/895 (0.1%)	1	0/450 (0%)	0
Thrombocytopenic purpura	0/895 (0%)	0	1/450 (0.2%)	1
Cardiac disorders
Angina pectoris	1/895 (0.1%)	1	0/450 (0%)	0
Atrioventricular block	1/895 (0.1%)	1	0/450 (0%)	0
Atrioventricular block second degree	1/895 (0.1%)	1	0/450 (0%)	0
Bradycardia	1/895 (0.1%)	1	1/450 (0.2%)	1
Cardiac arrest	2/895 (0.2%)	2	0/450 (0%)	0
Cardiac failure	1/895 (0.1%)	1	0/450 (0%)	0
Cardiac failure acute	1/895 (0.1%)	1	0/450 (0%)	0
Coronary artery disease	1/895 (0.1%)	1	1/450 (0.2%)	1
Intracardiac thrombus	1/895 (0.1%)	1	0/450 (0%)	0
Ischaemic cardiomyopathy	1/895 (0.1%)	1	0/450 (0%)	0
Left ventricular failure	1/895 (0.1%)	1	0/450 (0%)	0
Myocardial infarction	1/895 (0.1%)	1	1/450 (0.2%)	1
Myocardial ischaemia	2/895 (0.2%)	2	0/450 (0%)	0
Ear and labyrinth disorders
Vertigo	1/895 (0.1%)	1	0/450 (0%)	0
Vertigo positional	1/895 (0.1%)	1	0/450 (0%)	0
Endocrine disorders
Autoimmune thyroiditis	1/895 (0.1%)	1	0/450 (0%)	0
Basedow's disease	1/895 (0.1%)	1	0/450 (0%)	0
Lymphocytic hypophysitis	0/895 (0%)	0	1/450 (0.2%)	1
Polyglandular autoimmune syndrome type ii	0/895 (0%)	0	1/450 (0.2%)	1
Eye disorders
Retinal detachment	0/895 (0%)	0	1/450 (0.2%)	1
Retinal vascular thrombosis	1/895 (0.1%)	1	0/450 (0%)	0
Retinopathy	0/895 (0%)	0	1/450 (0.2%)	1
Vision blurred	1/895 (0.1%)	1	0/450 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/895 (0.1%)	1	0/450 (0%)	0
Diverticulum	1/895 (0.1%)	1	0/450 (0%)	0
Dysphagia	0/895 (0%)	0	1/450 (0.2%)	1
Ileal perforation	1/895 (0.1%)	1	0/450 (0%)	0
Inguinal hernia	1/895 (0.1%)	1	1/450 (0.2%)	1
Large intestine perforation	1/895 (0.1%)	1	0/450 (0%)	0
Nausea	1/895 (0.1%)	1	0/450 (0%)	0
Pancreatitis	1/895 (0.1%)	1	0/450 (0%)	0
Umbilical hernia	1/895 (0.1%)	1	0/450 (0%)	0
Vomiting	1/895 (0.1%)	1	0/450 (0%)	0
General disorders
Chest pain	1/895 (0.1%)	1	1/450 (0.2%)	1
Device dislocation	1/895 (0.1%)	1	0/450 (0%)	0
Impaired healing	0/895 (0%)	0	1/450 (0.2%)	1
Oedema peripheral	1/895 (0.1%)	1	0/450 (0%)	0
Pyrexia	1/895 (0.1%)	1	0/450 (0%)	0
Hepatobiliary disorders
Autoimmune hepatitis	0/895 (0%)	0	1/450 (0.2%)	1
Bile duct obstruction	0/895 (0%)	0	1/450 (0.2%)	1
Bile duct stone	0/895 (0%)	0	1/450 (0.2%)	1
Cholecystitis chronic	0/895 (0%)	0	1/450 (0.2%)	1
Cholelithiasis	0/895 (0%)	0	2/450 (0.4%)	2
Hepatic steatosis	1/895 (0.1%)	1	0/450 (0%)	0
Hepatitis acute	0/895 (0%)	0	1/450 (0.2%)	1
Hydrocholecystis	1/895 (0.1%)	1	0/450 (0%)	0
Jaundice	1/895 (0.1%)	1	0/450 (0%)	0
Immune system disorders
Sarcoidosis	0/895 (0%)	0	1/450 (0.2%)	1
Infections and infestations
Abscess limb	1/895 (0.1%)	1	0/450 (0%)	0
Appendicitis	2/895 (0.2%)	2	0/450 (0%)	0
Cellulitis	1/895 (0.1%)	1	5/450 (1.1%)	5
Cellulitis enterococcal	1/895 (0.1%)	1	0/450 (0%)	0
Cystitis	1/895 (0.1%)	1	0/450 (0%)	0
Endocarditis bacterial	1/895 (0.1%)	1	0/450 (0%)	0
Erysipelas	7/895 (0.8%)	9	5/450 (1.1%)	5
Escherichia urinary tract infection	1/895 (0.1%)	1	0/450 (0%)	0
H1n1 influenza	1/895 (0.1%)	1	0/450 (0%)	0
Localised infection	1/895 (0.1%)	1	0/450 (0%)	0
Lung infection	1/895 (0.1%)	1	0/450 (0%)	0
Lymph node abscess	1/895 (0.1%)	1	0/450 (0%)	0
Lymphangitis	2/895 (0.2%)	2	1/450 (0.2%)	1
Pharyngitis	1/895 (0.1%)	1	0/450 (0%)	0
Pilonidal cyst	1/895 (0.1%)	1	0/450 (0%)	0
Pneumonia haemophilus	1/895 (0.1%)	1	0/450 (0%)	0
Post procedural infection	0/895 (0%)	0	1/450 (0.2%)	1
Postoperative abscess	2/895 (0.2%)	2	0/450 (0%)	0
Prostatitis escherichia coli	0/895 (0%)	0	1/450 (0.2%)	1
Sepsis	2/895 (0.2%)	2	0/450 (0%)	0
Streptococcal infection	1/895 (0.1%)	1	0/450 (0%)	0
Subcutaneous abscess	0/895 (0%)	0	1/450 (0.2%)	1
Urinary tract infection	1/895 (0.1%)	1	0/450 (0%)	0
Urosepsis	1/895 (0.1%)	1	0/450 (0%)	0
Wound infection	1/895 (0.1%)	1	0/450 (0%)	0
Injury, poisoning and procedural complications
Asbestosis	1/895 (0.1%)	1	0/450 (0%)	0
Contrast media reaction	0/895 (0%)	0	1/450 (0.2%)	1
Electric shock	1/895 (0.1%)	1	0/450 (0%)	0
Femur fracture	1/895 (0.1%)	1	0/450 (0%)	0
Humerus fracture	0/895 (0%)	0	1/450 (0.2%)	1
Patella fracture	1/895 (0.1%)	1	0/450 (0%)	0
Periprosthetic fracture	1/895 (0.1%)	1	0/450 (0%)	0
Post procedural fistula	1/895 (0.1%)	1	0/450 (0%)	0
Post procedural haematoma	1/895 (0.1%)	1	0/450 (0%)	0
Postoperative hernia	1/895 (0.1%)	1	0/450 (0%)	0
Radius fracture	2/895 (0.2%)	2	0/450 (0%)	0
Tendon rupture	0/895 (0%)	0	1/450 (0.2%)	1
Tibia fracture	1/895 (0.1%)	1	0/450 (0%)	0
Investigations
Blood alkaline phosphatase increased	1/895 (0.1%)	1	0/450 (0%)	0
Gamma-glutamyltransferase increased	1/895 (0.1%)	1	0/450 (0%)	0
Transaminases increased	1/895 (0.1%)	1	0/450 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/895 (0.1%)	1	0/450 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	2/895 (0.2%)	2	1/450 (0.2%)	1
Lumbar spinal stenosis	1/895 (0.1%)	1	0/450 (0%)	0
Neck pain	1/895 (0.1%)	1	0/450 (0%)	0
Osteoarthritis	2/895 (0.2%)	2	1/450 (0.2%)	1
Pain in extremity	0/895 (0%)	0	1/450 (0.2%)	1
Synovial cyst	1/895 (0.1%)	1	0/450 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	25/895 (2.8%)	34	13/450 (2.9%)	14
Bladder transitional cell carcinoma	0/895 (0%)	0	1/450 (0.2%)	1
Clear cell renal cell carcinoma	1/895 (0.1%)	1	0/450 (0%)	0
Endometrial adenocarcinoma	0/895 (0%)	0	1/450 (0.2%)	1
Focal nodular hyperplasia	0/895 (0%)	0	1/450 (0.2%)	1
Glioblastoma	1/895 (0.1%)	1	0/450 (0%)	0
Invasive lobular breast carcinoma	0/895 (0%)	0	1/450 (0.2%)	1
Lentigo maligna	1/895 (0.1%)	1	1/450 (0.2%)	1
Lymphoma	1/895 (0.1%)	1	0/450 (0%)	0
Malignant melanoma	9/895 (1%)	9	3/450 (0.7%)	3
Malignant melanoma in situ	2/895 (0.2%)	2	0/450 (0%)	0
Malignant melanoma stage i	1/895 (0.1%)	1	0/450 (0%)	0
Non-hodgkin's lymphoma	1/895 (0.1%)	1	0/450 (0%)	0
Papillary thyroid cancer	0/895 (0%)	0	1/450 (0.2%)	1
Polycythaemia vera	1/895 (0.1%)	1	0/450 (0%)	0
Porocarcinoma	1/895 (0.1%)	1	0/450 (0%)	0
Prostate cancer	1/895 (0.1%)	1	1/450 (0.2%)	1
Prostatic adenoma	1/895 (0.1%)	1	0/450 (0%)	0
Renal cell carcinoma	2/895 (0.2%)	2	0/450 (0%)	0
Squamous cell carcinoma of skin	6/895 (0.7%)	9	3/450 (0.7%)	3
Superficial spreading melanoma stage unspecified	0/895 (0%)	0	1/450 (0.2%)	1
Thyroid cancer	1/895 (0.1%)	1	0/450 (0%)	0
Urinary tract neoplasm	1/895 (0.1%)	1	0/450 (0%)	0
Uterine leiomyoma	2/895 (0.2%)	2	0/450 (0%)	0
Nervous system disorders
Cerebral haemorrhage	1/895 (0.1%)	1	0/450 (0%)	0
Cerebrovascular accident	1/895 (0.1%)	1	0/450 (0%)	0
Meningism	1/895 (0.1%)	1	0/450 (0%)	0
Multiple sclerosis	1/895 (0.1%)	1	0/450 (0%)	0
Polyneuropathy	1/895 (0.1%)	1	0/450 (0%)	0
Psychomotor skills impaired	0/895 (0%)	0	1/450 (0.2%)	1
Subarachnoid haemorrhage	1/895 (0.1%)	1	0/450 (0%)	0
Psychiatric disorders
Major depression	0/895 (0%)	0	1/450 (0.2%)	1
Mental disorder	1/895 (0.1%)	1	0/450 (0%)	0
Mental status changes	1/895 (0.1%)	1	0/450 (0%)	0
Suicide attempt	0/895 (0%)	0	1/450 (0.2%)	2
Renal and urinary disorders
Bladder neck sclerosis	1/895 (0.1%)	2	0/450 (0%)	0
Nephrolithiasis	1/895 (0.1%)	1	0/450 (0%)	0
Renal failure	1/895 (0.1%)	1	0/450 (0%)	0
Urinary retention	1/895 (0.1%)	1	0/450 (0%)	0
Reproductive system and breast disorders
Ovarian cyst	0/895 (0%)	0	1/450 (0.2%)	1
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	3/895 (0.3%)	3	0/450 (0%)	0
Organising pneumonia	0/895 (0%)	0	1/450 (0.2%)	1
Pleural effusion	1/895 (0.1%)	1	0/450 (0%)	0
Pulmonary embolism	2/895 (0.2%)	2	0/450 (0%)	0
Pulmonary oedema	1/895 (0.1%)	1	0/450 (0%)	0
Respiratory failure	1/895 (0.1%)	1	0/450 (0%)	0
Vocal cord polyp	1/895 (0.1%)	1	0/450 (0%)	0
Skin and subcutaneous tissue disorders
Actinic elastosis	1/895 (0.1%)	1	0/450 (0%)	0
Dermal cyst	0/895 (0%)	0	1/450 (0.2%)	1
Vascular disorders
Aortic aneurysm	1/895 (0.1%)	1	0/450 (0%)	0
Deep vein thrombosis	2/895 (0.2%)	2	1/450 (0.2%)	1
Haematoma	0/895 (0%)	0	1/450 (0.2%)	1
Hypertension	1/895 (0.1%)	1	1/450 (0.2%)	1
Intermittent claudication	1/895 (0.1%)	1	0/450 (0%)	0
Lymphocele	0/895 (0%)	0	1/450 (0.2%)	1
Lymphoedema	1/895 (0.1%)	1	0/450 (0%)	0
Peripheral arterial occlusive disease	1/895 (0.1%)	2	0/450 (0%)	0
Thrombosis	0/895 (0%)	0	1/450 (0.2%)	1
Other (Not Including Serious) Adverse Events
	MAGE-A3 Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	819/895 (91.5%)		327/450 (72.7%)
Gastrointestinal disorders
Diarrhoea	46/895 (5.1%)	61	19/450 (4.2%)	26
Nausea	123/895 (13.7%)	266	32/450 (7.1%)	43
General disorders
Asthenia	149/895 (16.6%)	354	46/450 (10.2%)	68
Chills	179/895 (20%)	432	15/450 (3.3%)	23
Fatigue	210/895 (23.5%)	490	63/450 (14%)	116
Influenza like illness	261/895 (29.2%)	902	30/450 (6.7%)	46
Injection site erythema	90/895 (10.1%)	241	3/450 (0.7%)	3
Injection site oedema	48/895 (5.4%)	134	3/450 (0.7%)	5
Injection site pain	325/895 (36.3%)	1057	22/450 (4.9%)	37
Injection site reaction	160/895 (17.9%)	500	6/450 (1.3%)	9
Pain	191/895 (21.3%)	480	19/450 (4.2%)	26
Pyrexia	380/895 (42.5%)	1240	35/450 (7.8%)	44
Musculoskeletal and connective tissue disorders
Arthralgia	84/895 (9.4%)	165	31/450 (6.9%)	43
Myalgia	188/895 (21%)	456	23/450 (5.1%)	39
Pain in extremity	115/895 (12.8%)	207	26/450 (5.8%)	28
Nervous system disorders
Headache	205/895 (22.9%)	550	55/450 (12.2%)	128
Skin and subcutaneous tissue disorders
Erythema	138/895 (15.4%)	297	10/450 (2.2%)	10

Limitations/Caveats

The study was terminated early on 08 Sep 2015 following assessment of the two co-primary endpoints showed the lack of efficacy of the study product.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.