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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00942162

Acronym

PREDICT

Enrollment

125

Registered

2009-07-20

Start date

2009-08-14

Completion date

2015-04-01

Last updated

2020-12-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Melanoma

Keywords

ASCI, Melanoma, Immunotherapeutic, Tumor antigen, PREDICT

Brief summary

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

Detailed description

In this study, patients were to receive a maximum of 24 doses of recMAGE-A3 + AS15 according four cycles over a period of four years. An active follow-phase (up to five years after registration into the study) was planned for all patients. As of Amendment 2, there will no longer be an active follow-up of patients after discontinuation or completion of the treatment. The study will end approximately 30 days after the last dose will be administered. In addition, no more biological samples will be collected for protocol research purposes. For each biological sample already collected in the scope of this study and not tested yet, testing will not be performed by default, except if a scientific rationale remains relevant. Blood sampling for safety monitoring as per protocol will continue.

Interventions

BIOLOGICALImmunotherapeutic GSK2132231A

Intramuscular administration

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Male or female patients with histologically proven metastatic cutaneous melanoma that is measurable. * Patients with regional or distant cutaneous, subcutaneous or lymph-node metastasis can be included in the study, provided the disease is not amenable to curative treatment with surgery. In terms of the AJCC 2002 classification, this includes patients with unresectable stage III melanoma including in-transit metastases or patient with stage IV M1a melanoma. * Written informed consent obtained from the patient prior to performance of any study specific procedure. * Patient is \>= 18 years at the time of signature of the informed consent form. * The patient's tumor shows expression of MAGE-A3, as determined by RT-PCR analysis on a fresh tumor tissue sample obtained during the screening phase. * Fresh tissue from the same lesion as used for MAGE-A3 expression testing must be available for the testing of the predictive gene signature. * Formalin-fixed paraffin-embedded (FFPE) tissue must be available for complementary MAGE-A3 and gene signature testing. * Patient fully recovered from any previous intervention (i.e., biopsy). * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Adequate bone-marrow reserve, adequate renal function and adequate hepatic function as assessed by standard laboratory criteria * If the patient is female, she must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for at least 30 days prior to registration in the trial, have a negative pregnancy test and continue such precautions during the entire study treatment period and for 2 months after completion of the injection series. * In the opinion of the investigator, the patient can and will comply with the protocol requirements.

Exclusion criteria

* Patients with unresectable stage IV M1b,c melanoma and patients with ocular and mucosal melanoma. * The patient has at any time received any systemic anticancer treatment. * Prior systemic treatment with an immunomodulator or loco-regional radiotherapy is permitted as prior adjuvant treatment provided that the last dose was administered at least 30 days before the registration into this trial; * Previous adjuvant treatment with a cancer vaccine containing a tumor antigen other than MAGE-A3 is allowed if the last administration took place at least 8 weeks before registration into the trial. * Prior isolated limb perfusion is permitted provided that the last dose was administered at least 30 days before registration into this trial * The patient is scheduled to receive any anti-cancer specific treatment, including radiotherapy, other immunotherapy, chemotherapy and immunomodulating agents. * The patient requires concomitant chronic treatment (more than 7 consecutive days) with systemic corticosteroids, or any other immunosuppressive agents. * The patient has a history of autoimmune disease such as, but not limited to, multiple sclerosis, lupus, and inflammatory bowel disease. Patients with vitiligo are not excluded. * The patient has a family history of congenital or hereditary immunodeficiency. * The patient is known to be positive for Human Immunodeficiency Virus (HIV). * History of allergic disease or reactions likely to be exacerbated by any component of the ASCI treatment. * The patient has previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancer or carcinoma in situ of the cervix and effectively treated malignancy that has been in remission for over 5 years and is highly likely to have been cured. * The patient has psychiatric or addictive disorders * The patient has an uncontrolled bleeding disorder. * The patient has concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk. * Use of any investigational or non-registered product (drug or vaccine) other than the study medication within the 30 days preceding the first investigational treatment injection or planned use during the study period. * Concurrently participating in another clinical study, at any time during the study period, in which the patient has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device). For female patients: the patient is pregnant or lactating.

Design outcomes

Primary

Measure	Time frame	Description
One-year Overall Survival Rate (OSR) Estimated by Complete Case Method	Month 0 - Month 12	The 1-year overall survival rate (OSR) in the GS+ Population would be above 50% (target = 71%), a percentage which was reported together with its 95% confidence interval (CI). Maximum 1-year OSR of any currently available treatment in the MAGE-A3-positive population = 50% (P0). This median OS of 12 months is based on the observed median OS for MAGE-A3-positive patients, whose tumor did not present the predictive GS. The target 1-year OSR for patients presenting the predictive GS = 71% (P1). This corresponds to a median OS of 24 months when assuming an exponential distribution of OS.
Number of Patients Reported With Serious Adverse Events (SAEs)	Month 0 - Month 49	Serious adverse events (SAEs) assessed included medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/ incapacity. Events which were part of the natural course of the disease under study (i.e., disease progression, recurrence) were captured as part of the clinical activity outcome variables in this study; therefore these did not need to be reported as SAEs. Progression/recurrence of the tumor in a patient was recorded as part of the clinical assessment data collection, and deaths due to progressive disease was recorded on a specific form, but not as an SAE. However, if the investigator considered that there was a causal relationship between treatment or protocol design/procedures and the disease progression/recurrence, then the event was reported as an SAE. Any new primary cancer (non-related to the cancer under study) was reported as an SAE.

Secondary

Measure	Time frame	Description
Progression-free Survival (PFS) by GS	Month 0 - Month 24	From study start (Month 0) to Month 24, each patient was censored out of the analysis at 1st report of disease progression or death. PFS was defined and calculated as the time from first treatment to either the first progression of the disease or the date of death, whichever occurred first. In case a patient went off protocol treatment, the date of first documented progression (if applicable) was to be used as date of progression. Patients still alive with no evidence of disease progression at the time of their last visit or for whom date of first documented progression was not applicable, were censored at the time of the last examination. PFS analysis was performed using the non-parametric Kaplan-Meier method.
Kaplan-Meier Estimates of the Progression-free Survival (PFS) at Months 6, 12 and 24, by Gene Signature	Month 6, Month 12, Month 24	PFS was defined as the time from the date of registration of the patient to either the date of disease progression or the date of death, whichever comes first. Patients alive and without disease progression were censored at the date of their last tumor evaluation. The PFS estimates were assessed by the Kaplan-Meier method and expressed as the percentage of patients who did not progress and were alive at a given time.
Overall Survival (OS) by GS	Up to 5 years from the time of registration.	OS was defined as the time from registration of the patient until death, with patients alive at the time of analysis censored at the time of the last contact.
Time to Treatment Failure (TTF) by GS	Month 0 - Month 24	The TTF was defined as the time from registration of the patient until the date of the last treatment administration, irrespective of the reason for study treatment discontinuation.
Best Overall Response (BOR) by GS	Month 0 - Month 24	The BOR was the best response recorded from the start of the treatment until disease progression/ recurrence, except for confirmed objective response, which was reported as BOR independently of its time of occurrence. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions without any new lesions and/or progression of existing non-target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (PD) without any new lesions and/or progression of existing non-target lesions; PD, \>=20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; NE = Non-evaluable response.
Duration of Response (CR or PR)	Month 0 - Month 24	Duration of response was measured from the time when the measurement criteria for CR/ PR (whichever was recorded first) were met until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded since the treatment started). Note: As there was only one patient analysed in the GSK2132231A GS- Group, the median duration of response was not calculated for this latter group.
Duration of Stable Disease (SD), or Time-to-Progression (TTP) by GS	Month 0 - Month 24	The duration of stable disease (SD), or TTP, was tabulated for patients whose best response was SD. The minimal time interval required between 2 measurements for determination of SD was 12 weeks.
Number of Seropositive Patients for Anti-MAGE-A3	PRE = Pre any dose, PII(W4) = Post-Dose 2 (Week 4), PVI(W12) = Post-Dose 6 (Week 12), PXII(W31) = Post-Dose 12 (Week 31), PXVI(W54) = Post-Dose 16 (Week 54), PXVII(M18) = Post-Dose 17 (Month 18), PXXIV(M49) = Post-Dose 24 (Month 49).	Seropositive patients were those patients with anti-MAGE-A3 antibody concentrations ≥ 27 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).
Anti-MAGE-A3 Antibody Concentrations	PRE = Pre any dose, PII(W4) = Post-Dose 2 (Week 4), PVI(W12) = Post-Dose 6 (Week 12), PXII(W31) = Post-Dose 12 (Week 31), PXVI(W54) = Post-Dose 16 (Week 54), PXVII(M18) = Post-Dose 17 (Month 18), PXXIV(M49) = Post-Dose 24 (Month 49)	Anti-MAGE-A3 antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in EL.U/mL.
Concentrations of Antibodies Against Protein D (Anti-PD)	PRE = Pre any dose, PII(W4) = Post-Dose 2 (Week 4), PVI(W12) = Post-Dose 6 (Week 12), PXII(W31) = Post-Dose 12 (Week 31), PXVI(W54) = Post-Dose 16 (Week 54), PXVII(M18) = Post-Dose 17 (Month 18), PXXIV(M49) = Post-Dose 24 (Month 49)	Anti-PD antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in EL.U/mL.
Anti-MAGE-A3 Antibody Response	PII(W4) = Post-Dose 2 (Week 4), PVI(W12) = Post-Dose 6 (Week 12), PXII(W31) = Post-Dose 12 (Week 31), PXVI(W54) = Post-Dose 16 (Week 54), PXVII(M18) = Post-Dose 17 (Month 18), PXXIV(M49) = Post-Dose 24 (Month 49)	Anti-MAGE-A3 antibody response defined as: For initially seronegative patients: post-vaccination antibody concentration ≥ 27 EL.U/mL; For initially seropositive patients: post-vaccination antibody concentration ≥ 2 fold the pre-vaccination antibody concentration.
Anti-PD Antibody Response	PII(W4) = Post-Dose 2 (Week 4), PVI(W12) = Post-Dose 6 (Week 12), PXII(W31) = Post-Dose 12 (Week 31), PXVI(W54) = Post-Dose 16 (Week 54), PXVII(M18) = Post-Dose 17 (Month 18), PXXIV(M49) = Post-Dose 24 (Month 49)	Anti-PD antibody response defined as: For initially seronegative patients: post-vaccination antibody concentration ≥ 100 EL.U/mL; For initially seropositive patients: post-vaccination antibody concentration ≥ 2 fold the pre-vaccination antibody concentration.
Number of Seropositive Patients for Protein D	PRE = Pre any dose, PII(W4) = Post-Dose 2 (Week 4), PVI(W12) = Post-Dose 6 (Week 12), PXII(W31) = Post-Dose 12 (Week 31), PXVI(W54) = Post-Dose 16 (Week 54), PXVII(M18) = Post-Dose 17 (Month 18), PXXIV(M49) = Post-Dose 24 (Month 49)	Seropositive patients were those patients with anti-PD antibody concentrations ≥ 100 EL.U/mL.
Number of Patients With Abnormal Aspartate Aminotransferase (AST) Values by Maximum Grade	Month 0 - Month 49 (each patient was censored out of the analysis at time of death)	The status of each patient as regards AST laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1 and Unknown (UNK).
Number of Patients With Abnormal Alkaline Phosphatase (ALK) Values by Maximum Grade	Month 0 - Month 49 (each patient was censored out of the analysis at time of death)	The status of each patient as regards ALK laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1 and Unknown (UNK).
Number of Patients With Abnormal Bilirubine (BIL) Values by Maximum Grade	Month 0 - Month 49 (each patient was censored out of the analysis at time of death)	The status of each patient as regards BIL laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0), G1 and G2. CTC grade statuses reported at SE were G0, G1, G2 and Unknown (UNK).
Number of Patients With Abnormal Creatinine (CREA) Values by Maximum Grade	Month 0 - Month 49 (each patient was censored out of the analysis at time of death)	The status of each patient as regards CREA laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0), G1 and G2. CTC grade statuses reported at SE were G0, G1, G2 and Unknown (UNK).
Number of Patients With Abnormal Hemoglobin (HGB) Values by Maximum Grade	Month 0 - Month 49 (each patient was censored out of the analysis at time of death)	The status of each patient as regards HGB laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0), G1 and G2. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
Number of Patients With Abnormal Leukocytes (LEU) Values by Maximum Grade	Month 0 - Month 49 (each patient was censored out of the analysis at time of death)	The status of each patient as regards LEU laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0), G1 and G2. CTC grade statuses reported at SE were G0, G1, G2, G4, and Unknown (UNK).
Number of Patients With Abnormal Lymphopenia (LYM) Values by Maximum Grade	Month 0 - Month 49 (each patient was censored out of the analysis at time of death)	The status of each patient as regards LYM laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0), G1, G2 and G3. CTC grade statuses reported at SE were G0, G1, G2, G3 and Unknown (UNK).
Number of Patients With Abnormal Neutrophils (NEU) Values by Maximum Grade	Month 0 - Month 49 (each patient was censored out of the analysis at time of death)	The status of each patient as regards NEU laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0), G1 and G2. CTC grade statuses reported at SE were G0, G1, G2, G3 and Unknown (UNK).
Number of Patients With Abnormal Platelets (PLT) Values by Maximum Grade	Month 0 - Month 49 (each patient was censored out of the analysis at time of death)	The status of each patient as regards PLT laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G4, and Unknown (UNK).
Number of Patients With Autoimmune Diseases or Immune-mediated Inflammatory Disorders	Month 0 - Month 49	Auto-immune diseases or immune-mediated inflammatory disorders were tabulated during the whole duration of the study (up to 30 days after the last administration of the study treatment). The results were tabulated as Any event(s) reported.
Number of Patients Reported With Unsolicited Adverse Events (AEs) by Maximum Grade.	Through 30 days after the last administration of the study treatment, approximately 49 months	The assessed AEs were ASCI-related adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE; Grade 5 = Death due to AE. An unsolicited AE covers any untoward medical occurrence in a clinical investigation patient temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Number of Patients Reported With Unsolicited AE(s)	Through 30 days after the last administration of the study treatment, approximately 49 months	An unsolicited AE covers any untoward medical occurrence in a clinical investigation patient temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Number of Patients With Abnormal Alanine Aminotransferase (ALT) Values by Maximum Grade	Month 0 - Month 49 (each patient was censored out of the analysis at time of death)	The status of each patient as regards ALT laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3 and Unknown (UNK).
Number of Patients With Diseases Characteristics by GS	Month 0 - Month 49	Cancer staging (characteristics and categories) as by the categorization by the American Joint Committee on Cancer (AJCC) Staging Manual 2002: Stage IIIA patients have up to three microscopic nodal metastases arising from a non-ulcerating primary melanoma and have an ' intermediate risk' for distant metastases and melanom-specific survival. Stage IIIB patients have up to three microscopic nodal metastases arising from a non-ulcerating melanoma or have up to three microscopic nodal metastases arising from an ulcerating melanoma, or have intralymphatic metastases without nodal metastases. They constitute a 'high-risk' group prognostically. The remaining patients with regional melanoma are Stage IIIC patients are at 'very high risk' for distant metastases and melanoma-specific mortality. Stage IV melanoma patients have metastasis at any distant site and constitute the group with the worst prognosis. Stage MC patients are those with confirmed missing cancer.

Countries

France, Germany, Ireland, Italy, Poland, Russia, Spain, United States

Participant flow

Pre-assignment details

During the screening the following steps occurred: check for inclusion/ exclusion criteria, contraindications/ precautions, medical history of the patients and signing informed consent forms. While 125 subjects were enrolled, only 123 started the study, as 2 subjects did not receive treatment and were excluded.

Participants by arm

Arm	Count
GSK2132231A GS+ Group Patients with the pre-specified gene signature (GS), who received intramuscularly up to 24 doses of MAGE-A3 ASCI (the study product), in 4 cycles. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening.	71
GSK2132231A GS- Group Patients without the pre-specified gene signature (GS), planned to receive intramuscularly up to 24 doses of MAGE-A3 ASCI (the study product), in 4 cycles. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening.	50
GSK2132231A GS-unknown Group Patients with unknown gene signature (GS), planned to receive intramuscularly up to 24 doses of MAGE\_A3 ASCI (the study product), in 4 cycles. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening.	2
Total	123

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Death	45	35	0
Overall Study	Lost to Follow-up	4	0	0
Overall Study	Other	14	13	2
Overall Study	Withdrawal by Subject	7	2	0

Baseline characteristics

Characteristic	GSK2132231A GS+ Group	GSK2132231A GS- Group	GSK2132231A GS-unknown Group	Total
Age, Continuous	66.9 Years STANDARD_DEVIATION 13.9	62.1 Years STANDARD_DEVIATION 12.6	60.5 Years STANDARD_DEVIATION 6.36	64.9 Years STANDARD_DEVIATION 13.45
Race/Ethnicity, Customized White - Caucasian/European heritage	71 Participants	50 Participants	2 Participants	123 Participants
Sex: Female, Male Female	42 Participants	23 Participants	0 Participants	65 Participants
Sex: Female, Male Male	29 Participants	27 Participants	2 Participants	58 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	3 / 123
other Total, other adverse events	107 / 123
serious Total, serious adverse events	19 / 123

Outcome results

Primary

Number of Patients Reported With Serious Adverse Events (SAEs)

Serious adverse events (SAEs) assessed included medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/ incapacity. Events which were part of the natural course of the disease under study (i.e., disease progression, recurrence) were captured as part of the clinical activity outcome variables in this study; therefore these did not need to be reported as SAEs. Progression/recurrence of the tumor in a patient was recorded as part of the clinical assessment data collection, and deaths due to progressive disease was recorded on a specific form, but not as an SAE. However, if the investigator considered that there was a causal relationship between treatment or protocol design/procedures and the disease progression/recurrence, then the event was reported as an SAE. Any new primary cancer (non-related to the cancer under study) was reported as an SAE.

Time frame: Month 0 - Month 49

Population: The analysis was performed on the Total Treated Population (TTP), which included all patients who received at least one dose of study treatment. Safety was assessed in the overall population regardless of GS status.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
GSK2132231A GS+ Group	Number of Patients Reported With Serious Adverse Events (SAEs)	19 Participants

Primary

One-year Overall Survival Rate (OSR) Estimated by Complete Case Method

The 1-year overall survival rate (OSR) in the GS+ Population would be above 50% (target = 71%), a percentage which was reported together with its 95% confidence interval (CI). Maximum 1-year OSR of any currently available treatment in the MAGE-A3-positive population = 50% (P0). This median OS of 12 months is based on the observed median OS for MAGE-A3-positive patients, whose tumor did not present the predictive GS. The target 1-year OSR for patients presenting the predictive GS = 71% (P1). This corresponds to a median OS of 24 months when assuming an exponential distribution of OS.

Time frame: Month 0 - Month 12

Population: The analysis was performed on the Total Treated Population (TTP), which included all patients who received at least one dose of study treatment, but did not include patients who dropped out from the study (i.e. patients alive at the last evaluation visit and followed for less than 1 year at first database freeze).

Arm	Measure	Value (NUMBER)
GSK2132231A GS+ Group	One-year Overall Survival Rate (OSR) Estimated by Complete Case Method	83.08 Percentage of Participants
GSK2132231A GS- Group	One-year Overall Survival Rate (OSR) Estimated by Complete Case Method	83.33 Percentage of Participants
GSK2132231A GS-unknown Group	One-year Overall Survival Rate (OSR) Estimated by Complete Case Method	100 Percentage of Participants

Secondary

Anti-MAGE-A3 Antibody Concentrations

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

Time frame: PRE = Pre any dose, PII(W4) = Post-Dose 2 (Week 4), PVI(W12) = Post-Dose 6 (Week 12), PXII(W31) = Post-Dose 12 (Week 31), PXVI(W54) = Post-Dose 16 (Week 54), PXVII(M18) = Post-Dose 17 (Month 18), PXXIV(M49) = Post-Dose 24 (Month 49)

Population: The analysis was performed on the According-To-Protocol Population (ATP) for immunogenicity, which included all evaluable patients for whom immunogenicity data were available.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
GSK2132231A GS+ Group	Anti-MAGE-A3 Antibody Concentrations	Anti-MAGE-A3, PXVI(W54)	3289.8 EL.U/mL
GSK2132231A GS+ Group	Anti-MAGE-A3 Antibody Concentrations	Anti-MAGE-A3, PVI(W12)	6190.1 EL.U/mL
GSK2132231A GS+ Group	Anti-MAGE-A3 Antibody Concentrations	Anti-MAGE-A3, PXXIV(M49)	7063.9 EL.U/mL
GSK2132231A GS+ Group	Anti-MAGE-A3 Antibody Concentrations	Anti-MAGE-A3, PXII(W31)	6724.2 EL.U/mL
GSK2132231A GS+ Group	Anti-MAGE-A3 Antibody Concentrations	Anti-MAGE-A3, PII(W4)	906.1 EL.U/mL
GSK2132231A GS+ Group	Anti-MAGE-A3 Antibody Concentrations	Anti-MAGE-A3, PRE	11.2 EL.U/mL
GSK2132231A GS+ Group	Anti-MAGE-A3 Antibody Concentrations	Anti-MAGE-A3, PXVII(M18)	4118.6 EL.U/mL
GSK2132231A GS- Group	Anti-MAGE-A3 Antibody Concentrations	Anti-MAGE-A3, PXXIV(M49)	7063.9 EL.U/mL
GSK2132231A GS- Group	Anti-MAGE-A3 Antibody Concentrations	Anti-MAGE-A3, PRE	11.2 EL.U/mL
GSK2132231A GS- Group	Anti-MAGE-A3 Antibody Concentrations	Anti-MAGE-A3, PII(W4)	728.7 EL.U/mL
GSK2132231A GS- Group	Anti-MAGE-A3 Antibody Concentrations	Anti-MAGE-A3, PVI(W12)	5631 EL.U/mL
GSK2132231A GS- Group	Anti-MAGE-A3 Antibody Concentrations	Anti-MAGE-A3, PXII(W31)	7094.2 EL.U/mL
GSK2132231A GS- Group	Anti-MAGE-A3 Antibody Concentrations	Anti-MAGE-A3, PXVI(W54)	2570.9 EL.U/mL
GSK2132231A GS- Group	Anti-MAGE-A3 Antibody Concentrations	Anti-MAGE-A3, PXVII(M18)	4784.5 EL.U/mL
GSK2132231A GS-unknown Group	Anti-MAGE-A3 Antibody Concentrations	Anti-MAGE-A3, PXVII(M18)	3052.0 EL.U/mL
GSK2132231A GS-unknown Group	Anti-MAGE-A3 Antibody Concentrations	Anti-MAGE-A3, PRE	11.3 EL.U/mL
GSK2132231A GS-unknown Group	Anti-MAGE-A3 Antibody Concentrations	Anti-MAGE-A3, PVI(W12)	7500.1 EL.U/mL
GSK2132231A GS-unknown Group	Anti-MAGE-A3 Antibody Concentrations	Anti-MAGE-A3, PXII(W31)	6430.7 EL.U/mL
GSK2132231A GS-unknown Group	Anti-MAGE-A3 Antibody Concentrations	Anti-MAGE-A3, PXVI(W54)	4209.7 EL.U/mL
GSK2132231A GS-unknown Group	Anti-MAGE-A3 Antibody Concentrations	Anti-MAGE-A3, PII(W4)	1385.7 EL.U/mL
GSK2132231A GS-unknown Group	Anti-MAGE-A3 Antibody Concentrations	Anti-MAGE-A3, PII(W4)	387.0 EL.U/mL
GSK2132231A GS-unknown Group	Anti-MAGE-A3 Antibody Concentrations	Anti-MAGE-A3, PRE	10.0 EL.U/mL
GSK2132231A GS-unknown Group	Anti-MAGE-A3 Antibody Concentrations	Anti-MAGE-A3, PVI(W12)	5921.0 EL.U/mL

Secondary

Anti-MAGE-A3 Antibody Response

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

Time frame: PII(W4) = Post-Dose 2 (Week 4), PVI(W12) = Post-Dose 6 (Week 12), PXII(W31) = Post-Dose 12 (Week 31), PXVI(W54) = Post-Dose 16 (Week 54), PXVII(M18) = Post-Dose 17 (Month 18), PXXIV(M49) = Post-Dose 24 (Month 49)

Population: The analysis was performed on the According-To-Protocol Population (ATP) for immunogenicity, which included all evaluable patients for whom immunogenicity data were available.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
GSK2132231A GS+ Group	Anti-MAGE-A3 Antibody Response	Anti-MAGE-A3, PII (W4)	60 Participants
GSK2132231A GS+ Group	Anti-MAGE-A3 Antibody Response	Anti-MAGE-A3, PVI (W12)	52 Participants
GSK2132231A GS+ Group	Anti-MAGE-A3 Antibody Response	Anti-MAGE-A3, PXII (W31)	11 Participants
GSK2132231A GS+ Group	Anti-MAGE-A3 Antibody Response	Anti-MAGE-A3, PXVI (W54)	6 Participants
GSK2132231A GS+ Group	Anti-MAGE-A3 Antibody Response	Anti-MAGE-A3, PXVII (M18)	3 Participants
GSK2132231A GS+ Group	Anti-MAGE-A3 Antibody Response	Anti-MAGE-A3, PXXIV (M49)	4 Participants
GSK2132231A GS- Group	Anti-MAGE-A3 Antibody Response	Anti-MAGE-A3, PXXIV (M49)	4 Participants
GSK2132231A GS- Group	Anti-MAGE-A3 Antibody Response	Anti-MAGE-A3, PXVI (W54)	3 Participants
GSK2132231A GS- Group	Anti-MAGE-A3 Antibody Response	Anti-MAGE-A3, PII (W4)	37 Participants
GSK2132231A GS- Group	Anti-MAGE-A3 Antibody Response	Anti-MAGE-A3, PXII (W31)	5 Participants
GSK2132231A GS- Group	Anti-MAGE-A3 Antibody Response	Anti-MAGE-A3, PVI (W12)	34 Participants
GSK2132231A GS- Group	Anti-MAGE-A3 Antibody Response	Anti-MAGE-A3, PXVII (M18)	2 Participants
GSK2132231A GS-unknown Group	Anti-MAGE-A3 Antibody Response	Anti-MAGE-A3, PVI (W12)	17 Participants
GSK2132231A GS-unknown Group	Anti-MAGE-A3 Antibody Response	Anti-MAGE-A3, PXII (W31)	6 Participants
GSK2132231A GS-unknown Group	Anti-MAGE-A3 Antibody Response	Anti-MAGE-A3, PXVI (W54)	3 Participants
GSK2132231A GS-unknown Group	Anti-MAGE-A3 Antibody Response	Anti-MAGE-A3, PXXIV (M49)	0 Participants
GSK2132231A GS-unknown Group	Anti-MAGE-A3 Antibody Response	Anti-MAGE-A3, PXVII (M18)	1 Participants
GSK2132231A GS-unknown Group	Anti-MAGE-A3 Antibody Response	Anti-MAGE-A3, PII (W4)	22 Participants
GSK2132231A GS-unknown Group	Anti-MAGE-A3 Antibody Response	Anti-MAGE-A3, PXVII (M18)	0 Participants
GSK2132231A GS-unknown Group	Anti-MAGE-A3 Antibody Response	Anti-MAGE-A3, PXXIV (M49)	0 Participants
GSK2132231A GS-unknown Group	Anti-MAGE-A3 Antibody Response	Anti-MAGE-A3, PVI (W12)	1 Participants
GSK2132231A GS-unknown Group	Anti-MAGE-A3 Antibody Response	Anti-MAGE-A3, PXVI (W54)	0 Participants
GSK2132231A GS-unknown Group	Anti-MAGE-A3 Antibody Response	Anti-MAGE-A3, PII (W4)	1 Participants
GSK2132231A GS-unknown Group	Anti-MAGE-A3 Antibody Response	Anti-MAGE-A3, PXII (W31)	0 Participants

Secondary

Anti-PD Antibody Response

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

Population: The analysis was performed on the According-To-Protocol Population (ATP) for immunogenicity, which included all evaluable patients for whom immunogenicity data were available.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
GSK2132231A GS+ Group	Anti-PD Antibody Response	Anti-PD, PII (W4)	76 Participants
GSK2132231A GS+ Group	Anti-PD Antibody Response	Anti-PD, PVI (W12)	52 Participants
GSK2132231A GS+ Group	Anti-PD Antibody Response	Anti-PD, PXII (W31)	11 Participants
GSK2132231A GS+ Group	Anti-PD Antibody Response	Anti-PD, PXVI (W54)	6 Participants
GSK2132231A GS+ Group	Anti-PD Antibody Response	Anti-PD, PXVII (M18)	3 Participants
GSK2132231A GS+ Group	Anti-PD Antibody Response	Anti-PD, PXXIV (M49)	4 Participants
GSK2132231A GS- Group	Anti-PD Antibody Response	Anti-PD, PXXIV (M49)	4 Participants
GSK2132231A GS- Group	Anti-PD Antibody Response	Anti-PD, PXVI (W54)	3 Participants
GSK2132231A GS- Group	Anti-PD Antibody Response	Anti-PD, PII (W4)	45 Participants
GSK2132231A GS- Group	Anti-PD Antibody Response	Anti-PD, PXII (W31)	5 Participants
GSK2132231A GS- Group	Anti-PD Antibody Response	Anti-PD, PVI (W12)	34 Participants
GSK2132231A GS- Group	Anti-PD Antibody Response	Anti-PD, PXVII (M18)	2 Participants
GSK2132231A GS-unknown Group	Anti-PD Antibody Response	Anti-PD, PVI (W12)	17 Participants
GSK2132231A GS-unknown Group	Anti-PD Antibody Response	Anti-PD, PXII (W31)	6 Participants
GSK2132231A GS-unknown Group	Anti-PD Antibody Response	Anti-PD, PXVI (W54)	3 Participants
GSK2132231A GS-unknown Group	Anti-PD Antibody Response	Anti-PD, PXXIV (M49)	0 Participants
GSK2132231A GS-unknown Group	Anti-PD Antibody Response	Anti-PD, PXVII (M18)	1 Participants
GSK2132231A GS-unknown Group	Anti-PD Antibody Response	Anti-PD, PII (W4)	30 Participants
GSK2132231A GS-unknown Group	Anti-PD Antibody Response	Anti-PD, PXVII (M18)	0 Participants
GSK2132231A GS-unknown Group	Anti-PD Antibody Response	Anti-PD, PXXIV (M49)	0 Participants
GSK2132231A GS-unknown Group	Anti-PD Antibody Response	Anti-PD, PVI (W12)	1 Participants
GSK2132231A GS-unknown Group	Anti-PD Antibody Response	Anti-PD, PXVI (W54)	0 Participants
GSK2132231A GS-unknown Group	Anti-PD Antibody Response	Anti-PD, PII (W4)	1 Participants
GSK2132231A GS-unknown Group	Anti-PD Antibody Response	Anti-PD, PXII (W31)	0 Participants

Secondary

Best Overall Response (BOR) by GS

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

Time frame: Month 0 - Month 24

Population: The analysis was performed on the Total Treated Population (TTP), which included all patients who received at least one dose of study treatment.

Arm	Measure	Category	Value (COUNT_OF_PARTICIPANTS)
GSK2132231A GS+ Group	Best Overall Response (BOR) by GS	PR	3 Participants
GSK2132231A GS+ Group	Best Overall Response (BOR) by GS	PD	51 Participants
GSK2132231A GS+ Group	Best Overall Response (BOR) by GS	SD/ PR	3 Participants
GSK2132231A GS+ Group	Best Overall Response (BOR) by GS	CR	0 Participants
GSK2132231A GS+ Group	Best Overall Response (BOR) by GS	Missing	0 Participants
GSK2132231A GS+ Group	Best Overall Response (BOR) by GS	NE	3 Participants
GSK2132231A GS+ Group	Best Overall Response (BOR) by GS	SD	11 Participants
GSK2132231A GS- Group	Best Overall Response (BOR) by GS	SD/ PR	0 Participants
GSK2132231A GS- Group	Best Overall Response (BOR) by GS	CR	1 Participants
GSK2132231A GS- Group	Best Overall Response (BOR) by GS	PR	0 Participants
GSK2132231A GS- Group	Best Overall Response (BOR) by GS	SD	4 Participants
GSK2132231A GS- Group	Best Overall Response (BOR) by GS	PD	44 Participants
GSK2132231A GS- Group	Best Overall Response (BOR) by GS	NE	1 Participants
GSK2132231A GS- Group	Best Overall Response (BOR) by GS	Missing	0 Participants
GSK2132231A GS-unknown Group	Best Overall Response (BOR) by GS	PD	2 Participants
GSK2132231A GS-unknown Group	Best Overall Response (BOR) by GS	PR	0 Participants
GSK2132231A GS-unknown Group	Best Overall Response (BOR) by GS	Missing	0 Participants
GSK2132231A GS-unknown Group	Best Overall Response (BOR) by GS	NE	0 Participants
GSK2132231A GS-unknown Group	Best Overall Response (BOR) by GS	SD/ PR	0 Participants
GSK2132231A GS-unknown Group	Best Overall Response (BOR) by GS	SD	0 Participants
GSK2132231A GS-unknown Group	Best Overall Response (BOR) by GS	CR	0 Participants

Secondary

Concentrations of Antibodies Against Protein D (Anti-PD)

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

Population: The analysis was performed on the According-To-Protocol Population (ATP) for immunogenicity, which included all evaluable patients for whom immunogenicity data were available.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
GSK2132231A GS+ Group	Concentrations of Antibodies Against Protein D (Anti-PD)	Anti-PD, PXVI(W54)	12389.9 EL.U/mL
GSK2132231A GS+ Group	Concentrations of Antibodies Against Protein D (Anti-PD)	Anti-PD, PVI (W12)	15036.7 EL.U/mL
GSK2132231A GS+ Group	Concentrations of Antibodies Against Protein D (Anti-PD)	Anti-PD, PXXIV (M49)	10546.9 EL.U/mL
GSK2132231A GS+ Group	Concentrations of Antibodies Against Protein D (Anti-PD)	Anti-PD, PXII (W31)	23548.6 EL.U/mL
GSK2132231A GS+ Group	Concentrations of Antibodies Against Protein D (Anti-PD)	Anti-PD, PII (W4)	4588 EL.U/mL
GSK2132231A GS+ Group	Concentrations of Antibodies Against Protein D (Anti-PD)	Anti-PD, PRE	81.2 EL.U/mL
GSK2132231A GS+ Group	Concentrations of Antibodies Against Protein D (Anti-PD)	Anti-PD, PXVII (M18)	11386.1 EL.U/mL
GSK2132231A GS- Group	Concentrations of Antibodies Against Protein D (Anti-PD)	Anti-PD, PXXIV (M49)	10546.9 EL.U/mL
GSK2132231A GS- Group	Concentrations of Antibodies Against Protein D (Anti-PD)	Anti-PD, PRE	86.1 EL.U/mL
GSK2132231A GS- Group	Concentrations of Antibodies Against Protein D (Anti-PD)	Anti-PD, PII (W4)	4196.9 EL.U/mL
GSK2132231A GS- Group	Concentrations of Antibodies Against Protein D (Anti-PD)	Anti-PD, PVI (W12)	14091.9 EL.U/mL
GSK2132231A GS- Group	Concentrations of Antibodies Against Protein D (Anti-PD)	Anti-PD, PXII (W31)	25070.5 EL.U/mL
GSK2132231A GS- Group	Concentrations of Antibodies Against Protein D (Anti-PD)	Anti-PD, PXVI(W54)	9639.2 EL.U/mL
GSK2132231A GS- Group	Concentrations of Antibodies Against Protein D (Anti-PD)	Anti-PD, PXVII (M18)	13839.4 EL.U/mL
GSK2132231A GS-unknown Group	Concentrations of Antibodies Against Protein D (Anti-PD)	Anti-PD, PXVII (M18)	7707.0 EL.U/mL
GSK2132231A GS-unknown Group	Concentrations of Antibodies Against Protein D (Anti-PD)	Anti-PD, PRE	70.6 EL.U/mL
GSK2132231A GS-unknown Group	Concentrations of Antibodies Against Protein D (Anti-PD)	Anti-PD, PVI (W12)	16453.2 EL.U/mL
GSK2132231A GS-unknown Group	Concentrations of Antibodies Against Protein D (Anti-PD)	Anti-PD, PXII (W31)	22351.2 EL.U/mL
GSK2132231A GS-unknown Group	Concentrations of Antibodies Against Protein D (Anti-PD)	Anti-PD, PXVI(W54)	15925.5 EL.U/mL
GSK2132231A GS-unknown Group	Concentrations of Antibodies Against Protein D (Anti-PD)	Anti-PD, PII (W4)	5139.8 EL.U/mL
GSK2132231A GS-unknown Group	Concentrations of Antibodies Against Protein D (Anti-PD)	Anti-PD, PII (W4)	9167.0 EL.U/mL
GSK2132231A GS-unknown Group	Concentrations of Antibodies Against Protein D (Anti-PD)	Anti-PD, PRE	412.0 EL.U/mL
GSK2132231A GS-unknown Group	Concentrations of Antibodies Against Protein D (Anti-PD)	Anti-PD, PVI (W12)	29553.0 EL.U/mL

Secondary

Duration of Response (CR or PR)

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

Time frame: Month 0 - Month 24

Population: The analysis was performed on the Responders Population, including patients with an objective response \[complete (CR) or partial response (PR)\] as best overall clinical response as confirmed by repeated assessments performed at least 4 weeks apart at the time of analysis.

Arm	Measure	Value (MEDIAN)
GSK2132231A GS+ Group	Duration of Response (CR or PR)	8.3 Months
GSK2132231A GS- Group	Duration of Response (CR or PR)	6.9 Months
GSK2132231A GS-unknown Group	Duration of Response (CR or PR)	NA Months

Secondary

Duration of Stable Disease (SD), or Time-to-Progression (TTP) by GS

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

Time frame: Month 0 - Month 24

Population: The analysis was performed on the Stable Disease Population, which included the patients whose best response was stable disease. To qualify as SD for the best overall response, the patient should be in a SD status for a minimum of 12 weeks, as documented by two consecutive visits 12 weeks apart, or a SD status 12 weeks after baseline evaluation.

Arm	Measure	Value (MEDIAN)
GSK2132231A GS+ Group	Duration of Stable Disease (SD), or Time-to-Progression (TTP) by GS	5.4 Months
GSK2132231A GS- Group	Duration of Stable Disease (SD), or Time-to-Progression (TTP) by GS	5.4 Months
GSK2132231A GS-unknown Group	Duration of Stable Disease (SD), or Time-to-Progression (TTP) by GS	5.4 Months

Secondary

Kaplan-Meier Estimates of the Progression-free Survival (PFS) at Months 6, 12 and 24, by Gene Signature

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

Time frame: Month 6, Month 12, Month 24

Population: The analysis was performed on the Total Treated Population (TTP), which included all patients who received at least one dose of study treatment. PFS was not assessed in the GSK2132231A GS-unknown Group.

Arm	Measure	Group	Value (NUMBER)
GSK2132231A GS+ Group	Kaplan-Meier Estimates of the Progression-free Survival (PFS) at Months 6, 12 and 24, by Gene Signature	PFS 12M	6.02 Percentage of patients
GSK2132231A GS+ Group	Kaplan-Meier Estimates of the Progression-free Survival (PFS) at Months 6, 12 and 24, by Gene Signature	PFS 6M	13.53 Percentage of patients
GSK2132231A GS+ Group	Kaplan-Meier Estimates of the Progression-free Survival (PFS) at Months 6, 12 and 24, by Gene Signature	PFS 24M	1.5 Percentage of patients
GSK2132231A GS- Group	Kaplan-Meier Estimates of the Progression-free Survival (PFS) at Months 6, 12 and 24, by Gene Signature	PFS 6M	5 Percentage of patients
GSK2132231A GS- Group	Kaplan-Meier Estimates of the Progression-free Survival (PFS) at Months 6, 12 and 24, by Gene Signature	PFS 12M	5 Percentage of patients
GSK2132231A GS- Group	Kaplan-Meier Estimates of the Progression-free Survival (PFS) at Months 6, 12 and 24, by Gene Signature	PFS 24M	5 Percentage of patients

Secondary

Number of Patients Reported With Unsolicited Adverse Events (AEs) by Maximum Grade.

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

Time frame: Through 30 days after the last administration of the study treatment, approximately 49 months

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
GSK2132231A GS+ Group	Number of Patients Reported With Unsolicited Adverse Events (AEs) by Maximum Grade.	Any event, Grade 1	52 Participants
GSK2132231A GS+ Group	Number of Patients Reported With Unsolicited Adverse Events (AEs) by Maximum Grade.	Any event, Grade 2	35 Participants
GSK2132231A GS+ Group	Number of Patients Reported With Unsolicited Adverse Events (AEs) by Maximum Grade.	Any event, Grade 3	21 Participants
GSK2132231A GS+ Group	Number of Patients Reported With Unsolicited Adverse Events (AEs) by Maximum Grade.	Any event, Grade 4	5 Participants
GSK2132231A GS+ Group	Number of Patients Reported With Unsolicited Adverse Events (AEs) by Maximum Grade.	Any event, Grade 5	3 Participants

Secondary

Number of Patients Reported With Unsolicited AE(s)

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

Time frame: Through 30 days after the last administration of the study treatment, approximately 49 months

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
GSK2132231A GS+ Group	Number of Patients Reported With Unsolicited AE(s)	116 Participants

Secondary

Number of Patients With Abnormal Alanine Aminotransferase (ALT) Values by Maximum Grade

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