Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Melanoma, Cutaneous Malignant

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Subjects, male or female, 18 years of age or older, received up to 24 doses of GSK2132231A intramuscularly in 4 cycles. In Cycle 1 (ending Week 13) 6 doses were administered at 2-week intervals; in Cycle 2 (ending Week 32) 6 doses at 3-week intervals; in Cycle 3 (ending Week 54) 4 doses at 6-week intervals and in Cycle 4 4 doses at 12-week intervals, starting 12 weeks after end of Cycle 3, followed by, after an interruption of treatment of 6 months, 4 doses at 24-week intervals.

Administration by intramuscular injection

Immunotherapeutic GSK2132231A

GSK Clinical Trials

The clinical objective of this clinical trial is to examine the clinical activity in terms of tumor response and time to treatment failure of the immunotherapeutic product GSK2132231A when given to patients with unresectable and progressive metastatic cutaneous melanoma. The safety of the treatment will also be assessed just as its immunogenicity in terms of the humoral and cellular immune response induced by the GSK2132231A immunotherapeutic. Translational research objectives are to assess the effects of the study treatment in terms of various biological variables.

Study of GSK2132231A Antigen-Specific Cancer Immunotherapeutic in Patients With Inoperable Metastatic Cutaneous Melanoma

Clinical Activity, Safety and Immunogenic Properties of Cancer Immunotherapeutic GSK2132231A in Patients With Unresectable and Progressive Metastatic Cutaneous Melanoma

IPD is available via the Clinical Study Data Request site (click on the link provided below)

OR was defined as the best Overall Response (OR) in a patient. OR = Complete Response (CR) + Partial Response (PR). Responses were categorized as CR, PR, stable disease (SD), SD/PR, progressive disease (PD) and non-evaluable (NE). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by Magnetic-resonance imaging: Complete Response (CR) = disappearance of all target lesions; Partial Response (PR) = ≥30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD) = neither sufficient shrinkage to be PR, not sufficient increase to qualify for Progressive Disease (PD); PD = ≥20% increase in the sum of largest diameter for target lesions. Best objective response = PR or CR. Disease control = CR, or PR, or SD, or SD/PR.

Assessment was done based on a set of measurable lesions (MLs) identified at baseline as target lesions (TLs) and non-TLs (NTL) followed up until disease progression. MLs assessed for matching below MR definitions. If evaluability per RECIST: a) MR Type 1= at least (a.l.) 30% decrease in LD in a.l. one TL measured at baseline. Such response occurring in SD/PD status of LD of TL and without appearance of one or more new lesions (= SD/PD with TL regression); b) MR Type 2: appearance of one or more new lesions occurring in SD/PR status of LD of TL (= SD/PR with new lesion). If non-evaluability per RECIST (due to LD\<20mm): a) MR Type 1 = a clear decrease in diameters occurring in a.l. one TL measured at baseline. Such response occurring in SD/PD status of LD of (baseline) TL and without appearance of one or more new lesions (= SD/PD with TL regression); b) MR Type 2 = appearance of one or more new lesions occurring in SD/PR status of LD of TL (= SD/PR with new lesion).

TTF was defined as withdrawal from treatment with the GSK2132231A study product due to disease progression or death. TTF analysis was performed using the non-parametric Kaplan-Meier method.

Anti-MAGE-A3 antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in ELISA units per millilitre (EL.U/mL). A seropositive patient was defined as a patient whose anti-MAGE-A3 antibody concentration was greater than or equal to 27 EL.U/mL. D=Day W=Week

Seroconversion was defined as a concentration of antibodies assessed that was greater than the cut-off value for a patient whose concentration of such antibodies was below the cut-off level before the initiation of treatment. Seroconverted patients were those patients with anti-MAGE-A3 antibody concentrations ≥ 27 EL.U/mL.

For initially seronegative patients: post-administration antibody concentration ≥ 27 EL.U/mL For initially seropositive patients: post-administration antibody concentration ≥ 2 fold the pre-vaccination antibody concentration

This endpoint presents the geometric mean concentration, expressed in titers, of anti-MAGE-A3 specific CD4+ and CD8+ T-cells. These specific T-cells included the cluster of differentiation 4+ (CD4+) and CD8+ T-cells producing cytokines Tumor Necrosis Factor-alpha (TNF-α) and/or Interferon-gamma (INF-γ).

A patient was considered as a cellular mediated immune (CMI) responder if there was an increased amount of antigen-specific T-cells after immunization as compared to the patient's baseline value. These specific T-cells included the cluster of differentiation 4+ (CD4+) and CD8+ T-cells producing cytokines Tumor Necrosis Factor-alpha (TNF-α) and/or Interferon-gamma (INF-γ).

The assessed AEs were ASCI-related grade 3/4 adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. 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. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse. AEs may include pre- or post-treatment events that occur as a result of protocol-mandated procedures (i.e. invasive procedures, modification of patient's previous therapeutic regimen).

Serious adverse events (SAEs) include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a patient, is a Grade 4 AE according to the CTCAE, version3.0. Events which were part of the natural course of the disease under study were captured as part of the clinical activity outcome variables in this study; therefore did not need to be reported as SAEs. Progression/recurrence of the tumor 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.

The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).

The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). \[e.g. ALT - SCR G0; SE G3 = ALT with no abnormality/normal value at screening and with Severe abnormality at study end\].

The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).

The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). \[e.g. AST - SCR G0; SE G3 = AST with no abnormality/normal value at screening and with Severe abnormality at study end\].

The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).

The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). \[e.g. ALK - SCR G0; SE G3 = ALK with no abnormality/normal value at screening and with Severe abnormality at study end\].

The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).

The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). \[e.g. BIL - SCR G0; SE G3 = BIL with no abnormality/normal value at screening and with Severe abnormality at study end\].

The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).

The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). \[e.g. CREA - SCR G0; SE G3 = CREA with no abnormality/normal value at screening and with Severe abnormality at study end\].

The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).

The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). \[e.g. GGT - SCR G0; SE G3 = GGT with no abnormality/normal value at screening and with Severe abnormality at study end\].

The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).

The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). \[e.g. HGB - SCR G0; SE G3 = HGB with no abnormality/normal value at screening and with Severe abnormality at study end\].

The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).

The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). \[e.g. HCA - SCR G0; SE G3 = HCA with no abnormality/normal value at screening and with Severe abnormality at study end\].

The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).

The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). \[e.g. HKA - SCR G0; SE G3 = HKA with no abnormality/normal value at screening and with Severe abnormality at study end\].

The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).

The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). \[e.g. HNA - SCR G0; SE G3 = HNA with no abnormality/normal value at screening and with Severe abnormality at study end\].

The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).

The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). \[e.g. hAL - SCR G0; SE G3 = hAL with no abnormality/normal value at screening and with Severe abnormality at study end\].

The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).

The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). \[e.g. hCA - SCR G0; SE G3 = hCA with no abnormality/normal value at screening and with Severe abnormality at study end\].

The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).

The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). \[e.g. hKA - SCR G0; SE G3 = hKA with no abnormality/normal value at screening and with Severe abnormality at study end\].

The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).

The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). \[e.g. hNA - SCR G0; SE G3 = hNA with no abnormality/normal value at screening and with Severe abnormality at study end\].

The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).

The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). \[e.g. LEU - SCR G0; SE G3 = LEU with no abnormality/normal value at screening and with Severe abnormality at study end\].

The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).

The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). \[e.g. LYM - SCR G0; SE G3 = LYM with no abnormality/normal value at screening and with Severe abnormality at study end\].

The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).

The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). \[e.g. NEU - SCR G0; SE G3 = NEU with no abnormality/normal value at screening and with Severe abnormality at study end\].

The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).

The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). \[e.g. PLT - SCR G0; SE G3 = PLT with no abnormality/normal value at screening and with Severe abnormality at study end\].

An AE was any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs reported are here below tabulated irrespective of grade (any), as well as graded by maximum grade reported according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. Maximum grade reported and tabulated were Grade 1 (G1) - Mild AE, G2 - Moderate AE, G3 - Severe AE, G4 - Life threatening/Disabling AE and G5 - Death related to AE.

SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a patient. Events which were part of the natural course of the disease under study were captured as part of the clinical activity outcome variables in this study; therefore did not need to be reported as SAEs. Progression/recurrence of the tumor 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. SAEs reported are here below tabulated irrespective of grade (any), as well as graded by maximum grade reported according to the CTC Adverse event terminology, version 3.0. Maximum grade reported and tabulated were Grade 1 (G1) - Mild SAE, G2 - Moderate SAE, G3 - Severe SAE, G4 - Life threatening/Disabling SAE and G5 - Death related to SAE.

GlaxoSmithKline

Patients planned to receive intramuscularly up to 24 doses of GSK2132231A (the study product), in 4 cycles.

GSK2132231A Group

Subjects, male or female, 18 years of age or older, received up to 24 doses of GSK2132231A intramuscularly in 4 cycles. In Cycle 1 (ending Week 11) 6 doses were administered at 2-week intervals; in Cycle 2 (ending Week 30) 6 doses at 3-week intervals; in Cycle 3 (ending Week 52) 4 doses at 6-week intervals and in Cycle 4 4 doses at 12-week intervals, starting 12 weeks after end of Cycle 3, followed by, after an interruption of treatment of 6 months, 4 doses at 24-week intervals.

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

GSK Response Center

Best response CR

Best response PR

Best response SD

Best response SD/PR

Best response PD

Best response NE

Best objective response Yes

Best objective response No

Disease Control Yes

Disease Control No

Subset of subjects from the GSK2132231A Group having a gene signature positive for two biopsies, as assessed at screening.

GSK2132231A GS+/+ Group

Subset of subjects from the GSK2132231A Group having a gene signature positive for only one biopsies, as assessed at screening.

GSK2132231A GS+/- Group

Subset of subjects from the GSK2132231A Group having a gene signature negative for both biopsies, as assessed at screening.

GSK2132231A GS- Group

The Total Treated population included all patients who have received at least one Dose of the GSK2132231A study treatment

Number of Patients With Objective Tumor Response (OR) to GSK2132231A Study Treatment

Best response MR (SD/PR)

Best response MR (SD/PD)

Best response SD/PD

Best response PD (SPD)

Best response PD (SPD/MR)

Number of Patients With Mixed Response (MR) to GSK2132231A

Time to Treatment Failure (TTF), by Gene Signature

Anti-MAGE-A3, PRE

Anti-MAGE-A3, D2

Anti-MAGE-A3, D7

Anti-MAGE-A3, D15

Anti-MAGE-A3, D16

Anti-MAGE-A3, W5

Anti-MAGE-A3, W11

Anti-MAGE-A3, W13

Anti-MAGE-A3, W21

Anti-MAGE-A3, W32

Anti-MAGE-A3, W54

Anti-MAGE-A3, W76

Anti-MAGE-A3, W78

Anti-MAGE-A3, W100

Anti-MAGE-A3, W102

Anti-MAGE-A3, W124

Anti-MAGE-A3, W126

Anti-MAGE-A3, W148

Anti-MAGE-A3, W150

Anti-MAGE-A3, W174

Anti-MAGE-A3, CCL

The ATP population for Immunogenicity included all eligible patients, who have received at least the first 6 GSK2132231A study treatment doses and have provided a result for Immunogenicity measurement within 2 weeks following Dose 6.

Anti-MAGE-A3 Antibody Concentrations

Number of Seroconverted Patients for Anti-MAGE-A3

Number of Patients With Treatment Response for Anti-MAGE-A3 Antibodies

CD4.TNFα (+) + IFNγ (+) PRE

CD8.TNFα (+) + IFNγ (+) PRE

CD4.TNFα (+) + IFNγ (+) W5

CD8.TNFα (+) + IFNγ (+) W5

CD4.TNFα (+) + IFNγ (+) W13

CD8.TNFα (+) + IFNγ (+) W13

CD4.TNFα (+) + IFNγ (+) W32

CD8.TNFα (+) + IFNγ (+) W32

CD4.TNFα (+) + IFNγ (+) W54

CD8.TNFα (+) + IFNγ (+) W54

CD4.TNFα (+) + IFNγ (+) W78

CD8.TNFα (+) + IFNγ (+) W78

CD4.TNFα (+) + IFNγ (+) W102

CD8.TNFα (+) + IFNγ (+) W102

CD4.TNFα (+) + IFNγ (+) CCL

CD8.TNFα (+) + IFNγ (+) CCL

Geometric Mean Titers of Anti-MAGE-A3 Specific CD4+ and CD8+ T-cells Concentrations After Immunization

CD4.TNFα (+) + IFNγ (+) At any time point

CD8.TNFα (+) + IFNγ (+) At any time point

Number of Patients With CD4+ and CD8+ T Cell Frequency ≥ 1.24 Cut-off

Number of Patients With a Cellular Response (Anti-MAGE-A3 Specific CD4+ and CD8+ T-cells Concentrations After Immunization)

Any event, Grade 3

Any event, Grade 4

The Total Treated population included all patients who have received at least one Dose of the GSK2132231A study treatment.

Number of Patients Reported With Antigen Specific Cancer Immunotherapeutics (ASCI)-Related grade3/4 Adverse Events (AEs) According to the Common Terminology Criteria (CTCAE) Version 3.0.

The Total Treated population included all patients who have received at least one Dose of the GSK2132231A ASCI study treatment.

Spots Global Cancer Trial Database for Study of GSK2132231A Antigen-Specific Cancer Immunotherapeutic in Patients With Inoperable Metastatic Cutaneous Melanoma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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