Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Patients received up to 13 doses of GSK1572932, 5 doses every 3 weeks followed by 8 doses every 12 weeks.

Patients received up to 13 doses of placebo, 5 doses every 3 weeks followed by 8 doses every 12 weeks.

GSK1572932A Antigen-Specific Cancer Immunotherapeutic

Placebo Control

GSK Clinical Trials

The purpose of this clinical trial is to demonstrate the benefit of the immunotherapeutic product GSK1572932A when given to patients with Non-Small Cell Lung Cancer, after removal of their tumor. A course of 13 injections will be administered over 27 months. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

GSK1572932A Antigen-Specific Cancer Immunotherapeutic as Adjuvant Therapy in Patients With Non-Small Cell Lung Cancer

GSK1572932A Antigen-Specific Cancer Immunotherapeutic as Adjuvant Therapy in Patients With Resectable MAGE-A3 Positive Non-Small Cell Lung Cancer

IPD for this study is available via the Clinical Study Data Request site.

DFS = time interval from randomization to 1st evidence of recurrence/death, if occurring before. All recurrence types were included, including local, regional \& distant metastasis \& 2nd primary lung cancer (i.e. local recurrence, defined as a tumor within same lung or at bronchial stump; regional recurrence, involving a clinically or radiologically manifest disease in mediastinum or supraclavicular nodes; \& distant recurrence \[any tumor arising in contralateral lung or outside hemithorax\]). Deaths occurring without prior documentation of recurrence were considered as event \& not censored. If no event occurred by time of analysis, time to event was censored at last assessment date of patient. New 1ry cancers outside lungs were not considered as event. PYAR= n (number of subjects reported with at least 1 event) divided by T (sum of follow-up period \[in years\] censored at 1st occurrence of event in group). Median DFS estimates were obtained non-parametrically by Kaplan-Meier method.

DFS = time interval from randomization to 1st evidence of recurrence/death, if occurring before. All recurrence types were included, including local, regional \& distant metastasis \& 2nd primary lung cancer (i.e. local recurrence, defined as a tumor within same lung or at bronchial stump; regional recurrence, involving a clinically or radiologically manifest disease in mediastinum or supraclavicular nodes; \& distant recurrence \[any tumor arising in contralateral lung or outside hemithorax\]). Deaths occurring without prior documentation of recurrence were considered as event \& not censored. If no event occurred by time of analysis, time to event was censored at last assessment date of patient. New 1ry cancers outside lungs were not considered as event. PYAR = n (number of subjects reported with at least 1 event) divided by T (sum of follow-up period \[in years\] censored at 1st occurrence of event in group). Median DFS estimates were obtained non-parametrically by Kaplan-Meier method.

OS was defined as the time interval from randomization to the date of death, irrespective of the cause of death. Patients still alive were censored at the last visit they were known to be alive. PYAR = n (number of subjects reported with at least 1 event) divided by T (sum of follow-up period \[in years\] censored at 1st occurrence of event in group). Median OS estimates were obtained non-parametrically by Kaplan-Meier method.

LCSS was defined as the time interval from randomization to the date of death due to lung cancer. Deaths due to other or unknown causes were censored at the date of death. PYAR = n (number of subjects reported with at least 1 event) divided by T (sum of follow-up period \[in years\] censored at 1st occurrence of event in group). Median OS estimates were obtained non-parametrically by Kaplan-Meier method.

DFS = time interval from randomization to 1st evidence of recurrence/death, if occurring before. All recurrence types were included, including local, regional \& distant metastasis \& 2nd primary lung cancer (i.e. local recurrence, defined as a tumor within same lung or at bronchial stump; regional recurrence, involving a clinically or radiologically manifest disease in mediastinum or supraclavicular nodes; \& distant recurrence \[any tumor arising in contralateral lung or outside hemithorax\]). Deaths occurring without prior documentation of recurrence were considered as event \& not censored. If no event occurred by time of analysis, time to event was censored at last assessment date of patient. New 1ry cancers outside lungs were not considered as event. Median DFS KMEs in % were obtained non-parametrically by Kaplan-Meier method and confidence intervals (CIs) calculated using the Greenwood formula for standard error computation.

DFSS was defined as the interval from randomization to the date of disease recurrence or death due to lung cancer. Patients who had died due to another cause than lung cancer were censored on their date of death and patients alive at the time of analysis were censored on the date of last assessment. Patients with no assessment post-randomization were censored on the date of randomization. PYAR = n (number of subjects reported with at least 1 event) divided by T (sum of follow-up period \[in years\] censored at 1st occurrence of event in group). Median DFS estimates were obtained non-parametrically by Kaplan-Meier method.

A seropositive subject for anti-MAGE-A3 antibodies was a subject with anti-MAGE-A3 antibodies \>= the seropositivity cut-off of 27 Enzyme-linked immunosorbent assay (ELISA) units per millilitre (EL.U/mL).

A seropositive/seronegative subject for anti-MAGE-A3 antibodies was a subject with anti-MAGE-A3 antibodies \>=/\< the seropositivity cut-off of 27 Enzyme-linked immunosorbent assay (ELISA) units per millilitre (EL.U/mL). A humoral responder as regards anti-MAGE-A3 antibodies was defined as 1) for initially seronegative patients, a patient with post-administration Anti-MAGE-A3 antibody concentration \>= 27 EL.U/mL; 2) for initially seropositive patients: post-treatment administration antibody concentration \>= 2 fold the pre-treatment antibody concentration.

A seropositive subject for anti-PD antibodies was a subject with anti-PD antibodies \>= the seropositivity cut-off of 100 Enzyme-linked immunosorbent assay (ELISA) units per millilitre (EL.U/mL).

A seropositive/seronegative subject for anti-PD antibodies was a subject with anti-PD antibodies ≥/\< the seropositivity cut-off of 100 Enzyme-linked immunosorbent assay (ELISA) units per millilitre (EL.U/mL). A humoral responder as regards anti-PD antibodies was defined as 1) for initially seronegative patients, a patient with post-administration anti-PD antibody concentration ≥ 100 EL.U/mL; 2) for initially seropositive patients: post-administration antibody concentration ≥ 2 fold the pre-vaccination antibody concentration.

HQL was assessed using the EQ-5D generic health state classification and valuation system. The number and percentage of patients with each score within each dimension of the EQ-5D questionnaire (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) were tabulated at each assessment for each group. Each of these scores can take 3 levels: no problem (level 1), moderate problem (level 2) or extreme problem (level 3). Resulting descriptive mean and standard deviation (SD) for the EQ-5D Utility Value (EQ-5D UV) were tabulated. Valid EQ-5D data were defined as questionnaires assessed 1) on day of and before treatment administration; or 2) on day after treatment administration for W0, W6, W12; or 3)during follow-up visits or at time of recurrence. The EQ-5D total score ranges from -0.016 (worst health state) to 1.000 (best health state).

The status of each patient as regards ALT laboratory values at baseline (SCR) up to DLP 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 unknown (UNK), Grade 0 (G0), G1 and G2. CTC grade statuses reported at DLP were G0, G1, G2, G3, G4, and UNK.

The status of each patient as regards AST laboratory values at baseline (SCR) up to DLP 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 unknown (UNK), Grade 0 (G0), G1 and G2. CTC grade statuses reported at DLP were G0, G1, G2, G3, G4, and UNK.

The status of each patient as regards ALKP laboratory values at baseline (SCR) up to DLP 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 unknown (UNK), Grade 0 (G0), G1 and G2. CTC grade statuses reported at DLP were G0, G1, G2, G3, G4, and UNK.

The status of each patient as regards BIL laboratory values at baseline (SCR) up to DLP 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 unknown (UNK), Grade 0 (G0) and G1. CTC grade statuses reported at DLP were G0, G1, G2, G3, G4, and UNK.

The status of each patient as regards CREA laboratory values at baseline (SCR) up to DLP 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 unknown (UNK), Grade 0 (G0), G1 and G2. CTC grade statuses reported at DLP were G0, G1, G2, G3, G4, and UNK.

The status of each patient as regards HGB laboratory values at baseline (SCR) up to DLP 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 unknown (UNK), Grade 0 (G0), G1, G2 and G3. CTC grade statuses reported at DLP were G0, G1, G2, G3, G4, and UNK.

The status of each patient as regards LEU laboratory values at baseline (SCR) up to DLP 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 unknown (UNK), Grade 0 (G0), G1, G2 and G3. CTC grade statuses reported at DLP were G0, G1, G2, G3, G4, and UNK.

The status of each patient as regards LYM laboratory values at baseline (SCR) up to DLP 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 unknown (UNK), Grade 0 (G0), G1, G2 and G3. CTC grade statuses reported at DLP were G0, G1, G2, G3, G4, and UNK.

The status of each patient as regards NEU laboratory values at baseline (SCR) up to DLP 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 unknown (UNK), Grade 0 (G0), G1, G2, G3 and G4. CTC grade statuses reported at DLP were G0, G1, G2, G3, G4, and UNK.

The status of each patient as regards PLA laboratory values at baseline (SCR) up to DLP 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 unknown (UNK), Grade 0 (G0), G1 and G3. CTC grade statuses reported at DLP were G0, G1, G2, G3, G4, and UNK.

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, 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), G2, G3, G4 and G5. Any here below is defined as irrespective of CTC grade reported.

A SAE is any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study subject, or was a Grade 4 AE according to CTC for Adverse Events, Version 3.0. Events part of natural course of lung cancer (i.e., disease progression, recurrence) were captured towards clinical efficacy assessment (CEA) and were not reported as SAEs. Death due to a progressive disease was similarly recorded towards CEA, but not as an SAE. However, if progression of lung cancer disease was greater than normally be expected, or if investigators considered that there was a causal relationship between treatment or protocol design/procedures and disease progression/ recurrence, then it was reported as SAE. Any new cancer (non-related to lung cancer) was reported as SAE.

GlaxoSmithKline

GSK1572932 Group

Placebo Group

Total

Age, Continuous

Sex: Female, Male

Geographic ancestry

Race/Ethnicity, Customized

GSK Response Center

Analysis compared DFS PYAR between groups for period from 1st treatment dose to DLP. A Cox model was used to evaluate treatment efficacy (TE). TE was calculated as PYAR in GSK1572932 Group (PYAR1) divided by PYAR in Placebo Group (PYAR2), and weighed for adjustment factors. This comparison in all patients (overall population) also included taking into account stratification by previous CT vs. No-CT treatment and weighing using randomization-minimization factors (RMF) as regressors.

Patients received up to 13 doses of GSK1572932, 5 doses every 3 weeks followed by 8 doses every 12 weeks

The Total Treated population - as randomized included patients in the treatment group as allocated by the randomization system at the start of the study.

Person Year Rate (PYAR) as Regards Disease-free Survival (DFS) in the Overall Population

Analysis compared DFS PYAR between groups for the period from 1st treatment dose to DLP. A Cox model was used to evaluate treatment efficacy (TE). TE was calculated as PYAR in GSK1572932 No-CT Group (PYAR1) divided by PYAR in Placebo No-CT Group (PYAR2) and weighed for adjustment factors. This comparison in all patients (overall population) also included taking into account weighing using randomization-minimization factors (RMF) as regressors.

Patients received up to 13 doses (D) of GSK1572932 ASCI, 5 Ds every 3 weeks followed by 8 Ds every 12 weeks. Patients in this sub-group consisted solely of patients who had not received adjuvant chemotherapy prior to randomization (No-CT Population).

GSK1572932 No-CT Group

Patients received up to 13 doses (D) of placebo, 5 Ds every 3 weeks followed by 8 Ds every 12 weeks. Patients in this sub-group consisted solely of patients who had not received adjuvant chemotherapy prior to randomization (No-CT Population).

Placebo No-CT Group

Person Year Rate (PYAR) as Regards Disease-free Survival (DFS) in the No-CT Population

Patients received up to 13 doses (D) of GSK1572932, 5 Ds every 3 weeks followed by 8 Ds every 12 weeks. Patients in this sub-group consisted solely of patients who had received adjuvant chemotherapy prior to randomization (CT Population).

GSK1572932 CT Group

Patients received up to 13 doses (D) of placebo, 5 Ds every 3 weeks followed by 8 Ds every 12 weeks. Patients in this sub-group consisted solely of patients who had received adjuvant chemotherapy prior to randomization (CT Population).

Placebo CT Group

Person Year Rate (PYAR) as Regards Disease-free Survival (DFS) in the CT Population

Person Year Rate (PYAR) as Regards Overall-survival (OS) in the Overall Population

Person Year Rate (PYAR) as Regards Overall-survival (OS) in the No-CT Population

Person Year Rate (PYAR) as Regards Overall-survival (OS) in the CT Population

Person Year Rate (PYAR) as Regards Lung-cancer Specific Survival (LCSS) in the Overall Population

Person Year Rate (PYAR) as Regards Lung-cancer Specific Survival (LCSS) in the No-CT Population

Person Year Rate (PYAR) as Regards Lung-cancer Specific Survival (LCSS) in the CT Population

DFS KME at 2Y - Overall Population

DFS KME at 3Y - Overall Population

DFS KME at 4Y - Overall Population

DFS KME at 5Y - Overall Population

Kaplan-Meier Estimate (KME) of 2, 3, 4 and 5-year as Regards Disease-free Survival (DFS) in the Overall Population

DFS KME at 2Y - No-CT Population

DFS KME at 3Y - No-CT Population

DFS KME at 4Y - No-CT Population

DFS KME at 5Y - No-CT Population

Kaplan-Meier Estimate (KME) of 2, 3, 4 and 5-year as Regards Disease-free Survival (DFS) in the No-CT Population

DFS KME at 2Y - CT Population

DFS KME at 3Y - CT Population

DFS KME at 4Y - CT Population

DFS KME at 5Y - CT Population

Kaplan-Meier Estimate (KME) of 2, 3, 4 and 5-year as Regards Disease-free Survival (DFS) in the CT Population

Person Year Rate (PYAR) as Regards Disease-free Specific Survival (DFSS) in the Overall Population

Person Year Rate (PYAR) as Regards Disease-free Specific Survival (DFSS) in the No-CT Population

Person Year Rate (PYAR) as Regards Disease-free Specific Survival (DFSS) in the CT Population

Anti-MAGE-A3 S+, PRE

Anti-MAGE-A3 S+, W6

Anti-MAGE-A3 S+, W12

Anti-MAGE-A3 S+, M9

Anti-MAGE-A3 S+, M12

Anti-MAGE-A3 S+, M18

Anti-MAGE-A3 S+, M30

Anti-MAGE-A3 S+, at 12M post W120

Patients received up to 13 doses of placebo, 5 doses every 3 weeks followed by 8 doses every 12 weeks

The According-To-Protocol (ATP) population for immunogenicity including all evaluable patients (meeting all eligibility criteria, complying with protocol defined procedures and intervals, with no elimination criteria during the study) who received at least the 4 first doses and for whom data were available for the considered assay and time point.

Number of Subjects Seropositive for Anti-Melanoma AntiGEn (MAGE)-A3 Antibodies (Anti-MAGE-A3 S+)

Anti-MAGE-A3 HR, W6

Anti-MAGE-A3 HR, W12

Anti-MAGE-A3 HR, M9

Anti-MAGE-A3 HR, M12

Anti-MAGE-A3 HR, M18

Anti-MAGE-A3 HR, M30

Anti-MAGE-A3 HR, at 12M post W120

Number of Humoral Responders as Regards Anti-Melanoma AntiGEn (MAGE)-A3 Antibodies (Anti-MAGE-A3 HR)

Anti-PD S+, PRE

Anti-PD S+, W6

Anti-PD S+, W12

Anti-PD S+, M9

Anti-PD S+, M12

Anti-PD S+, M18

Anti-PD S+, M30

Anti-PD S+, at 12M post W120

Number of Subjects Seropositive for Anti-protein D (PD) Antibodies (Anti-PD S+)

Anti-PD HR, W6

Anti-PD HR, W12

Anti-PD HR, M9

Anti-PD HR, M12

Anti-PD HR, M18

Anti-PD HR, M30

Anti-PD HR, at 12M post W120

Number of Humoral Responders as Regards Anti-protein D (PD) Antibodies (Anti-PD HR)

EQ-5D UV, At W0 DoT

EQ-5D UV, At W0 DpT

EQ-5D UV, At W6 DoT

EQ-5D UV, At W6 DpT

EQ-5D UV, At W12 DoT

EQ-5D UV, At W12 DpT

EQ-5D UV, At M6

EQ-5D UV, At M9

EQ-5D UV, At M12

EQ-5D UV, At M24

EQ-5D UV, At 6M post W120

EQ-5D UV, At recurrence

EQ-5D UV, At 12M post W120

Health-related Quality of Life (HQL) Scores

ALT - SCR UNK; DLP G0

ALT - SCR UNK; DLP G1

ALT - SCR UNK; DLP G2

ALT - SCR UNK; DLP G3

ALT - SCR UNK; DLP G4

ALT - SCR UNK; DLP UNK

ALT - SCR G0; DLP G0

ALT - SCR G0; DLP G1

ALT - SCR G0; DLP G2

ALT - SCR G0; DLP G3

ALT - SCR G0; DLP G4

ALT - SCR G0; DLP UNK

ALT - SCR G1; DLP G0

ALT - SCR G1; DLP G1

ALT - SCR G1; DLP G2

ALT - SCR G1; DLP G3

ALT - SCR G1; DLP G4

ALT - SCR G1; DLP UNK

ALT - SCR G2; DLP G0

ALT - SCR G2; DLP G1

ALT - SCR G2; DLP G2

ALT - SCR G2; DLP G3

ALT - SCR G2; DLP G4

ALT - SCR G2; DLP UNK

The Total Treated population - as treated included patients in the treatment group as per treatment actually received.

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

AST - SCR UNK; DLP G0

AST - SCR UNK; DLP G1

AST - SCR UNK; DLP G2

AST - SCR UNK; DLP G3

AST - SCR UNK; DLP G4

AST - SCR UNK; DLP UNK

AST - SCR G0; DLP G0

AST - SCR G0; DLP G1

AST - SCR G0; DLP G2

AST - SCR G0; DLP G3

AST - SCR G0; DLP G4

AST - SCR G0; DLP UNK

AST - SCR G1; DLP G0

AST - SCR G1; DLP G1

AST - SCR G1; DLP G2

AST - SCR G1; DLP G3

AST - SCR G1; DLP G4

AST - SCR G1; DLP UNK

AST - SCR G2; DLP G0

AST - SCR G2; DLP G1

AST - SCR G2; DLP G2

AST - SCR G2; DLP G3

AST - SCR G2; DLP G4

AST - SCR G2; DLP UNK

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

ALKP - SCR UNK; DLP G0

ALKP - SCR UNK; DLP G1

ALKP - SCR UNK; DLP G2

ALKP - SCR UNK; DLP G3

ALKP - SCR UNK; DLP G4

ALKP - SCR UNK; DLP UNK

ALKP - SCR G0; DLP G0

ALKP - SCR G0; DLP G1

Number of Patients With Abnormal Alkaline Phosphatase (ALKP) Values by Maximum Grade

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
GSK1572932A Antigen-Specific Cancer Immunotherapeutic as Adjuvant Therapy in Patients With Non-Small Cell Lung Cancer	NCT00480025	Lung Cancer, No...	GSK1572932A Ant... Placebo Control	18 Years -	GlaxoSmithKline
Cancer Immunotherapy GSK1572932A as Adjuvant Therapy for Patients With Tumor-antigen-positive Non-Small Cell Lung Cancer	NCT00455572	Lung Cancer, No...	Immunotherapeut... Cisplatin (CDDP... Vinorelbine Radiotherapy	18 Years -	GlaxoSmithKline
GSK1572932A Antigen-Specific Cancer Immunotherapeutic as Adjuvant Therapy in Patients With Non-Small Cell Lung Cancer	NCT00480025	Lung Cancer, No...	GSK1572932A Ant... Placebo Control	18 Years -	GlaxoSmithKline
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	NCT00796445	Melanoma	GSK 2132231A Placebo	18 Years -	GlaxoSmithKline
Cancer Immunotherapy GSK1572932A as Adjuvant Therapy for Patients With Tumor-antigen-positive Non-Small Cell Lung Cancer	NCT00455572	Lung Cancer, No...	Immunotherapeut... Cisplatin (CDDP... Vinorelbine Radiotherapy	18 Years -	GlaxoSmithKline
Cancer Immunotherapy GSK1572932A as Adjuvant Therapy for Patients With Tumor-antigen-positive Non-Small Cell Lung Cancer	NCT00455572	Lung Cancer, No...	Immunotherapeut... Cisplatin (CDDP... Vinorelbine Radiotherapy	18 Years -	GlaxoSmithKline

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