Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase IIB Study to Assess the Efficacy of GSK 249553 as Adjuvant Therapy Given to MAGE-3-Positive Patients With Non-Small-Cell Lung Cancer in Stage IB (T2/N0) or II (T1/N1 or T2/N1 or T3/N0), Who Have Had Complete Surgical Resection
Brief Summary: Patients will receive injections of GSK 249553 vaccine . Appropriate tests will be performed to assess the safety of the treatment and its ability to induce an immune response.


Options:
A: Inclusion Criteria:

* Histologically or cytologically documented unresectable stage III non-small cell lung cancer (NSCLC)
* Documented stable disease or objective response, according to Response Evaluation Criteria In Solid Tumors Version 1.0 (RECIST v1.0) after primary concomitant chemo-radiotherapy for unresectable stage III disease, within four weeks (28 days) prior to randomization
* Receipt of concomitant chemo-radiotherapy. The chemotherapy-part must have been platinum-based, must have been administered with a minimum of two cycles overlap with radiotherapy (one cycle lasts either 3 or 4 weeks depending on the chemotherapy regimen), and a minimum of two platinum-based chemotherapy administrations must have been given during radiotherapy. Purely radio sensitizing doses of chemotherapy are not acceptable. Radiotherapy must have delivered a radiation dose of \>= (greater than or equal to) 50 Gray (Gy). Induction or consolidation chemotherapy is allowed and if given, should be accounted as part of primary thoracic chemoradiotherapy. Subjects must have completed the primary thoracic chemo-radiotherapy at least four weeks (28 days) and no later than 12 weeks (84 days) prior to randomization. Subjects who received prophylactic brain irradiation as part of primary chemo-radiotherapy are eligible
* Geographically accessible for ongoing follow-up, and committed to comply with the designated visits
* An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* A platelet count \>= the lower limit of normal for the site or \>= 100 x 10\^9 per liter (/Liter) (whichever is greater); white blood cell (WBC) \>= 2.5 x 10\^9/Liter and haemoglobin \>= 90 gram per liter (g/L)
* \>=18 years of age (or minimum age of legal consent consistent with local regulations, if minimum is greater than \[\>\] 18 years of age)
* Other protocol defined inclusion criteria could apply

Exclusion Criteria:

Pre-Therapies\*:

* Prior sequential chemo-radiotherapy
* Lung-cancer-specific therapy (including surgery) other than primary chemoradiotherapy
* Immunotherapy (e.g., interferons, tumor necrosis factor \[TNF\], interleukins, or biological response modifiers \[granulocyte macrophage colony stimulating factor {GMCSF}, granulocyte colony stimulating factor {G-CSF}, macrophage-colony stimulating factor {M-CSF}\], monoclonal antibodies) within four weeks (28 days) prior to randomization
* Investigational systemic drugs (including off-label use of approved products) within four weeks (28 days) prior to randomization

Disease Status:

* Metastatic disease
* Malignant pleural effusion at initial diagnosis and/or at trial entry
* Past or current history of neoplasm other than lung carcinoma, except for curatively treated non-melanoma skin cancer, in situ carcinoma of the cervix, or other cancer curatively treated and with no evidence of disease for at least 5 years
* Autoimmune disease
* A recognized immunodeficiency disease including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia; subjects who have hereditary or congenital immunodeficiencies
* Any preexisting medical condition requiring chronic steroid or immunosuppressive therapy (steroids for the treatment of radiation pneumonitis are allowed)
* Known active Hepatitis B infection and/or Hepatitis C infection
* Signs and symptoms suggestive of transmissible spongiform encephalopathy, or of family members who suffer(ed) from such

Physiological Functions:

* Clinically significant hepatic dysfunction
* Clinically significant renal dysfunction
* Clinically significant cardiac disease
* Splenectomy
* Infectious process that in the opinion of the investigator could compromise the subject's ability to mount an immune response

Standard Safety:

* Pregnant or breastfeeding women, women of childbearing potential, unless using effective contraception as determined by the investigator
* Known drug abuse or alcohol abuse
* Participation in another clinical trial (excluding purely observational studies) within the past 28 days
* Requires concurrent treatment with a non-permitted drug
* Known hypersensitivity to any of the trial treatment ingredients
* Legal incapacity or limited legal capacity
* Any other reason that, in the opinion of the investigator precludes the subject from participating in the trial
B: Inclusion Criteria:

* Written informed consent has been obtained prior to surgical tumour resection and prior to the performance of any other protocol-specific procedures.
* At least 18 years of age at the time of resection.
* Pathologically proven, surgically staged squamous or non-squamous IB, IIA or IIB NSCLC, and complete surgical resection.
* The operative technique for resection of the patient's tumour involves at least a lobectomy or a sleeve lobectomy, conforming to all of the following criteria:

  1. Removal of all gross disease with negative resection margins, by lobectomy, sleeve resection, bilobectomy or pneumonectomy, based on intra-operative findings.
  2. The level of nodal sampling is at least as follows:

Levels 4, 7, 10 in both right upper and right middle lobes Levels 4, 7, 9, 10 in right lower lobe Levels 5, 6, 7 in left upper lobe Levels 7, 9, 10 in left lower lobe. or at the maximum defined as systematic radical mediastinal lymphadenectomy: all ipsilateral and easily accessible lymph-node levels must be removed, independently of the location of the primary tumour. The level of nodal sampling is as follows: Levels 2, 4, 7, 8, 9, 10 in right-sided tumours, Levels 5, 6, 7, 8, 9, 10 in left-sided tumours

* Tumour shows expression of MAGE-3 antigen.
* Recovered from surgery for at least 4 weeks and not more than 6 weeks.
* ECOG performance status of ≤ 1 at the time of randomisation.
* Laboratory criteria (all of the following must be fulfilled): adequate bone marrow reserve, adequate renal function, adequate hepatic function, serum bilirubin within normal range, negative HIV antibody test, negative HBV antigen test, negative HCV antibody test.
* (For females): EITHER not of child-bearing potential OR sexually abstinent OR all of the following: negative urine/serum β-HCG pregnancy test, use of adequate contraceptive precautions for 30 days before first vaccination. Agree to continue such precautions for 2 months after completion of the course of vaccination.

Exclusion Criteria:

* Received any anti-cancer specific treatment including radiotherapy, prior to surgery, unless the treatment was for previous malignancies allowed by the protocol, i.e., basal and localised squamous-cell skin carcinoma that has been successfully treated, or carcinoma in situ of the cervix (see exclusion criterion no. 10).
* Candidate for post-surgery radiation therapy or any kind of anti-cancer-specific treatment.
* Pregnant/lactating.
* (For female patients of child-bearing potential): not agree to practice an effective method of contraception.
* Uncontrolled bleeding disorder.
* Autoimmune disease.
* History of anaphylaxis or severe allergic reaction.
* Undergone splenectomy or radiation to the spleen.
* Received a major organ allograft.
* Malignancies at other sites (except (i) basal and localised squamous-cell skin carcinoma that has been successfully treated, and (ii) carcinoma in situ of the cervix).
* Concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
* Uncontrolled congestive heart failure or hypertension.
* Unstable heart disease or uncontrolled arrhythmia at the time of enrolment.
* Psychiatric or addictive disorders that may compromise ability to give informed consent, or to comply with the trial procedures.
* Any evidence of residual tumour after surgery.
* Require concomitant treatment with systemic corticosteroids, or any other immunosuppressive agents.
* Received chemotherapy, immunotherapy related to NSCLC.
* Need home oxygenation.
* Received any investigational or non-registered drug or vaccine other than the study vaccine within the 30 days preceding the first dose of study vaccine, or plans to receive such a drug during the study period.
C: Inclusion criteria:

* Male or female patient with completely resected, pathologically proven stage IB, II or IIIA NSCLC.
* Written informed consent for MAGE-A3 expression screening on tumor biopsy has been obtained from the patient prior to shipment of the sample for expression testing (before or just after surgical resection), and written informed consent for the complete study has been obtained prior to the performance of any other protocol-specific procedure.
* Patient is ≥ 18 years of age at the time of signature of the first informed consent form.
* The patient's tumor shows expression of MAGE-A3 gene
* The surgical technique for resection of the patient's tumor is anatomical, involving at least a lobectomy or a sleeve lobectomy;
* The mediastinal lymph node sampling is done according to study protocol guidelines;
* The patient is free of metastasis, as confirmed by a negative baseline computer tomogram (CT scan) of the chest, upper abdomen and CT scan or MRI of the brain.

Other examinations should be performed as clinically indicated. Note that if randomization is taking place within 8 weeks after surgery, brain CT scans or brain MRI performed up to 4 weeks before surgery do not have to be repeated.

* ECOG performance status of 0, 1 or 2 at the time of randomization.
* Adequate bone-marrow reserve, adequate renal function and adequate hepatic function as assessed by standard laboratory criteria, and defined as:

Absolute neutrophil count ≥ 1.0 x 10E9/L Platelet count ≥ 75 x 10E9/L Serum creatinine ≤ 1.5 times the Upper Limit of Normal (ULN)

≤ 3.0 times the ULN if due to platinum adjuvant chemotherapy Total bilirubin ≤ 1.5 times the ULN Alanine transaminase (ALAT) ≤ 2.5 times the ULN

* If the patient is female, she must be of non-childbearing potential, i.e. have a current tubal ligation, hysterectomy, ovariectomy or be post menopausal, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to administration of study treatment, have a negative pregnancy test and continue such precautions during all study treatment period and for 2 months after completion of the injection series.
* In the view of the investigator, the patient can and will comply with the requirements of the protocol.

Exclusion criteria

* The primary tumor was removed by segmentectomy or wedge resection.
* The patient shows any evidence of residual tumor after surgery.
* The patient has received any anti-cancer specific treatment, including radiotherapy, immunotherapy, chemotherapy or neo-adjuvant chemotherapy, except:

For the treatment of previous malignancies as allowed by the protocol (i.e., non-melanoma skin cancers or carcinoma in situ of the cervix or effectively treated malignancy that has been in remission for over 5 years), Administration of adjuvant platinum-based chemotherapy for the treatment of the current NSCLC is allowed between surgery and randomization.

* The patient has previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers or carcinoma in situ of the cervix or effectively treated malignancy that has been in remission for over 5 years and highly likely to have been cured.
* History of allergic disease or reactions likely to be exacerbated by any component of the study investigational product.
* The patient has an autoimmune disease such as, but not limited to, multiple sclerosis, lupus, and inflammatory bowel disease. Patients with vitiligo are not excluded.
* The patient requires concomitant treatment with systemic corticosteroids, or any other immunosuppressive agents.

Note: The use of prednisone, or equivalent, \<0.5 mg/kg/day (absolute maximum 40 mg/day), or inhaled corticosteroids for COPD or topical steroids is permitted.

* The patient has received a major organ allograft.
* The patient is known to be HIV-positive.
* The patient has an uncontrolled bleeding disorder.
* The patient has uncontrolled congestive heart failure or hypertension, unstable heart disease (coronary artery disease or myocardial infarction) or uncontrolled arrhythmia at the time of enrolment.
* The patient needs home oxygenation.
* The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with the trial procedures.
* The patient has other concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
* The patient has received any investigational or non-registered medicinal product other than the study medication within the 30 days preceding the first dose of study medication, or plans to receive such a drug during the study period.
* For female patients: the patient is pregnant or lactating.
D: Inclusion criteria:

1. Pathologically proven (either histologic or cytologic) diagnosis of Stage IIIA or IIIB non-small cell lung cancer (NSCLC); excluding patients with N3 disease based on supraclavicular or contralateral hilar adenopathy, \[according to American Joint Committee on Cancer (AJCC) Staging, 6th edition; see appendix III\] within 12 weeks of registration; patients who present with N2 or N3 disease and an undetectable NSCLC primary tumor also are eligible.
2. Patients must be considered unresectable or inoperable; Note: Patients who have had a nodal recurrence after surgery for an early-stage NSCLC are eligible if the following criteria are met:

   * Nodal recurrence must be N1 or N2; N3 is not eligible.
   * The initial primary must have been staged as T1-2, N0, M0.
   * The node must be biopsied within 12 weeks of registration.
   * The node must be measurable.
   * The patient must not have received prior chemotherapy or radiation for this lung cancer.
   * Prior curative surgery must have been at least 6 months prior to the nodal recurrence.
   * The exception to a prior invasive malignancy does not apply to the initial lung primary.
3. Stage III A or B disease, including no distant metastases, based upon the following minimum diagnostic workup are acceptable:

   * History/physical examination, including documentation of height, weight, body surface area (BSA), and vital signs within 8 weeks prior to registration;
   * Computed tomographic (CT)/Magnetic Resonance Imaging (MRI) imaging of the lung and upper abdomen through the adrenal glands within 6 weeks prior to registration;
   * An MRI of the brain with contrast (or CT with contrast if MRI is medically contraindicated) within 6 weeks prior to registration; Note: The use of intravenous contrast is required for the MRI or CT. An MRI without contrast is only permitted if the patient has a contrast allergy.
   * Whole-body fluorodeoxyglucose (FDG) - Positron Emission Tomography(PET) or PET/CT or if no PET is available, a bone scan is required within 6 weeks prior to registration; Note: If a PET is done that shows clear adrenals and lungs, then a CT scan of chest only is permitted.
4. If a pleural effusion is present, the following criteria must be met to exclude malignant involvement (incurable T4 disease):

   * When pleural fluid is visible on both the CT scan and on a chest x-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative.
   * Exudative pleural effusions are excluded, regardless of cytology;
   * Effusions that are minimal (i.e. not visible on chest x-ray) that are too small to safely tap are eligible.
5. Patients must have measurable or evaluable disease.
6. Patients with post-obstructive pneumonia are eligible.
7. Patients must be at least 3 weeks from prior thoracotomy (if performed).
8. Zubrod Performance Status 0-1;
9. Age ≥ 18;
10. Pulmonary function tests (PFTs) including forced expiratory volume in one second (FEV1) within 12 weeks prior to registration; for FEV1, the best value obtained pre- or post bronchodilator must be ≥ 1.2 liters/second or ≥ 50% predicted.
11. Complete blood count (CBC)/differential obtained within 2 weeks prior to registration on study, with adequate bone marrow function defined as follows:

    * Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3;
    * Platelets ≥ 100,000 cells/mm3;
    * Hemoglobin ≥ 10.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 10.0 g/dl is acceptable.)
12. Serum creatinine within normal institutional limits or creatinine clearance ≥60 ml/min;
13. Bilirubin must be within or below normal institutional limits;
14. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) \< 2.5 x the institutional upper limit of normal (IULN);
15. Patient must sign study specific informed consent prior to study entry.

Exclusion Criteria:

1. N3 supraclavicular disease;
2. Greater than minimal, exudative, or cytologically positive pleural effusions;
3. Involved contralateral hilar nodes (i.e. greater than 1.5 cm on short axis or positive on PET scan);
4. ≥ 10% weight loss within the past month;
5. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; non-invasive conditions such as carcinoma in situ of the breast, oral cavity, or cervix are all permissible.
6. Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable.
7. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields;
8. Prior therapy that specifically and directly targets the epidermal growth factor receptor (EGFR) pathway;
9. Prior severe infusion reaction to a monoclonal antibody;
10. Severe, active co-morbidity, defined as follows:

    * Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, myocardial infarction within the last 6 months, uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction.
    * Transmural myocardial infarction within the last 6 months;
    * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
    * Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration;
    * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
    * Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients.
11. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
12. Any history of allergic reaction to paclitaxel or other taxanes, or to carboplatin;
13. Uncontrolled neuropathy grade 2 or greater regardless of cause.

Answer: B