Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multi-national, Double-blind, Placebo-controlled, Randomized, Phase III Clinical Trial of the Cancer Vaccine Stimuvax® (L-BLP25 or BLP25 Liposome Vaccine) in Asian Subjects With Stage III, Unresectable, Non-small Cell Lung Cancer (NSCLC) Who Have Demonstrated Either Stable Disease or Objective Response Following Primary Chemo-radiotherapy
Brief Summary: The purpose of this study is to determine whether the cancer vaccine tecemotide (L-BLP25) in addition to best supportive care is effective in prolonging the lives of Asian subjects with unresectable stage III non-small cell lung cancer in comparison to a placebo plus best supportive care (a so-called placebo controlled study).


Options:
A: Inclusion Criteria:

* Written informed consent obtained,
* Aged 18 or more,
* Pathologically proven stage IB, II or III NSCLC,
* Tumor expresses MAGE-A3,
* Free of distant metastasis,
* For Cohort 1, all of the following:

  1. Completely resected stage IB, II or IIIA NSCLC,
  2. Anatomical tumor resection, involving at least a lobectomy, and nodal sampling as per center standard
  3. ECOG performance status = 0 or 1
  4. Due to receive adjuvant chemotherapy as permitted in the protocol
  5. Not received, not receiving, and not due to receive adjuvant radiotherapy (except stage III patients)
  6. First administration of chemotherapy can be scheduled within 4-12 weeks after surgery
* For Cohort 2, all of the following:

  1. Resected stage IB, II or IIIA NSCLC,
  2. Anatomical tumor resection, involving at least a lobectomy, and nodal sampling as per center standard
  3. ECOG PS = 0 or 1
  4. Due to receive, or receiving, adjuvant chemotherapy as permitted in the protocol
  5. Not received, not receiving, and not due to receive, adjuvant radiotherapy (except stage III patients)
  6. First administration of ASCI treatment can be scheduled within 2-4 weeks after the last administration of chemotherapy
  7. Received at least 2 cycles of standard chemotherapy before ASCI treatment is initiated, whereafter no further chemotherapy is planned
* For Cohort 3, all of the following:

  1. Resected stage IB, II or IIIA NSCLC
  2. Anatomical tumor resection, involving at least a lobectomy, and nodal sampling as per center standard
  3. ECOG PS = 0 or 1 or 2
  4. Not received, not receiving, and not due to receive, adjuvant chemotherapy
  5. Not received, not receiving, and not due to receive, adjuvant radiotherapy (this does not apply to patients in stage III)
  6. First administration of ASCI treatment can be scheduled within 4-8 weeks after surgery
* For Cohort 4, all of the following:

  1. Unresectable stage III NSCLC
  2. ECOG PS = 0 or 1 or 2
  3. Due to receive, or receiving, chemo- and radiotherapy according to institution standard
  4. Received at least 2 cycles of standard chemotherapy before the initiation of ASCI treatment, whereafter no further chemo-/radiotherapy is planned
  5. Stable disease or objective response (confirmed by CT scan) after standard chemo-/radiotherapy
  6. Administration of ASCI treatment can be scheduled within 2-6 weeks after the last administration of chemo-/radiotherapy
* Laboratory criteria: adequate bone-marrow reserve, adequate renal function, adequate hepatic function.
* For females: EITHER not of child-bearing potential, OR sexually abstinent, OR negative urine pregnancy test + use of adequate contraceptive precautions from 30 days before first study treatment till 2 months after completion of study treatment course
* In the view of the investigator, the patient can and will comply with the requirements of the protocol

Exclusion criteria:

* Previous or concomitant other malignancies, except if effectively treated and considered by the investigator highly likely to have been cured
* Pregnant or lactating
* History of anaphylaxis or severe allergic reaction
* Concurrent severe medical problems, unrelated to the malignancy, limiting full compliance with the study or exposing the patient to unacceptable risk
* Psychiatric or addictive disorders compromising the ability to give informed consent, or to comply with the trial procedures
* HIV-positive
* Require treatment with systemic corticosteroids, or other immunosuppressive agents
* Need home oxygenation
* Received or plan to receive investigational or non-registered product other than the study medication from 30 days before first dose of study medication and during whole study period
* History of chronic alcohol consumption and/or drug abuse
B: 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.
C: 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.
D: 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

Answer: D