Study to Test the Efficacy of the Vaccine GSK 249553 in Treating Non-small-cell Lung Cancer After Tumour Removal by Surgery

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

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.

This Phase IIb study will be conducted at centres in several European countries according to a multicentre, international, randomised, double-blind design. It will provide information about the clinical and immunological efficacy and the tolerability of GSK 249553 when this is administered to patients with stage IB, II NSCLC. The study treatment will be administered by intramuscular injection; first administration will take place 4-6 weeks after surgery. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

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.