Immunotherapy With TG4010 in Patients With Advanced Non-Small Cell Lung Cancer

Inclusion Criteria:

• Histologically confirmed non-small cell carcinoma of the lung (adenocarcinoma, squamous cell carcinoma, or large cell carcinoma);
• Histological documentation of MUC1 antigen expression on the primary tumor or on metastasis, as defined by a positive staining by immuno-histo-chemistry in at least 25% of the tumor cells in the conditions described in the technical documentation of the monoclonal antibody;
• Patients will have stage IIIb "wet" (with pleural or pericardial effusion) or IV disease, with no prior systemic therapy for advanced disease except for adjuvant treatment. Prior surgery or radiation therapy aimed at local palliation or attempted local disease control is permitted;
• At least one measurable lesion by Computed Tomography (CT-scanner) according to WHO criteria (lesion accurately measured in two dimensions with longest diameter equal or greater to 10 mm with spiral CT scan);

• Adequate hematological, hepatic, and renal function:

  • Hemoglobin >= 10.0 g/dL; WBC >= 3.0x10e9/L including neutrophils >= 1.5x10e9/L and total lymphocytes count >= 0.5x10e9/L; platelets count >= 100x10e9/L;
  • Bilirubin =< 2x the upper limit of normal and serum transaminases =< 3x the upper limit of normal;
  • Glomerular Filtration Rate higher than 60 ml/mn according to Cockcroft formula;
• Performance status 0 or 1 on the ECOG scale (Appendix 2);
• Minimum estimated life expectancy of 4 months;
• Written informed consent from patient.

Exclusion Criteria:

• Concomitant brain metastases. If previous brain metastases were treated, the absence of evolution is to be demonstrated by the MRI or scanner performed at baseline;
• Prior history of other malignancy except basal cell carcinoma and intra-epithelial cervical cancer or other cancer with complete response since at least 5 years;
• History of any form of systemic therapy for advanced non-small cell cancer of the lung except for (neo)adjuvant treatment;
• Previous (within 4 weeks prior to day 1) or concomitant long term treatment with systemic steroids, immunosuppressive / immunomodulating drugs (e.g. Cyclosporine, corticoïds);
• Positive serology for HIV or HCV; positive antigens for hepatitis B;
• Serious concomitant medical disorder;
• Major surgery within 4 weeks prior to day 1;
• Patient with an organ allograft;
• Allergy to eggs;
• Participation in another experimental protocol during the study period, or within 4 weeks prior to day 1;
• Pregnancy at the entry or women who are breast feeding;
• Patient without adequate protection against pregnancy during the conduct of the study and for 3 months after the last injection of TG4010 and/or chemotherapy;
• History of substance abuse;
• Patient unable or unwilling to comply with the protocol requirements.