Study to Assess dHER2+AS15 Cancer Vaccine Given in Combination With Lapatinib to Patients With Metastatic Breast Cancer

Inclusion Criteria

The following criteria are to be checked at the time of study entry. The patients may only be included in the study if ALL of the following statements are FULLFILLED:

• The patient (male or female) is at least 18 years old at the time of signature of the informed consent form.
• Written informed consent has been obtained from the patient prior to the performance of any protocol-specific procedure.
• The patient is diagnosed with confirmed invasive breast cancer with stage IV disease.

Note: If the metastatic disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology or histology.

• The patient has documented disease progression or relapse following at least one prior standard therapy with trastuzumab (alone or in combination with chemotherapy).

Patients with prior lapatinib use are eligible. Furthermore,

• The administration of the chemotherapeutic agent(s) should have been stopped for at least 28 days by the time of the first ASCI administration.
• The administration of trastuzumab alone could be maintained after chemotherapy, but the last dose of trastuzumab should not have been given less than three weeks before the first ASCI administration.
• The patient will not be given trastuzumab during the trial.
• For metastatic patients whose disease is ER+ and/or PR+ the following criteria should be met:
• Patients with visceral disease that requires chemotherapy (eg., patients with liver or lung metastases).
• Rapidly progressing or life threatening disease, as determined by the investigator.
• Patients who received hormonal therapy and are no longer benefiting from this therapy.
• A tumor lesion from the patient biopsied before or during screening shows either:
• Overexpression of the HER2 protein, as determined by immunohistochemistry (IHC, with result IHC 3+) or
• Amplification of the HER2 gene as determined by FISH (at least 4 fold i.e. at least 8 copies).

Note: Overexpression/amplification measurements must be performed on a metastatic lesion in all cases where such a lesion is sufficiently easily accessible. If however such a biopsy is not possible, then these measurements can be performed on the primary tumor. Use of the primary tumor is to be documented and justified.

Ten FFPE tissue sections of the tumor on which the HER2 overexpression/amplification has been done -if available-may be requested. These may be used to retrospectively carry out part of the translational research (i.e. analysis of EGF receptor activity and of the presence of immune effector cells, refer to Section 7).

• The patient has at least one measurable lesion according to RECIST criteria.
• The patient has ECOG status of 0 or 1.
• The patient has adequate bone marrow reserve as indicated by:
• White blood cell count >/= 3,000/mm3.
• Neutrophil count >/= 1,500/mm3.
• Platelet count >/= 100,000/mm3.
• Hemoglobin levels >/= 10.0 g/dl.
• The patient has adequate renal function as shown by the creatinine levels (i.e. within the normal range).
• The patient has adequate hepatic function as shown by serum bilirubin levels i.e:
• Serum bilirubin levels within the normal limits.
• Both AST and ALT levels 45 years.
• Able to swallow and retain oral medication.
• In the view of the investigator, the patient can and will comply with the requirements of the protocol.

Exclusion Criteria

The following criteria should be checked at the time of study entry. If any apply, the patient must not be included in the study:

• The patient has received > 300 mg/m2 doxorubicin (cumulative dose) or > 600 mg/m2 epirubicin (cumulative dose).
• The patient is receiving treatment with bisphosphonate UNLESS the biphosphonate treatment was initiated more than three weeks before the first ASCI administration. (See also section 5.3.2.).
• The patient has received any investigational or non-registered product (drug or vaccine) other than the study treatment(s) within 30 days preceding the first do