IMP321 Plus First-line Paclitaxel in Metastatic Breast Carcinoma

• Patients with stage IV breast adenocarcinoma, histologically proven by biopsy of the primary tumor and/or a metastasis.
• Female not pregnant (or with negative pregnancy test) or male.
• Fertile patients must use effective contraception during and for 3 months after drug administration.
• 18 years or above.
• ECOG performance status 0-1.
• Expected survival longer than three months.
• Resolution of toxicity of prior therapy to grade \< 2 (except alopecia).
• With or without prior adjuvant or neoadjuvant chemotherapy (authorized).
• With or without hormone therapy in adjuvant and/or the advanced setting (authorized).
• Evidence of measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST).
• Biphosphonate therapy must have started at least 4 weeks prior to first dosing of the study drug.
• Asthma or chronic obstructive pulmonary disease allowed provided daily systemic corticosteroid therapy is not required.
• Total white cell count ≥ 3.109/L.
• Platelet count ≥ 100.109/L.
• Hemoglobin > 9 g/dL or > 5.58 mmol/L.
• Serum creatinine \< 160 µmol/L.
• Total bilirubin \< 20 mmol/L, except for familial cholemia (Gilbert's disease).
• Serum ASAT and ALAT \< 3 times the upper limit of normal or \< 5 times upper limit of normal if liver metastases are present.
• Able to give written informed consent and to comply with the protocol.

Exclusion Criteria:

• Prior chemotherapy for metastatic breast adenocarcinoma.
• Disease-free interval \< 12 months from last dose of adjuvant chemotherapy.
• Prior high-dose chemotherapy requiring hematopoietic stem cell rescue.
• Inflammatory carcinoma.
• Systemic chemotherapy, hormone or endocrine therapy given as breast cancer therapy within 30 days prior to first dosing of the study drug.
• Any investigational drug within 30 days prior to first dosing of the study drug.
• Candidate for treatment with trastuzumab or administration of trastuzumab within 30 days prior to first dosing of the study drug.
• Known cerebral or leptomeningeal metastases.
• Pregnancy or breast feeding.
• Serious intercurrent infection within the 30 days prior to first dosing of the study drug.
• Motor or sensory peripheral neuropathy ≥ 2 according to the National Cancer Institute criteria.
• Congestive heart failure.
• Active acute or chronic infection.
• Active autoimmune disease requiring immunosuppressive therapy.
• Known HIV positivity.
• Life threatening illness unrelated to cancer.
• Previous malignancies within the last two years other than breast carcinoma, successfully treated squamous cell carcinoma of the skin or in situ carcinoma of the cervix treated with cone biopsy.
• Previous history of major psychiatric disorder requiring hospitalization or any current psychiatric disorder that would impede the patient's ability to provide informed consent or to comply with the protocol.
• Corticosteroids unless used as substitutive therapy or before each injection of paclitaxel.
• Past history of severe allergic episodes and/or Quincke edema.
• Past or present history of any organic disorder likely to modify absorption, distribution or elimination of the study drug.
• Alcohol or substance abuse disorder.
• Radiotherapy within the 30 days prior to first dosing of the study drug.