IMP321 Plus First-line Paclitaxel in Metastatic Breast Carcinoma

Inclusion Criteria:

* 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.