Phase Ib/II Study of LY2780301 in Combination With Weekly PACLITAXEL in HER2-metastatic Breast Cancer

Inclusion Criteria: 1. Female or male patients (≥ 18 years) 2. WHO/ECOG performance status ≤ 1 for phase Ib part, \< 2 for phase II part 3. Patient with histologically confirmed inoperable locally advanced BC or MBC 4. Patient with tumor biopsy from metastatic tissue containing more than 50% tumor cells 5. Patient has known hormone receptor (ER/PR) status, positive and/or negative (local laboratory testing) 6. Patient has HER2-negative disease: IHC 0, 1 + or 2+ and/or in situ hybridization (FISH, CISH, SISH) negative (local laboratory testing) 7. Phase Ib: Patient has measurable or non-measurable disease according to RECIST 1.1 criteria only Phase II: Patient has measurable disease according to RECIST 1.1 criteria only 8. Patient has adequate bone marrow and organ function 9. Patient is able to swallow and retain oral medication 10. Negative serum pregnancy test within ≤ one week before first dose for childbearing potential women and for women \< 12 months after the onset of menopause 11. Males and Females of childbearing potential (FCBP) must agree to use a reliable form of contraception or to practice complete abstinence from heterosexual intercourse during the study treatment (and 3 months after the end of treatment) 12. Life expectancy \> 3 months 13. Affiliation to social security or beneficiary 14. Patient has signed the Informed Consent (ICF) prior to any screening procedures being performed Exclusion criteria 1. Previous treatment with AKT or PI3K inhibitor 2. no previous cytotoxic treatment for metastatic or inoperable locally advanced disease (phase II part); Adjuvant/neoadjuvant therapy will be counted as prior line of therapy for metastatic/recurrent disease if the patient had a progression/recurrence within 6 months after completion of the therapy (12 months for taxane-based therapy). Previous hormonal treatment for metastatic or locally advanced disease is allowed. 3. Patient with bone metastases only 4. Patient has symptomatic CNS metastases; patients with asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior local treatment for CNS metastases ≥ 15 days prior to the start of study treatment (including radiotherapy and/or surgery) and must have completed corticosteroid therapy. 5. Patient has a concurrent malignancy or malignancy within 3 years of study enrollment 6. Patient has received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study 7. Patients who have received chemotherapy or targeted anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C; 3 weeks for weekly chemotherapy) prior to starting study drug or who have not recovered from side effects of such therapy 8. Patients who have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) ≤ 5 effective half-lives prior to starting study drug or who have not recovered from side effects of such therapy 9. Patients who have undergone major surgery ≤ 28 days prior to starting study drug or who have not recovered from side effects of such therapy 10. Known diagnosis of human immunodeficiency virus (HIV) infection 11. Patient has a known hypersensitivity to paclitaxel or other products containing Cremophor 12. Patient has a contraindication to use the paclitaxel standard pre-treatment such as corticosteroids 13. Patients with any peripheral neuropathy ≥ CTCAE grade 2 14. Patients with diarrhea ≥ CTCAE grade 2 15. Patient has active cardiac disease 16. Patient has a history of cardiac dysfunction including 17. Patients who are currently receiving treatment with medication with a known risk prolong the QT interval or inducing Torsades de Pointes 18. Patient has poorly controlled diabetes mellitus (HbA1c \> 8 %) 19. Other concurrent severe and/or uncontrolled concomitant medical conditions 20. Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of LY2780301 21. Patient is currently receiving treatment with drugs known to be substrate of isoenzyme CYP3A4 22. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (\> 5 mIU/mL) 23. Patient who does not apply effective contraception during the study and through the duration as defined below after the final dose of study treatment. 24. Other experimental treatment