Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer)

ABI-007-MBC- 001 is a Phase 2/3, multicenter, open-label, randomized, study that will compare
the safety and efficacy of weekly nab-paclitaxel in combination with gemcitabine or
carboplatin to the combination of gemcitabine and carboplatin as first line therapy in female
subjects with Estrogen Receptor (ER), Progesterone Receptor (PgR), and human epidermal growth
factor receptor 2 (HER2) negative (triple negative) metastatic breast cancer (TNMBC) or
metastatic triple negative breast cancer. In the phase 2 portion of the study, the
combinations of nab-paclitaxel plus gemcitabine and nab-paclitaxel plus carboplatin will be
evaluated, and a comparator arm of gemcitabine combined with carboplatin will be used. In the
phase 3 portion of the study, the selected nab-paclitaxel combination treatment will be
compared to gemcitabine combined with carboplatin to evaluate progression free survival,
safety and tolerability, overall survival, disease control rate and duration of response in
women with metastatic triple negative breast cancer.

Due to changes in the treatment landscape since the initiation of this trial, the decision
was made not to proceed to the Phase 3 portion of the study.

Inclusion Criteria: A subject will be eligible for inclusion in this study only if all of
the following criteria are met:

1. Female subjects, age ≥ 18 years at the time informed consent is signed

2. Pathologically confirmed adenocarcinoma of the breast

3. Pathologically confirmed as triple negative, source documented, defined as both of the
following

1. Estrogen Receptor (ER) and Progesterone Receptor (PgR) negative: < 1% of tumor
cell nuclei are immunoreactive in the presence of evidence that the sample can
express ER or PgR (positive intrinsic controls)

2. Human Epidermal Growth Factor Receptor 2 (HER2) negative as per American Society
of Clinical Oncology - College of American Pathologists (ASCO/CAP) guidelines i.
Immunohistochemistry (IHC) 0 or 1 Fluorescence In Situ Hybridization (FISH)
negative (or equivalent negative test). Subjects with IHC 2 must have a negative
by Fluorescence In Situ Hybridization (FISH),, (or equivalent negative test).

4. Subjects with prior breast cancer history of different phenotypes (ie, ER/PgR/HER2
positive) must have pathologic confirmation of triple negative disease in at least one
of the current sites of metastasis

5. Subjects must have received prior adjuvant or neoadjuvant anthracycline therapy;
unless (a) anthracycline treatment was not indicated or was not the best treatment
option for the subject in the opinion of the treating physician; and (b) anthracycline
treatment remains not indicated or, in the opinion of the treating physician, is not
the best treatment option for the subject's metastatic disease.

a. Newly diagnosed subjects presenting with TNMBC are eligible for the study if
anthracycline treatment is not indicated or is not the best treatment option for the
subject in the opinion of the treating physician.

6. Subjects with measurable metastatic disease, defined by Response Evaluation Criteria
in Solid Tumors 1.1 (RECIST 1.1) guidelines

7. Life expectancy ≥ 16 weeks from randomization

8. No prior cytotoxic chemotherapy for metastatic breast cancer. Prior immunotherapy
and/or monoclonal antibody therapy are acceptable. Prior treatments must have been
discontinued at least 30 days prior to start of study treatment and all related
toxicities must have resolved to Grade 1 or less.

9. Prior neoadjuvant or adjuvant chemotherapy, if given, must have been completed at
least 6 months before randomization with all related toxicities resolved, and
documented evidence of disease progression per RECIST 1.1 guidelines is required.

a. If prior neoadjuvant or adjuvant chemotherapy contained taxane, gemcitabine, or
platinum agents, the treatment must have completed at least 12 months before
randomization

10. Prior radiotherapy must have completed before randomization, with full recovery from
acute radiation side effects. At least one measurable lesion must be completely
outside the radiation portal or there must be unequivocal radiologic or clinical exam
proof of progressive disease within the radiation portal, in accordance with RECIST
1.1 guidelines

11. At least 30 days from major surgery before randomization, with full recovery

12. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

13. Subject has the following blood counts at screening:

- Absolute Neutrophil Count (ANC) ≥ 1500/mm^2 ;

- Platelets ≥ 100,000/mm^2 ;

- Hemoglobin (Hgb) ≥ 9 g/dL

14. Subject has the following blood chemistry levels at screening:

- Aspartate aminotransferase (AST) Serum glutamic-oxaloacetic transaminase (SGOT),
Alanine Aminotransferase (ALT ) Serum Glutamic Pyruvate Transaminase (SGPT) ≤ 2.5
x upper limit of normal range (ULN); if hepatic metastases present ≤ 5.0 x ULN

- Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin
within normal range in subjects with documented Gilbert's Syndrome

- Creatinine clearance > 60 mL/min (by Cockcroft-Gault)

15. Females of child-bearing potential [defined as a sexually mature women who (1) have
not undergone hysterectomy (the surgical removal of the uterus) or bilateral
oophorectomy (the surgical removal of both ovaries) or (2) have not been naturally
postmenopausal for at least 24 consecutive months (i.e., has had menses at any time
during the preceding 24 consecutive months)] must:

- Demonstrate a negative serum pregnancy test result at screening (performed by
central lab) confirmed by local negative urine pregnancy dipstick within 72 hours
prior to the first dose of IP); pregnancy test with sensitivity of at least 25
mIU/mL; and

- Either commit to true abstinence* from heterosexual contact (which must be
reviewed on a monthly basis) or agree to use, and be able to comply with, two
physician approved effective contraception methods (oral, injectable, or
implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier
contraceptive with spermicide; or vasectomized partner) without interruption for
28 days or longer as required by local guidelines, prior to starting study drug,
during the study therapy (including dose interruptions), and for 28 days after
discontinuation of the study or longer as required by local guidelines

16. Females must abstain from breastfeeding starting at randomization, during study
participation and for 28 days or longer as required by local guidelines, after IP
discontinuation

17. Understand and voluntarily sign an informed consent document prior to any study
related assessments/procedures are conducted

18. Able to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria:

A subject will not be eligible for inclusion in this study if any of the following criteria
apply:

1. Male subjects

2. Concurrent chemotherapy or any other anti tumor therapy for breast cancer. Prior
immunotherapy & monoclonal antibody therapy are acceptable.

3. Subjects who received prior cytotoxic chemotherapy after incomplete resection of
locoregional recurrent disease

4. History of, or known current evidence of brain metastasis, including leptomeningeal
involvement.

5. Subjects with bone as the only site of metastatic disease

6. Subjects with regional lymph node as the only site of metastatic disease

7. Serious intercurrent medical or psychiatric illness, including serious active
infection

8. History of class II-IV congestive heart failure or myocardial infarction within 6
months of randomization

9. History of other primary malignancy in the last 5 years prior to randomization.
Subjects with prior breast cancer history are eligible, however, the most recently
obtained biopsy must demonstrate triple negative disease (source documented). Subjects
with prior history of in situ cancer or basal or localized squamous cell skin cancer
are eligible.

10. Subjects with a history of interstitial lung disease, history of slowly progressive
dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis,
pulmonary hypersensitivity pneumonitis or multiple uncontrolled or unstable allergies
which, in the opinion of the investigator, may lead to serious complications

11. Peripheral neuropathy Grade ≥ 2 by National Cancer Institute Common Terminology
Criteria for Adverse Events (NCI CTCAE) v4.0

12. Subjects who have received an investigational product within the previous 4 weeks
prior to randomization

13. Subject is currently enrolled, or will enroll in a different clinical study in which
investigational therapeutic procedures are performed or investigational therapies are
administered while participating in this study

14. Pregnant or nursing women

15. Subjects with prior hypersensitivity to nab-paclitaxel, gemcitabine, carboplatin or
any other platin, or nucleoside analogue agents

16. Any significant medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from participating in the study

17. Any condition including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if she were to participate in the study

18. Any condition that confounds the ability to interpret data from the study

19. History of seropositive human immunodeficiency virus (HIV)

20. Subjects who are receiving immunosuppressive or myelosuppressive medications that
would, in the opinion of the investigator, increase the risk of serious neutropenic
complications