MCS110 Combined With Neoadjuvant Doxorubicin, Cyclophosphamide, and Weekly Paclitaxel in Patients With Hormone-Receptor Positive and HER2- Breast Cancer

Inclusion Criteria:

- Histologically or cytologically confirmed ER+ HER2- breast cancer. ER-positivity is to
follow local guidelines. If IHC HER2 is 2+, a negative FISH test is required.

- Clinical stage II or stage III (by AJCC 7th edition) breast cancer eligible for
neoadjuvant chemotherapy with complete surgical excision of the breast cancer after
neoadjuvant therapy as the treatment goal.

- Clinically positive axillary lymph nodes.

- At least 18 years of age.

- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

- Normal bone marrow and organ function as defined below:

- Absolute neutrophil count ≥ 1,500/mcL

- Platelets ≥ 100,000/mcL

- Hemoglobin ≥ 9.0 g/dL

- Total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN)

- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN

- Creatinine ≤ 1.5 x IULN

- PT/INR ≤ 1.5 x IULN (for participants on anticoagulation therapy, ≤ 1.5 x
baseline value)

- aPTT ≤ 1.5 x IULN (for participants on anticoagulation therapy, ≤ 1.5 x baseline
value)

- Adequate cardiac function as defined below:

- LVEF ≥ 50%

- QTC ≤ 470 msec for females and ≤ 450 msec for males

- Women of childbearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control, abstinence) prior to study entry, for
the duration of study participation, and for 90 days after the last dose of MCS110.
Should a woman become pregnant or suspect she is pregnant while she or her partner is
participating in this study, she must inform her treating physician immediately. Men
treated or enrolled on this protocol must also agree to use adequate contraception
prior to the study, for the duration of study participation, and for 4 month after
completion of MCS110 administration.

- Ability to understand and willingness to sign an Institutional Review Board (IRB)
approved written informed consent document (or that of legally authorized
representative, if applicable).

Exclusion Criteria:

- Presence of metastatic disease.

- Therapy for underlying malignancy within 2 weeks prior to start of study treatment.

- A history of other malignancy ≤ 3 years previous with the exception of basal cell or
squamous cell carcinoma of the skin which were treated with local resection only or
carcinoma in situ of the cervix.

- Bilateral or inflammatory breast cancer.

- Currently receiving any other investigational agents.

- Receiving immunosuppressive agents or > 10 mg daily prednisone or equivalent of
corticosteroids.

- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to MCS110, doxorubicin, cyclophosphamide, paclitaxel, or other
agents used in the study.

- Known hypersensitivity to monoclonal antibodies.

- Personal or family history of long QT syndrome.

- Evidence of retinal pathology on ophthalmologic examination that is considered a risk
factor for neurosensory retinal detachment / central serous chorioretinopathy (CSCR),
retinal vein occlusion (RVO), or neovascular macular degeneration.

- Diagnosis of any type of muscle disease that may result in CK elevation.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac
arrhythmia. Clinically significant cardiovascular disease within 6 months of
screening.

- Presence of any Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or
greater toxicity.

- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
pregnancy test within 14 days of study entry.

- Known history of human immunodeficiency virus or infection with hepatitis requiring
antiviral therapy.