Neoadjuvant Tamoxifen, Palbociclib, Avelumab in Estrogen Receptor Positive Breast Cancer

Patients will be treated with tamoxifen (20mg PO daily) +/- palbociclib (125mg PO daily for
21 days, 7 days off ) for 1 cycle (1 cycle =28 days) and undergo a repeat biopsy, MRI, and
blood draw at Cycle 2, Day 1. Afterwards avelumab will be added to both arms. Avelumab will
be administered 10mg/kg IV every 14 days (1 cycle = 2 doses = 28 days). Patients will be
treated for 3 cycles of avelumab with tamoxifen +/- palbociclib (thus 4 cycles total,
including run-in without avelumab). Patients will be treated so long as there is no clinical
evidence of progression and therapy is tolerated. Patients who experience progressive disease
(25% increase) of their tumor will cease study treatment and undergo end-of-study assessment
(including repeat MRI) and surgery. Otherwise, patients completing all 4 cycles of therapy
will undergo MRI and surgery.

Inclusion Criteria:

- Stage II-III ER-positive breast cancer.

- Age ≥ 18 years.

- Eastern Cooperative Oncology Group performance status of 1 or less.

- Adequate organ and bone marrow function within 28 days prior to registration.

- Females of child-bearing potential and males must agree to use adequate contraception
prior to study entry, for the duration of study participation, and for 30 days
following completion of therapy.

- Females of child-bearing potential must have a negative pregnancy test within 7 days
prior to registration on study.

- Patients must have the ability to understand and the willingness to sign a written
informed consent prior to registration on study

Exclusion Criteria:

- Evidence of metastatic disease or inflammatory breast cancer.

- Patients not felt to benefit from endocrine therapy (i.e. clinically aggressive
presentation).

- Previous treatment with endocrine therapy within the last 10 years (i.e. tamoxifen,
aromatase inhibitors).

- Previous treatment with CDK4/6 inhibitors, or immune checkpoint inhibitors.

- May not be receiving any other investigational agents.

- May not be receiving immunosuppressive therapy within 2 weeks of study entry.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to tamoxifen, palbociclib, and avelumab are not eligible.

- May not have had a prior diagnosis of cancer if it has been < 3 years since their last
treatment (with the exception of squamous cell carcinoma or basal cell carcinoma of
the skin or cervical intraepithelial neoplasia).

NOTE: Patients with a history of breast cancer or breast cancer treatment within the last
10 years are also excluded. Any previous radiation to affected breast is excluded.

- Autoimmune disease within the last 3 years with the exception of: Vitiligo or alopecia,
Hypothyroidism on stable doses of thyroid medication, and Psoriasis not requiring systemic
therapy

- Uncontrolled intercurrent illness including, but not limited to any of the following, are
not eligible: Ongoing or active infection requiring systemic treatment (including HIV, TB,
hepatitis viruses), symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, psychiatric illness/social situations that would limit compliance with study
requirements, any other illness or condition that the treating investigator feels would
interfere with study compliance or would compromise the patient's safety or study endpoints

- Female patients who are pregnant or nursing are not eligible.