Olaparib, Palbociclib and Fulvestrant in Patients With BRCA Mutation-associated, Hormone Receptor-positive, HER2-negative Metastatic Breast Cancer

Inclusion Criteria:

- Females/males ≥ age 18

- Germline or somatic deleterious or suspected deleterious mutation in BRCA1 or BRCA2

- Metastatic or locally advanced unresectable breast cancer that is ER and/or PR
positive (>1%) and HER2 nonamplified

- Prior treatment with 0-2 prior lines of chemotherapy for metastatic breast cancer

- If the patient has received platinum chemotherapy, it must have been administered in
one of the following settings:

1. Adjuvant or neoadjuvant chemotherapy completed at least 12 months prior to study
entry

2. Platinum chemotherapy for locally advanced unresectable or metastatic breast
cancer with no evidence of disease progression during treatment

3. As potentially curative treatment for a prior non-breast cancer with no evidence
of disease for ≥ 5 years

- Deemed a candidate for endocrine therapy (any prior endocrine therapy is permitted; no
prior endocrine therapy is also permitted)

- Normal organ and bone marrow function

- ECOG performance status 0-1

- Life expectancy ≥ 16 weeks

- Measureable disease or disease that can be assessed by CT or MRI

- Postmenopausal (amenorrhea for 1+ year without exogenous hormone treatments during
this time; pharmacologic ovarian suppression; under 50 with LH and FSH within
post-menopausal range; radiation-induced ovarian suppression with >1 year since last
menses, chemotherapy-induced menopause with >1 year since last menses, surgical
menopause, pharmacologic ovarian suppression)

- Willing to comply with study requirements and procedures including use of appropriate
contraception, willingness to discontinue herbal preparations / medications, and study
biopsy if archival tissue is not available

Exclusion Criteria:

- Involvement in study planning or conduct

- Prior treatment with a PARP inhibitor or CDK4/6 inhibitor

- Participation in another clinical study with an investigational product during the
last 3 weeks

- Major surgery within 2 weeks of study treatment

- Systemic chemotherapy or radiotherapy (except palliative) within 3 weeks of study
treatment

- Other malignancy within the last 5 years with exceptions listed in the protocol

- Concomitant strong or moderate CYP3A inhibitors/ inducers

- Persistent toxicity of prior cancer therapy that is grade ≥ 2 except for alopecia or
neuropathy

- MDS or features suggestive of MDS/AML

- Symptomatic uncontrolled brain metastases

- Patients considered to be at poor medical risk

- QTc >470 msec on 2 or more time points or a family history of long QT syndrome

- Unable to swallow or absorb oral medication

- Immunocompromised patients

- Pregnant or breast-feeding

- Hypersensitivity to olaparib, palbociclib, fulvestrant, or any excipients of these
products

- Known active hepatitis or HIV

- Prior bone marrow transplant

- Whole blood transfusions 120 days prior to signing consent