Functional Imaging in Prediction of Response to Abemaciclib for Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer

Inclusion Criteria:

• Men or women with metastatic or locally advanced unresectable breast cancer

• Histologically confirmed ER+ / HER2-negative, breast cancer who is a candidate forendocrine therapy with pathology from the primary tumor or metastatic/recurrentsite. Based on American Society of Clinical Oncology/College of AmericanPathologists (ASCO CAP) Guidelines: ER+: >= 1% of tumor cell nuclei to beimmunoreactive. HER2-negative: HER2 of 0, 1+ by immunohistochemistry (IHC) ornegative by fluorescence in situ hybridization (FISH).

• In the case of bone biopsy which could yield false negative ER or PR status inpatients with historically HR+ disease, a patient may be eligible if thetreating physician and the study chair both agree that the patient is acandidate for further endocrine therapy (ET) based treatment.

• Note that baseline PR status by IHC does not influence results of deltaFFNP-PETimaging.

• If premenopausal, the patient has to be treated with GnRH agonist for at least 6weeks prior to FFNP-PET.

• Disease must be present in at least one non-liver site and measurable by ResponseEvaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and be 1.5 cm or greaterin longest dimension OR disease can be non-measurable but must be 1.5 cm in longestdimension on functional imaging (fluorodeoxyglucose [FDG]-PET/computed tomography [CT] preferred).

• No limits to prior lines of endocrine therapy in the metastatic setting includingsynergistic targeted therapy such as CDK4/6 inhibitors (other than Abemaciclib),PI3K inhibitor, mTOR inhibitor, etc. One line of prior cytotoxic chemotherapy in themetastatic setting is allowed. Washout from prior systemic anti-cancer therapy of atleast 2 weeks from chemotherapy or radiation, 2 weeks or 5 half lives (whichever islonger) from oral selective estrogen receptor degrader (SERD), 8 weeks from oralselective estrogen receptor modulator (SERM), and 16 weeks from intramuscular SERD (Fulvestrant) is required. Recovery of adverse events from the last therapy to grade 1 except alopecia. Patients may continue luteinizing hormone-releasing hormone (LHRH) agonist to remain post-menopausal without a need for washout

• Eastern Cooperative Oncology Group (ECOG) performance status =< 2

• At least 18 years of age

• Absolute neutrophil count >= 1,500/uL

• Platelets >= 100,000/uL

• Hemoglobin >= 9g/dL

• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN).

• In case of known Gilbert's syndrome, < 2 x ULN is allowed

• Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) /alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) =< 2.5xinstitutional ULN, or =< 5 x ULN for subjects with documented metastatic disease tothe liver

• eGFR (estimated glomerular filtration rate) ≥ 30 mL/min

• Women of childbearing potential must agree to use adequate contraception (barriermethod of birth control, abstinence) prior to study entry and for the duration ofstudy participation

• Ability to understand and willingness to sign an institutional review board (IRB)-approved written informed consent document (or that of legally authorizesrepresentative, if applicable)

• Consent to access archival tumor specimens for clinical sequencing data of tumortissue and blood

Exclusion Criteria:

• Prior abemaciclib in the metastatic setting or within 2 years of completion ofadjuvant abemaciclib

• Hepatic-only metastatic disease

• A history of other malignancy with the exception of malignancies for which alltreatment was completed at least 2 years before registration and the patient has noevidence of disease

• Currently receiving any other investigational agents

• Untreated/unstable brain metastases. Patients with treated/stable brain metastases,defines as patients who have received prior therapy for their brain metastases andwhose central nervous system (CNS) disease is radiographically stable at studyentry, are eligible

• A history of allergic reactions attributed to compounds of similar chemical orbiologic composition to FFNP, abemaciclib, or other agents used in the study

• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, orcardiac arrhythmia

• Pregnant and/or breastfeeding women of childbearing potential must have a negativepregnancy test within 14 days of study entry. Male participants and femaleparticipants of childbearing potential must utilize adequate contraceptive methodsthroughout study treatment and for at least 30 days after the last dose of studymedications

• Patients with human immunodeficiency virus (HIV) are eligible unless their CD4+T-cell counts are < 350 cells/mcL or they have a history of acquiredimmunodeficiency syndrome (AIDS)-defining opportunistic infection within the 12months prior to registration. Concurrent treatment with effective antiretroviraltherapy (ART) according to Department of Health and Human Services (DHHS) treatmentguidelines is recommended