Abemaciclib in Treating Patients With Advanced, Refractory, and Unresectable Digestive System Neuroendocrine Tumors

Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every
28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 4
months for up to 1 year.

Inclusion Criteria:

- Histologically confirmed GEP NET, radiographically progressed on at least one line of
standard therapy within the past 12 months

- Primary tumors may be in: pancreas, foregut (esophagus, stomach, duodenum),
midgut (small intestine, appendix), hindgut (large intestine, rectum), or unknown
origin

- Tumors may be functional (associated with clinical symptoms of hormone secretion)
or non-functional

- Well-differentiated low grade (Ki67 index < 3% or mitotic index < 2 mitoses/10 high
power fields [HPF]), or intermediate grade (Ki67 index 3-20% or mitotic index 2-20
mitoses/10 HPF) NETs

- Metastatic or locally advanced unresectable disease

- Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) as
per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1

- Prior or concurrent therapy with somatostatin analogs (SSAs) is allowed. If concurrent
therapy, dose must be stable for at least 2 months

- Patients with carcinoid syndrome must have symptoms controlled with stable doses of
SSAs for at least 2 months

* Telotristat is not allowed

- Available archival tumor tissue (formalin-fixed paraffin-embedded [FFPE]) or willing
to provide a fresh tumor biopsy

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

- Able to swallow oral medications

- Absolute neutrophil count >= 1500/uL

- Platelet count >= 100,000/uL (without platelet transfusion for at least two weeks)

- Hemoglobin >= 8 g/dL (without blood transfusion for at least two weeks)

- Total bilirubin =< 1.5 times upper limit of normal (ULN)

- Transaminases (aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT])
=< 3 x upper limit of normal (ULN) (=< 5 x ULN if liver metastases)

- Patients with Gilbert's syndrome with a total bilirubin =< 2.0 times ULN and direct
bilirubin within normal limits are permitted

- International normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.5 x
ULN

- Serum creatinine =< 1.5 x ULN

- Ability to understand and sign the consent form

- Women of child-bearing potential must:

- Have a negative serum pregnancy test within 7 days prior to initiation of
treatment, and

- Agree to use a highly effective method of contraception during the study and for
at least 3 months following the last dose of study drug

- Men must be sterile or agree to use a highly effective method of contraception during
the study and for at least 3 months following the last dose of study drug

Exclusion Criteria:

- Poorly differentiated or high-grade GEP NETs (Ki67 index > 20% or mitotic index > 20
mitoses/10 HPF)

- Prior treatment with abemaciclib or other CDK4/6 inhibitors

- Known hypersensitivity to abemaciclib or its components

- Receipt of any therapy or investigational agent within 4 weeks prior to study
registration, except SSAs

- Any surgery, radiation, or embolization within 4 weeks

- Peptide receptor radionuclide therapy within 6 weeks

- Patients receiving other investigational agents

- Patients who have not recovered from adverse events (AEs) of prior therapy to =< grade
1 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events
[CTCAE] version [v] 5), except for alopecia

- Patients with untreated or symptomatic brain metastases (must be off corticosteroids
for >= 4 weeks)

- Uncontrolled or untreated intercurrent illness including, but not limited to, active
infection, congestive heart failure, severe/unstable angina, interstitial lung
disease, severe dyspnea at rest or requiring oxygen supplementation, arterial or
venous thrombotic event, or psychiatric illness/social situations that would limit
compliance with study requirements

- Gastrointestinal tract disease resulting in an inability to take oral medication or a
requirement for intravenous (IV) alimentation, prior surgical procedures involving
stomach or small bowel in the last 28 days, active peptic ulcer disease, Crohn's
disease or ulcerative colitis

- Other malignancy diagnosed or recurrent in the past 3 years (except non-melanoma skin
cancer and in-situ cervical cancer)

- Pregnancy or breast-feeding