Phase 2 Trial of Selinexor (KPT-330) for Metastatic Triple Negative Breast Cancer (TNBC)

Inclusion Criteria:

- Histologically confirmed triple negative breast cancer (TNBC), defined as negative
immunohistochemical staining for estrogen and progesterone receptors (≤5% of nuclei
positive by IHC) and receptor tyrosine-protein kinase erbB-2 (HER2) negative (IHC 0-1+
or HER2-neu negative according to American Society of Clinical Oncology; College of
American Pathologists (ASCO-CAP) HER2 Test Guideline Recommendations)

- Written informed consent in accordance with federal, local, and institutional
guidelines

- Body surface area ≥1.4 m^2

- Age ≥18 years

- Estimated life expectancy of >3 months at study entry

- TNBC must be either locally recurrent or metastatic. Locally recurrent disease must
not be amenable to surgical resection or radiation with curative intent.

- Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

- Documented disease progression at study entry

- Must have received at least 1 chemotherapy regimens in the setting of metastatic
disease

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

- Adequate hematological function: Absolute neutrophil count (ANC) > 1500/mm^3,
platelets count >100,000mm^3

- Adequate hepatic function within 14 days prior to Cycle 1 Day 1 (C1D1): total
bilirubin <2 times the upper limit of normal (ULN) (except patients with Gilbert's
syndrome who must have a total bilirubin of < 3 times ULN) and aspartate
aminotransferase (AST), alanine aminotransferase (ALT) ≤2.5 x ULN. In the case of
known (radiological and/or biopsy documented) liver metastasis, AST/ALT ≤5.0 times ULN
is acceptable.

- Amylase and lipase ≤ 1.5 x ULN

- Adequate renal function within 14 days prior to C1D1: estimated creatinine clearance
of ≥ 30 mL/min

- Women of child-bearing potential (WOCBP) must agree to use dual methods of
contraception and have a negative serum pregnancy test at screening, and male
participants must use an effective barrier method of contraception if sexually active
with a female of child-bearing potential. For both male and female participants,
effective methods of contraception must be used throughout the study and for 3 months
following the last dose. To be considered of non-childbearing potential,
postmenopausal women must be amenorrheic for at least 12 months naturally (not in the
setting of post chemotherapy) or participants must be surgically sterile.

- Must have received prior anthracycline and taxane therapy unless clinically
contraindicated

Exclusion Criteria:

- Significant medical illness that in the investigator's opinion cannot be adequately
controlled with appropriate therapy or would compromise the participant's ability to
tolerate this therapy

- Women who are pregnant or lactating

- Radiation, chemotherapy, or immunotherapy or any other approved anticancer therapy ≤2
weeks prior to cycle 1 day 1

- Major surgery within 4 weeks before Day 1

- Unstable cardiovascular function: Electrocardiogram (ECG) abnormalities requiring
treatment, or congestive heart failure (CHF) of New York Hearth Association (NYHA)
Class ≥3; myocardial infarction (MI) within 3 months

- Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals
within one week prior to first dose. Potential participants with controlled infection
or on prophylactic antibiotics are permitted in the study.

- Known history of HIV

- Known active hepatitis A, B, or C infection that requires treatment

- Any underlying condition that would significantly interfere with the absorption of an
oral medication

- Grade >2 peripheral neuropathy at baseline (within 14 days prior to cycle 1 day 1)

- Participation in an investigational anti-cancer study within 3 weeks prior to Cycle 1
Day 1

- Coagulation problems and active major bleeding within 4 weeks prior to C1D1 (peptic
ulcer, epistaxis, spontaneous bleeding)

- Active central nervous system (CNS) malignancy. Asymptomatic small lesions are not
considered active. Treated lesions may be considered inactive if they are stable for
at least 3 months.

- Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤ 2 weeks
prior to Cycle 1 Day 1 or radio-immunotherapy ≤ 4 weeks prior to Cycle 1 Day 1

- Have not recovered to Grade ≤ 1 or to their baseline from clinically significant
adverse effects