A Study of SDX-7320 in Combination with Eribulin for the Treatment of Patients with Triple-Negative Breast Cancer, ARETHA Study

Inclusion Criteria

• Male or female with histologically and/or cytologically confirmed diagnosis of triple negative metastatic breast cancer defined as estrogen and progesterone receptor staining ≤ 10%; and HER2-negative defined as immunohistochemistry (IHC) 0 to 1+ at enrolling institution (note: if IHC is equivocal, non-amplified status by fluorescence in situ hybridization [FISH] is acceptable)
• Advanced (local regionally recurrent, not amenable to curative therapy or surgery) or metastatic stage with up to 2 prior lines of therapy in the advanced or metastatic setting
• Received prior anthracycline and taxane chemotherapy in the neoadjuvant, adjuvant, or metastatic settings and considered appropriate for treatment with single agent eribulin OR was otherwise ineligible to receive anthracycline and/or taxane per treating physician OR patients with de novo metastatic disease
• Evidence of metabolic dysfunction defined as hemoglobin A1c (HbA1c) >= 5.5 and/or body mass index (BMI) >= 30 kg/m^2
• Measurable disease per the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), OR at least one evaluable, predominantly lytic bone lesion
• Eastern Cooperative Oncology Group performance status (ECOG-PS) =< 1
• Adult >= 18 at the time of informed consent and has provided written informed consent before the performance of any study-related activities and according to local guidelines
• Absolute neutrophil count (ANC) >= 1,000 uL
• Platelet count >= 140,000uL
• Hemoglobin >= 9.0 g/dL
• Calcium (corrected for serum albumin) ≤ grade 1 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, and not considered by the investigator to be clinically significant * Calculate corrected calcium if the albumin and/or serum calcium are not within normal limits
• Potassium within normal limits, with or without correction with supplements
• In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x the upper limit of normal (ULN). If the patient has liver metastases, ALT and AST =< 5 x ULN
• Total bilirubin =< 1.5 x ULN except for patient with Gilbert’s syndrome who may only be included if the total bilirubin is =< 3.0 x ULN or direct bilirubin =< 1.5 x ULN
• Creatinine =< 1.5 mg/dL
• Patient is, in the treating investigator’s opinion, willing and able to comply with the study requirements, including the ability to fast prior to treatment days
• If sexually active female of childbearing potential, willing to use a contraception method listed below: * Oral, intravaginal, or transdermal combined (estrogen and progesterone containing) hormonal contraception * Oral, injectable, or implantable progesterone-only hormonal contraception * Intrauterine device (IUD) * Intrauterine hormone-releasing system (IUS) * Bilateral tubal occlusion * Vasectomized partner with documentation of successful vasectomy * Complete abstinence from heterosexual intercourse
• If a sexually active male, willing to use barrier contraception (condoms)

Exclusion Criteria

• Three or greater prior lines of therapy for metastatic TNBC
• Known primary brain malignancy, brain metastases or active central nervous system (CNS) pathology, any of which as determined by the treating investigator
• Currently participating in a study of an investigational agent
• Body mass index < 18.5 kg/m^2
• Known hypersensitivity to SDX-7320 or eribulin
• Established diagnosis of diabetes mellitus type I or uncontrolled or insulin-dependent type II. Uncontrolled is defined as fasting blood glucose > 140 mg/dL and/or HbA1c >= 8%
• Use of combination antihyperglycemic therapy (single agent metformin on stable dose for at least 3 months prior to enrollment is allowable)
• Concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated, basal or squamous cell carcinoma, nonmelanomatous skin cancer or curatively resected cervical cancer
• Uncontrolled human immunodeficiency virus (HIV) infection. (Testing is not mandatory)
• Evidence of uncontrolled active hepatitis B or C infection
• History of Stevens-Johnson Syndrome (SJS), erythema multiforme (EM), toxic epidermal necrolysis (TEN), or other severe medication-related cutaneous reactions
• Any other concurrent severe and/or uncontrolled medical condition that would, in the investigator’s judgment, contraindicate patient participation in the clinical study (e.g., chronic active hepatitis, severe hepatic impairment)
• Clinically significant, uncontrolled heart disease and/or recent cardiac events including any of the following: * History of angina pectoris, coronary artery bypass graft (CABG) symptomatic pericarditis, or myocardial infarction within 6 months prior to study entry * History of documented congestive heart failure (New York Heart Association functional classification III-IV) * Documented cardiomyopathy * Left ventricular ejection fraction (LVEF) < 45%, as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) * History of any cardiac arrhythmias, (e.g., ventricular tachycardia), complete left bundle block, high grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third-degree AV block) supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months * Uncontrolled hypertension, defined by a systolic blood pressure (SBP) >= 160 mmHg and/or diastolic blood pressure (DBP) >= 100 mmHg, with or without antihypertensive medication. Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening * Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome or any of the following: risk factors for torsades de pointe including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure or history of clinically significant/symptomatic bradycardia; concomitant medications with a known risk to prolong the QT interval and known to cause torsades de pointe that cannot be discontinued or replaced by safe alternative medications * Bradycardia (heart rate less than 50 at rest), by electrocardiogram (ECG) or pulse * Inability to determine the QT interval on the electrocardiogram (ECG) (i.e., unreadable or not interpretable) or corrected QT (QTcF) > 450 msec for males and > 470 msec for females (using Fridericia’s correction) during Screening, based on the mean of triplicate ECGs
• Currently receiving any of the following medications and cannot be discontinued 7 days prior to the start of the treatment: * Medications with a known risk to prolong the QT interval or induce Torsade de Pointes (TdP). CredibleMeds list of drugs known to cause TdP may be used as a reference for this study to determine which drugs are prohibited using the following link: https://crediblemeds.org/new-drug-list or a crediblemeds mobile application * Herbal preparations/medications, with the exception of cannabinoids, cannabidiol (CBD) compounds, etc.
• Participation in a prior investigational study within 14 days prior to the start of the study treatment
• History of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis
• Pregnant patients