a study of sdx-7320 in combination with eribulin for people with breast cancer

Conditions: Breast Cancer; Metastatic Triple-Negative Breast Cancer

Summary: the researchers are doing this study to find out whether the study drug, sdx-7320, when combined with the standard chemotherapy eribulin, is an effective treatment for people with tnbc and metabolic dysfunction. the researchers will also look at whether the study treatment (sdx-7320 combined with eribulin) is safe and causes few or mild side effects in participants. the researchers will compare this treatment approach to eribulin alone.

the study includes a safety run-in period in which the first 15 patients enrolled will be assigned to receive the study drug sdx-7320 in combination with eribulin. upon safety confirmation, randomization will commence for the subsequent 40 patients enrolled.

Eligibility criteria:
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 ihc 0 to 1+ at enrolling institution (note: if ihc is equivocal, non-amplified status by 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 hba1c \> 5.5 and/or 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. * adequate bone marrow and organ function as defined by the following laboratory values (as assessed by local laboratory for eligibility): * absolute neutrophil count (anc) ≥ 1,000 µl * platelet count ≥ 140,000 µl * hemoglobin ≥9.0 g/dl: * calcium (corrected for serum albumin) and magnesium ≤ grade 1 according to national cancer institute (nci) common terminology * calculate corrected calcium if the albumin and/or serum calcium are not within normal limits: corrected calcium= serum calcium + 0.8 x \[(normal albumin) - patient albumin\] normal albumin value = 4.4g/dl criteria for adverse events (ctcae), version 5.0, and not considered by the investigator to be clinically significant * potassium within normal limits, with or without correction with supplements. * in absence of liver metastases, alanine aminotransferase (alt) and aspartate aminotransferase (ast) ≤2.5×the upper limit of normal (uln). if the patient has liver metastases, alt and ast ≤5×uln. * total bilirubin ≤1.5×uln except for patient with gilbert's syndrome who may only be included if the total bilirubin is ≤3.0×uln or direct bilirubin ≤1.5×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 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/m2 * 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 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, cbd compounds, etc. * participation in a prior investigational study within 14 days prior to the start of the study treatment or within 5 half-lives of study drug, whichever is longer. * history of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis * pregnant patients

Keywords: evexomostat (sdx-7320) eribulin 22-074