A Study of SDX-7320 in Combination With Eribulin for People With Breast Cancer

"A Phase 2, Double Blinded, Randomized Controlled Trial of Evexomostat (SDX-7320) or Placebo in Combination With Eribulin for Patients With Metastatic Triple-Negative Breast Cancer and Metabolic Dysfunction: The ARETHA Study

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.

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