Combining SDX-7320 with Eribulin for Treating 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

This study is testing if adding the drug SDX-7320 to the standard chemotherapy eribulin can help people with metastatic triple-negative breast cancer and metabolic issues feel better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 55 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Memorial Sloan Kettering Cancer Center (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 10 sites (Miami, Florida and 9 other locations)
• Trial ID: NCT05570253 on ClinicalTrials.gov

What this trial studies

This study investigates the effectiveness of the drug SDX-7320 when used alongside the standard chemotherapy eribulin in patients with metastatic triple-negative breast cancer (TNBC) and metabolic dysfunction. Initially, a safety run-in period will involve 15 patients receiving the combination treatment, followed by a randomized phase for an additional 40 patients to compare the combination therapy against eribulin alone. The study aims to assess both the efficacy and safety of this new treatment approach.

Who should consider this trial

Good fit: Ideal candidates include individuals with confirmed metastatic triple-negative breast cancer who have metabolic dysfunction and have received prior chemotherapy.

Not a fit: Patients with non-metastatic breast cancer or those who do not have metabolic dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with metastatic triple-negative breast cancer.

How similar studies have performed: Other studies have shown promise in combining targeted therapies with standard chemotherapy, suggesting potential success for this approach.

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

Where this trial is running

Miami, Florida and 9 other locations

• BAPTIST ALLIANCE - MCI (Data Collection Only) — Miami, Florida, United States (Recruiting)
• Emory University (Data Collection Only) — Atlanta, Georgia, United States (Recruiting)
• Memorial Sloan Kettering Basking Ridge (All Protocol Activities) — Basking Ridge, New Jersey, United States (Recruiting)
• Hackensack Meridian Health — Hackensack, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Monmouth (All Protocol Activities) — Middletown, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Bergen (All Protocol Activities) — Montvale, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Suffolk - Commack (All Protocol Activities) — Commack, New York, United States (Recruiting)
• Memorial Sloan Kettering Westchester (All Protocol Activities) — Harrison, New York, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York, New York, United States (Recruiting)
• Memorial Sloan Kettering Nassau (All Protocol Activities) — Uniondale, New York, United States (Recruiting)

Study contacts

• Principal investigator: Sherry Shen, MD — Memorial Sloan Kettering Cancer Center
• Study coordinator: Sherry Shen, MD

Conditions Breast Cancer; Metastatic Triple-Negative Breast Cancer; Evexomostat; Eribulin; 22-074