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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Metastatic Triple-Negative Breast Cancer
• Intervention / Treatment: Other: Placebo; Drug: Eribulin; Drug: SDX-7320

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 55
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tiffany Trainia, MD; Phone Number: 646-888-4558
• Study Contact Backup: Name: Sherry Shen, MD; Phone Number: 646-888-5134; Email: shens1@mskcc.org

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33143
      • Recruiting
      • BAPTIST ALLIANCE - MCI (Data Collection Only)
      • Contact: Lauren Carcas, MD; Phone Number: 954-837-1490
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University (Data Collection Only)
      • Contact: Neil Iyengar, MD; Phone Number: 404-778-1900
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Recruiting
      • Memorial Sloan Kettering Basking Ridge (All Protocol Activities)
      • Contact: Sherry Shen, MD; Phone Number: 646-888-5134
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • Hackensack Meridian Health
      • Contact: Deena Graham, MD; Phone Number: 551-996-5811
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering Monmouth (All Protocol Activities)
      • Contact: Sherry Shen, MD; Phone Number: 646-888-5134
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering Bergen (All Protocol Activities)
      • Contact: Sherry Shen, MD; Phone Number: 646-888-5134
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan Kettering Suffolk - Commack (All Protocol Activities)
      • Contact: Sherry Shen, MD; Phone Number: 646-888-5134
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Westchester (All Protocol Activities)
      • Contact: Sherry Shen, MD; Phone Number: 646-888-5134
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center (All Protocol Activities)
      • Contact: Tiffany Traina, MD; Phone Number: 646-888-4558
      • Contact: Sherry Shen, MD; Phone Number: 646-888-5134
    • Uniondale, New York, United States, 11553
      • Recruiting
      • Memorial Sloan Kettering Nassau (All Protocol Activities)
      • Contact: Sherry Shen, MD; Phone Number: 646-888-5134

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SDX-7320 plus Eribulin (safety run-in period); During the safety run-in period, the first 15 patients enrolled will be assigned to received study drug SDX-7320 plus Eribulin. Not randomized.	Drug: Eribulin; Eribulin 1.4 mg/m2 IV on days 1 and 8 of an every 21 day cycle.; Drug: SDX-7320; SDX-7320 at the dose of 49 mg/m2 SC on a Q14D basis
Experimental: SDX-7320 plus Eribulin; Patients randomized to SDX-7320 plus Eribulin.	Drug: Eribulin; Eribulin 1.4 mg/m2 IV on days 1 and 8 of an every 21 day cycle.; Drug: SDX-7320; SDX-7320 at the dose of 49 mg/m2 SC on a Q14D basis
Placebo Comparator: Eribulin Plus Placebo; Patients randomized to the control arm will receive placebo plus Eribulin.	Other: Placebo; Placebo; Drug: Eribulin; Eribulin 1.4 mg/m2 IV on days 1 and 8 of an every 21 day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in insulin resistance scores (HOMA-IR)	The Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) is a validated tool for the assessment of insulin resistance.87 HOMA-IR is calculated as follows: fasting serum insulin (μU/mL) × fasting plasma glucose (mmol L -1 )/22.5).	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Type, frequency and severity of treatment-emergent adverse events	(TEAEs) and laboratory toxicities per the NCI CTCAE version 5.0.	2 years
Overall response rate	Response rate will be assessed by RECIST v1.1	1 year

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: SynDevRx, Inc.
• Investigators: Principal Investigator: Sherry Shen, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2022
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: October 4, 2022
• First Submitted That Met QC Criteria: October 4, 2022
• First Posted (Actual): October 6, 2022

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Eribulin; Evexomostat (SDX-7320); 22-074
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Substandard Drugs; Pharmaceutical Preparations; eribulin
• Other Study ID Numbers: 22-074

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No