A Phase 1, Open-Label, Dose-Escalation With Expansion Study of SX-682 Alone and in Combination With Oral or Intravenous Decitabine in Subjects With Myelodysplastic Syndrome SX-682

What's the purpose of this trial?

This study will determine the safety profile, maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and recommended Phase 2 dose (RP2D) of SX-682 in the treatment of patients with Myelodysplastic Syndromes (MDS).

This trial is currently open and accepting patients.

What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

Inclusion Criteria:

* Diagnosis of MDS by World Health Organization criteria, and either

1. International Prognostic Scoring System (IPSS) low risk or intermediate-1 risk without 5q deletion and failed treatment (no response, loss of response, progressive disease/treatment intolerance) following:

i. 4 cycles hypomethylating agent; or ii. 4 cycles hypomethylating agent, or lenalidomide or erythropoietin stimulating agent (ESA).
2. IPSS low risk or intermediate-1 risk with 5q deletion and failed treatment following:

i. 4 cycles of lenalidomide and hypomethylating agent; or ii. 4 cycles of lenalidomide.
3. IPSS intermediate-2 risk or high risk and failed treatment following 4 cycles hypomethylating agent.
* Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
* Screening laboratory values:

1. Renal glomerular filtration rate (GFR) ≥ 30 ml/min;
2. Aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) ≤ 3.0 times upper limit of normal;
3. Bilirubin \< 1.5 times upper limit of normal;
4. No history of HIV being HIV positive;
5. No active Hepatitis B or Hepatitis C infection.
* Life expectancy ≥ 12 weeks.
* Women of childbearing potential (WOCBP) must use study specified contraception.
* WOCBP demonstrate negative pregnancy test.
* Not breastfeeding.
* Men sexually active must use study specified contraception.

Exclusion Criteria:

* Use of chemotherapeutic agents or experimental agents for MDS within 14 days of the first day of study drug treatment.
* Use of erythroid stimulating agents, Granulocyte-colony stimulating factor (G-CSF), or Granulocyte-macrophage colony-stimulating factor (GM-CSF) within 14 days of the first day of study drug treatment, or during the study.
* Mean triplicate heart rate-corrected QT interval (QTc) \> 500 msec.
* Any of the following cardiac abnormalities:

1. QT interval \> 480 msec corrected using Fridericia's formula;
2. Risk factors for Torsade de Pointes;
3. Use of medication that prolongs the QT interval;
4. Myocardial infarction ≤ 6 months prior to first day of study drug treatment;
5. Unstable angina pectoris or serious uncontrolled cardiac arrhythmia.
* Any serious or uncontrolled medical disorder.
* Prior malignancy within the previous 3 years except for local cancers that have been cured.
* Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
* Use of other investigational drugs within 30 days of study drug administration.
* Major surgery within 4 weeks of study drug administration.
* Live-virus vaccination within 30 days of study drug administration.
* Allergy to study drug component.

Additional Trial Information

Phase 1

Enrollment: 151 patients (estimated)

View More

Published Results

Phase 1 Results of the First-in-Class CXCR1/2 Inhibitor SX-682 in Patients with Hypomethylating Agent Failure Myelodysplastic Syndromes

November 15, 2022

17 MDS pts received SX-682 (median 1 prior therapies; range 1-4) with 6 pts in the 200 mg cohort, 3 pts in each of the 25, 50 and 100 cohorts and 2 pts in the 400 mg cohort (Table). Median age was 76, and pts were low (n=1), intermediate-1 (n=10), intermediate-2 (n=5) and high (n=1) risk by the International Prognostic Scoring System (IPSS). All pts were transfusion-dependent and all had failed prior HMA and 24% lenalidomide. Steady-state PK exhibits increasing drug plasma concentration with dose comparable to pts with solid tumors. The ANC PD marker exhibited a dose-dependent decrease from baseline (ΔANC) that plateaued in the 200 and 400 mg dose cohorts consistent with maximum receptor inhibition (Table). Marrow MDSCs and LSCs were reduced after initiation of SX-682. SX-682 was well-tolerated with no maximally tolerated dose and no pt discontinued treatment for adverse events. Treatment-emergent adverse events > grade 3 were most common in the 200 and 400 mg dose cohorts, and those related to neutrophils are consistent with being related to SX-682. Effects on neutrophils reversed on cessation of drug dosing. There was a dose-dependent increase in overall response rate (ORR) from 0% at 25 mg BID to 50% at 200 mg BID consistent with the observed clinical benefit being related to CXCR1/2 inhibition by SX-682 (Table). Four of the five responders had mutant genes (MGs) involving splicing factors (60% of responders; SF3B1, SRSF2) and/or epigenetic regulation (60% of responders; TET2, ASXL1, IDH2). Across all dose cohorts, 8 of 17 (47%) pts had a reduction in marrow blasts after initiating SX-682 (Figure). The 200 mg dose yielded the most rapid and deep reduction in blasts with 2 of 6 pts (33%) achieving a marrow complete remission (mCR) in keeping with this dose providing maximum receptor inhibition. There was hematologic improvement (HI) in 3 pts with one having a durable near-CR response (on SX-682 >500 days) consisting of trilineage HI (hemoglobin > 10 g/dL) and transfusion independence for over 4 months (pt required 16 transfusions in the 7 weeks before starting SX-682 therapy). Based on ANC PD, ORR and marrow blast responses, the 200 mg BID dose was selected for the expansion phase of the trial.

Trial Locations

All Trial Locations

View all clinical trial locations sorted by state.


AdventHealth - Blood & Marrow Transplant Center (East Orlando)

Orlando, FL

Open and Accepting

Moffitt Cancer Center Magnolia Campus

Tampa, FL

Open and Accepting


Winship Cancer Institute Emory University

Atlanta, GA

Open and Accepting


Sidney Kimmel Comprehensive Cancer Center Johns Hopkins Medicine

Baltimore, MD

Open and Accepting
Interested in this trial?
  • Call us today 😀 keyboard_arrow_right

    We know how difficult and confusing this process can be. If you are interested in this clinical trial or have questions, you can call us at any time. You can also send us a direct message with questions.

    (888) 828-2206
  • If you are interested in keeping an eye on this trial, you can add it to your list of favorite trials. We'll send you alerts when this trial is updated.

  • Talk to your doctor keyboard_arrow_right

    You can print an overview of this trial to take in to your next appointment. Your doctor can help you understand if this trial may be right for you.

Still need help? Send us a message