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Testing CA-4948 for treating Acute Myelogenous Leukemia and Myelodysplastic Syndrome

A Phase 1/2A, Open Label Dose Escalation and Expansion Study of Orally Administered CA-4948 as a Monotherapy in Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndrome

PHASE1; PHASE2 · Curis, Inc. · NCT04278768

This study is testing a new drug called CA-4948 to see if it can help adults with Acute Myelogenous Leukemia or higher-risk Myelodysplastic Syndrome feel better and improve their condition.

Quick facts

PhasePHASE1; PHASE2
Study typeInterventional
Enrollment366 (estimated)
Ages18 Years and up
SexAll
SponsorCuris, Inc. (industry)
Drugs / interventionschemotherapy, radiation
Locations30 sites (Tampa, Florida and 29 other locations)
Trial IDNCT04278768 on ClinicalTrials.gov

What this trial studies

This multicenter, open-label study evaluates the safety and efficacy of emavusertib (CA-4948) as a monotherapy in adult patients with Acute Myelogenous Leukemia (AML) or higher-risk Myelodysplastic Syndrome (hrMDS). The study consists of a Phase 1 dose escalation to determine the maximum tolerated dose and a Phase 2a expansion to assess anti-cancer activity at the recommended dose. Patients must have specific genetic mutations or treatment histories to qualify, and treatment cycles last 28 days with ongoing administration until disease progression or intolerable toxicity occurs.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with relapsed or refractory AML or higher-risk MDS who have specific genetic mutations.

Not a fit: Patients with early-stage AML or MDS who have not undergone prior treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat forms of AML and MDS.

How similar studies have performed: Other studies have shown promise with similar targeted therapies in AML and MDS, indicating potential for success with this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Males and females ≥18 years of age
2. Life expectancy of at least 3 months
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤1
4. Cytomorphology based confirmed diagnosis of MDS or AML (as per World Health Organisation \[WHO\] 2016 classification) with the following characteristics.

   Phase 1 Dose Escalation (Monotherapy)

   • AML (primary or secondary, including treatment-related) after failing at least 1 standard treatment (may include chemotherapy, re induction therapy or stem cell transplantation).

   OR

   • Higher-risk R/R MDS that are considered resistant/refractory following at least 2 to 3 cycles of hypermethylating agent (HMA) or evidence of early progression

   Phase 2a Dose Expansion (Monotherapy)

   Patients with:
   * R/R AMLwith FLT3 mutations who have been previously treated with a FLT3 inhibitor
   * R/R AML with spliceosome mutations of SF3B1 or U2AF1
   * R/R hrMDS (IPSS-R score \> 3.5) with spliceosome mutations of SF3B1 or U2AF1
   * Number of pretreatments: 1 or 2
5. Acceptable organ function at screening
6. Ability to swallow and retain oral medications
7. Negative serum pregnancy test in women of childbearing potential
8. Women of childbearing potential and men who partner with a woman of childbearing potential must agree to use highly effective contraceptive methods for the duration of the study and for 90 days after the last dose of emavusertib
9. Willing and able to provide written informed consent and comply with the requirements of the trial
10. Able to undergo serial bone marrow sampling and peripheral blood sampling

Exclusion Criteria:

1. Diagnosed with acute promyelocytic leukemia (APL, M3)
2. Has known active central nervous system (CNS) leukemia
3. Allogeneic hematopoietic stem cell transplant (Allo-HSCT) within 60 days of the first dose of emavusertib, or clinically significant graft-versus-host disease (GVHD) requiring ongoing up titration of immunosuppressive medications prior to start of emavusertib
4. Chronic myeloid leukemia (CML)
5. Any prior systemic anti-cancer treatment such as chemotherapy, immunomodulatory drug therapy, etc., received within 3 weeks (or 5 half-lives) prior to start of emavusertib.

   Localized radiation or surgical resection of skin cancers allowed.
6. Use of any investigational agent within 3 weeks or 5 half-lives, whichever is shorter, prior to start of emavusertib
7. Presence of an acute or chronic toxicity resulting from prior anti-cancer therapy, with the exception of alopecia that has not resolved to Grade ≤ 1within 7 days prior to start of emavusertib; presence of any acute or chronic non-hematological toxicity ≥ Grade 3 at Screening, or prior to start of emavusertib must resolve to ≤ Grade 2.
8. Known allergy or hypersensitivity to any component of the formulation of emavusertib
9. Major surgery, other than diagnostic surgery, \<28 days from the start of emavusertib; minor surgery \<14 days from the start of emavusertib
10. Patients with active advanced malignant solid tumors
11. Known to be human immunodeficiency virus (HIV) positive or have an acquired immunodeficiency syndrome-related illness
12. Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) positive or Hepatitis C virus (HCV) infection \<6 months prior to start of emavusertib unless viral load is undetectable, or HCV with cirrhosis
13. Uncontrolled or severe cardiovascular disease including myocardial infarction or unstable angina within 6 months prior to CA-4948, New York Heart Association Class II or greater congestive heart failure, or left ventricular ejection fraction \< 40% by echocardiogram or multi-gated acquisition scan, serious arrhythmias uncontrolled on treatment, clinically significant pericardial disease, cardiac amyloidosis, congenital long QT syndrome, or QTc with Fridericia's correction (QTcF) that is unmeasurable or \> 450 milliseconds (msec) on Screening electrocardiogram (ECG)
14. Gastrointestinal disease or disorder that could interfere with the swallowing, oral absorption, or tolerance of emavusertib
15. Pregnant or lactating
16. Systemic fungal, bacterial, viral, or other infection that is not controlled
17. Any other severe, acute, or chronic medical, psychiatric or social condition, or laboratory abnormality that may increase the risk of trial participation or emavusertib administration

Where this trial is running

Tampa, Florida and 29 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Acute Myelogenous Leukemia, Myelodysplastic Syndrome, AML, MDS, Interleukin-1 receptor-associated kinase 4, FLT3-ITD or TKD mutant, FLT3 Wild Type, Relapse/refractory to hypermethylating agent

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.