Dose Escalation/ Expansion Study of CA-4948 as Monotherapy in Patients With Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndrome (MDS)

Paused · Phase 1/Phase 2

Conditions studied: Acute Myelogenous Leukemia, Myelodysplastic Syndrome

In brief

This is a multicenter, open-label, Phase 1/2a dose escalation and expansion study of orally administered emavusertib (CA-4948) monotherapy in adult patients with AML or higher- risk Myelodysplastic Syndrome (hrMDS). Patients enrolling in the Phase 1 dose escalation of the study must meet one of the following criteria prior to consenting to the study: * Relapse/refractory (R/R) AML with FMS-like tyrosine kinase-3 (FLT3) mutations who have been previously treated with a FLT3 inhibitor * R/R AML with spliceosome mutations of splicing factor 3B subunit 1 (SF3B1) or U2AF1 * R/R hrMDS with spliceosome mutations of SF3B1 or U2 small nuclear RNA auxiliary factor 1 (U2AF1) * Number of pretreatments: 1 or 2 The Phase 2a Dose Expansion will be in 3 Cohorts of patients: 1. R/R AML with FLT3 mutations who have been previously treated with a FLT3 inhibitor; 2. R/R AML with spliceosome mutations of SF3B1 or U2AF1; and 3. R/R hrMDS (Revised International Prognostic Scoring System \[IPSS-R\] score \> 3.5) with spliceosome mutations of SF3B1 or U2AF1. All patients above have had ≤ 2 lines of prior systemic anticancer treatment. In previous versions of this protocol there was a Phase 1b portion of the study, in which patients with AML or hrMDS received CA-4948 in combination with venetoclax. This part of the study is no longer open for enrollment.

Key facts

Study ID

NCT04278768

Run by

Curis, Inc.

People needed

366

Starts

2020-07-06

Expected to finish

2026-04-01

Last updated by the study team

2026-03-19

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Males and females ≥18 years of age
• Life expectancy of at least 3 months
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤1
• 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 hypomethylating 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 prior treatments: 1 or 2
• Acceptable organ function at screening
• Ability to swallow and retain oral medications
• Negative serum pregnancy test in women of childbearing potential
• 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 180 days after the last dose of emavusertib
• Willing and able to provide written informed consent and comply with the requirements of the trial
• Able to undergo serial bone marrow sampling and peripheral blood sampling

You may not qualify if…

• Diagnosed with acute promyelocytic leukemia (APL, M3)
• Has known active central nervous system (CNS) leukemia
• 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
• Chronic myeloid leukemia (CML)
• 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.
• Use of any investigational agent within 3 weeks or 5 half-lives, whichever is shorter, prior to start of emavusertib
• Presence of an acute or chronic toxicity resulting from prior anti-cancer therapy, with the exception of alopecia that has not resolved to Grade ≤ 1 within 7 days prior to start of emavusertib.
• Known allergy or hypersensitivity to any component of the formulation of emavusertib
• Major surgery, other than diagnostic surgery, <28 days from the start of emavusertib; minor surgery <14 days from the start of emavusertib
• Patients with active advanced malignant solid tumors
• Known to be human immunodeficiency virus (HIV) positive or have an acquired immunodeficiency syndrome-related illness
• 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
• 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 < 50% 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)
• Gastrointestinal disease or disorder that could interfere with the swallowing, oral absorption, or tolerance of emavusertib
• Pregnant or lactating
• Systemic fungal, bacterial, viral, or other infection that is not controlled
• 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 it is running

• Moffitt Cancer Center — Tampa, Florida, United States
• Winship Cancer Institute — Atlanta, Georgia, United States
• Northwestern Memorial Hospital — Chicago, Illinois, United States
• University of Chicago Medical Center — Chicago, Illinois, United States
• Dana Farber Cancer Institute — Boston, Massachusetts, United States
• Karmanos Cancer Institute — Detroit, Michigan, United States
• Oncology Hematology West, PC dba Nebraska Cancer Specialists — Omaha, Nebraska, United States
• University of Rochester Medical Center — Rochester, New York, United States
• Albert Einstein Medical College — The Bronx, New York, United States
• Novant Health Hematology - Forsyth — Winston-Salem, North Carolina, United States
• The Ohio State University Wexner Medical Center - James Cancer Hospital — Columbus, Ohio, United States
• The University of Texas MD Anderson Cancer Center — Houston, Texas, United States
• Vseobecna Fakultni nemocnice v Praze — Prague, Czechia
• Service d'hématologie clinique CHU de Nice — Nice, France
• APHP - Sorbonne Universite — Paris, France
• APHP - Hopital Saint Louis — Paris, France
• Marien Hospital Dusseldorf; Klinik fur Onkologie und Hamatologie, Palliativmedizin — Düsseldorf, Germany
• Universitätsklinikum Hamburg-Eppendorf (UKE) — Hamburg, Germany
• Universitatsklinikum Leipzig; Medizinische Klinik und Poliklinik I — Leipzig, Germany
• Klinikum rechts der Isar der Technischen Universitat Munchen — München, Germany
• Universitatsklinikum Munster — Münster, Germany
• Soroka University MC — Beersheba, Israel
• Edith Wolfson Medical Center — Holon, Israel
• Hadassah University MC — Jerusalem, Israel
• Azienda Ospedaliera Santa Croce e Carle — Cuneo, Italy

Full record on ClinicalTrials.gov

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