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

NCT04278768 · Status: SUSPENDED · Phase: PHASE1/PHASE2 · Type: INTERVENTIONAL · Enrollment: 366

Last updated 2026-03-19

No results posted yet for this study

Summary

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.

Conditions

Interventions

DRUG

Emavusertib

Emavusertib is formulated as a tablet for oral administration for BID dosing in consecutive 28-day cycles. Emavusertib is a novel small molecule inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK4). IRAK4 kinase plays an essential role in toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling pathways and these pathways are frequently dysregulated in non-Hodgkin's lymphoma and AML/MDS malignancies.

DRUG

Venetoclax

Ventoclax is B-cell lymphoma-2 (BCL-2) inhibitor. Venetoclax will be administered at 100 mg orally (Day 1) per the product label at the same time each day with a ramp up over 3 days to 400 mg for 21days of a 28-day Cycle. Second and subsequent cycles start with target dose level. This arm of the study has been closed to enrollment.

DRUG

Emavusertib

Emavusertib is formulated as a tablet for oral administration for BID dosing for 21 days (Days 1-21) of a 28-day Cycle.

Sponsors & Collaborators

  • Curis, Inc.

    lead INDUSTRY

Study Design

Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
SEQUENTIAL

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2020-07-06
Primary Completion
2026-04-01
Completion
2026-04-01
FDA Drug
Yes

Countries

  • United States
  • Czechia
  • France
  • Germany
  • Israel
  • Italy
  • Poland
  • Spain

Study Locations

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Entities

Drugs
Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04278768 on ClinicalTrials.gov