TakeAim Leukemia: 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 and in Combination With Azacitidine or Venetoclax TAKEAIM

What's the purpose of this trial?

This is a multicenter, open-label, Phase 1/2a dose escalation and expansion study of orally administered emavusertib (CA-4948) monotherapy and in combination with azacitidine or venetoclax in adult patients with Acute Myelogenous Leukemia (AML) or high risk Myelodysplastic Syndrome (MDS). * R/R AML with FLT3 mutations, R/R including a FLT3 inhibitor * R/R AML with sliceosome mutations of SF3B1 or U2AF1 * R/R hrMDS with spliceosome mutations of SF3B1 or U2AF1; bone marrow blast count \>/= 8%; ineligible for intensive chemotherapy * Number of pretreatments: 1 or 2

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:

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 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).


• High-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 1b (Combination Therapy) Doublet Arm: emavusertib + AZA

* with International Prognostic Scoring System- revised (IPSS- R) High, high risk myelodysplastic syndrome (hrMDS)
* ineligible for intensive chemotherapy

Doublet Arm: emavusertib + Venetoclax

Patients with:

• R/R AML or hrMDS, after first line therapy

Phase 2a Dose Expansion (Monotherapy)

Patients with:
* R/R AMLwith FLT3 mutations, R/R including a FLT3 inhibitor
* R/R AML with spliceosome mutations of SF3B1 or U2AF1
* R/R hrMDS with spliceosome mutations of SF3B1 or U2AF1; bone marrow blast count \>/= 8%; ineligible for intensive chemotherapy
* 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 14 days prior to start of emavusertib. Localized radiation or surgical resection of skin cancers allowed.
6. Use of any investigational agent within 28 days 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 ≤1 within 7 days prior to start of emavusertib
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. Known hypersensitivity to azacitidine or mannitol, as stated per label (Phase 1b only)
11. Patients with active advanced malignant solid tumors
12. Known to be human immunodeficiency virus (HIV) positive or have an acquired immunodeficiency syndrome-related illness
13. Hepatitis B virus (HBV) DNA positive or Hepatitis C virus (HCV) infection \<6 months prior to start of emavusertib unless viral load is undetectable, or HCV with cirrhosis
14. Uncontrolled or severe cardiovascular disease
15. Gastrointestinal disease or disorder that could interfere with the swallowing, oral absorption, or tolerance of emavusertib
16. History of other invasive malignancy, unless definitively treated with curative intent, provided it is deemed to be at low risk for recurrence by the treating physician
17. Pregnant or lactating
18. Systemic fungal, bacterial, viral, or other infection that is not controlled
19. 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

Additional Trial Information

Phase 1/2

Enrollment: 325 patients (estimated)

View More

Published Results

Phase 1/2a study of the IRAK4 inhibitor CA-4948 as monotherapy or in combination with azacitidine or venetoclax in patients with relapsed/refractory (R/R) acute myeloid leukemia or lyelodysplastic syndrome

June 02, 2022

As of December 16th, 2021, 49 patients have been treated in the phase 1 portion, of whom 43 started by September 30th, allowing 2 on-study disease assessments. The median number of prior therapies was 2 (range 1-5). Four monotherapy dose levels of CA-4948 were tested (200 to 500 mg orally BID). No dose-limiting toxicities were observed at 200 mg and 300 mg BID. No Grade 4 or 5 treatment-related AEs (TRAEs) were reported, and all the TRAEs were manageable. Reversible, manageable Grade 3 rhabdomyolysis occurred in 1/26 (4%) patients at 300 mg BID, 2/17 (12%) at 400 mg BID, and 1/3 (33%) at 500 mg BID. RP2D was determined as 300 mg BID. Of 43 patients starting before Sept 30th, 2021, 14 had SF3B1, U2AF1 or FLT3 mutations and demonstrated more promising efficacy. In the 5 evaluable AML patients with spliceosome mutations, 40% reached CR/CRh (1 CR, 1 CRh), both with study duration >6 months. In the 7 spliceosome-mutated HR-MDS patients, 57% reached marrow CR, including 1 with RBC transfusion independence and 1 proceeding to HSCT. One of the three FLT3-mutated AML reached CR, and 2 became FLT3-negative. Among the 29 patients without SF3B1/U2AF1/FLT3 mutations, 1 reached CR and 2 PR. Phase 1b and Phase 2a are ongoing. RNA-seq on selected samples showed decrease in relative expression of IRAK4-long isoforms with response to CA-4948. Conclusions: CA-4948 is well tolerated and effective in heavily pretreated AML and HR-MDS patients, especially in those with U2AF1/SF3B1/FLT3 mutations. No dose-limiting myelosuppression was reported, suggesting CA-4948 may be a candidate for combination therapy. Accrual of Phases 1b and 2a is ongoing.

Trial Locations

All Trial Locations

View all clinical trial locations sorted by state.


Moffitt Cancer Center Magnolia Campus

Tampa, FL

Open and Accepting


Winship Cancer Institute Emory University

Atlanta, GA

Open and Accepting


University of Chicago Medicine Comprehensive Cancer Center

Chicago, IL

Not Yet Accepting


Dana-Farber Cancer Institute (Main)

Boston, MA

Open and Accepting


New York

Albert Einstein College of Medicine Montefiore

Bronx, NY

Open and Accepting

North Carolina

Novant Health Forsyth Cancer Institute - Bethesda Court

Winston-Salem, NC

Open and Accepting



MD Anderson Cancer Center The University of Texas

Houston, TX

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