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Chronic Lymphocytic LeukemiaPhase 2NCT07271667

A Study of Emavusertib + An Approved Bruton Tyrosine Kinase Inhibitor (BTKi) in Participants With Chronic Lymphocytic Leukemia (CLL) and Other B-cell Malignancies

A Phase 2 study testing Emavusertib and Zanubrutinib in people with Chronic Lymphocytic Leukemia and B-cell Malignancies, run by Curis, Inc. at 11 sites in 3 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The primary objective of the study for Cohort 1 and Cohort 2 is to assess the anticancer activity of emavusertib in combination with zanubrutinib in participants with CLL. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Emavusertib and Zanubrutinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
108 participants
Where
11 sitesin 3 countries
Study dates
23 Apr 2026to Nov 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Males and females ≥ 18 years of age.
  • Life expectancy of ≥ 3 months.
  • Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2.
  • Histopathologically confirmed diagnosis of CLL (medical record is acceptable), as per the World Health Organization 2016 classification.
  • At least 1 criterion for measurable disease per International Workshop on Chronic Lymphocytic Leukemia (iwCLL).
  • For Cohort 1 only:
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  • Participant must be in a partial response (PR) or partial response with lymphocytosis (PR-L) and measurable residual disease positive (MRD+) per Hallek et al, (2018) criteria.
  • Participant must have detectable measurable residual disease (MRD) as determined by the ClonoSEQ assay
  • Must be actively taking zanubrutinib for at least 12 months.
  • Acceptable organ function at Screening within 28 days prior to Cycle 1 Day 1 (C1D1)
  • For Cohort 2 only:
  • Relapsed disease for which participants are ineligible for or have exhausted standard therapeutic options that would be considered standard of care
  • Must be actively taking zanubrutinib.
  • Participants must have had direct progression on zanubrutinib (within 3 months prior to study entry; administered as monotherapy or in combination) and no other anticancer therapy administered since.
  • Acceptable organ function at Screening within 28 days prior to C1D1.
  • Creatine phosphokinase (CPK) < 2.5 × ULN.
  • Ability to tolerate a contrast-enhanced computed tomography (CT) scan.
  • Ability to swallow and retain oral medications.
  • Negative serum pregnancy test in women of childbearing potential (WOCP).
  • WOCP and men who partner with WOCP must agree to use highly effective contraceptive methods for the duration of the study and for 180 days after the last dose of study treatment.
  • Ability to understand and willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Who cannot join

  • Active second malignancy unless in remission with a life expectancy of > 2 years and with documented Sponsor approval.
  • Active malignancy other than CLL requiring systemic therapy (exceptions may be granted following a discussion with the Sponsor Medical Monitor).
  • Have high-risk CLL TP53 mutations and 17P deletion.
  • History of Grade ≥ 3 rhabdomyolysis without complete recovery.
  • Received prior chimeric antigen receptor-T cell therapy.
  • Received prior investigational drugs (including treatment in clinical research, unapproved combination products, and new dosage forms) within 28 days or 5 half-lives, whichever is shorter, prior to C1D1; allogeneic hematopoietic stem cell transplant (HSCT) within 60 days prior to C1D1; or had clinically significant graft-versus-host disease (GVHD) requiring ongoing uptitration of immunosuppressive medications prior to Screening.
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  • Any prior systemic anticancer treatment such as chemotherapy, immunomodulatory drug therapy, etc., received within 21 days or 5 half-lives, whichever is shorter, prior to C1D1 (with the exception of zanubrutinib, which may be continued until the day before C1D1).
  • Receiving the following medications within 7 days or 5 half-lives, whichever is shorter, prior to C1D1:
  • Medications that, in the opinion of the Investigator, have a high risk of causing prolonged QT interval, corrected (QTc) and/or Torsades de Pointes.
  • Peg-filgrastim or equivalent.
  • St John's Wort.
  • History of or ongoing drug-induced pneumonitis.
  • History of stroke or intracranial hemorrhage within 6 months prior to C1D1. Participants with post-biopsy hemorrhagic sequela defined as a small hyperdense lesion < 3 millimeters (mm) on T2 sequence will not be excluded.
  • Requirement for anticoagulation with warfarin or equivalent vitamin K antagonists, including dual antiplatelet agents, within 5 half-lives of the anticoagulant or 7 days, whichever is longer, prior to C1D1. Low molecular weight heparin is allowed. Participants who require the use of antiplatelet agents should be discussed with the Sponsor Medical Monitor (e.g., use of factor Xa inhibitors).
  • Vaccinated with a live-attenuated vaccine within 4 weeks prior to C1D1.
  • Prior history of hypersensitivity or anaphylaxis to emavusertib, zanubrutinib, or any of their excipients.
  • Prior history of Stevens-Johnson syndrome or toxic epidermal necrolysis.
  • Intolerance to contrast-enhanced CT scan due to allergic reactions to contrast agents.
  • Major surgery < 28 days prior to C1D1; minor surgery < 7 days prior to C1D1.
  • Viral infections:
  • Known to be human immunodeficiency virus (HIV) positive or have an acquired immunodeficiency syndrome (AIDS)-related illness. If HIV is undetectable or maintained on treatment, enrollment may be allowed after discussion with the Sponsor Medical Monitor.
  • Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) positive or hepatitis C virus (HCV) infection < 6 months prior to C1D1, unless viral load is undetectable, or HCV with cirrhosis.
  • Active systemic infection, including HIV, cytomegalovirus infection, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, or has had, within 28 days prior to C1D1, an infection (other than nail trichophytosis) that requires hospitalization or an intravenous antibiotic.
  • Concomitant illness that would preclude safe participation in the study.
  • Pregnant or lactating female.

Trial locations and contacts

11 sites in 3 countries. Contact the study team or a site near you to ask about taking part.

Ahmed Hamdy, MD contact

617-503-6500

clinicaltrials@curis.com

11 sites in 3 countries

United States6 sites, 6 recruiting

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

    Recruiting

  • Texas Oncology - Sammons Cancer Center

    Dallas, Texas, 75246

    Recruiting

  • Summit Medical Group

    Florham Park, New Jersey, 07932

    Recruiting

  • Mt Sinai Comprehensive Cancer Center

    Miami Beach, Florida, 33140

    Recruiting

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

    Recruiting

  • Mayo Clinic

    Rochester, Minnesota, 55905

    Recruiting

Other trials in United States

Italy3 sites, 3 recruiting

  • IRCCS Ospedale San Raffaele

    Milan, 20132

    Recruiting

  • Azienda Ospedaliero Universitaria Maggiore Della Carità

    Novara, 28100

    Recruiting

  • Azienda Ospedale Università Padova

    Padova, 35128

    Recruiting

Other trials in Italy

Spain2 sites, 2 recruiting

  • MD Anderson Cancer Center Madrid

    Madrid, 28033

    Recruiting

  • Hospital Universitario Fundación Jiménez Díaz - START MADRID

    Madrid, 28040

    Recruiting

Other trials in Spain

About this study

Official title: A Phase 2 Study of Emavusertib in Combination With an Approved Bruton Tyrosine Kinase Inhibitor in Patients With Chronic Lymphocytic Leukemia and Other B-cell Malignancies

The primary objective of the study for Cohort 1 and Cohort 2 is to assess the anticancer activity of emavusertib in combination with zanubrutinib in participants with CLL.

Being tested
Emavusertib, Zanubrutinib
Keywords
Emavusertib, BTKi, B-cell Malignancies, Chronic Lymphocytic Leukemia, CLL, Zanubrutinib
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EmavusertibDrug

    Oral tablets

  • ZanubrutinibDrug

    Also called BRUKINSA®

    Oral capsules

Study groups in NCT07271667
Study groupRoleWhat they receive
Cohort 1: Emavusertib and ZanubrutinibExperimentalParticipants in Cohort 1 include CLL participants who have been on zanubrutinib for at least 12 months and are currently in a partial response (PR) or partial response with lymphocytosis (PR-L) and measurable residual disease positive (MRD+). In Part A, participants will receive one of two doses of emavusertib twice daily (BID) and an approved dose of zanubrutinib per label. In Part B, additional participants will be enrolled in an expansion if pre-defined criteria for Part A are met. Participants will receive one of two doses of emavusertib BID and an approved dose of zanubrutinib per label.
Receives: Drug: Emavusertib; Drug: Zanubrutinib
Cohort 2: Emavusertib and ZanubrutinibExperimentalParticipants in Cohort 2 include relapsed CLL participants who have directly progressed on zanubrutinib after a confirmed response (PR or better lasting 6 months or longer). In Part A, participants will receive one of two doses of emavusertib BID and an approved dose of zanubrutinib per label. In Part B, additional participants will be enrolled in an expansion if pre-defined criteria for Part A are met. Participants will receive one of two doses of emavusertib BID and an approved dose of zanubrutinib per label.
Receives: Drug: Emavusertib; Drug: Zanubrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Cohort 1: Undetectable Measurable Residual Disease (uMRD) Rate

    Measured: Up to approximately 23 months

  2. Cohort 2: Overall Response Rate (ORR)

    Measured: Up to approximately 23 months

Secondary outcomes (14)

  1. Cohort 1: Duration of uMRD

    Measured: Up to approximately 23 months

  2. Cohort 1: Time to Measurable Residual Disease (MRD) Conversion

    Measured: Up to approximately 23 months

  3. Cohort 1: Complete Response (CR) Rate

    Measured: Up to approximately 23 months

  4. Cohort 1: Duration of CR

    Measured: Up to approximately 23 months

  5. Cohort 1: Time to CR

    Measured: Up to approximately 23 months

  6. Cohort 2: Duration of Response (DOR)

    Measured: Up to approximately 23 months

  7. Cohort 2: Time to Response

    Measured: Up to approximately 23 months

  8. Cohorts 1 and 2: Progression-free Survival (PFS)

    Measured: Up to approximately 23 months

  9. Cohorts 1 and 2: Overall Survival (OS)

    Measured: Up to approximately 23 months

  10. Cohorts 1 and 2: Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Treatment-related Adverse Events

    Measured: Up to approximately 23 months

  11. Cohorts 1 and 2: Maximum Plasma Concentration (Cmax) of Emavusertib and Zanubrutinib

    Measured: Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle = 28 days)

  12. Cohorts 1 and 2: Time to Maximum Concentration (Tmax) of Emavusertib and Zanubrutinib

    Measured: Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle = 28 days)

  13. Cohorts 1 and 2: Area Under the Curve (AUC) from 0 to t Hours (AUC0-t) of Emavusertib and Zanubrutinib

    Measured: Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle = 28 days)

  14. Cohorts 1 and 2: Trough Plasma Concentration (Cmin) of Emavusertib and Zanubrutinib

    Measured: Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle = 28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Dec 2025
  2. Study start23 Apr 2026
  3. Primary completionNov 2027 (estimated)
  4. Study completionNov 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
108 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07271667
Sponsor's protocol ID
CA-4948-203
Other IDs
2025-523600-68-00, 2025
Status last verified
Jun 2026
First submitted
26 Nov 2025
Last updated
12 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Emavusertib and Zanubrutinib in people with Chronic Lymphocytic Leukemia and B-cell Malignancies, run by Curis, Inc. at 11 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 12 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States, Italy, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Ahmed Hamdy, MD (617-503-6500, clinicaltrials@curis.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cohort 1: Undetectable Measurable Residual Disease (uMRD) Rate (time frame: Up to approximately 23 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07271667.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2026.

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