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

NCT07271667 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: CA-4948-2032025-523600-68-00
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Chronic Lymphocytic Leukemia; B-cell Malignancies

Keywords

Emavusertib; BTKi; B-cell Malignancies; Chronic Lymphocytic Leukemia; CLL; Zanubrutinib

Outcome Measures

Primary Outcomes (2)

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

  Up to approximately 23 months

• Cohort 2: Overall Response Rate (ORR)

  Up to approximately 23 months

Secondary Outcomes (14)

• Cohort 1: Duration of uMRD

  Up to approximately 23 months

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

  Up to approximately 23 months

• Cohort 1: Complete Response (CR) Rate

  Up to approximately 23 months

• Cohort 1: Duration of CR

  Up to approximately 23 months

• Cohort 1: Time to CR

  Up to approximately 23 months

Study Arms (2)

Cohort 1: Emavusertib and Zanubrutinib

EXPERIMENTAL

Participants 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.

Drug: Emavusertib; Drug: Zanubrutinib

Cohort 2: Emavusertib and Zanubrutinib

EXPERIMENTAL

Participants 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.

Drug: Emavusertib; Drug: Zanubrutinib

Interventions

Emavusertib DRUG

Oral tablets

Cohort 1: Emavusertib and Zanubrutinib; Cohort 2: Emavusertib and Zanubrutinib

Zanubrutinib DRUG

Oral capsules

Also known as: BRUKINSA®

Cohort 1: Emavusertib and Zanubrutinib; Cohort 2: Emavusertib and Zanubrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Curis, Inc.: lead

Study Sites (3)

Mt Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Texas Oncology - Sammons Cancer Center

Dallas, Texas, 75246, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

zanubrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Ahmed Hamdy, MD

CONTACT

617-503-6500; clinicaltrials@curis.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2025
• First Posted: December 9, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)