Zanubrutinib in Combination With Sonrotoclax for the Treatment of Underrepresented Ethnic and Racial Minorities With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

NCT06859008 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: 24273NCI-2025-01388P30CA033572
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial tests zanubrutinib in combination with sonrotoclax for treating underrepresented ethnic and racial minorities with B-cell non-Hodgkin lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Many racial and ethnic minorities face additional treatment challenges which may lead to poorer outcomes, however, there are fewer racial and ethnic minorities participating in clinical trials. Zanubrutinib, a type of tyrosine kinase inhibitor, blocks a protein called Bruton tyrosine kinase (BTK), which may help keep cancer cells from growing. Sonrotoclax works by blocking a protein called B-cell lymphoma-2 (Bcl-2). This protein helps certain types of blood cancer cells to survive and grow. When sonrotoclax blocks Bcl-2, it slows down or stops the growth of cancer cells and causes them to die. Zanubrutinib and sonrotoclax have been shown to be an effective treatment for B-cell cancers. Giving zanubrutinib in combination with sonrotoclax may be effective in treating ethnic and racial minorities with relapsed or refractory B-cell non-Hodgkin lymphoma.

Conditions

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; Recurrent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3a Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Nodal Marginal Zone Lymphoma; Recurrent Splenic Marginal Zone Lymphoma; Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Refractory Grade 1 Follicular Lymphoma; Refractory Grade 2 Follicular Lymphoma; Refractory Grade 3a Follicular Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Nodal Marginal Zone Lymphoma; Refractory Splenic Marginal Zone Lymphoma; Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue

Outcome Measures

Primary Outcomes (2)

• Feasibility of completing zanubrutinib lead-in (cycle 1 and cycle 2) and sonrotoclax ramp up (cycle 3)

  Will be estimated as a binary proportion along with the 95% exact binomial confidence interval.

  From start of cycle 1 through end of cycle 3 (cycle length = 28 days)

• Feasibility of patient retention through 2 cycles of the combination therapy at a steady dose

  Will be estimated as a binary proportion along with the 95% exact binomial confidence interval.

  From start of cycle 4 though end of cycle 5 (cycle length = 28 days)

Secondary Outcomes (6)

• Incidence of adverse events (AEs)

  Up to 30 days after last dose of study treatment

• Overall response rate

  After the start of protocol therapy and prior to disease progression and/or start of other anti-lymphoma therapy, assessed up to 3 years

• CR rate

  After the start of protocol therapy and prior to disease progression and/or start of other anti-lymphoma therapy, assessed up to 3 years

• Time to response

  From start of protocol treatment to the time CR or PR is first achieved, assessed up to 3 years

• Progression-free survival (PFS)

  From start of protocol treatment to time of disease relapse/progression or death due to any cause, whichever occurs earlier, assessed up to 3 years

Study Arms (1)

Treatment (zanubrutinib, sonrotoclax)

EXPERIMENTAL

Patients receive zanubrutinib PO QD on days 1-28 of each cycle. Starting with cycle 3, patients also receive sonrotoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 28 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo urine and blood sample collection, and CT or MRI throughout the study. Additionally, patients may undergo biopsy at progression and bone marrow aspiration and biopsy throughout the study.

Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Other: Questionnaire Administration; Drug: Sonrotoclax; Drug: Zanubrutinib

Interventions

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (zanubrutinib, sonrotoclax)

Biospecimen Collection PROCEDURE

Undergo urine and blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (zanubrutinib, sonrotoclax)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration and biopsy

Treatment (zanubrutinib, sonrotoclax)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow aspiration and biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (zanubrutinib, sonrotoclax)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (zanubrutinib, sonrotoclax)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (zanubrutinib, sonrotoclax)

Questionnaire Administration OTHER

Ancillary studies

Treatment (zanubrutinib, sonrotoclax)

Sonrotoclax DRUG

Given PO

Also known as: B-cell Lymphoma-2 Inhibitor BGB-11417, Bcl-2 Inhibitor BGB-11417, BGB 11417, BGB-11417, BGB11417

Treatment (zanubrutinib, sonrotoclax)

Zanubrutinib DRUG

Given PO

Also known as: BGB 3111, BGB-3111, BGB3111, Brukinsa, BTK-InhB

Treatment (zanubrutinib, sonrotoclax)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Age: ≥ 18 years on the day of signing the informed consent form
• Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Patients are of the following self-identified racial/ethnic groups:
• Cohort 1: Patients in any of the following categories:
• Black or African American
• Hispanic or Latino
• American Indian/Native Alaskan
• Pacific Islander/Native Hawaiian
• Any other patient that does not fit the definition of Cohort 2
• Cohort 2: Patients in either of following categories:
• Non-Hispanic White
• Non-Hispanic Asian
• Confirmed diagnosis (per World Health Organization \[WHO\] guidelines, unless otherwise noted) of one of the following disease subtypes. Note that for disease subtypes that are known to respond to BTK inhibitor (BTKi) and/or BCL2 inhibitor (BCL2i) (e.g., marginal zone lymphoma \[MZL\], mantle cell lymphoma \[MCL\], CLL/SLL), newly diagnosed or r/r patients are allowed

You may not qualify if:

• Major surgery ≤ 4 weeks of the first dose of study drug
• Prior autologous stem cell transplant unless ≥ 30 days after transplant; or prior chimeric antigen receptor T cell (CAR-T) therapy unless ≥ 30 days after cell infusion
• Prior allogeneic stem cell transplant with active graft-versus-host disease (GVHD), or requiring immunosuppressive drugs for treatment of GVHD, or have taken calcineurin inhibitors within 4 weeks prior to consent
• Prior therapy ≥ 2 months with or progression on a Bcl2 inhibitor (eg, venetoclax)
• Vaccination or requirement for vaccination with a live vaccine within 35 days prior to the first dose of study drug or at any time during planned study treatment
• Requires ongoing treatment with a strong CYP3A inducer
• Requires ongoing treatment with warfarin or warfarin derivatives
• Concurrent participation in another therapeutic clinical trial
• Use of the following substances prior to the first dose of study drug:
• ≤ 28 days before first dose of study drug: Any biologic and/or immunologic-based therapy(ies) including experimental therapy(ies) for leukemia, lymphoma, or myeloma (including, but not limited to, monoclonal antibody therapy, eg, rituximab, and/or cancer vaccine therapy)
• ≤ 14 days before the first dose of study drug: systemic chemotherapy or radiation therapy
• ≤ 7 days before the first dose of study drug: corticosteroid given with antineoplastic intent other than control of BTK inhibitor withdrawal flare
• ≤ 5 half-lives before the first dose of study drug: BTK inhibitor, tyrosine kinase inhibitor, or other targeted small molecule given with antineoplastic intent
• Known current central nervous system involvement by lymphoma/leukemia
• Known plasma cell neoplasm, prolymphocytic leukemia, history of or currently suspected Richter's syndrome

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Follicular; Lymphoma, Mantle-Cell

Interventions

Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; 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; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Geoffrey Shouse

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2025
• First Posted: March 5, 2025
• Study Start: August 25, 2025
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): January 31, 2029
• Last Updated: April 20, 2026

Record last verified: 2026-04

Locations

US (1)