Non-covalent BTK Inhibitor Nemtabrutinib in Combination With the CD20 Monoclonal Antibody Rituximab for the Treatment of Marginal Zone Lymphoma

NCT07583810 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 260148NCI-2026-03180P30CA033572
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests the effect of nemtabrutinib in combination with rituximab in treating patients with marginal zone lymphoma. Nemtabrutinib, a non-covalent Bruton's tyrosine kinase (BTK) inhibitor, may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Giving nemtabrutinib in combination with rituximab may be safe, tolerable and/or effective in treating patients with marginal zone lymphoma.

Conditions

Conjunctival Mucosa-Associated Lymphoid Tissue Lymphoma; Marginal Zone Lymphoma; Nodal Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Gastric Mucosa-Associated Lymphoid Tissue Lymphoma; Lymphoma; Extranodal Marginal Zone Lymphoma

Keywords

Lymphoma

Outcome Measures

Primary Outcomes (2)

• Incidence of unacceptable toxicity (Safety lead-in)

  Observed toxicities will be summarized by type, severity, and attribution.

  During cycle 1 (cycle length = 28 days)

• Complete response (CR) rate (Phase 2)

  Will be defined as achieving a best response of CR at any time on the study prior to any disease progression or start of other non-protocol anti-lymphoma therapy. CR rate will be estimated along with the 95% exact binomial confidence interval.

  Up to 3 years

Secondary Outcomes (5)

• Overall response rate (ORR)

  Up to 3 years

• Progression-free survival (PFS)

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

• Duration of response (DOR)

  From the first achievement of PR or CR to the time of disease relapse/progression or death due to any cause, whichever earlier, assessed up to 3 years

• Overall survival (OS)

  From start of protocol treatment to death due to any cause, assessed up to 3 years

• Incidence of adverse events

  Up to 30 days after last dose of study treatment

Study Arms (1)

Treatment (nemtabrutinib, rituximab)

EXPERIMENTAL

Patients receive nemtabrutinib PO QD on days 1-28 of each cycle and rituximab IV on days 1, 8, 15, and 22 of cycles 1 and 3 and on day 1 of cycles 5-12. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. After 12 cycles, patients with a CR or PR may optionally continue to receive nemtabrutinib PO QD for up to an additional 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and PET/CT, CT, or MRI throughout the study. Additionally, patients may optionally undergo bone marrow biopsy and tissue biopsy on study.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Nemtabrutinib; Procedure: Positron Emission Tomography; Biological: Rituximab

Interventions

Biopsy Procedure PROCEDURE

Undergo tissue biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (nemtabrutinib, rituximab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

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

Treatment (nemtabrutinib, rituximab)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

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

Treatment (nemtabrutinib, rituximab)

Computed Tomography PROCEDURE

Undergo CT or PET/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, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (nemtabrutinib, rituximab)

Rituximab BIOLOGICAL

Given IV

Also known as: ABP 798, ABP-798, ABP798, BI 695500, BI-695500, BI695500, Blitzima, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT P10, CT-P10, CTP10, GP 2013, GP-2013, GP2013, IDEC 102, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, IDEC102, Ikgdar, Mabtas, MabThera, Monoclonal Antibody IDEC-C2B8, PF 05280586, PF-05280586, PF05280586, Riabni, Ritemvia, Rituxan, Rituximab ABBS, Rituximab ARRX, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar GP2013, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, Rituximab Biosimilar SIBP-02, rituximab biosimilar TQB2303, Rituximab PVVR, Rituximab-abbs, Rituximab-arrx, Rituximab-blit, Rituximab-pvvr, Rituximab-rite, Rituximab-rixa, Rituximab-rixi, Rixathon, Riximyo, RTXM 83, RTXM-83, RTXM83, Ruxience, Truxima

Treatment (nemtabrutinib, rituximab)

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 (nemtabrutinib, rituximab)

Nemtabrutinib DRUG

Given PO

Also known as: ARQ 531, ARQ-531, ARQ531, Bruton's Tyrosine Kinase Inhibitor ARQ 531, BTK Inhibitor ARQ 531, MK-1026

Treatment (nemtabrutinib, rituximab)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Treatment (nemtabrutinib, rituximab)

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
• Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Diagnosis of MZL including splenic marginal zone lymphoma (SMZL), extra nodal marginal zone lymphoma (ENMZL) and nodal marginal zone lymphoma (NMZL), established by histologic assessment
• Requiring treatment for MZL. Patients receiving prior systemic therapy as well as treatment naïve patients are eligible
• Local radiotherapy not exceeding a total dose of 20 Gy at least 2 weeks prior the first dose of study therapy is allowed
• Radiographically measurable lymphadenopathy or extra nodal lymphoid malignancy (as defined by Lugano Classification for non-Hodgkin lymphoma \[NHL\])
• Subjects with splenic MZL who do not meet the radiographically measurable disease criteria described herein are eligible for participation provided that bone marrow infiltration of MZL is histologically confirmed
• Subjects with skin extranodal marginal zone lymphoma (EMZL) who do not meet the radiographically measurable disease criteria described herein are eligible provided that skin lesion measures ≥ 1.5 cm in diameter and is documented by photo or there are multiple skin lesions measuring \> 1cm in diameter on the body that cannot be incorporated in one radiation field and at least one of them is histologically confirmed as MZL
• Subjects with gastric extra nodal MZL histologically confirmed and need therapy but do not have measurable disease and in which response to treatment can be assess by multiple random gastric biopsies
• Subjects with conjunctival EMZL who do not meet the radiographically measurable disease criteria described herein are eligible provided that conjunctival lesion measures ≥ 1 cm in diameter and is documented by photo or there are multiple conjunctival lesions measuring together \> 1 5cm that cannot be treated by radiation because of previous radiation therapy, contraindications to radiation and patient refusal to receive radiation therapy. At least one of these lesions needs be histologically confirmed as MZL
• Willing to provide a lymph node or tissue biopsy from the most recent available archival tissue or undergo an incisional or excisional lymph node or tissue biopsy
• Subjects with splenic MZL who do not have a tumor to biopsy or an archival tumor tissue sample are eligible provided subject is willing to undergo a bone marrow biopsy or provide an archival bone marrow biopsy that was obtained before the date of the first dose of study treatment; bone marrow sample must show histologically confirmed infiltration of MZL
• At least one of the following criteria for treatment initiation:

You may not qualify if:

• Evidence of diffuse large B-cell lymphoma (DLBCL) transformation
• Subjects with presumptive evidence of transformation based on clinical assessment of factors such as, but not limited to, increasing lactate dehydrogenase, rapidly worsening disease, or frequent B-symptoms, must be ruled out for a transformation to a more aggressive disease, such as DLBCL
• History of central nervous system lymphoma (either primary or metastatic) or leptomeningeal disease
• Active graft versus host disease
• Concurrent anticancer therapy (eg, chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, hormonal therapy, investigational therapy, or tumor embolization)
• Allogeneic stem cell transplant within the last 6 months, or autologous stem cell transplant within the last 3 months before the date of the first dose of study treatment
• Receipt of anticancer medications or investigational drugs within the following intervals before the date of the first dose of study treatment:
• \< 10 weeks from completion of any radio- or toxin-immunoconjugates
• \< 4 weeks for immunotherapy
• \< 3 weeks for radiotherapy
• \< 2 weeks for any investigational agent or other anticancer medications
• Steroids that are used for treatment of allergy or other underlying condition are permittable, but not steroids started to treat lymphoma. Subjects receiving corticosteroids must be at a dose level ≤ 10 mg/day within 7 days of the study treatment administration
• Inadequate recovery from adverse events related to prior therapy to grade ≤ 1 (excluding grade 2 alopecia and neuropathy)
• Prior non-covalent BTK inhibitor (prior covalent BTK inhibitors are allowed)
• Major surgery (under general anesthesia) within 30 days prior to therapy initiation

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

Location

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal Zone; Lymphoma

Interventions

Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; ARQ531; Rituximab; CT-P10

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

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; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Geoffrey Shouse

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2026
• First Posted: May 13, 2026
• Study Start (Estimated): December 16, 2026
• Primary Completion (Estimated): May 2, 2028
• Study Completion (Estimated): May 2, 2028
• Last Updated: May 15, 2026

Record last verified: 2026-05

Locations

US (1)