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

Starting soon · Phase 2

Conditions studied: Conjunctival Mucosa-Associated Lymphoid Tissue Lymphoma, Gastric Mucosa-Associated Lymphoid Tissue Lymphoma, Marginal Zone Lymphoma, Nodal Marginal Zone Lymphoma, Splenic Marginal Zone Lymphoma, Lymphoma, Extranodal Marginal Zone Lymphoma

In brief

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.

Key facts

Study ID: NCT07583810
Run by: City of Hope Medical Center
People needed: 35
Starts: 2026-12-16
Expected to finish: 2028-05-02
Last updated by the study team: 2026-05-15

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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:
Involvement of ≥ 3 nodal sites, each with diameter of ≥ 3 cm
Any nodal or extra nodal tumor mass with a diameter of ≥ 5 cm
B symptoms (fever ≥ 38 degrees Celsius of unclear etiology, night sweats, weight loss > 10% within the prior 6 months) or other symptoms attributed to disease or specific organ involvement associated with the relapse
Risk of local compressive symptoms that may result in organ compromise
Splenomegaly or splenic lesion without splenomegaly
Leukopenia attributed to MZL (leukocytes < 1000/mm\^3)
Leukemia (> 5,000 lymphoma cells/mm\^3)
Threatened organ function, especially for extra nodal MZL
Requirement for transfusion or growth factor support attributed to lymphoma
Involvement of 2 or more extra nodal sites, with tumor/lesion in each extra nodal site ≥ 1 cm

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
Live vaccine within 30 days
Use of strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers within 2 weeks of the first day of study therapy
History of prior malignancy except:
Malignancy treated with curative intent and no known active disease present for ≥ 2 years prior to initiation of therapy
Adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in situ) without evidence of disease
Adequately treated in situ carcinomas (e.g., cervical, esophageal, etc.) without evidence of disease
Asymptomatic prostate cancer managed with "watch and wait" strategy
Superficial bladder cancer
Myelodysplastic syndrome which is clinically well controlled and no evidence of the cytogenetic abnormalities characteristic of myelodysplasia on the bone marrow at screening
History of severe bleeding disorder defined as an ongoing congenital or acquired condition that leads to an increased likelihood of bleeding

Where it is running

City of Hope Medical Center — Duarte, California, United States

Full record on ClinicalTrials.gov

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