LymphomaPhase 2NCT06563505
A Phase 2 Trial of Mosunetuzumab and Zanubrutinib for Patients With Relapsed/Refractory Marginal Zone Lymphoma
A Phase 2 study testing Mosunetuzumab and Zanubrutinib in people with Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
To assess the efficacy and safety of mosunetuzumab combined with zanubrutinib in patients with relapsed or refractory MZL. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma
- What is being tested?
- Mosunetuzumab and Zanubrutinib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Dec 2024to 31 Dec 2028
- 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
- Patients must meet the following criteria for study entry:
- Histologically diagnosed marginal zone lymphoma (any subtypes)
- o Low grade or indolent B-cell lymphoma unclassifiable is also eligible
- Have received at least 1 prior treatment including CD20 monoclonal antibody
- Patients have relapsed or refractory disease to their most recent regimen
- Stage II, III or IV disease
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- Age ≥18 years. Because no dosing or adverse event data are currently available on the use of mosunetuzumab and zanubrutinib combination in patients <18 years of age, children are excluded from this study.
- Performance status ≤2 on the ECOG scale (≤3 if due to lymphoma)
- Requiring systemic therapy assessed by investigator based on tumor size, symptoms and/or GELF criteria
- A nodal or extranodal (except spleen) mass > 7 cm in its greater diameter
- At least 3 nodal or extranodal sites ≥ 3 cm in diameter
- Presence of at least one B symptom
- Fever (>38 C), night sweats, weight loss > 10% in the past 6 months
- Symptomatic splenomegaly (or size >13cm)
- Impending organ compression or involvement (ureteral, orbital, gastrointestinal)
- Any of the following cytopenias due to bone marrow involvement of lymphoma
- Hemoglobin ≤ 10 g/dL
- Platelets ≤ 100 x 109/L
- Absolute neutrophil count (ANC) < 1.5x109/L
- Pleural effusion or ascites
- LDH > ULN or β2 microglobulin > ULN
- Bi-dimensionally measurable disease, with at least one nodal lesion ≥ 1.5 cm or one extra-nodal lesion > 1 cm in longest diameter by CT, PET/CT, and/or MRI
- Subjects with splenic MZL who do not meet the radiographically measurable disease criteria are eligible for participation if spleen is enlarged over 16 cm and MZL is histologically confirmed by bone marrow biopsy or peripheral blood flow cytometry
- Subjects with EMZL such as skin of conjunctival EMZL who do not meet the radiographically measurable disease criteria are eligible for participation if at least one of the skin lesions is histologically confirmed as MZL and measures ≥1.5 cm in diameter
- Patients must have adequate organ and marrow function as defined below:
- Total bilirubin ≤ 1.5 institutional ULN, unless consistent with Gilbert's (ratio between total and direct bilirubin > 5)
- AST (SGOT) and ALT (SGPT) ≤ 3 x institutional ULN
- Alkaline phosphatase < 2.5 ULN
- Creatinine clearance ≥ 40 ml/min calculated by modified Cockcroft-Gault formula
- Blood counts below if without lymphoma cause for cytopenia
- Hemoglobin ≥ 8 g/dL
- Platelets ≥ 75 x 109/L
- Absolute neutrophil count (ANC) ≥ 1.0x109/L
- Blood counts below if cytopenia are due to lymphoma (such as bone marrow involvement or splenomegaly)
- Hemoglobin ≥ 6 g/dL (no transfusion within 7 days prior to treatment)
- Platelets ≥ 50 x 109/L
- Absolute neutrophil count (ANC) ≥ 0.5x109/L
Who cannot join
- Subjects will be ineligible for this study if they meet any of following criteria:
- Known active central nervous system lymphoma or leptomeningeal disease.
- Treatment with any chemotherapeutic agent, or treatment with any other anti-lymphoma agent (investigational or otherwise) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to first investigational agent administration.
- Any prior history of other malignancy besides B-NHL, unless the patient has been free of disease for ≥ 1 year and felt to be at low risk for recurrence by the treating physician, except:
- Adequately treated localized skin cancer without evidence of disease.
- Adequately treated or monitored low risk localized prostate cancer.
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- Adequately treated localized breast cancer without evidence of disease.
- Adequately treated cervical carcinoma in situ without evidence of disease.
- Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of lenalidomide capsules, or put the study outcomes at undue risk.
- Uncontrolled human immunodeficiency virus (HIV), or active Hepatitis C Virus, or active Hepatitis B Virus infection, or any uncontrolled active significant infection, including suspected or confirmed JC virus infection and SARS-CoV2.
- Patients with inactive hepatitis B infection must adhere to hepatitis B reactivation prophylaxis unless contraindicated. Hepatitis B or C serologic status: subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR). Those who are hepatitis B surface antigen (HBsAg) positive or hepatitis B PCR positive will be excluded. Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded. Subjects with a history of Hepatitis C who received antiviral treatment are eligible as long as PCR is negative.
- History of immunodeficiency (with the exception of hypogammaglobulinemia) or concurrent systemic immunosuppressant therapy (e.g., cyclosporine, tacrolimus, etc., or chronic administration glucocorticoid equivalent of >10mg/day of prednisone) within 28 days of the first dose of study drug with exception of steroid used for IV contrast allergy. In addition, use of inhaled, topical, intranasal corticosteroids or local steroid injection (eg, intra- articular injection) is permitted.
- Use of strong/moderate inhibitors within 7 days or 5 half-lives prior to the first dose of zanubrutinib; usage of strong/moderate CYP3A inducers within 14 days prior to the first dose of zanubrutinib.
- Requiring ongoing therapy with strong or moderate CYP3A inducers.
- Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification. Subjects with controlled, asymptomatic atrial fibrillation during screening can enroll on study.
- Significant screening electrocardiogram (ECG) abnormalities including 2nd degree atrioventricular (AV) block, type II AV block, or 3rd degree block.
- Active bleeding or known bleeding diathesis (e.g., von Willebrand's disease) or hemophilia.
- History of stroke or intracranial hemorrhage within 6 months prior to study entry.
- Lactating or pregnant subjects.
- Administration of any investigational agent within 28 days of first dose of study drug.
- Patients who have undergone major surgery within 28 days or minor surgery within 3 days of first dose of study drug.
- Patients taking corticosteroids during the last 4 weeks, unless administered at a dose equivalent to < 10 mg/day prednisone (over these 4 weeks) with the exception of pre-study steroid treatment with prednisone up to 100mg x 5 days which is allowed to improve symptoms and treatment tolerance.
- Known or suspected chronic active Epstein-Barr virus (CAEBV) infection
- Administration of a live, attenuated vaccine within 4 weeks before first mosunetuzumab administration or anticipation that such a live, attenuated vaccine will be required during the study.
- Prior solid organ transplantation
- Prior allogeneic stem cell transplant (autologous stem cell transplants are allowed if conducted at least 100 days prior to C1D1.)
- Contraindication to tocilizumab
- Patients who have difficulty with or are unable to swallow oral medication, or have disease significantly affecting gastrointestinal function that would limit absorption of oral medication.
- Patients who have an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
- Patients who have a history of (non-infectious) autoimmune pneumonitis that required steroids or has current autoimmune pneumonitis.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Dai Chihara, MD,PHD, 713-794-3074, dchihara@mdanderson.org
Dai Chihara, MD,PHD
About this study
To assess the efficacy and safety of mosunetuzumab combined with zanubrutinib in patients with relapsed or refractory MZL.
Read the detailed description
Primary Objectives:
To determine the safety and efficacy of mosunetuzumab in combination with zanubrutinib as determined by best complete response (CR) rate of combination treatment for patients with relapsed or refractory marginal zone lymphoma (MZL).
Secondary Objectives:
To determine best overall response rate (ORR), duration of response (DOR), time to next treatment, progression-free survival (PFS), overall survival (OS), and evaluation of tolerability of mosunetuzumab and zanubrutinib as treatment for patients with relapsed/refractory MZL.
Exploratory Objective:
To determine the impact of total metabolic tumor volume to ORR, CR rate and survival outcomes
To determine the biomarkers that correlates with response and mechanisms of resistance to mosunetuzumab and zanubrutinib in relapsed/refractory MZL.
To determine the surrogate endpoint for future trials in MZL.
- Conditions
- Lymphoma
- Being tested
- Mosunetuzumab, Zanubrutinib
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MosunetuzumabDrug
Also called RO7030816
Given by IV
ZanubrutinibDrug
Given by IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment w/Mosunetuzumab + Zanubrutinib | Experimental | Not described Receives: Drug: Mosunetuzumab; Drug: Zanubrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Adverse Events (AEs)
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Measured: Through study completion; an average of 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2024
- Study start11 Dec 2024
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dai Chihara, MD,PHD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06563505
- Sponsor's protocol ID
- 2024-0243
- Other IDs
- NCI-2024-06965
- Status last verified
- Sep 2026
- First submitted
- 19 Aug 2024
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Trial of Mosunetuzumab and Zanubrutinib for Patients With Relapsed/Refractory Marginal Zone Lymphoma
- ClinicalTrials.gov ID
- NCT06563505
- Acronym / sponsor ID
- 2024-0243
- Conditions
- Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 11 Dec 2024 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 20 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To assess the efficacy and safety of mosunetuzumab combined with zanubrutinib in patients with relapsed or refractory MZL.
Detailed description
Primary Objectives:
To determine the safety and efficacy of mosunetuzumab in combination with zanubrutinib as determined by best complete response (CR) rate of combination treatment for patients with relapsed or refractory marginal zone lymphoma (MZL).
Secondary Objectives:
To determine best overall response rate (ORR), duration of response (DOR), time to next treatment, progression-free survival (PFS), overall survival (OS), and evaluation of tolerability of mosunetuzumab and zanubrutinib as treatment for patients with relapsed/refractory MZL.
Exploratory Objective:
To determine the impact of total metabolic tumor volume to ORR, CR rate and survival outcomes
To determine the biomarkers that correlates with response and mechanisms of resistance to mosunetuzumab and zanubrutinib in relapsed/refractory MZL.
To determine the surrogate endpoint for future trials in MZL.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment w/Mosunetuzumab + Zanubrutinib | Experimental | Drug: Mosunetuzumab, Drug: Zanubrutinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (37 listed)
- Histologically diagnosed marginal zone lymphoma (any subtypes)
- o Low grade or indolent B-cell lymphoma unclassifiable is also eligible
- Have received at least 1 prior treatment including CD20 monoclonal antibody
- Patients have relapsed or refractory disease to their most recent regimen
- Stage II, III or IV disease
Key exclusion criteria (30 listed)
- Known active central nervous system lymphoma or leptomeningeal disease.
- Treatment with any chemotherapeutic agent, or treatment with any other anti-lymphoma agent (investigational or otherwise) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to first investigational agent administration.
- Any prior history of other malignancy besides B-NHL, unless the patient has been free of disease for ≥ 1 year and felt to be at low risk for recurrence by the treating physician, except:
- Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of lenalidomide capsules, or put the study outcomes at undue risk.
- Uncontrolled human immunodeficiency virus (HIV), or active Hepatitis C Virus, or active Hepatitis B Virus infection, or any uncontrolled active significant infection, including suspected or confirmed JC virus infection and SARS-CoV2.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MosunetuzumabAlso: RO7030816Given by IV | Drug | Treatment w/Mosunetuzumab + Zanubrutinib |
| ZanubrutinibGiven by IV | Drug | Treatment w/Mosunetuzumab + Zanubrutinib |
Primary outcome
Safety and Adverse Events (AEs)
Time frame: Through study completion; an average of 1 year.
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2026.
- MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Dai Chihara, MD,PHD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mosunetuzumab and Zanubrutinib in people with Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.
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 37 inclusion and 30 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 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 Dai Chihara, MD,PHD (713-794-3074, dchihara@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Adverse Events (AEs) (time frame: Through study completion; an average of 1 year.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Oct 2026.