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Follicular LymphomaPhase 2FIL_MOZARTNCT06492837

Study With Mosunetuzumab and Zanubrutinib in R/R Follicular Lymphoma Patients

A Phase 2 study testing Mosunetuzumab in combination with Zanubrutinib in people with Follicular Lymphoma, run by Fondazione Italiana Linfomi - ETS at 20 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This is a Phase 2, multicenter study evaluating the efficacy and safety of mosunetuzumab + zanubrutinib (M+Z) used as salvage strategy in patients with R/R FL who have received at least one line of prior systemic therapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Follicular Lymphoma
What is being tested?
Mosunetuzumab in combination with Zanubrutinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
56 participants
Where
20 sitesin 2 countries
Study dates
23 Oct 2024to 15 Sep 2033
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

  • Able to provide written informed consent form approved by the National Ethics Committee (NEC) prior to the initiation of any screening or study-specific procedures and able to understand and to comply with the requirements of the study and the schedule of assessments.
  • Histologically documented diagnosis of cFL (CD20+ by flow cytometry or immunohistochemistry) as defined in the International Consensus Classification of Mature Lymphoid Neoplasms (Campo E., 2022) and in the World Health Organization Classification (WHO) 5th edition 2022.
  • Age ≥18 years.
  • Relapsed or refractory disease. Histologic confirmation of FL relapse is not mandatory but is highly recommended.
  • At least one and up to three lines of systemic therapy containing an anti-CD20 antibody (anti-CD20 alone and/or in combination with radiotherapy is not considered as a line of therapy).
  • FL requiring systemic therapy assessed by investigator based on tumor size and/or Groupe d'Etude des Lymphomes Folliculaires criteria.
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  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.
  • Availability of histological material for centralized revision. Central pathology review is not mandatory for start of treatment.
  • At least one measurable or evaluable site of disease at relapse as documented by CT scan (nodes ≥ 1.5 cm in the longest transverse diameter) or FDG-PET (avid FDG sites). Note: MRI is allowed only if CT scan cannot be performed. Patients with exclusive bone marrow involvement are eligible.
  • Adequate hematological counts defined as follows:
  • Absolute neutrophil count (ANC) > 1.0 x 109/L;
  • Platelet count ≥ 75 x 109/L;
  • Hemoglobin ≥ 9 g/dL.
  • Adequate renal function defined as creatinine clearance ≥ 40 mL/min (Cockcroft-Gault formula, normalized to 1.72 m2).
  • Adequate hepatic function per local laboratory reference range as follows:
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN;
  • Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin).
  • Subject must be able to adhere to the study visit schedule and other protocol requirements.
  • Subject must be able to swallow capsules or tablets.
  • Women must be:
  • postmenopausal for at least 1 year (must not have had a natural menses for at least 12 months);
  • surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy);
  • if they are childbearing potential, completely abstinent (periodic abstinence is not permitted) or if sexually active, be practicing a highly effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double barrier method (e.g.: condoms, diaphragm, or cervical cap, with spermicidal foam, cream, or gel, male partner sterilization), before entry, and must agree to continue to use the same method of contraception throughout the study and for 30 days after receiving the last dose of zanubrutinib and 3 months after receiving the last dose of mosunetuzumab.
  • Women of childbearing potential must have a negative pregnancy test at screening.
  • Men must agree to use an acceptable method of contraception for the duration of the study and for 1 week after receiving the last dose of study drug.
  • Male even if surgically sterilized (i.e., status post vasectomy) must agree to 1 of the following:
  • practice effective barrier contraception (e.g.: condoms) , or
  • agree to practice abstinence, when this is in line with the usual lifestyle of the subject (periodic abstinence is not permitted).

Who cannot join

  • Histological diagnosis different from cFL (Campo E., 2022).
  • R/R FL who were treated with more than three lines of previous treatment (autologous stem cell transplant performed as part of consolidation to a previous line of therapy should not be considered as a line of therapy; rituximab maintenance as part of a previous line of therapy should not be considered as a line of therapy; radiotherapy alone or in combination with rituximab is not considered a line of therapy).
  • Patients with stage I or II (limited stage) suitable for RT alone treatment.
  • Prior exposure to a Bruton's tyrosine kinase (BTK) inhibitor (BTKi).
  • Prior exposure to an anti-CD20xCD3 bispecific antibody (bsAbs).
  • Need of anticoagulation with warfarin or equivalent vitamin K antagonists (e.g. phenprocoumon). Requires ongoing treatment with a strong CYP3A inducer.
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  • Evidence or any history of transformation from FL to other aggressive histology.
  • Prior allogeneic hematopoietic stem cell transplantation.
  • History of severe bleeding disorder (G>3), or history of spontaneous bleeding requiring blood transfusion or other medical intervention. History of stroke or intracranial hemorrhage within 6 months before first dose of study drug
  • Life expectancy < 6 months.
  • History of progressive multifocal leukoencephalopathy (PML).
  • History of hemophagocytic lymphohistiocytosis (HLH) or chronic active EBV.
  • History of autoimmune disease, including, but not limited to: myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
  • Primary central nervous system (CNS) lymphoma or CNS involvement by lymphoma at screening as confirmed by mandatory brain computed tomography (CT) scan and, if clinically indicated, by lumbar puncture.
  • Subject has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, investigational therapy, including targeted small molecule agents within 14 days prior to the first dose of study drug. If receiving glucocorticoid treatment at screening, must be a maximum daily dose of prednisone 10 mg (or equivalent).
  • Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 90 days prior to first therapy administration.
  • Any uncontrolled or significant cardiovascular disease [NYHA class ≥2].
  • Myocardial infarction within 6 months before screening
  • Unstable angina within 3 months before screening
  • New York Heart Association class III or IV congestive heart failure
  • History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes)
  • Significant history of neurologic, psychiatric, endocrinological, metabolic, immunologic, or hepatic disease that would preclude participation in the study or compromise ability to give informed consent.
  • Any history of other active malignancies within 3 years prior to study entry, except for adequately treated in situ carcinoma of the uterine cervix, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin, non-muscle-invasive bladder cancer, localized Gleason score 6 prostate cancer, previous malignancy confined and surgically resected with curative intent.
  • Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
  • Uncontrolled and/or active systemic infection (viral, bacterial or fungal), including active ongoing infection from SARS-CoV-2;
  • Chronic or acute hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen (Ag) negative, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from previous infection or intravenous immunoglobulins (IVIG) may participate; inactive carriers (HBsAg positive with undetectable HBV- DNA) are eligible. Patients with presence of HCV antibody are eligible only if PCR negative for HCV-RNA;
  • HIV seropositivity.
  • Pregnant or lactating women. If female, the patient is pregnant or breast-feeding.
  • Severe or debilitating pulmonary disease.
  • Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
  • Underlying medical conditions that, in the investigator's opinion, will render the administration of study drug hazardous or obscure the interpretation of toxicity or AEs.
  • Major surgery within 4 weeks of the first dose of study drug.
  • Vaccination or requirement for vaccination with a live vaccine within 28 days prior to the first dose of study drug or at any time during planned study treatment.
  • Ongoing alcohol or drug addiction or any psychiatric condition(s) which would compromise ability to comply with study procedures.
  • Hypersensitivity to zanubrutinib or mosunetuzumab or any of the other ingredients of the applicable study drugs.
  • Active and/or ongoing autoimmune anemia and/or autoimmune thrombocytopenia (eg, idiopathic thrombocytopenia purpura).

Trial locations and contacts

20 sites in 2 countries.

20 sites in 2 countries

Italy16 sites

  • AOU SS. Antonio e Biagio e Cesare Arrigo, SCDU Ematologia

    Alessandria

  • AOU Ospedali Riuniti, Clinica di Ematologia

    Ancona

  • Policlinico S.Orsola-Malpighi, Istituto di Ematologia "Seragnoli"

    Bologna

  • ASST Spedali Civili di Brescia, Ematologia

    Brescia

  • Fondazione del Piemonte per l'Oncologia - IRCCS, Ematologia

    Candiolo, Torino

  • Azienda Ospedaliera Universitaria Policlinico - S. Marco, UOC di Ematologia

    Catania

  • Azienda Ospedaliera Universitaria Careggi, Unità funzionale di Ematologia

    Florence

  • ASST Grande Ospedale Metropolitano Niguarda, SC Ematologia

    Milan

  • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Ematologia

    Milan

  • AOU Maggiore della Carità di Novara, SCDU Ematologia

    Novara

  • A.O. Ospedali Riuniti Villa Sofia-Cervello, Divisione di Ematologia

    Palermo

  • Azienda USL Piacenza, UOC Ematologia e Centro Trapianti

    Piacenza

  • Azienda Unitа Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova, Ematologia

    Reggio Emilia

  • Ospedale degli Infermi di Rimini, U.O. di Ematologia

    Rimini

  • Policlinico Umberto I - Università La Sapienza, Istituto Ematologia, Dipartimento di Medicina Traslazionale e di Precisione

    Roma

  • Ospedale Ca' Foncello, S.C di Ematologia

    Treviso

Other trials in Italy

Australia4 sites

  • Royal Adelaide Hospital

    Adelaide

  • Liverpool Hospital

    Liverpool

  • St. Vincent Hospital Melbourne

    Melbourne

  • Princess Alexandra Hospital

    Woolloongabba

Other trials in Australia

About this study

Official title: A Phase II Trial Investigating MOsunetuzumab and ZAnubrutinib (BGB-3111) in Relapsed/refracTory Follicular Lymphoma Patients (MOZART)

This is a Phase 2, multicenter study evaluating the efficacy and safety of mosunetuzumab + zanubrutinib (M+Z) used as salvage strategy in patients with R/R FL who have received at least one line of prior systemic therapy.

Read the detailed description

Eligible patients receive a pre-phase with oral zanubrutinib followed by an induction phase with mosunetuzumab combined with oral zanubrutinib.

Patients responsive to induction phase with M+Z (C1-12) and achieving at least SD will receive maintenance with zanubrutinib for additional 12 months (C13-24).

There will be an initial safety run-in (SRI) phase of 10 patients which will be closely monitored for the observed toxicities during the first three cycles of induction (from C1D1 to C3D28). No patients will be further enrolled until SRI analyses is completed.

If no unexpected toxicity has been observed, subsequent patients will be monitored only for patient informed consent, grade 3-5 toxicities and SAEs as well as remission status.

Safety data will be evaluated by an independent data safety monitoring board (DSMB) that will advise the principal investigators on the continuation of the study. Safety events will be analyzed and compared with the previously described safety profile of mosunetuzumab alone and other bispecific-containing regimens to exclude the risk of potential toxicity for all study participants.

Being tested
Mosunetuzumab in combination with Zanubrutinib
Keywords
Follicular lymphoma, Mosunetuzumab, Zanubrutinib, Relapsed/refractory follicular lymphoma
Medical subject headings
Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Mosunetuzumab in combination with ZanubrutinibDrug

    Also called LUNSUMIO in combination with BRUSINKA

    Combinations of Mosunetuzumab and Zanubrutinib as salvage strategy in patients with relapsed/refractory follicular lymphoma who have received at least one line of prior systemic therapy.

Study groups in NCT06492837
Study groupRoleWhat they receive
Mosunetuzumab in combination with ZanubrutinibExperimentalPre-phase: Zanubrutinib 320 mg daily by mouth (D-15 to D-1) Induction phase cycle 1 (Q21 days): * Zanubrutinib 320 mg daily by mouth (D1-21) * Mosunetuzumab 5 mg, SC (D1) * Mosunetuzumab 45 mg, SC (D8) * Mosunetuzumab 45 mg, SC (D15) Induction phase cycles 2-12 (Q28 days): * Zanubrutinib 320 mg daily by mouth (D1-28) * Mosunetuzumab 45 mg, SC (D1) Maintenance phase cycles 13-24 (Q28 days): Zanubrutinib 320 mg daily by mouth (D1-28) Tocilizumab will be administered as needed to manage cytokine release syndrome (CRS) events.
Receives: Drug: Mosunetuzumab in combination with Zanubrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Complete Response Rate (CRR)

    CRR at the end of the induction therapy

    Measured: 36 months

Secondary outcomes (10)

  1. Overall Response Rate (ORR), Partial Response (PR) Rate at the end of induction treatment (EOI)

    ORR and PR Rate at the end of induction treatment (EOI)

    Measured: 36 months

  2. Overall Response Rate (ORR), Partial Response (PR) Rate at the end of maintenance (EOT, end of treatment)

    ORR and PR Rate at the end of maintenance (EOT, end of treatment)

    Measured: 48 months

  3. Progression Free Survival (PFS)

    PFS defined as the time between the start of prephase and the first documentation of recurrence, progression or death from any cause.

    Measured: 108 months

  4. Overall Survival (OS)

    OS defined as the time between the start of prephase and death from any cause.

    Measured: 108 months

  5. Duration of Response (DOR)

    DOR defined as the time from the first documentation of tumor response (CR or PR) to disease progression or death from any cause

    Measured: 108 months

  6. Duration of Complete Response (DOCR)

    DOCR defined as the time from the first documentation of tumor complete response to disease progression or death from any cause.

    Measured: 108 months

  7. Time-to-next-treatment (TTNT)

    TTNT defined as the time between start of prephase and the initiation of the next line of therapy.

    Measured: 108 months

  8. Event free survival (EFS)

    EFS defined as the time from the start of prephase to disease progression, death, or discontinuation of treatment for any reason (e.g. toxicity, patient preference), or initiation of a new treatment without documented progression.

    Measured: 108 months

  9. Frequency and severity of Adverse Events (AEs) and Serious AEs (SAEs)

    AEs and SAEs classified as per the latest version of CTCAE.

    Measured: 108 months

  10. Frequency and severity of cytokine release syndrome (CRS) and Neurological Adverse Events (NAE)

    CRS and NAE will be evaluated according to the American Society for Transplantation and Cellular Therapy (ASTCT) Grading Criteria

    Measured: 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jul 2024
  2. Study start23 Oct 2024
  3. Primary completion15 Sep 2028 (estimated)
  4. Study completion15 Sep 2033 (estimated)

Resources

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
56 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06492837
Sponsor's protocol ID
FIL_MOZART
Acronym
FIL_MOZART
Status last verified
Sep 2026
First submitted
1 Jul 2024
Last updated
11 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers may contact the FIL board at segreteriadirezione@filinf.it to share invidual-level patients' clinical data analysed for this manuscript (for the avoidance of doubt, no identifiable data, such as name, address, hospital name, date of birth, or any other identifying data, will be shared and should not be requested).

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Mosunetuzumab in combination with Zanubrutinib in people with Follicular Lymphoma, run by Fondazione Italiana Linfomi - ETS at 20 sites in 2 countries.

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 28 inclusion and 36 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: under way, not looking for participants, as of the sponsor's last update on 11 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Italy, Australia. 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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete Response Rate (CRR) (time frame: 36 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06492837.

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 11 Sep 2026.

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