Study With Mosunetuzumab and Zanubrutinib in R/R Follicular Lymphoma Patients (FIL_MOZART)

January 26, 2026 updated by: Fondazione Italiana Linfomi - ETS

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

56

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
  • Italy
      • Alessandria, Italy
        • Recruiting
        • AOU SS. Antonio e Biagio e Cesare Arrigo, SCDU Ematologia
        • Contact:
        • Principal Investigator:
          • Marco Ladetto, Prof
      • Ancona, Italy
      • Avellino, Italy
        • Recruiting
        • Azienda Ospedaliera S.Giuseppe Moscati, S.C. Ematologia e Trapianto emopoietico
        • Contact:
        • Principal Investigator:
          • Sonya De Lorenzo, MD
      • Bari, Italy
        • Recruiting
        • IRCCS Istituto Tumori Giovanni Paolo II, U.O.C Ematologia
        • Contact:
        • Principal Investigator:
          • Attilio Guarini, MD
      • Bologna, Italy
        • Recruiting
        • Policlinico S.Orsola-Malpighi, Istituto di Ematologia "Seragnoli"
        • Contact:
        • Principal Investigator:
          • Pier Luigi Zinzani, Prof
      • Brescia, Italy
        • Recruiting
        • ASST Spedali Civili di Brescia, Ematologia
        • Principal Investigator:
          • Antonella Anastasia, MD
        • Contact:
      • Catania, Italy
        • Recruiting
        • Azienda Ospedaliera Universitaria Policlinico - S. Marco, UOC di Ematologia
        • Contact:
        • Principal Investigator:
          • Annalisa Chiarenza, MD
      • Florence, Italy
        • Recruiting
        • Azienda Ospedaliera Universitaria Careggi, Unità funzionale di Ematologia
        • Principal Investigator:
          • Luca Nassi, MD
        • Contact:
      • Milan, Italy
      • Milan, Italy
        • Recruiting
        • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Ematologia
        • Contact:
        • Principal Investigator:
          • Paolo Corradini, Prof
      • Monza, Italy
      • Novara, Italy
        • Recruiting
        • AOU Maggiore della Carità di Novara, SCDU Ematologia
        • Principal Investigator:
          • Gloria Margiotta Casaluci, MD
        • Contact:
      • Palermo, Italy
        • Recruiting
        • A.O. Ospedali Riuniti Villa Sofia-Cervello, Divisione di Ematologia
        • Contact:
        • Principal Investigator:
          • Caterina Patti, MD
      • Piacenza, Italy
        • Recruiting
        • Azienda USL Piacenza, UOC Ematologia e Centro Trapianti
        • Contact:
        • Principal Investigator:
          • Annalisa Arcari, MD
      • Reggio Emilia, Italy
        • Recruiting
        • Azienda Unitа Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova, Ematologia
        • Contact:
        • Principal Investigator:
          • Stefano Luminari, Prof
      • Rimini, Italy
        • Recruiting
        • Ospedale degli Infermi di Rimini, U.O. di Ematologia
        • Contact:
        • Principal Investigator:
          • Melania Celli, MD
      • Roma, Italy
        • Recruiting
        • Policlinico Umberto I - Università La Sapienza, Istituto Ematologia, Dipartimento di Medicina Traslazionale e di Precisione
        • Principal Investigator:
          • Ilaria Del Giudice, MD
        • Contact:
      • Torino, Italy
        • Not yet recruiting
        • A.O.U. Città della Salute e della Scienza di Torino, S.C.Ematologia
        • Contact:
        • Principal Investigator:
          • Carola Boccomini, MD
      • Treviso, Italy
        • Recruiting
        • Ospedale Ca' Foncello, S.C di Ematologia
        • Contact:
        • Principal Investigator:
          • Piero Maria Stefani, MD
    • Torino
      • Candiolo, Torino, Italy
        • Recruiting
        • Fondazione del Piemonte per l'Oncologia - IRCCS, Ematologia
        • Principal Investigator:
          • Francesca Bonello, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 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.
  2. 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.
  3. Age ≥18 years.
  4. Relapsed or refractory disease. Histologic confirmation of FL relapse is not mandatory but is highly recommended.
  5. 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).
  6. FL requiring systemic therapy assessed by investigator based on tumor size and/or Groupe d'Etude des Lymphomes Folliculaires criteria.
  7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.
  8. Availability of histological material for centralized revision. Central pathology review is not mandatory for start of treatment.
  9. 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.

  10. 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.
  11. Adequate renal function defined as creatinine clearance ≥ 40 mL/min (Cockcroft-Gault formula, normalized to 1.72 m2).

  12. 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).
  13. Subject must be able to adhere to the study visit schedule and other protocol requirements.
  14. Subject must be able to swallow capsules or tablets.

  15. 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.
  16. Women of childbearing potential must have a negative pregnancy test at screening.
  17. 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.

  18. 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).

Exclusion Criteria:

  1. Histological diagnosis different from cFL (Campo E., 2022).
  2. 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).
  3. Patients with stage I or II (limited stage) suitable for RT alone treatment.
  4. Prior exposure to a Bruton's tyrosine kinase (BTK) inhibitor (BTKi).
  5. Prior exposure to an anti-CD20xCD3 bispecific antibody (bsAbs).
  6. Need of anticoagulation with warfarin or equivalent vitamin K antagonists (e.g. phenprocoumon). Requires ongoing treatment with a strong CYP3A inducer.
  7. Evidence or any history of transformation from FL to other aggressive histology.
  8. Prior allogeneic hematopoietic stem cell transplantation.
  9. 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
  10. Life expectancy < 6 months.
  11. History of progressive multifocal leukoencephalopathy (PML).
  12. History of hemophagocytic lymphohistiocytosis (HLH) or chronic active EBV.
  13. 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.
  14. 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.
  15. 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).
  16. Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 90 days prior to first therapy administration.

  17. Any uncontrolled or significant cardiovascular disease [NYHA class ≥2].

    1. Myocardial infarction within 6 months before screening
    2. Unstable angina within 3 months before screening
    3. New York Heart Association class III or IV congestive heart failure
    4. History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes)
  18. 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.
  19. 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.

  20. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:

    1. Uncontrolled and/or active systemic infection (viral, bacterial or fungal), including active ongoing infection from SARS-CoV-2;
    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;
  21. HIV seropositivity.
  22. Pregnant or lactating women. If female, the patient is pregnant or breast-feeding.
  23. Severe or debilitating pulmonary disease.
  24. 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.
  25. 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.
  26. Major surgery within 4 weeks of the first dose of study drug.
  27. 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.
  28. Ongoing alcohol or drug addiction or any psychiatric condition(s) which would compromise ability to comply with study procedures.
  29. Hypersensitivity to zanubrutinib or mosunetuzumab or any of the other ingredients of the applicable study drugs.
  30. Active and/or ongoing autoimmune anemia and/or autoimmune thrombocytopenia (eg, idiopathic thrombocytopenia purpura).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Mosunetuzumab in combination with Zanubrutinib

Pre-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.
Drug: Mosunetuzumab in combination with Zanubrutinib
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.
Other Names:
  • LUNSUMIO in combination with BRUSINKA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete Response Rate (CRR)
Time Frame: 36 months
CRR at the end of the induction therapy
36 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR), Partial Response (PR) Rate at the end of induction treatment (EOI)
Time Frame: 36 months
ORR and PR Rate at the end of induction treatment (EOI)
36 months
Overall Response Rate (ORR), Partial Response (PR) Rate at the end of maintenance (EOT, end of treatment)
Time Frame: 48 months
ORR and PR Rate at the end of maintenance (EOT, end of treatment)
48 months
Progression Free Survival (PFS)
Time Frame: 108 months
PFS defined as the time between the start of prephase and the first documentation of recurrence, progression or death from any cause.
108 months
Overall Survival (OS)
Time Frame: 108 months
OS defined as the time between the start of prephase and death from any cause.
108 months
Duration of Response (DOR)
Time Frame: 108 months
DOR defined as the time from the first documentation of tumor response (CR or PR) to disease progression or death from any cause
108 months
Duration of Complete Response (DOCR)
Time Frame: 108 months
DOCR defined as the time from the first documentation of tumor complete response to disease progression or death from any cause.
108 months
Time-to-next-treatment (TTNT)
Time Frame: 108 months
TTNT defined as the time between start of prephase and the initiation of the next line of therapy.
108 months
Event free survival (EFS)
Time Frame: 108 months
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.
108 months
Frequency and severity of Adverse Events (AEs) and Serious AEs (SAEs)
Time Frame: 108 months
AEs and SAEs classified as per the latest version of CTCAE.
108 months
Frequency and severity of cytokine release syndrome (CRS) and Neurological Adverse Events (NAE)
Time Frame: 36 months
CRS and NAE will be evaluated according to the American Society for Transplantation and Cellular Therapy (ASTCT) Grading Criteria
36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione Italiana Linfomi - ETS

Investigators

  • Principal Investigator: Marco Ladetto, Prof, Department of Translational Medicine of the Università degli Studi del Piemonte Orientale, Novara, Italy. AO SS Antonio e Biagio e C. Arrigo, Alessandria, Italy.
  • Principal Investigator: Stefano Luminari, Prof, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy. Hematology Unit of AUSL-IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, Reggio Emilia, Italy.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 23, 2024

Primary Completion (Estimated)

September 15, 2028

Study Completion (Estimated)

September 15, 2033

Study Registration Dates

First Submitted

July 1, 2024

First Submitted That Met QC Criteria

July 1, 2024

First Posted (Actual)

July 9, 2024

Study Record Updates

Last Update Posted (Actual)

January 28, 2026

Last Update Submitted That Met QC Criteria

January 26, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FIL_MOZART

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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).

IPD Sharing Time Frame

In compliance with the domestic ethics guideline and applicable legislation, invidual deindentified patients' data underlying the results reported in the publication article (including study protocol, statistical analysis plan and data coding) can be shared until 5 years after the publication of the article.

IPD Sharing Access Criteria

For each data sharing request, it is essential that a proforma (available on request) is completed that describes the general purpose, specific aims, data items requested, analysis plan and acknowledgment of the trial management team. Requests will be reviewed based on scientific merit and ethical principles. Requestors who are granted access to the data will be required to complete a data sharing agreement that will be signed by the requester and FIL.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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