A Study Evaluating the Safety, Efficacy, and Pharmacokinetics of Mosunetuzumab Monotherapy in Participants With Select B-Cell Malignancies

NCT ID: NCT05207670

Last Updated: 2025-12-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

320 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-02-01

Study Completion Date

2028-07-31

Brief Summary

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This study will evaluate the efficacy, safety, and pharmacokinetics of mosunetuzumab subcutaneous (SC) formulation in participants with selected B-cell malignancies (types of non-Hodgkin's lymphoma \[NHL\]).

Detailed Description

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Conditions

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Non-Hodgkin Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort A

Participants with high tumor burden with untreated follicular lymphoma (FL) will receive SC mosunetuzumab monotherapy for up to 17 cycles or until radiographic disease progression, study discontinuation, or death, whichever occurs first. Participants that achieve complete or partial metabolic response will have the option of receiving maintenance therapy with mosunetuzumab every 8 weeks for 1 year.

Group Type EXPERIMENTAL

Tocilizumab

Intervention Type DRUG

Participants can be treated with tocilizumab if they present with CRS after receiving mosunetuzumab

Mosunetuzumab (Cohorts A-C)

Intervention Type DRUG

Participants will receive SC mosunetuzumab for up to 17 cycles and for optional maintenance (Cohort A only)

Cohort B

Elderly participants with untreated diffuse large B-cell lymphoma (DLBCL) will receive SC mosunetuzumab monotherapy for up to 17 cycles or until radiographic disease progression, study discontinuation, or death, whichever occurs first.

Group Type EXPERIMENTAL

Tocilizumab

Intervention Type DRUG

Participants can be treated with tocilizumab if they present with CRS after receiving mosunetuzumab

Mosunetuzumab (Cohorts A-C)

Intervention Type DRUG

Participants will receive SC mosunetuzumab for up to 17 cycles and for optional maintenance (Cohort A only)

Cohort C

Participants with untreated marginal zone lymphoma (MZL) will receive SC mosunetuzumab monotherapy for up to 17 cycles or until radiographic disease progression, study discontinuation, or death, whichever occurs first.

Group Type EXPERIMENTAL

Tocilizumab

Intervention Type DRUG

Participants can be treated with tocilizumab if they present with CRS after receiving mosunetuzumab

Mosunetuzumab (Cohorts A-C)

Intervention Type DRUG

Participants will receive SC mosunetuzumab for up to 17 cycles and for optional maintenance (Cohort A only)

Cohort D

Participants with relapsed or refractory (R/R) mantle cell lymphoma (MCL) will receive SC mosunetuzumab monotherapy for up to 34 cycles or until radiographic disease progression, study discontinuation, or death, whichever occurs first.

Group Type EXPERIMENTAL

Tocilizumab

Intervention Type DRUG

Participants can be treated with tocilizumab if they present with CRS after receiving mosunetuzumab

Mosunetuzumab (Cohorts D-E)

Intervention Type DRUG

Participants will receive SC mosunetuzumab for up to 34 cycles

Cohort E

Participants with R/R Richter's transformation (RT), or R/R transformed follicular lymphoma (tFL) will receive SC mosunetuzumab monotherapy for up to 34 cycles or until radiographic disease progression, study discontinuation, or death, whichever occurs first.

Group Type EXPERIMENTAL

Tocilizumab

Intervention Type DRUG

Participants can be treated with tocilizumab if they present with CRS after receiving mosunetuzumab

Mosunetuzumab (Cohorts D-E)

Intervention Type DRUG

Participants will receive SC mosunetuzumab for up to 34 cycles

Interventions

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Tocilizumab

Participants can be treated with tocilizumab if they present with CRS after receiving mosunetuzumab

Intervention Type DRUG

Mosunetuzumab (Cohorts A-C)

Participants will receive SC mosunetuzumab for up to 17 cycles and for optional maintenance (Cohort A only)

Intervention Type DRUG

Mosunetuzumab (Cohorts D-E)

Participants will receive SC mosunetuzumab for up to 34 cycles

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* At least one bi-dimensionally measurable nodal lesion, defined as \>1.5 cm in its longest dimension, or one bi-dimensionally measurable lesion, defined as \>1.0 cm in its longest diameter by computed tomography (CT) scan, positivie emission tomography - computed tomography (PET- CT), or magnetic resonance imaging (MRI)
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
* Adequate hematologic function
* No active infection
* Negative HIV test at screening, with the following exception: Individuals with a positive HIV test at screening are eligible provided they are stable on antiretroviral therapy for at least 4 weeks, have a CD4 count ≥ 200/µL, have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months
* For women of childbearing potential (except those in Cohort B): agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating eggs, as defined by the protocol
* For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined by the protocol


* Previously untreated FL with indication to start systemic therapy
* Adequate renal function


* Aged ≥ 80 years at the time of signing informed consent form (ICF), or aged 65-79 years and considered ineligible for chemoimmunotherapy (R-CHOP) with at least one of the following: Impairment in ≥ 2 Activities of Daily Living (ADL); impairment in ≥ 2 Instrumental Activities of Daily Living (IADL); or Cumulative Illness Rating Scale-Geriatric (CIRS-G) score of ≥ 1 comorbidity with a severity of 3-4 or a score of 2 in ≥ 8 comorbidities
* Histologically confirmed DLBCL according to WHO 2016 classification expected to express the CD20 antigen (Swerdlow et al. 2016)
* Previously untreated DLBCL with indication to start systemic therapy and are not eligible for curative therapy
* High-grade B-cell lymphomas, not otherwise specified (HGBL NOS) and HGBL with MYC and B-cell lymphoma (BCL)-2 and/or BCL-6 rearrangements
* Adequate end-organ function


* Histologically conformed MZL (splenic, nodal, and extra-nodal)
* Previously untreated MZL with indication to start systemic therapy
* Helicobacter pylori-positive disease that has remained stable, progressed, or relapsed following antibiotic therapy and requires therapy, as assessed by the investigator (for cases of gastric/MALT MZL)
* Adequate renal function


* Histologically confirmed MCL
* Relapsed after or failed to respond to at least one prior treatment regimen containing a Bruton's tyrosine kinase (BTK) inhibitor
* Adequate renal function
* Adverse events from prior anti-cancer therapy resolved to Grade \</= 1


* Histologically confirmed RT or tFL
* Relapsed after or failed to respond to at least one prior systemic treatment regimen for RT or tFL
* Adequate renal function
* Absolute lymphocyte count \</= 5000 uL
* Adverse events from prior anti-cancer therapy resolved to Grade \</= 1

Exclusion Criteria

* Current or past history of central nervous system (CNS) lymphoma or leptomeningeal infiltration
* Prior treatment with mosunetuzumab
* History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
* History of confirmed progressive multifocal leukoencephalopathy (PML)
* Known active SARS-CoV-2 infection
* Known or suspected chronic active Epstein-Barr virus (CAEBV) infection
* Patients with history of macrophage activation syndrome (MAS)/hemophagocytic lymphohistiocytosis (HLH)
* Positive test results for chronic hepatitis B infection (HBV), acute or chronic hepatitis C virus (HCV) infection, or known or suspected HIV 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 allogenic stem cell transplant
* Treatment with CAR-T therapy within 30 days prior to C1D1
* History of autoimmune disease, including, but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
* Received systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) with the exception of corticosteroid treatment \</= 10 mg/day prednisone or equivalent within 2 weeks prior to the first dose of mosunetuzumab
* Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
* History of other malignancy that could affect compliance with the protocol or interpretation of results
* Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results or that could increase risk to the patient
* Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks before C1D1
* Clinically significant history of liver disease, including viral or other hepatitis, or cirrhosis
* Recent major surgery within 4 weeks before the start of C1D1, other than superficial lymph node biopsies for diagnosis
* Prior treatment with radiotherapy within 2 weeks prior to C1D1
* Adverse events from prior anti-cancer therapy not resolved to Grade \</= 1 (with the exception of alopecia, anorexia, nausea, vomiting, and fatigue)
* Significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, congestive heart failure, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina) or significant pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
* History of severe allergic or anaphylactic reaction to humanized, chimeric or murine monoclonal antibodies (MAbs)
* Contraindication to tocilizumab
* Prior anti-lymphoma treatment with monoclonal antibodies, radioimmunoconjugates, or antibody-drug conjugates within 4 weeks before first mosunetuzumab administration


* Prior anti-lymphoma treatment with any monoclonal antibody (e.g., anti-CD20), radioimmunoconjugate, or antibody-drug conjugate therapy within 4 weeks before first mosunetuzumab administration
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Infirmary Cancer Care

Mobile, Alabama, United States

Site Status

Alaska Oncology & Hematology, LLC

Anchorage, Alaska, United States

Site Status

Mayo Clinic Arizona

Phoenix, Arizona, United States

Site Status

City of Hope

Duarte, California, United States

Site Status

Rocky Mountain Cancer Centers (Aurora) - USOR

Aurora, Colorado, United States

Site Status

Medical Oncology Hematology Consultants

Newark, Delaware, United States

Site Status

SCRI Florida Cancer Specialists South

Fort Myers, Florida, United States

Site Status

Mayo Clinic Jacksonville - PPDS

Jacksonville, Florida, United States

Site Status

Cancer Specialists of North Florida - Jacksonville

Jacksonville, Florida, United States

Site Status

Florida Cancer Specialists - NORTH - SCRI - PPDS

St. Petersburg, Florida, United States

Site Status

Florida Cancer Specialists - EAST - SCRI - PPDS

West Palm Beach, Florida, United States

Site Status

Mission Blood and Cancer - MercyOne Cancer Center

Des Moines, Iowa, United States

Site Status

University of Kansas Medical Center

Westwood, Kansas, United States

Site Status

Oncology Hematology Care - SCRI

Zachary, Louisiana, United States

Site Status

American Oncology Partners of Maryland, PA

Bethesda, Maryland, United States

Site Status

Mayo Clinic - PPDS

Rochester, Minnesota, United States

Site Status

St. Vincent Frontier Cancer Center

Billings, Montana, United States

Site Status

Astera Cancer Care East Brunswick

East Brunswick, New Jersey, United States

Site Status

San Juan Oncology Associates

Farmington, New Mexico, United States

Site Status

New York Oncology Hematology, P.C.

Albany, New York, United States

Site Status

New York Cancer & Blood Specialists - New Hyde Park

New Hyde Park, New York, United States

Site Status

NY Cancer & Blood Specialist

New York, New York, United States

Site Status

North Shore Hematology Oncology Association PC

Shirley, New York, United States

Site Status

New York Cancer & Blood Specialists - Bronx

The Bronx, New York, United States

Site Status

Oncology Hematology Care Inc - Cincinnati - USOR

Cincinnati, Ohio, United States

Site Status

Oncology Associates of Oregon, P.C.

Eugene, Oregon, United States

Site Status

Providence Cancer Institute

Portland, Oregon, United States

Site Status

Kaiser Foundation Hospitals

Portland, Oregon, United States

Site Status

McGlinn Cancer Institute at Reading Hospital

West Reading, Pennsylvania, United States

Site Status

Tennessee Oncology Chattanooga

Chattanooga, Tennessee, United States

Site Status

Tennessee Oncology - Nashville

Nashville, Tennessee, United States

Site Status

Texas Oncology (Amarillo) - USOR - 1826 Point West Pkwy

Amarillo, Texas, United States

Site Status

Texas Oncology-Austin Midtown

Austin, Texas, United States

Site Status

Texas Oncology (Worth) - USOR

Dallas, Texas, United States

Site Status

Texas Oncology (Tyler) - USOR

Tyler, Texas, United States

Site Status

Virginia Cancer Specialists - Gainsville

Gainesville, Virginia, United States

Site Status

Kadlec Clinic Hematology and Oncology

Kennewick, Washington, United States

Site Status

VA Puget Sound Health Care System - NAVREF - PPDS

Seattle, Washington, United States

Site Status

MultiCare Deaconess Cancer and Blood Specialty Center

Spokane, Washington, United States

Site Status

Countries

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United States

Other Identifiers

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ML43389

Identifier Type: -

Identifier Source: org_study_id

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