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

NCT05207670 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: ML43389
• Study Type: interventional
• Target: 320
• Locations: 1 country
• Sites: 39

Brief Summary

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 \[NHL\]).

Conditions

Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• Progression-free survival (PFS) rate at 24 months after the first study treatment (Cohorts A1, A2, and B)

  From the first study treatment to the first occurrence of disease progression, relapse, or death from any cause, whichever occurs first, as determined by the investigator according to Lugano Criteria 2014 (minimum 2 years)

• Objective response rate (ORR), defined as the proportion of participants with a complete metabolic response (CMR) or partial response (PR), as determined by the investigator according to the Lugano Criteria 2014 (Cohorts C, D, and E)

  Cycles 4, 8, 12 and 17 (cycle length=21 days)

Secondary Outcomes (10)

• Overall survival (OS) (all cohorts)

  From first study treatment to death from any cause (minimum 2 years for Cohorts A1 - C or 1 year for Cohorts D and E)

• ORR, defined as the proportion pf participants with a CMR or PR, as determined by the investigator according to the Lugano Criteria 2014 (Cohorts A1, A2, and B)

  Cycles 4, 8, 12 and 17 (cycle length=21 days)

• Time to response (TTR) (all cohorts)

  From first study treatment to the first occurrence of a documented objective response observed for patients who achieved a CMR or PR (minimum 2 years for Cohorts A1 - C or 1 year for Cohorts D and E)

• Duration of response (DOR) (all cohorts)

  From the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (minimum 2 years for Cohorts A1 - C or 1 year for Cohorts D and E)

• DOR for participants with best response of CMR (all cohorts)

  From documentation of CMR to the time of progression or death, whichever occurs first (minimum 2 years for Cohorts A1 - C or 1 year for Cohorts D and E)

Study Arms (5)

Cohort A

EXPERIMENTAL

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.

Drug: Mosunetuzumab (Cohorts A-C); Drug: Tocilizumab

Cohort B

EXPERIMENTAL

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.

Drug: Mosunetuzumab (Cohorts A-C); Drug: Tocilizumab

Cohort C

EXPERIMENTAL

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.

Drug: Mosunetuzumab (Cohorts A-C); Drug: Tocilizumab

Cohort D

EXPERIMENTAL

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.

Drug: Mosunetuzumab (Cohorts D-E); Drug: Tocilizumab

Cohort E

EXPERIMENTAL

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.

Drug: Mosunetuzumab (Cohorts D-E); Drug: Tocilizumab

Interventions

Mosunetuzumab (Cohorts A-C) DRUG

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

Cohort A; Cohort B; Cohort C

Mosunetuzumab (Cohorts D-E) DRUG

Participants will receive SC mosunetuzumab for up to 34 cycles

Cohort D; Cohort E

Tocilizumab DRUG

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

Cohort A; Cohort B; Cohort C; Cohort D; Cohort E

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (39)

Infirmary Cancer Care

Mobile, Alabama, 36607-3513, United States

Location

Alaska Oncology & Hematology, LLC

Anchorage, Alaska, 99508, United States

Location

Mayo Clinic Arizona

Phoenix, Arizona, 85054-4504, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Rocky Mountain Cancer Centers (Aurora) - USOR

Aurora, Colorado, 80012-5405, United States

Location

Medical Oncology Hematology Consultants

Newark, Delaware, 19713-2055, United States

Location

SCRI Florida Cancer Specialists South

Fort Myers, Florida, 33916, United States

Location

Mayo Clinic Jacksonville - PPDS

Jacksonville, Florida, 32224-1865, United States

Location

Cancer Specialists of North Florida - Jacksonville

Jacksonville, Florida, 32256, United States

Location

Florida Cancer Specialists - NORTH - SCRI - PPDS

St. Petersburg, Florida, 33705-1449, United States

Location

Florida Cancer Specialists - EAST - SCRI - PPDS

West Palm Beach, Florida, 33401-3406, United States

Location

Mission Blood and Cancer - MercyOne Cancer Center

Des Moines, Iowa, 50314-3030, United States

Location

University of Kansas Medical Center

Westwood, Kansas, 66205, United States

Location

Oncology Hematology Care - SCRI

Zachary, Louisiana, 70791, United States

Location

American Oncology Partners of Maryland, PA

Bethesda, Maryland, 20817-1915, United States

Location

Mayo Clinic - PPDS

Rochester, Minnesota, 55905, United States

Location

St. Vincent Frontier Cancer Center

Billings, Montana, 59101, United States

Location

Astera Cancer Care East Brunswick

East Brunswick, New Jersey, 08816, United States

Location

San Juan Oncology Associates

Farmington, New Mexico, 87401, United States

Location

New York Oncology Hematology, P.C.

Albany, New York, 12206, United States

Location

New York Cancer & Blood Specialists - New Hyde Park

New Hyde Park, New York, 11042-1116, United States

Location

NY Cancer & Blood Specialist

New York, New York, 10028-0506, United States

Location

North Shore Hematology Oncology Association PC

Shirley, New York, 11967, United States

Location

New York Cancer & Blood Specialists - Bronx

The Bronx, New York, 10469-5930, United States

Location

Oncology Hematology Care Inc - Cincinnati - USOR

Cincinnati, Ohio, 45236-2725, United States

Location

Oncology Associates of Oregon, P.C.

Eugene, Oregon, 97401, United States

Location

Providence Cancer Institute

Portland, Oregon, 97213-2933, United States

Location

Kaiser Foundation Hospitals

Portland, Oregon, 97227, United States

Location

McGlinn Cancer Institute at Reading Hospital

West Reading, Pennsylvania, 19611, United States

Location

Tennessee Oncology Chattanooga

Chattanooga, Tennessee, 37404-3230, United States

Location

Tennessee Oncology - Nashville

Nashville, Tennessee, 37203, United States

Location

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

Amarillo, Texas, 79124-2167, United States

Location

Texas Oncology-Austin Midtown

Austin, Texas, 78705, United States

Location

Texas Oncology (Worth) - USOR

Dallas, Texas, 75246-2008, United States

Location

Texas Oncology (Tyler) - USOR

Tyler, Texas, 75702-8363, United States

Location

Virginia Cancer Specialists - Gainsville

Gainesville, Virginia, 20155-3257, United States

Location

Kadlec Clinic Hematology and Oncology

Kennewick, Washington, 99336-7774, United States

Location

VA Puget Sound Health Care System - NAVREF - PPDS

Seattle, Washington, 98108-1532, United States

Location

MultiCare Deaconess Cancer and Blood Specialty Center

Spokane, Washington, 99218-8205, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2021
• First Posted: January 26, 2022
• Study Start: February 1, 2022
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2028
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (39)