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

Non-Hodgkin Lymphoma Clinical Trial

— MorningSun  

Official title:

An Open-Label, Multicenter, Phase II Trial Evaluating the Safety, Efficacy, and Pharmacokinetics of Subcutaneous Mosunetuzumab Monotherapy in Patients With Select B-Cell Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05207670
• Other study ID #: ML43389
• Status: Recruiting
• Phase: Phase 2
• Start date: February 1, 2022
• Est. completion date: July 31, 2028

Study information

• Verified date: March 2024
• Source: Genentech, Inc.
• Contact: Reference Study ID Number: ML43389 https://forpatients.roche.com
• Phone: 888-662-6728
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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]).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 345
• Est. completion date: July 31, 2028
• Est. primary completion date: July 31, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 Inclusion Criteria Specific to Cohorts A1 and A2
• Previously untreated FL with indication to start systemic therapy
• Adequate renal function Inclusion Criteria Specific to Cohort B
• 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 Inclusion Criteria Specific to Cohort C
• 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 Inclusion Criteria Specific to Cohort D
• 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 Inclusion Criteria Specific to Cohort E
• 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 Exclusion Criteria Specific to Cohorts D and E
• 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

Related Conditions & MeSH terms

• Lymphoma, Non-Hodgkin
• Non-Hodgkin Lymphoma

Intervention

Drug:
• Mosunetuzumab (Cohorts A-C)
Participants will receive SC mosunetuzumab for up to 17 cycles and for optional maintenance (Cohort A only)
• Mosunetuzumab (Cohorts D-E)
Participants will receive SC mosunetuzumab for up to 34 cycles
• Tocilizumab
Participants can be treated with tocilizumab if they present with CRS after receiving mosunetuzumab

Locations

Country	Name	City	State
Puerto Rico	Auxilio Mutuo Cancer Center	San Juan
United States	New York Oncology Hematology, P.C.	Albany	New York
United States	Texas Oncology (Amarillo) - USOR - 1826 Point West Pkwy	Amarillo	Texas
United States	Alaska Oncology & Hematology, LLC	Anchorage	Alaska
United States	Rocky Mountain Cancer Centers (Aurora) - USOR	Aurora	Colorado
United States	Texas Oncology-Austin Midtown	Austin	Texas
United States	Hematology Oncology Clinic	Baton Rouge	Louisiana
United States	American Oncology Partners of Maryland, PA	Bethesda	Maryland
United States	St. Vincent Frontier Cancer Center	Billings	Montana
United States	St Luke?s Cancer Institute	Boise	Idaho
United States	New York Cancer & Blood Specialists - Bronx	Bronx	New York
United States	SCRI Tennessee Oncology Chattanooga	Chattanooga	Tennessee
United States	Oncology Hematology Care Inc - Cincinnati - USOR	Cincinnati	Ohio
United States	Texas Oncology (Worth) - USOR	Dallas	Texas
United States	Mission Blood and Cancer - MercyOne Cancer Center	Des Moines	Iowa
United States	City of Hope	Duarte	California
United States	Astera Cancer Care East Brunswick	East Brunswick	New Jersey
United States	Englewood Hospital and Medical Center	Englewood	New Jersey
United States	San Juan Oncology Associates	Farmington	New Mexico
United States	Summit Medical Group; MD Anderson Cancer Center	Florham Park	New Jersey
United States	SCRI Florida Cancer Specialists South	Fort Myers	Florida
United States	Tennessee Oncology PLLC - Franklin	Franklin	Tennessee
United States	Virginia Cancer Specialists - Gainsville	Gainesville	Virginia
United States	Asante Spears Cancer Center	Grants Pass	Oregon
United States	Benefis Hospital Sletten Cancer Institute	Great Falls	Montana
United States	Marin Cancer Care Inc	Greenbrae	California
United States	Marin General Hospital	Greenbrae	California
United States	Prisma Health Cancer Institute; Research Pharmacy	Greenville	South Carolina
United States	Ascension Health Van Elsander Cancer Center	Grosse Pointe Woods	Michigan
United States	Cancer Specialists of North Florida (AC Skinner Bldg 100)	Jacksonville	Florida
United States	Mayo Clinic Jacksonville - PPDS	Jacksonville	Florida
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Lancaster General Hospital	Lancaster	Pennsylvania
United States	Asante Heimann Cancer Center - Medford	Medford	Oregon
United States	Asante Rogue Regional Medical Center	Medford	Oregon
United States	Infirmary Cancer Care	Mobile	Alabama
United States	Atlantic Hematology Oncology	Morristown	New Jersey
United States	New York Cancer & Blood Specialists - New Hyde Park	New Hyde Park	New York
United States	NY Cancer & Blood Specialist	New York	New York
United States	Medical Oncology Hematology Consultants	Newark	Delaware
United States	Hightower Clinical	Oklahoma City	Oklahoma
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	Kaiser Foundation Hospitals	Portland	Oregon
United States	Providence Cancer Center	Portland	Oregon
United States	Mayo Clinic - PPDS	Rochester	Minnesota
United States	Florida Cancer Specialists - NORTH - SCRI - PPDS	Saint Petersburg	Florida
United States	Swedish Medical Center	Seattle	Washington
United States	VA Puget Sound Health Care System - NAVREF - PPDS	Seattle	Washington
United States	North Shore Hematology Oncology Association PC	Shirley	New York
United States	Cancer Care Northwest	Spokane	Washington
United States	MultiCare Deaconess Cancer and Blood Specialty Center	Spokane	Washington
United States	Oncology Associates of Oregon, P.C.; Willamette Valley Cancer Institute	Springfield	Oregon
United States	Overlook Medical Center	Summit	New Jersey
United States	Northwest Medical Specialties	Tacoma	Washington
United States	Texas Oncology (Tyler) - USOR	Tyler	Texas
United States	Florida Cancer Specialists - EAST - SCRI - PPDS	West Palm Beach	Florida
United States	McGlinn Cancer Institute at Reading Hospital	West Reading	Pennsylvania
United States	University of Kansas Medical Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Duration of complete response (DoCR) (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)
Secondary	Time to next treatment (TTNT) (all cohorts)		From first study treatment to the start of new anti-lymphoma therapy (NALT) or death (minimum 2 years for Cohorts A1-C or 1 year for Cohorts D and E)
Secondary	PFS (all cohorts)		From first study treatment to first occurrence of disease progression, relapse, or death from any cause, whichever occurs first, as determined by investigator according to Lugano Criteria 2014 (min. 2 years for Cohorts A1 - C or 1 year for Cohorts D, E)
Secondary	Percentage of participants with adverse events (AEs) (all cohorts)		Minimum 2 years for Cohorts A-C or 1 year for Cohorts D and E
Secondary	Serum concentration of mosunetuzumab (all cohorts)		Cycle 1 Days 1,2,8,15; thereafter Day 1 of Cycles 2,3,4,6,8,12,16 (cycle length = 21 days)