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

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ClinicalTrials.gov Identifier: NCT05207670
Recruitment Status : Recruiting
First Posted : January 26, 2022
Last Update Posted : September 14, 2022
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

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]).

Condition or disease Intervention/treatment Phase
Non-Hodgkin Lymphoma Drug: Mosunetuzumab (Cohorts A-C) Drug: Mosunetuzumab (Cohorts D-E) Drug: Tocilizumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 275 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 1, 2022
Estimated Primary Completion Date : December 17, 2026
Estimated Study Completion Date : December 17, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Cohort A
Participants 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.
Drug: Mosunetuzumab (Cohorts A-C)
Participants will receive SC mosunetuzumab for up to 17 cycles

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

Experimental: 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.
Drug: Mosunetuzumab (Cohorts A-C)
Participants will receive SC mosunetuzumab for up to 17 cycles

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

Experimental: 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.
Drug: Mosunetuzumab (Cohorts A-C)
Participants will receive SC mosunetuzumab for up to 17 cycles

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

Experimental: 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.
Drug: Mosunetuzumab (Cohorts D-E)
Participants will receive SC mosunetuzumab for up to 34 cycles

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

Experimental: 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.
Drug: Mosunetuzumab (Cohorts D-E)
Participants will receive SC mosunetuzumab for up to 34 cycles

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




Primary Outcome Measures :
  1. Progression-free survival (PFS) rate at 24 months after the first study treatment (Cohorts A1, A2, and B) [ Time Frame: 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) ]
  2. 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) [ Time Frame: Cycles 4, 8, 12 and 17 (cycle length=21 days) ]

Secondary Outcome Measures :
  1. Overall survival (OS) (all cohorts) [ Time Frame: From first study treatment to death from any cause (minimum 2 years for Cohorts A1 - C or 1 year for Cohorts D and E) ]
  2. 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) [ Time Frame: Cycles 4, 8, 12 and 17 (cycle length=21 days) ]
  3. Time to response (TTR) (all cohorts) [ Time Frame: 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) ]
  4. Duration of response (DOR) (all cohorts) [ Time Frame: 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) ]
  5. DOR for participants with best response of CMR (all cohorts) [ Time Frame: 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) ]
  6. Duration of complete response (DoCR) (all cohorts) [ Time Frame: 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) ]
  7. PFS [ Time Frame: 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) ]
  8. Percentage of participants with adverse events (AEs) (all cohorts) [ Time Frame: Minimum 2 years for Cohorts A-C or 1 year for Cohorts D and E ]
  9. Serum concentration of mosunetuzumab (all cohorts) [ Time Frame: Cycle 1 Days 1,2,8,15; thereafter Day 1 of Cycles 2,3,4,6,8,12,16 (cycle length = 21 days) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  • 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 at least 80 years at the time of signing informed consent form (ICF)
  • 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
  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05207670


Contacts
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Contact: Reference Study ID Number: ML43389 https://forpatients.roche.com/ 888-662-6728 global-roche-genentech-trials@gene.com

Locations
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Sponsors and Collaborators
Genentech, Inc.
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT05207670    
Other Study ID Numbers: ML43389
First Posted: January 26, 2022    Key Record Dates
Last Update Posted: September 14, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma, Non-Hodgkin
Neoplasms
Lymphoma
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases