A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Mosunetuzumab + Lenalidomide (+Len), and the Safety, Tolerability, and Pharmacokinetics of SC Versus IV Mosunetuzumab + Len in Participants With Follicular Lymphoma

NCT04246086 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: CO419422019-004291-20
• Study Type: interventional
• Target: 237
• Locations: 5 countries
• Sites: 26

Brief Summary

This study will evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of mosunetuzumab (Mosun) + lenalidomide (Len) (Mosun + Len) in participants with follicular lymphoma (FL). This study will also compare the pharmacokinetics, pharmacodynamics, safety, efficacy, and immunogenicity of IV mosunetuzumab + len vs subcutaneous (SC) mosunetuzumab + len.

Conditions

Follicular Lymphoma

Outcome Measures

Primary Outcomes (5)

• Dose-Limiting Toxicities (DLTs)

  Cycle 2 Days 1-28 (cycle length = 28 days)

• Percentage of Participants with Adverse Events

  From baseline to 90 days after the last dose of study drug

• Cumulative Area under the Curve over Cycles 1-3 (AUC1-3) of Mosunetuzumab

  Day 1 - Day 78

• Serum Trough Concentration at Steady State Approximated by Cycle 4 (Ctrough, c4) of Mosunetuzumab

  Day 106

• Overall Response Rate (ORR) as Determined by the Independent Review Committee (IRC)

  Up to the end of Cycle 12 (cycle length = 28 days)

Secondary Outcomes (15)

• Complete Response Rate (CRR) as determined by the investigator (non-randomized stage)

  Up to the end of Cycle 12 (cycle length = 28 days)

• CRR as determined by Independent Review Committee (IRC) (randomized stage)

  Up to the end of Cycle 12 (cycle length = 28 days)

• Objective Response Rate (ORR) as determined by the investigator (non-randomized stage)

  Up to the end of Cycle 12 (cycle length = 28 days)

• ORR as determined by IRC (randomized stage)

  Up to the end of Cycle 12 (cycle length = 28 days)

• Duration of Response (DOR) as determined by the investigator (non-randomized stage)

  From the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, up to the end of Cycle 8 (cycle length = 28 days)

Study Arms (4)

Intravenous (IV) Mosunetuzumab + Lenalidomide (Non-randomized)

EXPERIMENTAL

Participants will receive treatment with IV mosunetuzumab plus lenalidomide for 12 cycles total (cycle length = 21 days for Cycle 1, 28 days from Cycle 2 onward)

Drug: Mosunetuzumab (IV); Drug: Tocilizumab; Drug: Lenalidomide

Subcutaneous (SC) Mosunetuzumab + Lenalidomide (Non-randomized)

EXPERIMENTAL

Participants will receive treatment with SC mosunetuzumab plus lenalidomide for 12 cycles total (cycle length = 21 days for Cycle 1, 28 days from Cycle 2 onward). Participants that have received complete metabolic response (CMR) or partial metabolic response (PMR) after 12 cycles of induction therapy with mosunetuzumab + lenalidomide will receive maintenance therapy with SC mosunetuzumab every 8 weeks (Q8W) for an additional 9 cycles.

Drug: Tocilizumab; Drug: Lenalidomide

Arm A: IV Mosunetuzumab + Len (Randomized)

EXPERIMENTAL

Participants will receive treatment with IV mosunetuzumab plus lenalidomide for 12 cycles total (cycle length = 21 days for Cycle 1, 28 days from Cycle 2 onward)

Drug: Mosunetuzumab (IV); Drug: Lenalidomide

Arm B: SC Mosunetuzumab + Len (Randomized)

EXPERIMENTAL

Participants will receive treatment with SC mosunetuzumab plus lenalidomide for 12 cycles total (cycle length = 21 days for Cycle 1, 28 days from Cycle 2 onward)

Drug: Lenalidomide; Drug: Mosunetuzumab (SC)

Interventions

Mosunetuzumab (SC) DRUG

Participants will receive SC mosunetuzumab as defined by the study protocol

Also known as: RO7030816

Arm B: SC Mosunetuzumab + Len (Randomized)

Mosunetuzumab (IV) DRUG

Participants will receive IV mosunetuzumab as defined by the study protocol

Also known as: RO7030816

Arm A: IV Mosunetuzumab + Len (Randomized); Intravenous (IV) Mosunetuzumab + Lenalidomide (Non-randomized)

Tocilizumab DRUG

Participants will receive IV tocilizumab as needed for adverse reactions as defined by the study protocol

Also known as: RO4877533

Intravenous (IV) Mosunetuzumab + Lenalidomide (Non-randomized); Subcutaneous (SC) Mosunetuzumab + Lenalidomide (Non-randomized)

Lenalidomide DRUG

Participants will receive oral lenalidomide as defined by the study protocol

Arm A: IV Mosunetuzumab + Len (Randomized); Arm B: SC Mosunetuzumab + Len (Randomized); Intravenous (IV) Mosunetuzumab + Lenalidomide (Non-randomized); Subcutaneous (SC) Mosunetuzumab + Lenalidomide (Non-randomized)

Eligibility Criteria

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

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
• R/R FL after treatment with at least one prior systemic lymphoma therapy, which includes prior immunotherapy or chemoimmunotherapy
• Previously untreated participants with FL must require systemic therapy assessed by investigator based on the Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria and have a Follicular Lymphoma International Prognostic Index (FLIPI) score of 2-5
• Histologically documented FL of Grade 1, 2, or 3a, and that expresses CD20 at time of diagnosis as determined by the local laboratory
• Fluorodeoxyglucose avid lymphoma (i.e., positron emission tomography (PET) positive lymphoma)
• At least one bi dimensionally measurable nodal lesion (\>1.5 cm in its largest dimension by PET- computed tomography (CT) scan), or at least one bi dimensionally measurable extranodal lesion (\>1.0 cm in its largest dimension by PET-CT scan)
• Availability of a representative tumor specimen and the corresponding pathology report for confirmation of the diagnosis of FL
• Adequate hematologic function (unless due to underlying lymphoma, per the investigator) as defined by the protocol
• 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/mL, have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months
• Normal laboratory values (unless due to underlying lymphoma) as defined by the protocol
• Agreement to comply with all local requirements of the Len risk minimization plan
• For women of childbearing potential: agreement to remain abstinent or use two adequate methods of contraception, including at least one method with a failure rate of \< 1% per year, for at least 28 days prior to Day 1 of Cycle 1, during the treatment period, and for at least 12 months after the final dose of glofitamab, 28 days after the last dose of Len, 18 months after the last dose of G, 3 months after the final dose of tocilizumab, and 3 months after the final dose of Mosun. Women must refrain from donating eggs during this same period
• For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm, with female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 2 months after the final dose of glofitamab, 28 days after last dose of Len, 18 months after the last dose of G, 3 months after the final dose of tocilizumab, and 3 months after the final dose of Mosun

You may not qualify if:

• Any history of Grade 3b FL
• Suspicion or clinical evidence of transformed lymphoma at enrollment by investigator assessment
• Any history of disease transformation and/or diffuse large B-cell lymphoma (DLBCL)
• Documented refractoriness to an obinutuzumab monotherapy containing regimen in glofitamab-containing treatment combination
• Active or history of central nervous system (CNS) lymphoma or leptomeningeal infiltration
• Documented refractoriness to lenalidomide, defined as no response (partial response (PR) or complete response (CR)) within 6 months of therapy
• Prior standard or investigational anti-cancer therapy as specified by the protocol
• Clinically significant toxicity (other than alopecia) from prior treatment that has not resolved to Grade \<=2 prior to Day 1 of Cycle 1
• Known history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis or evidence of active pneumonitis on screening chest CT scan
• Treatment with systemic immunosuppressive medications, including, but not limited to, prednisone, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to Day 1 of Cycle 1
• History of solid organ transplantation
• History of severe allergic or anaphylactic reaction to humanized, chimeric or murine MAbs
• Known sensitivity or allergy to murine products
• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the glofitamab, Mosun, G, Len, or thalidomide formulation, including mannitol
• History of erythema multiforme, Grade \>=3 rash, or blistering following prior treatment with immunomodulatory derivatives

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (26)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136-1002, United States

Location

Norton Cancer Institute - St. Matthews

Louisville, Kentucky, 40207-4723, United States

Location

Mary Bird Perkins Cancer Ctr

Baton Rouge, Louisiana, 70809, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710-4000, United States

Location

Fairview Hospital

Cleveland, Ohio, 44111, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195-0001, United States

Location

Hillcrest Hospital

Mayfield Heights, Ohio, 44124, United States

Location

Rhode Island Hematology/Oncology Program

Woonsocket, Rhode Island, 02895-4720, United States

Location

Tennessee Oncology;Chattanooga Oncology & Hematology Associates

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology PLLC - Franklin

Franklin, Tennessee, 37067, United States

Location

Swedish Medical Center

Seattle, Washington, 98122, United States

Location

The First Hospital of Jilin University

Changchun, 130021, China

Location

West China Hospital, Sichuan University

Chengdu, 610041, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200120, China

Location

Tianjin Medical University Cancer Institute & Hospital

Tianjing, 300060, China

Location

The First Affiliated Hospital of Xiamen University

Xiamen, 361003, China

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

CHU Rennes - Hopital Pontchaillou

Rennes, 35033, France

Location

Hospital Universitario Fundacion Jimenez Diaz.

Madrid, 28040, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

University College London Hospitals NHS Foundation Trust - University College Hospital

London, NW1 2PG, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Freeman Hospital

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Nottingham University Hospitals NHS Trust - City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

tocilizumab; Lenalidomide

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2020
• First Posted: January 29, 2020
• Study Start: August 12, 2020
• Primary Completion (Estimated): September 6, 2030
• Study Completion (Estimated): September 6, 2030
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

CN (5); ES (2); FR (2); US (13); GB (4)