A Study Evaluating the Efficacy and Safety of Mosunetuzumab in Combination With Lenalidomide in Comparison to Rituximab in Combination With Lenalidomide With a US Extension of Mosunetuzumab in Combination With Lenalidomide in Participants With Follicular Lymphoma (Celestimo)

Phase III Randomized, Open-Label, Multicenter Study Evaluating Efficacy and Safety of Mosunetuzumab in Combination With Lenalidomide in Comparison to Rituximab in Combination With Lenalidomide With a Non-Randomized Single Arm US Extension of Mosunetuzumab in Combination With Lenalidomide in Patients With Follicular Lymphoma After at Least One Line of Systemic Therapy

This study will evaluate the efficacy and safety of mosunetuzumab in combination with lenalidomide (M + Len) compared to rituximab in combination with lenalidomide (R + Len) in participants with relapsed or refractory (R/R) follicular lymphoma (FL) who have received at least one line of prior systemic therapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Relapsed or Refractory Follicular Lymphoma
• Intervention / Treatment: Drug: Mosunetuzumab; Drug: Lenalidomide; Drug: Tociluzumab; Drug: Rituximab

• Study Type: Interventional
• Enrollment (Actual): 478
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital Woolloongabba
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Geelong, Victoria, Australia, 3220
      • Geelong Hospital
• Brazil
  • Paraná
    • Curitiba, Paraná, Brazil, 80510-130
      • ICTR Curitiba
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Hospital das Clinicas - UFRGS
    • Porto Alegre, Rio Grande do Sul, Brazil, 90470-340
      • Hospital Mae de Deus
  • São Paulo
    • São Paulo, São Paulo, Brazil, 01327-001
      • Hospital Alemao Oswaldo Cruz
• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Beijing, China, 100191
    • Peking University Third Hospital
  • Beijing, China, 100034
    • Peking University First Hospital
  • Changchun, China, 130021
    • The First Hospital of Jilin University
  • Guangzhou, China, 510060
    • Cancer Center, Sun Yat-sen University of Medical Sciences
  • Harbin, China, 150081
    • Harbin Medical University Cancer Hospital
  • Nanchang, China, 330200
    • The 1st Affiliated Hospital of Nanchang Unversity
  • Nanjing, China, 210036
    • Jiangsu Province Hospital
  • Shanghai, China, 200032
    • Fudan University Shanghai Cancer Center
  • Tianjin, China, 301636
    • Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
  • Wuhan, China, 430030
    • Tongji Hospital Tongji Medical College Huazhong University of Science and Technology
  • Wuhan, China, 430023
    • Union Hospital Tongji Medical College Huazhong University of Science and Technology
  • Xiamen, China, 361003
    • The First Affiliated Hospital of Xiamen University
  • Zhejiang, China, 310022
    • Zhejiang Cancer Hospital
  • Zhengzhou, China, 450052
    • The First Affiliated Hospital of Zhengzhou University
• France
  • Bayonne, France, 64109
    • Centre Hospitalier de la Côte Basque
  • Chambéry, France, 73011
    • Ch De Chambery
  • Créteil, France, 94010
    • Hôpital Henri Mondor
  • Lille, France, 59037
    • Hopital Claude Huriez
  • Marseille, France, 13009
    • Institut Paoli Calmettes
  • Montpellier, France, 34295
    • Chu Saint Eloi
  • Nantes, France, 44093
    • CHU Nantes - Hotel Dieu
  • Nice, France, 06189
    • Centre Antoine Lacassagne
  • Nîmes, France, 30029
    • CHU de Nîmes - Hôpital Carémeau
  • Paris, France, 75571
    • Hôpital Saint Antoine
  • Paris, France, 75475
    • Hôpital Saint-Louis
  • Pessac, France, 33604
    • Hopital De Haut Leveque
  • Pierre-Bénite, France, 69495
    • CH Lyon Sud
  • Poitiers, France, 86021
    • Hôpital de la Milétrie
  • Reims, France, 51100
    • CHU de Reims
  • Rennes, France, 35033
    • CHU Pontchaillou
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • Strasbourg, France, 67098
    • CHU de Strasbourg
• Germany
  • Berlin, Germany, 10967
    • Vivantes Klinikum Am Urban Klinik für Innere Medizin Hämatologie und Onkologie
  • Dresden, Germany, 01307
    • BAG Freiberg-Richter, Jacobasch, Illmer, Wolf
  • Halle, Germany, 06120
    • Universitätsklinikum Halle
  • Heidelberg, Germany, 69120
    • Uniklinik Heidelberg, Medizinische Klinik & Poliklinik V
  • Regensburg, Germany, 93053
    • Klinik und Poliklinik f. Innere Medizin III des Universitätsklinikums Regensburg
  • Rostock, Germany, 18057
    • Universitätsklinik Rostock
  • Ulm, Germany, 89081
    • Universtitätsklinikum Ulm
• Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna
    • Ravenna, Emilia-Romagna, Italy, 48121
      • U.O. Ematologia AUSL Ravenna
  • Sicily
    • Palermo, Sicily, Italy, 90146
      • Ospedale V. Cervello
  • The Marches
    • Ancona, The Marches, Italy, 60100
      • Ospedali Riuniti Umberto I
  • Tuscany
    • Florence, Tuscany, Italy, 50134
      • Azienda Ospedaliera Universitaria Careggi
  • Veneto
    • Padova, Veneto, Italy, 35128
      • Ematologia/immunologia Clinica Azienda Ospedaliera Policlinico di Padova
• Japan
  • Aichi, Japan, 464-8681
    • Aichi Cancer Center
  • Chiba, Japan, 277-8577
    • National Cancer Center Hospital East
  • Kyoto, Japan, 602-8566
    • University Hospital Kyoto Prefectural University of Medicine
  • Mie, Japan, 514-8507
    • Mie University Hospital
  • Miyagi, Japan, 980-8574
    • Tohoku University Hospital
  • Okayama, Japan, 700-8558
    • Okayama University Hospital
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital
  • Tokyo, Japan, 135-8550
    • The Cancer Institute Hospital of JFCR
• Poland
  • Gdansk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne
  • Gdynia, Poland, 81-519
    • Szpitale Pomorskie Sp. z o. o.
  • Katowice, Poland, 41-500
    • Pratia Onkologia Katowice
  • Późna, Poland, 60-569
    • Uniwersytecki Szpital Kliniczny W Poznaniu
  • Warsaw, Poland, 02-776
    • Instytut Hematologii i Transfuzjologii
  • Wroc?aw, Poland, 50-367
    • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
• Russia
  • Moscow, Russia, 129110
    • City Clinical Botkin's Hospital
  • Penza, Russia, 440071
    • Penza Regional Oncology Dispensary
• South Korea
  • Busan, South Korea, 49241
    • Pusan National University Hospital
  • Seongnam-si, South Korea, 13605
    • Seoul National University Bundang Hospital
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 06591
    • Seoul St Mary's Hospital
  • Seoul, South Korea, (0)6351
    • Samsung Medical Center
• Spain
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Murcia, Spain, 30008
    • Hospital General Universitario J.M Morales Meseguer
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocío
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Guipuzcoa
    • Guipuzcoa, Guipuzcoa, Spain, 20014
      • Hospital de Donostia
• Taiwan
  • Kaoisung, Taiwan, 833
    • Chang Gung Medical Foundation - Kaohsiung;Oncology
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 100
    • National Taiwan Universtiy Hospital
  • Taoyuan, Taiwan, 333
    • Chang Gung Medical Foundation - Linkou
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06100
    • Hacettepe Uni Medical Faculty
  • Istanbul, Turkey (Türkiye), 34303
    • Atakent Acibadem Private Hosptial Halkali Merkez Mh.,
  • Istanbul, Turkey (Türkiye)
    • Marmara Ün?Vers?Tes? ?Stanbul Pend?K E??T?M Ve Ara?Tirma Hastanes?
  • Yellowplace, Turkey (Türkiye), 34450
    • Koc Universitesi (KU) Tip Fakultesi (Koc University School of Medicine)
• United Kingdom
  • Cornwall, United Kingdom, TR1 3LJ
    • Royal Cornwall Hospitals NHS Trust
  • Gloucester, United Kingdom, GL1 3NN
    • Gloucestershire Royal Hospital
  • London, United Kingdom, W12 0HS
    • Hammersmith Hospital
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham City Hospital
  • Torquay, United Kingdom, TQ2 7AA
    • Torbay Hospital
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Medical Oncology and Hematology, Inc
    • Noblesville, Indiana, United States, 46062
      • Investigative Clinical Research of Indiana, LLC
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins Uni
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System
    • Grand Rapids, Michigan, United States, 49503
      • Cancer & Hematology Center of West Michigan
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University
  • New York
    • Mineola, New York, United States, 11501
      • NYU Long Island Hospital
    • New York, New York, United States, 10016
      • NYU Langone Ambulatory Care Center
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • The Bronx, New York, United States, 10461
      • Montefiore Medical Center - Montefiore Medical Park
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Univ Health Svcs
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Washington
    • Kennewick, Washington, United States, 99336-7774
      • Kadlec Clinic Hematology and Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
• Histologically documented CD20+ FL (Grades 1-3a)
• Requiring systemic therapy assessed by investigator based on tumor size and/or Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria
• Received at least one prior systemic lymphoma therapy, which included prior immunotherapy or chemoimmunotherapy
• Availability of a representative tumor specimen and the corresponding pathology report at the time of relapse/persistence for confirmation of the diagnosis of FL. Pretreatment sample of at least 1 core-needle, excisional or incisional tumor biopsy is required. Cytological or fine-needle aspiration samples are not acceptable. Fresh pretreatment biopsy is preferred. Patients who are unable to undergo biopsy procedures may be eligible for study enrollment if an archival tumor tissue sample (preferably from the most recent relapse/persistence) as paraffin blocks or at least 15 unstained slides, or in accordance with local regulatory requirements, can be sent to the Sponsor.
• Adequate hematologic function (unless due to underlying lymphoma, per the investigator)
• Agreement to comply with all local requirements of the lenalidomide risk minimization plan, which includes the global pregnancy prevention program.
• For women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use 2 adequate methods of contraception, including at least 1 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 (including periods of treatment interruption), and for at least 28 days after the last dose of lenalidomide, 3 months after the final dose of tocilizumab (if applicable), mosunetuzumab, and 12 months after final dose of rituximab. Women must refrain from donating eggs during this same period.
• For men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm, as defined: 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 28 days after last dose of lenalidomide, 3 months after the final dose of tocilizumab (if applicable), mosunetuzumab and 12 months after the final dose of rituximab. Men must refrain from donating sperm during this same period.

Exclusion Criteria:

• Grade 3b FL
• Any history of disease transformation and/or diffuse-large B cell lymphoma (DLBCL)
• Documented refractoriness to lenalidomide, defined as no response (partial response or complete response) or relapse within 6 months of therapy
• Active or history of CNS lymphoma or leptomeningeal infiltration
• Prior standard or investigational anti-cancer therapy as specified: Lenalidomide exposure within 12 months prior to Day 1 of Cycle 1; Chimeric antigen receptor T cell therapy within 30 days prior to Day 1 of Cycle 1; Radioimmunoconjugate within 12 weeks prior to Day 1 of Cycle 1; Monoclonal antibody or antibody-drug conjugate within 4 weeks prior to Cycle 1 Day 1; Treatment with any anti-cancer agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to first dose of study treatment
• Clinically significant toxicity (other than alopecia) from prior treatment that has not resolved to Grade </= 1 (per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0) prior to Day 1 of Cycle 1
• Treatment with systemic immunosuppressive medications, including, but not limited to prednisone (> 20 mg), 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 monoclonal antibodies
• Known sensitivity or allergy to murine products
• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary (CHO) cells or any component of the mosunetuzumab, rituximab, tocilizumab, lenalidomide, or thalidomide formulation, including mannitol
• History of erythema multiforme, Grade >/= 3 rash, or blistering following prior treatment with immunomodulatory derivatives
• History of interstitial lung disease, drug-induced pneumonitis, and autoimmune pneumonitis
• Known active bacterial, viral, fungal, or other infection, or any major episode of infection requiring treatment with IV antibiotics within 4 weeks of Day 1 of Cycle 1
• Known or suspected chronic active Epstein-Barr virus (EBV) infection
• Known or suspected history of hemophagocytic lymphohistiocytosis
• Clinically significant history of liver disease, including viral or other hepatitis, or cirrhosis
• Active Hepatitis B infection
• Active Hepatitis C infection
• Known history of HIV positive status
• History of progressive multifocal leukoencephalopathy (PML)
• Administration of a live, attenuated vaccine within 4 weeks before first dose of study treatment or anticipation that such a live attenuated vaccine will be required during the study
• Other malignancy that could affect compliance with the protocol or interpretation of results
• Active autoimmune disease requiring treatment
• History of autoimmune disease, including, but not limited to: myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
• Prior allogeneic stem cell transplantation
• Contraindication to treatment for thromboembolism prophylaxis
• Evidence of any significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including, but not limited to, significant cardiovascular disease (e.g., New York Heart Association Class III or IV cardiac disease, myocardial infarction within the previous 6 months, unstable arrhythmia, or unstable angina) or significant pulmonary disease (such as obstructive pulmonary disease or history of bronchospasm)
• Major surgical procedure other than for diagnosis within 28 days prior to Day 1 of Cycle 1 Day 1 or anticipation of a major surgical procedure during the course of the study
• Pregnant or lactating or intending to become pregnant during the study
• Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study, or which could affect compliance with the protocol or interpretation of results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: M + Len (Arm A); Participants will receive mosunetuzumab for 12 cycles, plus lenalidomide from cycles 2-12 (Cycle length = 21 days for Cycle 1; cycle length = 28 days for Cycles 2-12)	Drug: Mosunetuzumab; Participants will receive intravenous (IV) mosunetuzumab in a step-up dosing schedule on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-12; Drug: Lenalidomide; Participants will receive oral lenalidomide once daily on Days 1-21 of Cycles 2-12 (M + Len) or Cycles 1-12 (R + Len); Drug: Tociluzumab; Tocilizumab will be administered as needed to manage cytokine release syndrome (CRS) events
Experimental: R + Len (Arm B); Participants will receive weekly rituximab in Cycle 1, then on Day 1 of Cycles 3, 5, 7, 9, and 11. Participants will also receive lenalidomide in Cycles 1-12. (Cycle length = 28 days for Cycles 1-12)	Drug: Lenalidomide; Participants will receive oral lenalidomide once daily on Days 1-21 of Cycles 2-12 (M + Len) or Cycles 1-12 (R + Len); Drug: Tociluzumab; Tocilizumab will be administered as needed to manage cytokine release syndrome (CRS) events; Drug: Rituximab; Participants will receive IV rituximab on Days 1, 8, 15, and 22 of Cycle 1, then on Day 1 of Cycles 3, 5, 7, 9, and 11
Experimental: M + Len (US Extension Arm C); Participants will receive mosunetuzumab for 12 cycles, plus lenalidomide from cycles 2-12 (Cycle length = 21 days for Cycle 1; cycle length = 28 days for Cycles 2-12)	Drug: Mosunetuzumab; Participants will receive intravenous (IV) mosunetuzumab in a step-up dosing schedule on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-12; Drug: Lenalidomide; Participants will receive oral lenalidomide once daily on Days 1-21 of Cycles 2-12 (M + Len) or Cycles 1-12 (R + Len); Drug: Tociluzumab; Tocilizumab will be administered as needed to manage cytokine release syndrome (CRS) events

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression Free Survival (PFS) according to 2014 Lugano Response Criteria	From randomization to the first occurrence of disease progression as determined by an independent review committee (IRC) or death from any cause (up to approximately 8.5 years)

Secondary Outcome Measures

Outcome Measure	Time Frame
PFS as Determined by the Investigator	From randomization to the first occurrence of disease progression or death from any cause (up to approximately 8.5 years)
Complete Response Rate	Up to approximately 8.5 years
Objective Response Rate (ORR)	Up to approximately 8.5 years
Overall Survival (OS)	From randomization to death from any cause (up to approximately 8.5 years)
Duration of Objective Response (DOR)	From the first occurrence of a documented objective response (complete response or partial response) to disease progression or death from any cause, whichever occurs first (up to approximately 8.5 years)
Duration of Complete Reponse (DOCR)	From the first occurrence of a documented CR to disease progression or death from any cause, whichever occurs first (up to approximately 8.5 years)
Time to Deterioration in Physical Functioning and Fatigue, as Measured by the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30)	Up to approximately 8.5 years
Time to Deterioration in Lymphoma Symptoms, as Measured by the Functional Assessment of Cancer Therapy-Lymphoma Subscale (FACT-LymS)	Up to approximately 8.5 years
Percentage of Participants with Adverse Events (AEs)	Up to approximately 8.5 years
Serum Concentration of M + Len	Up to approximately 8.5 years
Area Under the Curve (AUC) of M + Len	Up to approximately 8.5 years
Percentage of Participants with Anti-Drug Antibodies (ADAs)	Up to approximately 8.5 years
Time to New Anti-Lymphoma Treatment (TTNALT)	From randomization to the first documented administration of a new anti-lymphoma treatment (up to approximately 8.5 years)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2021
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: January 13, 2021
• First Submitted That Met QC Criteria: January 13, 2021
• First Posted (Actual): January 15, 2021

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Lymphoma, Follicular; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Piperidines; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; Rituximab
• Other Study ID Numbers: GO42909; 2020-005239-53 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No