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

NCT04712097 | Active Not Recruiting Phase 3 FDA Drug

• 2 other identifiers: GO429092020-005239-53
• Study Type: interventional
• Target: 478
• Locations: 15 countries
• Sites: 112

Brief Summary

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.

Conditions

Relapsed or Refractory Follicular Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• 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)

Study Arms (3)

M + Len (Arm A)

EXPERIMENTAL

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; Drug: Lenalidomide; Drug: Tociluzumab

R + Len (Arm B)

EXPERIMENTAL

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; Drug: Rituximab; Drug: Tociluzumab

M + Len (US Extension Arm C)

EXPERIMENTAL

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; Drug: Lenalidomide; Drug: Tociluzumab

Interventions

Tociluzumab DRUG

Tocilizumab will be administered as needed to manage cytokine release syndrome (CRS) events

M + Len (Arm A); M + Len (US Extension Arm C); R + Len (Arm B)

Mosunetuzumab DRUG

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

M + Len (Arm A); M + Len (US Extension Arm C)

Lenalidomide DRUG

Participants will receive oral lenalidomide once daily on Days 1-21 of Cycles 2-12 (M + Len) or Cycles 1-12 (R + Len)

M + Len (Arm A); M + Len (US Extension Arm C); R + Len (Arm B)

Rituximab DRUG

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

R + Len (Arm B)

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
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (112)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Fort Wayne Medical Oncology and Hematology, Inc

Fort Wayne, Indiana, 46804, United States

Location

Investigative Clinical Research of Indiana, LLC

Noblesville, Indiana, 46062, United States

Location

Johns Hopkins Uni

Baltimore, Maryland, 21231, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Cancer & Hematology Center of West Michigan

Grand Rapids, Michigan, 49503, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

NYU Long Island Hospital

Mineola, New York, 11501, United States

Location

NYU Langone Ambulatory Care Center

New York, New York, 10016, United States

Location

Montefiore Medical Center - Montefiore Medical Park

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest Univ Health Svcs

Winston-Salem, North Carolina, 27157, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Kadlec Clinic Hematology and Oncology

Kennewick, Washington, 99336-7774, United States

Location

Calvary Mater Newcastle

Waratah, New South Wales, 2298, Australia

Location

Princess Alexandra Hospital Woolloongabba

Woolloongabba, Queensland, 4102, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Geelong Hospital

Geelong, Victoria, 3220, Australia

Location

ICTR Curitiba

Curitiba, Paraná, 80510-130, Brazil

Location

Hospital das Clinicas - UFRGS

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Hospital Mae de Deus

Porto Alegre, Rio Grande do Sul, 90470-340, Brazil

Location

Hospital Alemao Oswaldo Cruz

São Paulo, São Paulo, 01327-001, Brazil

Location

Peking University First Hospital

Beijing, 100034, China

Location

Beijing Cancer Hospital

Beijing, 100142, China

Location

Peking University Third Hospital

Beijing, 100191, China

Location

The First Hospital of Jilin University

Changchun, 130021, China

Location

Cancer Center, Sun Yat-sen University of Medical Sciences

Guangzhou, 510060, China

Location

Harbin Medical University Cancer Hospital

Harbin, 150081, China

Location

The 1st Affiliated Hospital of Nanchang Unversity

Nanchang, 330200, China

Location

Jiangsu Province Hospital

Nanjing, 210036, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200032, China

Location

Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences

Tianjin, 301636, China

Location

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, 430023, China

Location

Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, 430030, China

Location

The First Affiliated Hospital of Xiamen University

Xiamen, 361003, China

Location

Zhejiang Cancer Hospital

Zhejiang, 310022, China

Location

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, 450052, China

Location

Centre Hospitalier de La Cote Basque

Bayonne, 64109, France

Location

Ch De Chambery

Chambéry, 73011, France

Location

Hopital Henri Mondor

Créteil, 94010, France

Location

Hopital Claude Huriez

Lille, 59037, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

CHU Saint Eloi

Montpellier, 34295, France

Location

CHU NANTES - Hôtel Dieu

Nantes, 44093, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

CHU de Nîmes - Hôpital Carémeau

Nîmes, 30029, France

Location

Hôpital Saint-Louis

Paris, 75475, France

Location

Hopital Saint Antoine

Paris, 75571, France

Location

Hopital De Haut Leveque

Pessac, 33604, France

Location

Ch Lyon Sud

Pierre-Bénite, 69495, France

Location

Hopital De La Miletrie

Poitiers, 86021, France

Location

CHU de Reims

Reims, 51100, France

Location

CHU Pontchaillou

Rennes, 35033, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

CHU de Strasbourg

Strasbourg, 67098, France

Location

Vivantes Klinikum Am Urban Klinik für Innere Medizin Hämatologie und Onkologie

Berlin, 10967, Germany

Location

BAG Freiberg-Richter, Jacobasch, Illmer, Wolf

Dresden, 01307, Germany

Location

Universitätsklinikum Halle

Halle, 06120, Germany

Location

Uniklinik Heidelberg, Medizinische Klinik & Poliklinik V

Heidelberg, 69120, Germany

Location

Klinik und Poliklinik f. Innere Medizin III des Universitätsklinikums Regensburg

Regensburg, 93053, Germany

Location

Universitätsklinik Rostock

Rostock, 18057, Germany

Location

Universtitätsklinikum Ulm

Ulm, 89081, Germany

Location

A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna

Bologna, Emilia-Romagna, 40138, Italy

Location

U.O. Ematologia AUSL Ravenna

Ravenna, Emilia-Romagna, 48121, Italy

Location

Ospedale V. Cervello

Palermo, Sicily, 90146, Italy

Location

Ospedali Riuniti Umberto I

Ancona, The Marches, 60100, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, Tuscany, 50134, Italy

Location

Ematologia/immunologia Clinica Azienda Ospedaliera Policlinico di Padova

Padova, Veneto, 35128, Italy

Location

Aichi Cancer Center

Aichi, 464-8681, Japan

Location

National Cancer Center Hospital East

Chiba, 277-8577, Japan

Location

University Hospital Kyoto Prefectural University of Medicine

Kyoto, 602-8566, Japan

Location

Mie University Hospital

Mie, 514-8507, Japan

Location

Tohoku University Hospital

Miyagi, 980-8574, Japan

Location

Okayama University Hospital

Okayama, 700-8558, Japan

Location

National Cancer Center Hospital

Tokyo, 104-0045, Japan

Location

The Cancer Institute Hospital of JFCR

Tokyo, 135-8550, Japan

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-214, Poland

Location

Szpitale Pomorskie Sp. z o. o.

Gdynia, 81-519, Poland

Location

Pratia Onkologia Katowice

Katowice, 41-500, Poland

Location

Uniwersytecki Szpital Kliniczny w Poznaniu

Późna, 60-569, Poland

Location

Instytut Hematologii i Transfuzjologii

Warsaw, 02-776, Poland

Location

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu

Wroc?aw, 50-367, Poland

Location

City Clinical Botkin's Hospital

Moscow, 129110, Russia

Location

Penza Regional Oncology Dispensary

Penza, 440071, Russia

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, 13605, South Korea

Location

Samsung Medical Center

Seoul, (0)6351, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Seoul St Mary's Hospital

Seoul, 06591, South Korea

Location

Hospital de Donostia

Guipuzcoa, Guipuzcoa, 20014, Spain

Location

Hospital Universitario la Paz

Madrid, 28046, Spain

Location

Hospital General Universitario J.M Morales Meseguer

Murcia, 30008, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Chang Gung Medical Foundation - Kaohsiung;Oncology

Kaoisung, 833, Taiwan

Location

National Taiwan Universtiy Hospital

Taipei, 100, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

Chang Gung Medical Foundation - Linkou

Taoyuan, 333, Taiwan

Location

Hacettepe Uni Medical Faculty

Ankara, 06100, Turkey (Türkiye)

Location

Atakent Acibadem Private Hosptial Halkali Merkez Mh.,

Istanbul, 34303, Turkey (Türkiye)

Location

Marmara Ün?Vers?Tes? ?Stanbul Pend?K E??T?M Ve Ara?Tirma Hastanes?

Istanbul, Turkey (Türkiye)

Location

Koc Universitesi (KU) Tip Fakultesi (Koc University School of Medicine)

Yellowplace, 34450, Turkey (Türkiye)

Location

Royal Cornwall Hospitals NHS Trust

Cornwall, TR1 3LJ, United Kingdom

Location

Gloucestershire Royal Hospital

Gloucester, GL1 3NN, United Kingdom

Location

Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

Nottingham City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

Torbay Hospital

Torquay, TQ2 7AA, United Kingdom

Location

MeSH Terms

Conditions

Recurrence; Lymphoma, Follicular

Interventions

Lenalidomide; Rituximab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; 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; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2021
• First Posted: January 15, 2021
• Study Start: October 27, 2021
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2029
• Last Updated: May 5, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

FR (18); TU (4); PL (6); DE (7); US (17); ES (5); CN (15); RU (2); IT (6); TW (4); BR (4); GB (5); JP (8); KR (7); AU (4)