A Study to Evaluate Glofitamab as a Single Agent vs. Investigator's Choice in Participants With Relapsed/Refractory Mantle Cell Lymphoma (GLOBRYTE)

A Phase III, Open-Label, Multicenter Randomized Study Evaluating Glofitamab as a Single Agent Versus Investigator's Choice in Patients With Relapsed/Refractory Mantle Cell Lymphoma

The purpose of this study is to evaluate the efficacy of glofitamab monotherapy compared with an investigator's choice of either rituximab plus bendamustine (BR), or lenalidomide with rituximab (R-Len) in patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL).

Study Overview

• Status: Recruiting
• Conditions: Lymphoma
• Intervention / Treatment: Drug: Obinutuzumab; Drug: Glofitamab; Drug: Tocilizumab; Drug: Rituximab; Drug: Bendamustine; Drug: Lenalidomide

• Study Type: Interventional
• Enrollment (Estimated): 182
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: GO43878 https://forpatients.roche.com/; Phone Number: 888-662-6728; Email: global-roche-genentech-trials@gene.com
• Study Contact Backup: Name: Fastest response: use the inquiry form. No email attachments. https://www.gene.com/contact-us/submit-medical-inquiry

Study Locations

• Australia
  • New South Wales
    • Waratah, New South Wales, Australia, 2298
      • Recruiting
      • Calvary Mater Newcastle
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • Royal Adelaide Hospital
  • Victoria
    • Richmond, Victoria, Australia, 3121
      • Recruiting
      • Epworth Hospital
• Brazil
  • Rio de Janeiro, Brazil, 22775-001
    • Recruiting
    • Americas Medical City
  • São Paulo, Brazil, 01321-00
    • Recruiting
    • Beneficencia Portuguesa de Sao Paulo
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 41253-190
      • Withdrawn
      • Hospital Sao Rafael - HSR
  • Paraná
    • Curitiba, Paraná, Brazil, 80510-130
      • Recruiting
      • ICTR Curitiba
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90110-000
      • Recruiting
      • Hospital Mae de Deus
  • São Paulo
    • São Paulo, São Paulo, Brazil, 01327-001
      • Recruiting
      • Hospital Alemao Oswaldo Cruz
    • São Paulo, São Paulo, Brazil, 01321-000
      • Recruiting
      • Hospital Paulistano
    • São Paulo, São Paulo, Brazil, 01509-010
      • Recruiting
      • Hospital A. C. Camargo
    • São Paulo, São Paulo, Brazil, 04502-001
      • Recruiting
      • Instituto D'Or Pesquisa e Ensino
• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Recruiting
      • Victoria Hospital - London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1H 8L6
      • Recruiting
      • The Ottawa Hospital - General Campus
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • Princess Margaret Cancer Center
• China
  • Beijing, China, 100730
    • Recruiting
    • Beijing Tong Ren Hospital, Capital Medical University
  • Changchun, China, 130021
    • Recruiting
    • The First Hospital of Jilin University
  • Chengdu, China, 610041
    • Active, not recruiting
    • West China Hospital of Sichuan University
  • Chongqing, China, 400030
    • Recruiting
    • Chongqing Cancer Hospital
  • Fuzhou, China, 350014
    • Recruiting
    • Fujian Provincial Cancer Hospital
  • Guangzhou, China, 510060
    • Active, not recruiting
    • Sun yat-sen University Cancer Center
  • Nanning, China, 530021
    • Recruiting
    • Guangxi Cancer Hospital of Guangxi Medical University
  • Shanghai, China, 200032
    • Active, not recruiting
    • Fudan University Shanghai Cancer Center
  • Shenyang, China, 110001
    • Recruiting
    • The First Affiliated Hospital of China Medical University
  • Wenzhou, China, 325035
    • Completed
    • The First Affiliated Hospital of Wenzhou Medical University
  • Zhengzhou, China, 450008
    • Recruiting
    • Henan Cancer Hospital
  • Zhengzhou, China, 450003
    • Recruiting
    • The First Affiliated Hospital of Zhengzhou University
• France
  • Lille, France, 59037
    • Recruiting
    • Hopital Claude Huriez
  • Montpellier, France, 34295
    • Recruiting
    • Hopital Saint Eloi
  • Nantes, France, 44093
    • Recruiting
    • CHU Nantes - Hotel Dieu
  • Paris, France, 75743
    • Recruiting
    • Hopital Necker
  • Paris, France, 75005
    • Recruiting
    • INSTITUT CURIE_SITE PARIS - Service d'Oncologie Médicale.
• Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Recruiting
      • Policlinico S.Orsola-Malpighi
  • Lombardy
    • Bergamo, Lombardy, Italy, 24121
      • Recruiting
      • Humanitas Gavazzeni
    • Milan, Lombardy, Italy, 20141
      • Recruiting
      • Irccs Istituto Europeo di Oncologia (IEO)
  • Piedmont
    • Alessandria, Piedmont, Italy, 15121
      • Recruiting
      • SC Ematologia, AO SS. Antonio e Biagio e C. Arrigo
    • Turin, Piedmont, Italy, 10126
      • Recruiting
      • A.O. Città della Salute e della Scienza D - Osp. S. Giov. Battista Molinette
• Puerto Rico
  • San Juan, Puerto Rico, 00918
    • Recruiting
    • Auxilio Mutuo Cancer Center
• South Korea
  • Daejeon, South Korea, 35015
    • Withdrawn
    • Chungnam National University Hospital
  • Seoul, South Korea, 003-722
    • Active, not recruiting
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 05505
    • Active, not recruiting
    • Asan Medical Center
  • Seoul, South Korea, 135-710
    • Active, not recruiting
    • Samsung Medical Center
  • Seoul, South Korea, 03080
    • Completed
    • Seoul National University Hospital
• Spain
  • A Coruña, Spain, 15006
    • Recruiting
    • Complejo Hospitalario Universitario A Coruña (CHUAC)
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clínic de Barcelona
  • Murcia, Spain, 30008
    • Recruiting
    • Hospital General Universitario J.M Morales Meseguer
  • Cadiz
    • Cadiz, Cadiz, Spain, 11009
      • Recruiting
      • Hospital Universitario Puerta Del Mar
• Sweden
  • Lund, Sweden, 221 85
    • Recruiting
    • Skånes University Hospital, Skånes Department of Onclology
  • Uppsala, Sweden, 751 85
    • Recruiting
    • Akademiska sjukhuset, Onkologkliniken
• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan Universtiy Hospital
  • Taoyuan, Taiwan, 333
    • Recruiting
    • Chang Gung Medical Foundation - Linkou
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Recruiting
    • NHS Greater Glasgow and Clyde
  • Lincoln, United Kingdom, LN2 5QY
    • Recruiting
    • Lincolnshire County Hospital
  • London, United Kingdom, NW1 2PG
    • Recruiting
    • University College London Hospital
  • Manchester, United Kingdom, M2O 4BX
    • Recruiting
    • Christie Hospital NHS Trust
  • Oxford, United Kingdom, OX3 7LE
    • Recruiting
    • Oxford Churchill Hospital
  • Plymouth, United Kingdom, PL6 8DH
    • Recruiting
    • Derriford Hospital
• United States
  • California
    • Berkeley, California, United States, 94704
      • Withdrawn
      • Alta Bates Summit Medical Center
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope Cancer Center
    • Santa Monica, California, United States, 90404-2023
      • Recruiting
      • University of California Los Angeles (UCLA) - Cancer Care - Santa Monica
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale Cancer Center
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Recruiting
      • Georgetown University
  • Florida
    • Coral Gables, Florida, United States, 33146
      • Recruiting
      • University of Miami
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Withdrawn
      • Indiana University
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan Health System
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Recruiting
      • St. Luke's Hospital
  • Nevada
    • Reno, Nevada, United States, 89502
      • Recruiting
      • Renown Regional Medical Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Rutgers Cancer Institute of New Jersey
  • New York
    • Rochester, New York, United States, 14642
      • Recruiting
      • University of Rochester
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Withdrawn
      • Medical University of S. Carolina
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Withdrawn
      • Avera Cancer Institute
  • Texas
    • El Paso, Texas, United States, 79915
      • Recruiting
      • Renovatio Clinical - El Paso
    • The Woodlands, Texas, United States, 77380
      • Recruiting
      • Renovatio Clinical
  • Virginia
    • Charlottesville, Virginia, United States, 22906
      • Recruiting
      • University of Virginia
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Recruiting
      • West Virginia University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Life expectancy at least 12 weeks
• Histologically-confirmed MCL, with documentation of either overexpression of cyclin D1 or the presence of t(11:14) within 12 months of study entry
• Relapsed (disease progression after the last treatment regimen) or refractory (failure to achieve a partial or complete response from the last treatment regimen) disease
• At least 1 line of prior systemic therapy including a BTK inhibitor and additional systemic therapy option
• Confirmed availability of tumor tissue, unless deemed unsafe per investigator assessment
• At least one bi-dimensionally measurable (defined as at least 1.5 cm) nodal lesion, or one bi-dimensionally measurable (at least 1 cm) extranodal lesion, as measured on CT scan
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Negative HIV test at screening
• Adequate hematological function

Exclusion Criteria:

• Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 3 months after the final dose of tocilizumab, 2 months after the final dose of glofitamab, whichever is longer
• Leukemic, non-nodal MCL
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products
• Contraindication to obinutuzumab or rituximab, and either bendamustine or lenalidomide
• Prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3
• Prior treatment with CAR-T cell therapy
• Treatment with systemic therapy or BTK inhibitors, or any investigational agent for the purposes of treating cancer within 2 weeks or 5 half-lives (whichever is shorter) prior to first study treatment
• Primary or secondary CNS lymphoma at the time of recruitment or history of CNS lymphoma
• Current or history of CNS disease, such as stroke, epilepisy, CNS vasculitis, or neurodegenerative disease
• History of other malignancy that could affect compliance with the protocol or interpretation of results
• Significant or extensive cardiovascular disease
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection at study enrollment or any major episode of infection within 4 weeks prior to the first study treatment
• Suspected or latent tuberculosis
• Positive test for hepatitis B virus (HBV) or hepatitis C virus (HCV)
• Known or suspected chronic active Epstein-Barr viral infection (EBV)
• Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
• Known history of progressive multifocal leukoencephalopathy (PML)
• Adverse events from prior anti-cancer therapy that have not resolved to Grade 1 or better
• Administration of a live, attenuated vaccine within 4 weeks before first study treatment administration or anticipation that such a live, attenuated vaccine will be required during the study
• Prior solid organ transplantation or allogenic stem cell transplant
• Eligibility for stem cell transplantation (SCT)
• Active autoimmune disease requiring treatment
• Prior treatment with systemic immunosuppressive medications within 2 weeks or five half-lives (whichever is shorter) prior to the first dose of study treatment
• Corticosteroid therapy within 2 weeks prior to first dose of study treatment
• Recent major surgery (within 4 weeks before the first study treatment) other than for diagnosis
• Clinically significant history of cirrhotic liver disease

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Glofitamab monotherapy; Participants will receive two intravenous (IV) obinutuzumab pretreatments prior to receiving IV glofitamab for 12 cycles (cycle length = 21 days).	Drug: Obinutuzumab; Participants will receive two 1000 mg pretreatments of intravenous (IV) obinutuzumab from Cycle 1 Day 1; Drug: Glofitamab; Participants will receive IV glofitamab beginning Cycle 1 Day 8 for 12 cycles (cycle length = 21 days).; Drug: Tocilizumab; Participants will receive IV tocilizumab as required to manage cytokine release syndrome (CRS) events.
Active Comparator: BR or R-Len; Participants will receive bendamustine + rituximab for up to 6 cycles (cycle length = 28 days), or rituximab + lenalidomide (cycle length = 28 days) until disease progression.	Drug: Tocilizumab; Participants will receive IV tocilizumab as required to manage cytokine release syndrome (CRS) events.; Drug: Rituximab; Participants will receive IV rituximab every 28 days for up to 6 cycles (when in combination with bendamustine), or until disease progression (when in combination with lenalidomide).; Drug: Bendamustine; Participants will receive IV bendamustine on Days 1 and 2 Q4W for 6 cycles (cycle length = 28 days).; Drug: Lenalidomide; Participants will receive oral lenalidomide once daily on Days 1-21 Q4W until disease progression.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival (PFS)	From randomization to the first occurrence of disease progression or death from any cause (up to approximately 24 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)		Up to approximately 24 months
Complete response (CR) rate		Up to approximately 24 months
Overall survival (OS)		From randomization to death from any cause (up to approximately 24 months)
Time to deterioration in physical functioning/fatigue		From randomization to a 10-point decrease in physical functioning/10-point increase in fatigue compared to baseline (up to approximately 24 months)
Investigator-assessed PFS		From randomization to disease progression or death from any cause (up to approximately 24 months)
Investigator-assessed CR rate		Up to approximately 24 months
Investigator-assessed ORR		Up to approximately 24 months
Duration of Complete Response (DOCR)		From the initial occurrence of a documented CR until documented disease progression or death due to any cause, whichever occurs first (up to approximately 24 months)
Duration of Response (DOR)		From the initial occurrence of a documented CR until documented disease progression or death due to any cause, whichever occurs first (up to approximately 24 months)
Proportion of participants reporting each response option for item GP5 from the Functional Assessment of Cancer Therapy - General (FACT-G) subscale		Up to approximately 24 months
Time to deterioration in lymphoma symptoms		From randomization to the first documentation of a 3-point or more decrease in score as assessed by the FACT-Lym lymphoma subscale (LymS) questionnaire (up to approximately 24 months)
Proportion of participants experiencing a clinically meaningful improvement (3-point or more increase) in lymphoma symptoms as assessed through use of the FACT-Lym LymS		Up to approximately 24 months
Change from baseline in physical functioning and fatigue at each cycle as assessed by the European Organization for Research and Treatment (EORTC) core Quality of Life Questionnaire (QLQ-C30)	The EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, and pain), global health status and quality of life (QoL), and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The functioning and symptoms items are scored on a 4-point scale that ranges from "not at all" to "very much," and the global health status and QoL items are scored on a 7-point scale that ranges from "very poor" to "excellent."	Up to approximately 24 months
Change from baseline in lymphoma symptoms at each cycle as assessed by the FACT-Lym LymS		Up to approximately 24 months
Serum concentration of glofitamab		Up to approximately 24 months
Incidence of anti-drug antibodies (ADAs)		Up to approximately 24 months

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Please use this form to submit your questions for a faster response: https://www.gene.com/contact-us/submit-medical-inquiry. Do not include or attach any medical records when emailing or completing the form. A nurse will respond within 24 business hours.

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2023
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: September 14, 2023
• First Submitted That Met QC Criteria: October 12, 2023
• First Posted (Actual): October 16, 2023

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemic and Lymphatic Diseases; Lymphoma; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Acids, Acyclic; Carboxylic Acids; Piperidines; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Butyrates; Antibodies, Monoclonal, Murine-Derived; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; Bendamustine Hydrochloride; Rituximab; tocilizumab; obinutuzumab; glofitamab
• Other Study ID Numbers: GO43878

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