A Phase III Study Evaluating Glofitamab in Combination With Gemcitabine + Oxaliplatin vs Rituximab in Combination With Gemcitabine + Oxaliplatin in Participants With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

A Phase III, Open-Label, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Glofitamab in Combination With Gemcitabine Plus Oxaliplatin Versus Rituximab in Combination With Gemcitabine and Oxaliplatin in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

This study will evaluate the efficacy and safety of glofitamab in combination with gemcitabine plus oxaliplatin (Glofit-GemOx) compared with rituximab in combination with gemcitabine plus oxaliplatin (R-GemOx) in patients with R/R DLBCL.

Study Overview

• Status: Active, not recruiting
• Conditions: Diffuse Large B-cell Lymphoma
• Intervention / Treatment: Drug: Obinutuzumab; Drug: Glofitamab; Drug: Tocilizumab; Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Rituxumab

• Study Type: Interventional
• Enrollment (Estimated): 270
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Prince of Wales Hospital; Haematology
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital; Haematology Clinical Trials
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health Monash Medical Centre
    • Fitzroy, Victoria, Australia, 3065
      • St Vincent's Hospital Melbourne
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
  • Liège, Belgium, 4000
    • CHU Sart-Tilman
• China
  • Beijing, China, 100191
    • Peking University Third Hospital
  • Guangzhou City, China, 510663
    • Sun Yet-sen University Cancer Center
  • Harbin, China, 150081
    • Harbin Medical University Cancer Hospital
  • Shanghai City, China, 200120
    • Fudan University Shanghai Cancer Center
  • Tianjin, China, 300060
    • Tianjin Cancer Hospital
  • Wuhan City, China, 430022
    • Wuhan Union Hospital Tongji Medical College, Huazhong University of Science and Technology
  • Zhejiang, China, 310022
    • Zhejiang Cancer Hospital
  • Zhengzhou, China, 450008
    • Henan Cancer Hospital
• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus Universitetshospital Skejby; Blodsygdomme
  • København Ø, Denmark, 2100
    • Rigshospitalet; Hæmatologisk Klinik
• France
  • Bordeaux, France, 33076
    • Institut Bergonie; Hematologie Oncologie
  • Creteil, France, 94010
    • Hopital Henri Mondor; 51 Av Mal Lattre De Tassigny
  • Lille, France, 59037
    • Hopital Claude Huriez; Hematologie
  • Montpellier, France, 34295
    • CHU DE MONTPELLIER-ST ELOI; Département d'Hématologie Clinique
  • Pierre Benite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Rennes, France, 35003
    • CHU Pontchaillou; Service Hématologie
• Germany
  • Frankfurt, Germany, 60590
    • Universitatsklinikum Frankfurt
  • Giessen, Germany, 35392
    • Universitätsklinikum Gießen und Marburg GmbH Standort Gießen Medizinische Klinik I
  • Regensburg, Germany, 93053
    • Universitaetsklinikum Regensburg
  • Stuttgart, Germany, 70174
    • Katharinenhospital Stuttgart; Klinik für Hämatologie, Onkologie und Palliativmedizin
• Korea, Republic of
  • Busan, Korea, Republic of, 602-739
    • Pusan National University Hospital
  • Goyang-si, Korea, Republic of, 10408
    • National Cancer Center
  • Seongnam-si, Korea, Republic of, 463-707
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
• Poland
  • Gdansk, Poland
    • Uniwersyteckie Centrum Kliniczne
  • Lublin, Poland, 20-090
    • Centrum Onkologii Ziemi Lubelskiej im. ?w. Jana z Dukli
  • Olsztyn, Poland, 10-228
    • Oddzial Kliniczny Hematologii SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie
  • Pozna?, Poland, 60-569
    • Uniwersytecki Szpital Kliniczny w Poznaniu; Oddzial Hematologii i Transplantacji Szpiku
  • Warszawa, Poland, 02-776
    • Instytut Hematologii i Transfuzjologii; Klinika Hematologii
  • Wroc?aw, Poland, 50-367
    • Uniwersytecki Szpital Kliniczny; Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku
• Puerto Rico
  • San Juan, Puerto Rico, 00935
    • PanOncology Trials; Hospital Oncológico, Puerto Rico Medical Center
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron; Servicio de Hematologia
  • Barcelona, Spain, 08036
    • Hospital Clínic i Provincial; Servicio de Hematología y Oncología
  • Madrid, Spain, 28046
    • Hospital Universitario la Paz; Servicio de Hematologia
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio; Servicio de Hematologia
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques de Valdecilla; Servicio de Hematologia
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital Bern, Insel-Gruppe AG
  • Zürich, Switzerland, 8091
    • Universitatsspital Zurich
• Taiwan
  • Kaoisung, Taiwan, 833
    • Chang Gung Medical Foundation - Kaohsiung; Oncology; Division of Hematology-Oncology
  • Taoyuan, Taiwan, 333
    • Chang Gung Medical Foundation - Linkou; Division of Hematology- Oncology
  • Xitun Dist., Taiwan, 40705
    • Taichung Veterans General Hospital
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre
  • Leeds, United Kingdom, LS9 7TF
    • St James's Institute of Oncology; Dept of Haematology
  • London, United Kingdom, N7 9NH
    • UCLH - Clinical Trials Pharmacy B&D Centre
  • Manchester, United Kingdom, M20 4BX
    • Christie Hospital; Department of Haematology and Transplant
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham City Hospital; Dept of Haematology
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • University of Alabama at Birmingham
  • California
    • Fresno, California, United States, 93720
      • Community Cancer Institute (CCI)
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist - MD Anderson Cancer Center
    • Jacksonville, Florida, United States, 32207-8202
      • Baptist Medical Center - Jacksonville
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
    • Baltimore, Maryland, United States, 21287
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Cancer Institute of New Jersey
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

• Histologically confirmed diffuse large B-cell lymphoma (DLBCL), not otherwise specified
• Relapsed/refractory (R/R) disease, defined as follows: Relapsed = disease that has recurred ≥6 months after completion of the last line of therapy; Refractory = disease that either progressed during the last line of therapy or progressed within 6 months (<6 months) of the last line of prior therapy
• At least one (≥1) line of prior systemic therapy
• Participants who have failed only one prior line of therapy must not be a candidate for high-dose chemotherapy followed by autologous stem cell transplant, as defined by the study protocol
• Confirmed availability of tumor tissue, unless unobtainable per investigator assessment. Freshly collected biopsy is preferred. Archival tissue is acceptable
• At least one bi-dimensionally measurable (≥1.5 cm) nodal lesion, or one bi-dimensionally measurable (≥1 cm) extranodal lesion, as measured on computed tomography (CT) scan
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
• Adequate hematologic function (unless attributable to the underlying disease, as established by extensive bone marrow involvement or associated with hypersplenism secondary to the involvement of the spleen by DLBCL per the investigator), as defined by the study protocol
• Negative SARS-CoV-2 antigen or PCR test within 7 days prior to enrollment
• Adequate renal function, defined as an estimated creatinine clearance ≥30 mL/min

Exclusion Criteria

• Patient has failed only one prior line of therapy and is a candidate for stem cell transplantation
• History of transformation of indolent disease to DLBCL
• High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, and high-grade B-cell lymphoma not otherwise specified, as defined by 2016 WHO guidelines
• Primary mediastinal B-cell lymphoma
• 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, rituximab, gemcitabine or oxaliplatin, or tocilizumab
• Prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3
• Peripheral neuropathy assessed to be Grade >1 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 at enrollment
• Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to first study treatment
• Treatment with monoclonal antibodies for the purposes of treating cancer within 4 weeks prior to first study treatment
• Primary or secondary central nervous system (CNS) lymphoma at the time of recruitment or history of CNS lymphoma
• Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
• 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 (as evaluated by the investigator) within 4 weeks prior to the first study treatment
• Positive SARS-CoV-2 infection within 30 days prior to the first study treatment, including asymptomatic SARS-CoV-2 infection
• Documented SARS-CoV-2 infection within 6 months of first study treatment
• Suspected or latent tuberculosis
• Positive for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
• Known or suspected chronic active Epstein-Barr viral infection
• Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
• Known history of progressive multifocal leukoencephalopathy
• Adverse events from prior anti-cancer therapy not resolved to Grade 1 or better (with the exception of alopecia and anorexia)
• 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
• Prior allogeneic stem cell transplant
• Active autoimmune disease requiring treatment
• Prior treatment with systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents), within 4 weeks prior to first dose of study treatment
• Corticosteroid therapy within 2 weeks prior to first dose of study treatment (exceptions defined by study protocol)
• 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: Glofit-GemOx; Participants will receive up to 8 cycles of glofitamab (Glofit) in combination with gemcitabine and oxaliplatin (GemOx), followed by up to 4 cycles of glofitamab monotherapy. A single dose of obinutuzumab will be administered 7 days prior to the first dose of glofitamab. Treatment is administered in 21-day cycles.	Drug: Obinutuzumab; Participants will receive a single dose of intravenous (IV) obinutuzumab pre-treatment 7 days prior to the first dose of glofitamab.; Drug: Glofitamab; Participants will receive IV glofitamab for up to 12 cycles.; Drug: Tocilizumab; Participants will receive IV tocilizumab as needed for treatment of cytokine-release syndrome (CRS).; Drug: Gemcitabine; Participants will receive IV gemcitabine prior to oxaliplatin administration for up to 8 cycles.; Drug: Oxaliplatin; Participants will receive IV oxaliplatin after gemcitabine administration for up to 8 cycles.
Experimental: R-GemOx; Participants will receive rituxumab (R) in combination with gemcitabine and oxaliplatin (GemOx) for up to 8 cycles. Treatment is administered in 21-day cycles.	Drug: Gemcitabine; Participants will receive IV gemcitabine prior to oxaliplatin administration for up to 8 cycles.; Drug: Oxaliplatin; Participants will receive IV oxaliplatin after gemcitabine administration for up to 8 cycles.; Drug: Rituxumab; Participants will receive IV rituxumab on Day 1 of each cycle for up to 8 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS), defined as the time from randomization to date of death from any cause	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival (PFS), defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first, as determined by the Independent Review Committee (IRC)	Up to 5 years
PFS, defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first, as determined by the investigator	Up to 5 years
Complete response (CR) rate, defined as the proportion of patients whose best overall response is a CR on positron emission tomography/computed tomography (PET/CT) during the study, as determined by the IRC	Up to 5 years
CR rate, defined as the proportion of patients whose best overall response is a CR on positron emission tomography/computed tomography (PET/CT) during the study, as determined by the investigator	Up to 5 years
Objective response rate (ORR), defined as the proportion of patients whose best overall response is a partial response (PR) or a CR during the study, as determined by the IRC	Up to 5 years
ORR, defined as the proportion of patients whose best overall response is a partial response (PR) or a CR during the study, as determined by the investigator	Up to 5 years
Duration of objective response (DOR), defined as the time from the first occurrence of a documented objective response (CR or PR) to disease progression, or death from any cause, whichever occurs first	Up to 5 years
Duration of CR, defined as the time from the first occurrence of a documented CR to disease progression, or death from any cause, whichever occurs first	Up to 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 5 years
Time to deterioration in lymphoma symptoms, as measured by the Functional Assessment of Cancer Therapy-Lymphoma subscale (FACT-Lym LymS)	Up to 5 years
Percentage of Participants with Adverse Events	Up to 5 years
Tolerability, as assessed by dose interruptions, dose reductions, and dose intensity, and study treatment discontinuation because of adverse events	Up to 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): February 23, 2021
• Primary Completion (Estimated): April 15, 2025
• Study Completion (Estimated): April 15, 2025

Study Registration Dates

• First Submitted: May 26, 2020
• First Submitted That Met QC Criteria: May 26, 2020
• First Posted (Actual): May 29, 2020

Study Record Updates

• Last Update Posted (Actual): May 6, 2024
• Last Update Submitted That Met QC Criteria: May 3, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Oxaliplatin; Obinutuzumab; Gemcitabine
• Other Study ID Numbers: GO41944; 2020-001021-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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).

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