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

NCT04408638 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: GO419442020-001021-31
• Study Type: interventional
• Target: 270
• Locations: 13 countries
• Sites: 63

Brief Summary

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.

Conditions

Diffuse Large B-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS), defined as the time from randomization to date of death from any cause

  Up to 5 years

Secondary Outcomes (12)

• 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

Study Arms (2)

Glofit-GemOx

EXPERIMENTAL

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; Drug: Glofitamab; Drug: Tocilizumab; Drug: Gemcitabine; Drug: Oxaliplatin

R-GemOx

EXPERIMENTAL

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: Rituxumab; Drug: Gemcitabine; Drug: Oxaliplatin

Interventions

Obinutuzumab DRUG

Participants will receive a single dose of intravenous (IV) obinutuzumab pre-treatment 7 days prior to the first dose of glofitamab.

Glofit-GemOx

Glofitamab DRUG

Participants will receive IV glofitamab for up to 12 cycles.

Glofit-GemOx

Rituxumab DRUG

Participants will receive IV rituxumab on Day 1 of each cycle for up to 8 cycles.

R-GemOx

Tocilizumab DRUG

Participants will receive IV tocilizumab as needed for treatment of cytokine-release syndrome (CRS).

Glofit-GemOx

Gemcitabine DRUG

Participants will receive IV gemcitabine prior to oxaliplatin administration for up to 8 cycles.

Glofit-GemOx; R-GemOx

Oxaliplatin DRUG

Participants will receive IV oxaliplatin after gemcitabine administration for up to 8 cycles.

Glofit-GemOx; R-GemOx

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (63)

University of Alabama at Birmingham

Birmingham, Alabama, 35294-3300, United States

Location

Community Cancer Institute (CCI)

Fresno, California, 93720, United States

Location

Baptist - MD Anderson Cancer Center

Jacksonville, Florida, 32207, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Monash Health Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

St Vincent's Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

Location

Peter Maccallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

CHU de Liège (Sart Tilman)

Liège, 4000, Belgium

Location

Peking University Third Hospital

Beijing, 100083, China

Location

Sun Yet-sen University Cancer Center

Guangzhou, 510060, China

Location

Harbin Medical University Cancer Hospital

Harbin, 150081, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200120, China

Location

Tianjin Cancer Hospital

Tianjin, 300060, China

Location

Wuhan Union Hospital Tongji Medical College, Huazhong University of Science and Technology

Wuhan, 430022, China

Location

Zhejiang Cancer Hospital

Zhejiang, 310022, China

Location

Henan Cancer Hospital

Zhengzhou, 450008, China

Location

Aarhus Universitetshospital Skejby

Aarhus N, 8200, Denmark

Location

Rigshospitalet

København Ø, 2100, Denmark

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Hopital Henri Mondor

Créteil, 94010, France

Location

Hopital Claude Huriez

Lille, 59037, France

Location

Chu de Montpellier-St Eloi

Montpellier, 34295, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

CHU Pontchaillou

Rennes, 35003, France

Location

Universitatsklinikum Frankfurt

Frankfurt, 60590, Germany

Location

Universitätsklinikum Gießen und Marburg GmbH Standort Gießen Medizinische Klinik I

Giessen, 35392, Germany

Location

Universitaetsklinikum Regensburg

Regensburg, 93053, Germany

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-214, Poland

Location

Centrum Onkologii Ziemi Lubelskiej im. ?w. Jana z Dukli

Lublin, 20-090, Poland

Location

Oddzial Kliniczny Hematologii SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie

Olsztyn, 10-228, 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

Pusan National University Hospital

Busan, 49241, South Korea

Location

National Cancer Center

Goyang-si, 10408, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, 13605, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic i Provincial

Barcelona, 08036, Spain

Location

Hospital Universitario la Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Inselspital Bern, Insel-Gruppe AG

Bern, 3010, Switzerland

Location

Universitätsspital Zürich

Zurich, 8091, Switzerland

Location

Chang Gung Medical Foundation - Kaohsiung;Oncology

Kaoisung, 833, Taiwan

Location

Chang Gung Medical Foundation - Linkou

Taoyuan District, 333, Taiwan

Location

Taichung Veterans General Hospital

Xitun Dist., 40705, Taiwan

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 OYN, United Kingdom

Location

St James's Institute of Oncology

Leeds, LS9 7TF, United Kingdom

Location

UCLH - Clinical Trials Pharmacy B&D Centre

London, NW1 2PG, United Kingdom

Location

Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

Nottingham City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

Related Publications (2)

• Sam J, Leclercq-Cohen G, Gebhardt S, Surowka M, Herter S, Lechner K, Relf J, Briner S, Varol A, Appelt B, Domocos I, Nicolini V, Bez M, Bommer E, Jenni S, Schoenle A, Le Clech M, Colombetti S, Klein C, Umana P, Lundberg P, Korfi K, Bottos A, Bacac M. Preclinical advances in glofitamab combinations: a new frontier for non-Hodgkin lymphoma. Blood. 2025 Oct 9;146(15):1824-1836. doi: 10.1182/blood.2025028863.

  PMID: 40749164 DERIVED

• Abramson JS, Ku M, Hertzberg M, Huang HQ, Fox CP, Zhang H, Yoon DH, Kim WS, Abdulhaq H, Townsend W, Herbaux C, Zaucha JM, Zhang QY, Chang H, Liu Y, Cheah CY, Ghesquieres H, Simko S, Orellana-Noia V, Ta R, Relf J, Dixon M, Kallemeijn M, Mulvihill E, Huang H, Lundberg L, Gregory GP. Glofitamab plus gemcitabine and oxaliplatin (GemOx) versus rituximab-GemOx for relapsed or refractory diffuse large B-cell lymphoma (STARGLO): a global phase 3, randomised, open-label trial. Lancet. 2024 Nov 16;404(10466):1940-1954. doi: 10.1016/S0140-6736(24)01774-4.

  PMID: 39550172 DERIVED

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

obinutuzumab; glofitamab; tocilizumab; Gemcitabine; Oxaliplatin

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; 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)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

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: May 26, 2020
• First Posted: May 29, 2020
• Study Start: February 23, 2021
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2028
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

TW (3); AU (6); ES (5); DK (2); CN (8); GB (5); BE (2); FR (6); DE (3); PL (5); KR (6); CH (2); US (10)