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
Obinutuzumab: Participants will receive a single dose of intravenous (IV) obinutuzumab pre-treatment 7 days prior to the first dose of glofitamab.
Glofitamab: Participants will receive IV glofitamab for up to 12 cycles.
Rituxumab: Participants will receive IV rituxumab on Day 1 of each cycle for up to 8 cycles.
Tocilizumab: Participants will receive IV tocilizumab as needed for treatment of cytokine-release syndrome (CRS).
Gemcitabine: Participants will receive IV gemcitabine prior to oxaliplatin administration for up to 8 cycles.
Oxaliplatin: Participants will receive IV oxaliplatin after gemcitabine administration for up to 8 cycles.
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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
Primary outcome measure(s)
Overall survival (OS), defined as the time from randomization to date of death from any cause — Up to 5 years
Trial sites (63)
Facility
City
Region
Status
University of Alabama at Birmingham
Birmingham
Alabama
Community Cancer Institute (CCI)
Fresno
California
Baptist - MD Anderson Cancer Center
Jacksonville
Florida
University of Maryland Medical Center
Baltimore
Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore
Maryland
Massachusetts General Hospital
Boston
Massachusetts
University of Mississippi Medical Center
Jackson
Mississippi
Rutgers Cancer Institute of New Jersey
New Brunswick
New Jersey
Icahn School of Medicine at Mount Sinai
New York
New York
Duke University Medical Center
Durham
North Carolina
Prince of Wales Hospital
Randwick
New South Wales
Royal Adelaide Hospital
Adelaide
South Australia
Monash Health Monash Medical Centre
Clayton
Victoria
St Vincent's Hospital Melbourne
Fitzroy
Victoria
Peter Maccallum Cancer Centre
Melbourne
Victoria
Sir Charles Gairdner Hospital
Nedlands
Western Australia
UZ Leuven Gasthuisberg
Leuven
Belgium
CHU de Liège (Sart Tilman)
Liège
Belgium
Peking University Third Hospital
Beijing
China
Sun Yet-sen University Cancer Center
Guangzhou
China
Harbin Medical University Cancer Hospital
Harbin
China
Fudan University Shanghai Cancer Center
Shanghai
China
Tianjin Cancer Hospital
Tianjin
China
Wuhan Union Hospital Tongji Medical College, Huazhong University of Science and Technology
Wuhan
China
Zhejiang Cancer Hospital
Zhejiang
China
Henan Cancer Hospital
Zhengzhou
China
Aarhus Universitetshospital Skejby
Aarhus N
Denmark
Rigshospitalet
København Ø
Denmark
Institut Bergonie
Bordeaux
France
Hopital Henri Mondor
Créteil
France
Hopital Claude Huriez
Lille
France
Chu de Montpellier-St Eloi
Montpellier
France
Centre Hospitalier Lyon Sud
Pierre-Bénite
France
CHU Pontchaillou
Rennes
France
Universitatsklinikum Frankfurt
Frankfurt
Germany
Universitätsklinikum Gießen und Marburg GmbH Standort Gießen Medizinische Klinik I
Giessen
Germany
Universitaetsklinikum Regensburg
Regensburg
Germany
Uniwersyteckie Centrum Kliniczne
Gdansk
Poland
Centrum Onkologii Ziemi Lubelskiej im. ?w. Jana z Dukli
Lublin
Poland
Oddzial Kliniczny Hematologii SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie
Olsztyn
Poland
+ 23 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time.