A Dose Escalation Study of Glofitamab (RO7082859) as a Single Agent and in Combination With Obinutuzumab, Administered After a Fixed, Single Pre-treatment Dose of Obinutuzumab in Participants With Relapsed/Refractory B-cell Non-hodgkin's Lymphoma
NCT ID: NCT03075696
Last Updated: 2026-01-07
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1/PHASE2
940 participants
INTERVENTIONAL
2017-02-21
2029-12-31
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Part I: Dose Escalation
Participants (single participant cohorts) will receive obinutuzumab pretreatment (Gpt) 1000 milligrams (mg) single dose IV infusion on Day -7 followed by glofitamab IV infusion on Day 1 and Day 8 of Cycle 1. From Cycle 2 onwards, ascending doses of glofitamab will be administered on Day 1 of every 2 week (Q2W) cycle up to Cycle 12 (24 weeks) or until unacceptable toxicity or disease progression. Glofitamab dosing will be initiated at 5 micrograms (mcg) (flat dose) followed by doses of 15 mcg, 45 mcg, 135 mcg, 405 mcg and 810 mcg.
Tocilizumab
Tocilizumab will be administered as an IV infusion, if required, for the management of severe Cytokine Release Syndrome (CRS) occurring during or after any infusion of glofitamab, as per the methods described in the Summary of Product Characteristics (SmPC) or other similar local prescribing documents.
Glofitamab
Glofitamab will be administered at a dose and as per the schedule specified in the respective arms.
Obinutuzumab
Obinutuzumab 1000 mg single dose IV infusion on Day -7; or 2000 mg single dose administered on Day -7, or split into two 1000 mg doses administered on Days -1 and -7, and per the schedule specified in the respective arms.
Part II: Dose Escalation
In each treatment regimen, participants will receive Gpt 1000 mg IV infusion on Day -7; or 2000 mg either administered on Day -7, or split into two 1000 mg doses on Days -1 and -7. The first glofitamab IV infusion will be given on Day 1 of Cycle 1 and a total of 12 cycles will be administered.
Monotherapy, glofitamab as a single agent: ascending doses of glofitamab administered on Day 1 of Q2W or every 3 week (Q3W) cycle until either the MTD/OBD is defined.
Combination Therapy: From Cycle 2 onwards, a fixed dose of 1000 mg obinutuzumab will be administered via IV infusion in combination with ascending doses of glofitamab on Day 1 of Q3W cycle until either the MTD/OBD is defined.
Step-up dosing: Q3W, participants will receive an initial low dose of glofitamab on Cycle 1 Day 1, followed by a higher dose on Cycle 1 Day 8; the total dose in Cycle 1 will not exceed the previously determined MTD. Higher doses may be explored from Cycle 2 or later cycles.
Tocilizumab
Tocilizumab will be administered as an IV infusion, if required, for the management of severe Cytokine Release Syndrome (CRS) occurring during or after any infusion of glofitamab, as per the methods described in the Summary of Product Characteristics (SmPC) or other similar local prescribing documents.
Glofitamab
Glofitamab will be administered at a dose and as per the schedule specified in the respective arms.
Obinutuzumab
Obinutuzumab 1000 mg single dose IV infusion on Day -7; or 2000 mg single dose administered on Day -7, or split into two 1000 mg doses administered on Days -1 and -7, and per the schedule specified in the respective arms.
Part III: Dose Expansion
Part III will start once MTD/OBD is defined. Participants will receive Gpt 1000 mg single dose IV infusion on Day -7, followed by glofitamab at a fixed dose regimen or step-up dose regimen on a Q2W or Q3W dosing schedule as determined in Part II. A total of 12 cycles will be administered.
Combination Therapy: From Cycle 2 onwards, a fixed dose of 1000 mg obinutuzumab will be administered via IV infusion in combination with glofitamab at the dosing regimen determined in Part II.
Tocilizumab
Tocilizumab will be administered as an IV infusion, if required, for the management of severe Cytokine Release Syndrome (CRS) occurring during or after any infusion of glofitamab, as per the methods described in the Summary of Product Characteristics (SmPC) or other similar local prescribing documents.
Glofitamab
Glofitamab will be administered at a dose and as per the schedule specified in the respective arms.
Obinutuzumab
Obinutuzumab 1000 mg single dose IV infusion on Day -7; or 2000 mg single dose administered on Day -7, or split into two 1000 mg doses administered on Days -1 and -7, and per the schedule specified in the respective arms.
Interventions
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Tocilizumab
Tocilizumab will be administered as an IV infusion, if required, for the management of severe Cytokine Release Syndrome (CRS) occurring during or after any infusion of glofitamab, as per the methods described in the Summary of Product Characteristics (SmPC) or other similar local prescribing documents.
Glofitamab
Glofitamab will be administered at a dose and as per the schedule specified in the respective arms.
Obinutuzumab
Obinutuzumab 1000 mg single dose IV infusion on Day -7; or 2000 mg single dose administered on Day -7, or split into two 1000 mg doses administered on Days -1 and -7, and per the schedule specified in the respective arms.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Measurable disease, defined as at least one bi-dimensionally measurable nodal lesion, defined as \> 1.5 cm in its longest dimension, or at least one bi-dimensionally measurable extranodal lesion, defined as \> 1.0 cm in its longest dimension
* Able to provide a tumor tissue pretreatment biopsy at last relapse or during screening from a safely accessible site, per investigator determination, providing the patient has more than one measurable target lesion
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Life expectancy of \>/=12 weeks
* AEs from prior anti-cancer therapy must have resolved to Grade less than or equal to (\</=) 1
* Adequate liver, hematological and renal function
* Negative serologic or polymerase chain reaction (PCR) test results for acute or chronic Hepatitis B virus (HBV) infection
* Negative test results for Hepatitis C virus (HCV) and human immunodeficiency virus (HIV)
* Negative serum pregnancy test within 7 days prior to study treatment in women of childbearing potential. Women who are not of childbearing potential who are considered to be post-menopausal (at least 12 months of non-therapy amenorrhea) or surgically sterile (absence of ovaries and/or uterus) are not required to have a pregnancy test
Exclusion Criteria
* Participants with chronic lymphocytic leukemia (CLL), Burkitt lymphoma and lymphoplasmacytic lymphoma
* Participants with a known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
* Participants with acute bacterial, viral, or fungal infection at baseline, confirmed by a positive blood culture within 72 hours prior to obinutuzumab infusion or by clinical judgment in the absence of a positive blood culture
* Participants with known active infection, or reactivation of a latent infection, whether bacterial, viral, fungal, mycobacterial, or other pathogens or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of dosing
* Prior treatment with systemic immunotherapeutic agents, including, but not limited to, radio-immunoconjugates, antibody-drug conjugates, immune/cytokines and monoclonal antibodies (e.g., anti-cytotoxic T-lymphocyte-associated protein 4 \[anti-CTLA4\], anti-programmed death 1 \[anti-PD1\] and anti-programmed death ligand 1 \[anti-PDL1\]) within 4 weeks or five half-lives of the drug, whichever is shorter, before obinutuzumab infusion on Cycle 1 Day -7
* History of treatment-emergent immune-related AEs associated with prior immunotherapeutic agents
* Documented refractoriness to an obinutuzumab-containing regimen
* Treatment with standard radiotherapy, any chemotherapeutic agent, or treatment with any other investigational anti-cancer agent, including chimeric antigen receptor therapy (CAR-T) within 4 weeks prior to obinutuzumab infusion
* Prior solid organ transplantation
* Prior allogeneic stem cell transplantation (SCT)
* Autologous SCT within 100 days prior to obinutuzumab infusion
* Participant with history of confirmed progressive multifocal leukoencephalopathy (PML)
* Current or past history of central nervous system (CNS) lymphoma
* Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease. Participants with a past history of stroke that have not experienced a stroke or transient ischemic attack in the past 2 years and have no residual neurologic deficits are allowed
* Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders and known autoimmune diseases
* Participants with another invasive malignancy in the last 2 years (with the exception of basal cell carcinoma and tumors deemed by the Investigator to be of low likelihood for recurrence)
* Significant or extensive history of cardiovascular disease such as New York Heart Association Class III or IV or Objective Class C or D cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina
* Administration of a live, attenuated vaccine within 4 weeks before obinutuzumab infusion or anticipation that such a live attenuated vaccine will be required during the study
* Received systemic immunosuppressive medications (including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within two weeks prior to obinutuzumab infusion. Treatment with corticosteroid \</= 25 mg/day prednisone or equivalent is allowed. Inhaled and topical steroids are permitted
* Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
* History of autoimmune disease, including but not limited to myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus, erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Participants with a remote history of, or well controlled autoimmune disease, may be eligible to enroll after consultation with the Medical Monitor
* In Part III diffuse large B-cell lymphoma (DLBCL) dexamethasone cohort, participants with a history of hypersensitivity to dexamethasone or systemic corticosteroids will be excluded
18 Years
ALL
No
Sponsors
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Hoffmann-La Roche
INDUSTRY
Responsible Party
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Principal Investigators
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Clinical Trials
Role: STUDY_DIRECTOR
Hoffmann-La Roche
Locations
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Ingalls Memorial Hospital
Harvey, Illinois, United States
University of Michigan
Ann Arbor, Michigan, United States
Washington University
St Louis, Missouri, United States
Mount Sinai Medical Center
New York, New York, United States
MSKCC
New York, New York, United States
Allegheny Health Network (Pittsburg PA)
Pittsburgh, Pennsylvania, United States
Hunstman Cancer Institute
Salt Lake City, Utah, United States
Swedish Cancer Inst.
Seattle, Washington, United States
Prince of Wales Hospital
Randwick, New South Wales, Australia
Peter Maccallum Cancer Centre
Melbourne, Victoria, Australia
Cliniques Universitaires St-Luc
Brussels, , Belgium
UZ Gent
Ghent, , Belgium
Princess Margaret Cancer Center
Toronto, Ontario, Canada
Vseobecna Fakultni Nemocnice v Praze, I. Interni Klinika - Klinika Hematoonkologie VFN a 1. LF UK
Prague, , Czechia
Rigshospitalet
København Ø, , Denmark
Helsinki University Central Hospital
Helsinki, , Finland
Hopital Henri Mondor
Créteil, , France
Hopital Claude Huriez
Lille, , France
CHU Saint Eloi
Montpellier, , France
Ch Lyon Sud
Pierre-Bénite, , France
CHU DE RENNES - CHU Pontchaillou
Rennes, , France
AUSL della Romagna
Ravenna, Emilia-Romagna, Italy
Fond. IRCCS Istituto Nazionale Tumori
Milan, Lombardy, Italy
Istituto Clinico Humanitas
Rozzano, Lombardy, Italy
A.O.U. Citta' Della Salute E Della Scienza-P.O. Molinette
Turin, Piedmont, Italy
Auckland Cancer Trial Centre
Auckland, , New Zealand
Uniwersyteckie Centrum Kliniczne
Gda?sk, , Poland
Uniwersytecki Szpital Kliniczny w Poznaniu
Późna, , Poland
Centrum Onkologii-Instytut im. M. Sklodowskiej-Curie
Warsaw, , Poland
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
Wroc?aw, , Poland
Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, Spain
Hospital Duran i Reynals L'Hospitalet
L'Hospitalet de Llobregat, Barcelona, Spain
Hospital Universitario Marques de Valdecilla
Santander, Cantabria, Spain
Hospital del Mar
Barcelona, , Spain
Hospital Universitari Vall d'Hebron
Barcelona, , Spain
Hospital Univ. 12 de Octubre
Madrid, , Spain
China Medical University Hospital
Taichung, , Taiwan
National Taiwan Universtiy Hospital
Taipei, , Taiwan
Countries
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Central Contacts
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Reference Study ID Number: NP30179 https://forpatients.roche.com/
Role: CONTACT
References
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Phillips TJ, Carlo-Stella C, Morschhauser F, Bachy E, Crump M, Trneny M, Bartlett NL, Zaucha J, Wrobel T, Offner F, Humphrey K, Relf J, Filezac de L'Etang A, Carlile DJ, Byrne B, Qayum N, Lundberg L, Dickinson M. Glofitamab in Relapsed/Refractory Mantle Cell Lymphoma: Results From a Phase I/II Study. J Clin Oncol. 2025 Jan 20;43(3):318-328. doi: 10.1200/JCO.23.02470. Epub 2024 Oct 4.
Dickinson MJ, Carlo-Stella C, Morschhauser F, Bachy E, Corradini P, Iacoboni G, Khan C, Wrobel T, Offner F, Trneny M, Wu SJ, Cartron G, Hertzberg M, Sureda A, Perez-Callejo D, Lundberg L, Relf J, Dixon M, Clark E, Humphrey K, Hutchings M. Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med. 2022 Dec 15;387(24):2220-2231. doi: 10.1056/NEJMoa2206913. Epub 2022 Dec 11.
Frances N, Bacac M, Bray-French K, Christen F, Hinton H, Husar E, Quackenbush E, Schafer M, Schick E, Vyver AV, Richter WF. Novel in Vivo and in Vitro Pharmacokinetic/Pharmacodynamic-Based Human Starting Dose Selection for Glofitamab. J Pharm Sci. 2022 Apr;111(4):1208-1218. doi: 10.1016/j.xphs.2021.12.019. Epub 2021 Dec 22.
Broske AE, Korfi K, Belousov A, Wilson S, Ooi CH, Bolen CR, Canamero M, Alcaide EG, James I, Piccione EC, Carlile DJ, Dimier N, Umana P, Bacac M, Weisser M, Dickinson M. Pharmacodynamics and molecular correlates of response to glofitamab in relapsed/refractory non-Hodgkin lymphoma. Blood Adv. 2022 Feb 8;6(3):1025-1037. doi: 10.1182/bloodadvances.2021005954.
Hutchings M, Morschhauser F, Iacoboni G, Carlo-Stella C, Offner FC, Sureda A, Salles G, Martinez-Lopez J, Crump M, Thomas DN, Morcos PN, Ferlini C, Broske AE, Belousov A, Bacac M, Dimier N, Carlile DJ, Lundberg L, Perez-Callejo D, Umana P, Moore T, Weisser M, Dickinson MJ. Glofitamab, a Novel, Bivalent CD20-Targeting T-Cell-Engaging Bispecific Antibody, Induces Durable Complete Remissions in Relapsed or Refractory B-Cell Lymphoma: A Phase I Trial. J Clin Oncol. 2021 Jun 20;39(18):1959-1970. doi: 10.1200/JCO.20.03175. Epub 2021 Mar 19.
Other Identifiers
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2016-001185-28
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
2023-505625-14-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
NP30179
Identifier Type: -
Identifier Source: org_study_id
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