A Study Evaluating the Safety and Efficacy of Glofitamab + Gemcitabine + Oxaliplatin in U.S. Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Phase 1

Recruiting

• Conditions: Lymphoma
• Interventions: Drug: Glofitamab; Drug: Tocilizumab; Drug: Obinutuzumab; Drug: Gemcitabine; Drug: Oxaliplatin

• Registration Number: NCT06624085
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

The purpose of the study is to evaluate glofitamab + gemcitabine + oxaliplatin in participants in the United States, including under-represented racial and ethnic populations, that have relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2024-10-01
• Study First Submitted QC: 2024-10-01
• Study First Posted: 2024-10-02
• Status Verified: 2024-11
• Study Start: 2024-11-15
• Last Update Submitted: 2024-11-15
• Last Update Posted: 2024-11-18
• Primary Completion: 2028-02-14
• Study Completion: 2030-01-14

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Histologically confirmed DLBCL, not otherwise specified (NOS)
• Relapsed (disease that has recurred following a response that lasted ≥ 6 months after completion of the last line of therapy) or refractory ( disease that did not respond to or that progressed < 6 months after completion of the last line of therapy) disease
• At least one prior line of 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 (ASCT)
• At least one bi-dimensionally measurable (> 1.5 cm) nodal lesion, or one bi-dimensionally measurable (> 1 cm) extranodal lesion, as measured on CT scan
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2

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Exclusion Criteria

• Prior enrollment in Study GO41944 (STARGLO; NCT04408638)
• Participant 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 NOS, 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
• Prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3
• Prior treatment with gemcitabine or oxaliplatin
• Peripheral neuropathy or paresthesia assessed to be Grade >/= 2 according to 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 CNS lymphoma at the time of recruitment or history of CNS lymphoma
• Prior CNS involvement that has been definitively treated and confirmed via MRI or cerebrospinal fluid analysis to be in complete remission is permissible
• Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
• History of other primary malignancy, with exceptions defined by the protocol
• Significant or extensive cardiovascular disease, or significant pulmonary disease
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (exclusing fungal infections of nail beds) at study enrollment or any major episode of infection within 4 weeks prior to the first study treatment
• Documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 6 months of first study treatment, or positive SARS-CoV-2 test within 7 days prior to enrollment
• Suspected or latent tuberculosis
• Positive test results for hepatitis B (HBV) or hepatitis C (HCV)
• Known or suspected chronic active Epstein-Barr viral infection
• Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
• Known history of progressive multifocal leukoencephalopathy
• Prior solid organ transplantation
• Prior allogenic stem cell transplant
• Active autoimmune disease requiring treatment
• Prior treatment with systemic immunosuppressive medications within 4 weeks prior to first dose of study treatment
• Ongoing systemic corticosteroid use which, in the opinion of the investigator, puts the patient at increased risk of steroid-related iatrogenic adrenal insufficiency
• Recent major surgery (within 4 weeks before the first study treatment) other than for diagnosis
• Clinically significant history of cirrhotic liver disease

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Gemcitabine + Glofitamab + Oxaliplatin	Obinutuzumab	Participants will receive a single dose of intravenous (IV) obinutuzumab pretreatment 7 days prior to the first dose of glofitamab, followed by up to 8 cycles of glofitamab + gemcitabine + oxaliplatin. This will be followed by up to 4 cycles of glofitamab monotherapy, for a total of up to 12 cycles of glofitamab (cycle length = 21 days).
Gemcitabine + Glofitamab + Oxaliplatin	Glofitamab	Participants will receive a single dose of intravenous (IV) obinutuzumab pretreatment 7 days prior to the first dose of glofitamab, followed by up to 8 cycles of glofitamab + gemcitabine + oxaliplatin. This will be followed by up to 4 cycles of glofitamab monotherapy, for a total of up to 12 cycles of glofitamab (cycle length = 21 days).
Gemcitabine + Glofitamab + Oxaliplatin	Tocilizumab	Participants will receive a single dose of intravenous (IV) obinutuzumab pretreatment 7 days prior to the first dose of glofitamab, followed by up to 8 cycles of glofitamab + gemcitabine + oxaliplatin. This will be followed by up to 4 cycles of glofitamab monotherapy, for a total of up to 12 cycles of glofitamab (cycle length = 21 days).
Gemcitabine + Glofitamab + Oxaliplatin	Gemcitabine	Participants will receive a single dose of intravenous (IV) obinutuzumab pretreatment 7 days prior to the first dose of glofitamab, followed by up to 8 cycles of glofitamab + gemcitabine + oxaliplatin. This will be followed by up to 4 cycles of glofitamab monotherapy, for a total of up to 12 cycles of glofitamab (cycle length = 21 days).
Gemcitabine + Glofitamab + Oxaliplatin	Oxaliplatin	Participants will receive a single dose of intravenous (IV) obinutuzumab pretreatment 7 days prior to the first dose of glofitamab, followed by up to 8 cycles of glofitamab + gemcitabine + oxaliplatin. This will be followed by up to 4 cycles of glofitamab monotherapy, for a total of up to 12 cycles of glofitamab (cycle length = 21 days).

Primary Outcome Measures

Name	Time	Method
Incidence of Adverse Events (AEs)	Up to 3 years
Complete response (CR) rate	Up to 3 years

Secondary Outcome Measures

Name	Time	Method
Objective response rate (ORR)	Up to 3 years
Duration of CR	From the first occurrence of a documented CR to disease progression or death from any cause, whichever occurs first (up to 3 years)
Progression-free survival (PFS)	From enrollment to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 3 years)
Overall Survival (OS)	From enrollment to date of death from any cause (up to 3 years)
Duration of response (DOR)	From the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 3 years)
Serum concentration of glofitamab	Up to 3 years
Incidence of anti-drug antibodies to glofitamab	Baseline up to 3 years

Trial Locations

Locations (1)

Saddleback Memorial Medical Center; 🇺🇸 Laguna Hills, California, United States