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

Roche

Status and phase: Active, not recruiting; Phase 3

Conditions: Diffuse Large B-cell Lymphoma

Treatments: Drug: Oxaliplatin; Drug: Tocilizumab; Drug: Gemcitabine; Drug: Obinutuzumab; Drug: Rituxumab; Drug: Glofitamab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04408638

2020-001021-31 (EudraCT Number)

GO41944

Details and patient eligibility

About

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.

Enrollment: 270 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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270 participants in 2 patient groups

Glofit-GemOx

Experimental group

Description:

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.

Treatment:

Drug: Glofitamab

Drug: Obinutuzumab

Drug: Gemcitabine

Drug: Tocilizumab

Drug: Oxaliplatin

R-GemOx

Experimental group

Description:

Participants will receive rituxumab (R) in combination with gemcitabine and oxaliplatin (GemOx) for up to 8 cycles. Treatment is administered in 21-day cycles.

Treatment:

Drug: Rituxumab

Drug: Gemcitabine

Drug: Oxaliplatin