A Study of Glofitamab Plus GemOx Compared With Standard of Care in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Inclusion Criteria:

* Signed Informed Consent Form.
* Age 18 years or older at the time of signing the Informed Consent Form.
* Histologically proven diffuse large B-cell lymphoma (DLBCL), including transformation from follicular lymphoma.
* Relapsed or refractory disease after first-line chemoimmunotherapy, defined as refractory disease (no complete remission to first-line therapy, progressive disease as best response, stable disease after 3-4 cycles, or partial response after 6-8 cycles/progression within 12 months of first-line therapy) or relapsed disease (complete remission followed by biopsy-proven relapse within 12 months of first-line therapy).
* No known history or suspicion of central nervous system (CNS) involvement by lymphoma.
* Life expectancy of at least 12 weeks.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
* At least one bi-dimensionally measurable nodal lesion (1.5 cm or larger) or extranodal lesion (1 cm or larger) as measured on a CT scan.
* Negative HIV test at screening.
* Adequate hematologic function defined as hemoglobin 9.0 g/dL or higher without transfusion in the past 7 days, absolute neutrophil count 1.0 x 10\^9/L or higher, and platelet count 75 x 10\^9/L or higher.
* Adequate organ function defined as estimated creatinine clearance 60 mL/min or higher, ALT/AST 2.5 times the upper limit of normal (ULN) or lower, and total bilirubin 1.5 mg/dL or lower (or 3 x ULN or lower in subjects with Gilbert's syndrome).
* Cardiac ejection fraction greater than 50%, no evidence of pericardial effusion, and no clinically significant electrocardiogram findings.
* No clinically significant pleural effusion.
* Baseline oxygen saturation greater than 92% on room air.
* Able to understand and complete study-related questionnaires.
* Agreement to remain abstinent or use adequate contraceptive methods for both female and male participants during the treatment period and for the protocol-specified duration after the final dose.

Exclusion Criteria:

* Contraindication to glofitamab components or a history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
* Not eligible for autologous stem cell transplantation (ASCT).
* Prior solid organ transplantation.
* History of Richter's transformation or of indolent disease to diffuse large B-cell lymphoma (DLBCL) or primary mediastinal B-cell lymphoma (PMBCL).
* Peripheral neuropathy assessed to be greater than Grade 1 at enrollment.
* Prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3.
* Use of any investigational therapy for treating cancer within 28 days prior to Cycle 1, any monoclonal antibody within 3 months, or systemic immunotherapeutic agents within 4 weeks or five half-lives (whichever is shorter).
* Prior radiotherapy to the mediastinal or pericardial region.
* History of autologous or allogeneic stem cell transplant.
* Adverse events from prior anti-cancer therapy that have not resolved to Grade 1 or better, except for alopecia and anorexia.
* Administration of a live, attenuated vaccine within 4 weeks before the first study treatment administration.
* Received more than one line of therapy for DLBCL.
* Corticosteroid use greater than 50 mg/day of prednisone or equivalent for purposes other than lymphoma symptom control.
* Recent major surgery within 4 weeks before the first study treatment.
* History of other malignancy that could affect compliance or interpretation of results, with exceptions for adequately treated low-grade or in situ carcinomas and malignancies in remission for at least 2 years.
* Significant cardiovascular disease, such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 3 months, unstable arrhythmias, or unstable angina.
* Current or past history of central nervous system (CNS) disease, such as stroke, epilepsy, CNS vasculitis, neurodegenerative disease, or CNS lymphoma.
* Known or suspected history of hemophagocytic lymphohistiocytosis (HLH).
* Current or past history of Waldenstrom macroglobulinemia.
* History or presence of a clinically significant abnormal ECG.
* Known or suspected active infection, reactivation of a latent infection, or any major episode of infection requiring hospitalization or IV antibiotics within 4 weeks of dosing.
* History of severe treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents.
* History of autoimmune disease, with specific protocol-defined exceptions for well-controlled conditions.
* Clinically significant liver disease, including active viral/other hepatitis or cirrhosis.
* Abnormal coagulation laboratory values defined as INR or PT greater than 1.5 x ULN, or PTT/aPTT greater than 1.5 x ULN.
* Suspected active or latent tuberculosis.
* Positive test results for chronic hepatitis B infection (HBsAg positive) or positive test results for hepatitis C with positive HCV RNA.
* Diagnosis with SARS-CoV-2 infection within 30 days prior to first study treatment, or documented infection within 6 months with persistent respiratory symptoms.
* History of progressive multifocal leukoencephalopathy (PML).
* Pregnancy, breastfeeding, or intention of becoming pregnant during the study.