The purpose of this study is to evaluate the efficacy of glofitamab monotherapy compared with an investigator's choice of either rituximab plus bendamustine (BR), or lenalidomide with rituximab (R-Len) in patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL).

Inclusion Criteria:

• Life expectancy at least 12 weeks
• Histologically-confirmed MCL, with documentation of either overexpression of cyclin D1 or the presence of t(11:14) within 12 months of study entry
• Relapsed (disease progression after the last treatment regimen) or refractory (failure to achieve a partial or complete response from the last treatment regimen) disease
• At least 1 line of prior systemic therapy including a BTK inhibitor and additional systemic therapy option
• Confirmed availability of tumor tissue, unless deemed unsafe per investigator assessment
• At least one bi-dimensionally measurable (defined as at least 1.5 cm) nodal lesion, or one bi-dimensionally measurable (at least 1 cm) extranodal lesion, as measured on CT scan
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Negative HIV test at screening
• Adequate hematological function

Exclusion Criteria:

• Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 3 months after the final dose of tocilizumab, 2 months after the final dose of glofitamab, whichever is longer
• Leukemic, non-nodal MCL
• 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 or rituximab, and either bendamustine or lenalidomide
• Prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3
• Prior treatment with CAR-T cell therapy
• Treatment with systemic therapy or BTK inhibitors, or any investigational agent for the purposes of treating cancer within 2 weeks or 5 half-lives (whichever is shorter) prior to first study treatment
• Primary or secondary CNS lymphoma at the time of recruitment or history of CNS lymphoma
• Current or history of CNS disease, such as stroke, epilepisy, CNS vasculitis, or neurodegenerative disease
• History of other malignancy that could affect compliance with the protocol or interpretation of results
• Significant or extensive cardiovascular disease
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection at study enrollment or any major episode of infection within 4 weeks prior to the first study treatment
• Suspected or latent tuberculosis
• Positive test for hepatitis B virus (HBV) or hepatitis C virus (HCV)
• Known or suspected chronic active Epstein-Barr viral infection (EBV)
• Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
• Known history of progressive multifocal leukoencephalopathy (PML)
• Adverse events from prior anti-cancer therapy that have not resolved to Grade 1 or better
• 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 or allogenic stem cell transplant
• Eligibility for stem cell transplantation (SCT)
• Active autoimmune disease requiring treatment
• Prior treatment with systemic immunosuppressive medications within 2 weeks or five half-lives (whichever is shorter) prior to the first dose of study treatment
• Corticosteroid therapy within 2 weeks prior to first dose of study treatment
• Recent major surgery (within 4 weeks before the first study treatment) other than for diagnosis
• Clinically significant history of cirrhotic liver disease

For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing