A Phase III, Open-Label, Multicenter Randomized Study Evaluating Glofitamab as a Single Agent Versus Investigator's Choice in Patients With Relapsed/Refractory Mantle Cell Lymphoma

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)
• 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