This study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of intravenous (IV) or subcutaneous (SC) mosunetuzumab in combination with polatuzumab vedotin in participants with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). It will consist of a dose finding portion followed by an expansion phase for second line or later (2L+) participants with relapsed or refractory (R/R) DLBCL and 2L+ R/R FL. In addition, subcutaneous mosunetuzumab in combination with polatuzumab vedotin will be evaluated in participants with at least 2 prior lines of systemic therapy (3L+) for the treatment of R/R mantle cell lymphoma (MCL) and in participants with 2L+ R/R DLBCL.

Key Inclusion Criteria:

• ECOG PS of 0, 1, or 2
• Histologically confirmed FL, DLBCL, or MCL
• Must have received at least one prior systemic treatment regimen containing an anti-CD20-directed therapy for DLBCL or FL
• For MCL, participants must have received at least two prior systemic treatment regiments, which include 1) anti-CD20-directed therapy, 2) BTK inhibitor, and 3) anthracycline or bendamustine
• Relapsed to prior regimen(s) after having a documented history of response (complete response [CR], CR unconfirmed [CRu], or partial response [PR]) of >/= 6 months in duration from completion of regimen(s); or, refractory to any prior regimen, defined as no response to the prior therapy, or progression within 6 months of completion of the last dose of therapy
• Measurable disease, defined as at least one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in its longest dimension, or at least one bi-dimensionally measurable extranodal lesion, defined as > 1.0 cm in its longest dimension
• Adequate hematologic, renal, and hepatic function

Key Exclusion Criteria:

• Prior treatment with mosunetuzumab or other CD20-directed bispecific antibodies
• Prior treatment with polatuzumab vedotin
• Current > Grade 1 peripheral neuropathy
• Prior use of any monoclonal antibody, radioimmunoconjugate or antibody-drug conjugate (ADC) within 4 weeks before first dose of study treatment
• Treatment with any chemotherapeutic agent, or treatment with any other anti-cancer agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to first dose of study treatment
• Treatment with radiotherapy within 2 weeks prior to the first dose of study treatment
• Autologous stem-cell transplantation (SCT) within 100 days prior to first study treatment administration
• Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 30 days before first study treatment administration
• Prior allogeneic SCT
• Prior solid organ transplantation
• Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
• Patients with history of confirmed progressive multifocal leukoencephalopathy (PML)
• Current or past history of central nervous system (CNS) lymphoma or CNS disease
• History of autoimmune 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