This study will evaluate the safety, pharmacokinetics, and preliminary efficacy of mosunetuzumab following first-line diffuse large B-cell lymphoma (DLBCL) immunochemotherapy in participants with a best response of stable disease or partial response, or in elderly/unfit participants with previously untreated DLBCL, or subcutaneous mosunetuzumab in combination with polatuzumab vedotin IV in elderly/unfit participants with previously untreated DLBCL.

Inclusion Criteria for All Cohorts

• At least one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in its longest dimension, or one bi-dimensionally measurable extranodal lesion, defined as > 1.0 cm in its longest diameter
• Adequate hematologic function
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2; with the exception of South Korea, where participants 80 years or older with ECOG >/= 2 will not be eligible

Inclusion Criteria Specific to Cohort A

Participants in Cohort A must also meet the following criteria for study entry:

• Histologically confirmed DLBCL according to World Health Organization (WHO) 2016 expected to express the cluster of differentiation-20 (CD20) antigen
• One prior therapy with any systemic anthracycline-based chemoimmunotherapy containing regimen for previously untreated DLBCL
• Best response of SD or PR to prior systemic chemoimmunotherapy at the end of induction treatment in accordance with the Lugano 2014 criteria

Inclusion Criteria Specific to Cohorts B and C

Participants in Cohorts B and C must also meet the following criteria for study entry:

• Previously untreated, histologically confirmed, DLBCL according to WHO 2016 classification
• Age >/= 80 years, or
• Age 65-79 years and considered ineligible for chemoimmuotherapy (R-CHOP) with at least one of the following: Impairment in at least two activity of daily living (ADL) components as defined in the protocol; impairment in at least two instrumental ADL components as defined in the protocol; cumulative illness rating scale - geriactic (CIRS-G) score of at least one cormorbidity with a severity score of 3-4 (not including lymphoma and hematologic deficiencies due to lymphoma) or a score of 2 in >/= 8 comorbidities; impairment in cardiac function, renal function, liver function, or other comorbidities such that the participant is unfit for full-dose immunochemotherapy, such as rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)
• Participants with an initial ECOG performance status of 3 may be considered during screening if the performance status is DLBCL-related and if pre-phase treatment during the screening phase (not more than 100 mg/day up to 7 days prior to Cycle 1 Day 1) results in an improvement of ECOG performance status to </= 2 prior to enrollment

Exclusion Criteria for All Cohorts

Participants who meet any of the following criteria will be excluded from study entry:

• Transformed lymphoma
• CNS lymphoma
• Prior treatment with mosunetuzumab
• Prior stem cell transplant (autologous and allogeneic)
• History of confirmed progressive multifocal leukoencephalopathy (PML)
• Known or suspected chronic active Epstein Barr virus (CAEBV), hepatitis B, hepatitis C (HCV), or Human Immunodeficiency Virus (HIV)
• Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
• Positive SARS-CoV-2 antigen or PCR test within 30 days prior to Cycle 1 Day 1
• Prior solid organ transplantation
• Current or past history of central nervous system (CNS) disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
• Clinically significant history of liver disease
• Prior treatment with radiotherapy within 2 weeks prior to Cycle 1, Day 1 (C1D1)
• Significant cardiovascular disease

Exclusion Criteria Specific to Cohort A

Participants in Cohort A who meet the following criteria will be excluded from study entry:

- Prior anti-lymphoma treatment with chemotherapy, immunotherapy, or biologic therapy 4 weeks prior to C1D1

Exclusion Criterion Specific to Cohorts B and C

Participants in Cohorts B and C who meet the following criterion will be excluded from study entry:

- Prior treatment for DLBCL with chemotherapy, immunotherapy, and biologic therapy

Exclusion Criteria Specific to Cohort C

Participants in Cohort C who meet the following criteria will be excluded from study entry:

- Current Grade >1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth 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