trial of mosunetuzumab (btct4465a) as consolidation therapy in participants with diffuse large b-cell lymphoma following first-line immunochemotherapy and as monotherapy or in combination with polatuzumab vedotin in elderly/unfit participants with previously untreated diffuse large b-cell lymphoma

Conditions: Diffuse Large B-cell Lymphoma

Summary: 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.


Eligibility criteria:
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