A Study to Evaluate the Safety and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With Polatuzumab Vedotin in B-Cell Non-Hodgkin Lymphoma

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.


Eligibility Criteria:
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