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

Roche

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: B-cell Non-Hodgkin Lymphoma

Treatments: Drug: Polatuzumab vedotin; Drug: Tocilizumab; Drug: Mosunetuzumab (SC); Drug: Mosunetuzumab (IV); Drug: Rituximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03671018

2018-001141-13 (EudraCT Number)

GO40516

Details and patient eligibility

About

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.

Enrollment: 422 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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422 participants in 5 patient groups

Dose Finding

Experimental group

Description:

Participants will receive mosunetuzumab in combination with polatuzumab vedotin. Dose finding will be guided by the observed incidence of dose-limiting toxicities (DLTs) at each dose level.

Treatment:

Drug: Mosunetuzumab (IV)

Drug: Tocilizumab

Drug: Polatuzumab vedotin

Mosunetuzumab + Polatuzumab Vedotin 2L+ R/R FL

Experimental group

Description:

Participants with at least one line of prior therapy (2L+) and that have relapsed or refractory (R/R) follicular lymphoma (FL) will receive mosunetuzumab + polatuzumab vedotin.

Treatment:

Drug: Mosunetuzumab (IV)

Drug: Tocilizumab

Drug: Polatuzumab vedotin

Mosunetuzumab + Polatuzumab Vedotin 2L+R/R DLBCL

Experimental group

Description:

2L+ participants with R/R diffuse large B-cell lymphoma will receive mosunetuzumab + polatuzumab vedotin.

Treatment:

Drug: Rituximab

Drug: Mosunetuzumab (IV)

Drug: Tocilizumab

Drug: Polatuzumab vedotin

Mosunetuzumab SC + Polatuzumab Vedotin 3L+R/R MCL

Experimental group

Description:

Participants with at least 2 lines of prior therapy (3L+) will receive subcutaneous (SC) mosunetuzumab + polatuzumab vedotin.

Treatment:

Drug: Mosunetuzumab (SC)

Drug: Tocilizumab

Drug: Polatuzumab vedotin

Mosunetuzumab SC + Polatuzumab Vedotin 2L+R/R DLBCL

Experimental group

Description:

2L+ participants with R/R DLBCL will receive SC mosunetuzumab and polatuzumab vedotin.

Treatment:

Drug: Mosunetuzumab (SC)

Drug: Tocilizumab

Drug: Polatuzumab vedotin