An Open-Label Study Comparing Glofitamab and Polatuzumab Vedotin + Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone Versus Pola-R-CHP in Previously Untreated Patients With Large B-Cell Lymphoma

Roche

Status and phase: Enrolling; Phase 3

Conditions: Large B-Cell Lymphoma

Treatments: Drug: Rituximab; Drug: Glofitamab; Drug: Prednisone; Drug: Doxorubicin; Drug: Polatuzumab vedotin; Drug: Cyclophosphamide

Study type: Interventional

Funder types: Industry

Identifiers

NCT06047080

GO44145

Details and patient eligibility

About

The purpose of this study is to compare the efficacy and safety of glofitamab in combination with polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) vs Pola-R-CHP in participants with previously untreated CD20-positive large B-cell lymphoma (LBCL).

Enrollment: 1,130 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Previously untreated participants with CD20-positive LBCL
• Ability to provide tumor tissue
• International prognostic index (IPI) score 2-5
• Eastern cooperative oncology group (ECOG) performance status of 0, 1, or 2
• At least one bi-dimensionally measurable lesion, defined as > 1.5 cm in its longest dimension as measured by CT or MRI
• Left ventricular ejection fraction (LVEF) >/=50% on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)
• Adequate hematologic function
• Negative HIV test at screening with exceptions as defined by the protocol
• Negative SARS-CoV-2 antigen or PCR test

Exclusion criteria

• Contraindication to any of the individual components of Pola-R-CHP or glofitamab, including prior receipt of anthracyclines, or history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, or known sensitivity or allergy to murine products
• Prior solid organ transplantation
• Participants receiving systemic immunosuppressive agent such as, but not limited to cyclosporin, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 4 weeks prior to first dose of study treatment
• Current Grade > 1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease
• History of indolent lymphoma (e.g., Follicular Lymphoma, Marginal Zone Lymphoma, Waldenstrom macroglobulinemia)
• Current diagnosis of the following: Follicular lymphoma grade 3B; transformations of indolent B-cell lymphomas (e.g., de novo transformed follicular lymphoma); mediastinal grey zone lymphoma; primary mediastinal (thymic) large B-cell lymphoma; Burkitt lymphoma; primary large B-cell lymphoma of immune-privileged sites (encompassing primary diffuse large B-cell lymphoma of the CNS, primary large B-cell lymphoma of the vitreoretina and primary large B-cell lymphoma of the testis); primary effusion DLBCL; and primary cutaneous DLBCL, leg type
• Primary or secondary CNS lymphoma at the time of recruitment or history of CNS lymphoma
• Prior treatment with systemic immunotherapeutic agents
• Prior use of any monoclonal antibody for the purposes of treating cancer within 3 months of the start of Cycle 1
• Any investigational therapy for the purposes of treating cancer within 28 days prior to the start of Cycle 1
• Prior radiotherapy to the mediastinal/pericardial region
• Prior therapy for LBCL, with the exception of corticosteriods
• Corticosteroid use > 30 mg/day of prednisone or equivalent, for purposes other than lymphoma symptom control
• History of other malignant or non-malignant diseases that could affect compliance with the protocol or interpretation of results
• Significant or extensive history of cardiovascular disease
• Recent major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis
• Current or past history of central nervous system (CNS) disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
• Known or suspected chronic active Epstein-Barr viral infection
• Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
• Active autoimmune disease requiring treatment
• Clinically significant liver disease
• Live, attenuated vaccine within 4 weeks before study treatment infusion on Day 1 of Cycle 1 or anticipation that such a live, attenuated vaccine will be required during the study. Live vaccines during the study and until participants B cells recover are prohibited
• Any active infection within 7 days prior to Cycle 1 Day 1 that would impact participant safety
• Suspected active or latent tuberculosis
• Positive test results for chronic hepatitis B infection, hepatitis C, or the human T-lymphotropic virus type 1 (HTLV-1)
• History of progressive multifocal leukoencephalopathy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,130 participants in 2 patient groups

Glofitamab + Pola-R-CHP

Experimental group

Description:

Participants will receive glofitamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP).

Treatment:

Drug: Cyclophosphamide

Drug: Polatuzumab vedotin

Drug: Prednisone

Drug: Doxorubicin

Drug: Glofitamab

Drug: Rituximab

Pola-R-CHP

Active Comparator group

Description:

Participants will receive Pola-R-CHP.

Treatment:

Drug: Cyclophosphamide

Drug: Polatuzumab vedotin

Drug: Prednisone

Drug: Doxorubicin

Drug: Rituximab