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

Phase 3

Recruiting

• Conditions: Large B-Cell Lymphoma
• Interventions: Drug: Glofitamab; Drug: Polatuzumab vedotin; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone

• Registration Number: NCT06047080
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-09-14
• Study First Submitted QC: 2023-09-14
• Study Start: 2023-09-18
• Study First Posted: 2023-09-21
• Status Verified: 2025-08
• Last Update Submitted: 2025-08-01
• Last Update Posted: 2025-08-03
• Primary Completion: 2027-12-31
• Study Completion: 2030-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1130

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Glofitamab + Pola-R-CHP	Glofitamab	Participants will receive glofitamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP).
Glofitamab + Pola-R-CHP	Polatuzumab vedotin	Participants will receive glofitamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP).
Glofitamab + Pola-R-CHP	Rituximab	Participants will receive glofitamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP).
Glofitamab + Pola-R-CHP	Cyclophosphamide	Participants will receive glofitamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP).
Glofitamab + Pola-R-CHP	Doxorubicin	Participants will receive glofitamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP).
Glofitamab + Pola-R-CHP	Prednisone	Participants will receive glofitamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP).
Pola-R-CHP	Polatuzumab vedotin	Participants will receive Pola-R-CHP.
Pola-R-CHP	Rituximab	Participants will receive Pola-R-CHP.
Pola-R-CHP	Cyclophosphamide	Participants will receive Pola-R-CHP.
Pola-R-CHP	Doxorubicin	Participants will receive Pola-R-CHP.
Pola-R-CHP	Prednisone	Participants will receive Pola-R-CHP.

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS) as determined by Independent Review Facility (IRF)	From randomization to the first occurrence of disease progression or relapse, or death due to any cause, whichever occurs first (up to approximately 65 months)

Secondary Outcome Measures

Name	Time	Method
PFS as determined by the investigator	From randomization to the first occurrence of disease progression or relapse or death from any cause, whichever occurs first (up to approximately 65 months)
PFS as determined by the investigator and IRF for participants with international prognostic index (IPI) 3-5	From randomization to the first occurrence of disease progression or relapse or death from any cause, whichever occurs first (up to 65 months)
Event-free survival efficacy causes (EFSeff)	From randomization to the earliest occurrence of disease progression or relapse; death due to any cause; initiation of new anti-lymphoma treatment; or positive biopsy for residual disease after treatment completion (up to approximately 65 months)
Serum concentration of glofitamab	Up to approximately 65 months
Incidence of anti-drug antibodies (ADAs)	Baseline up to approximately 65 months
Proportion of participants experiencing a clinically meaningful improvement in physical functioning and fatigue (EORTC QLQ-C30) and lymphoma symptoms (FACT-Lym LymS)	Up to approximately 65 months
Time to deterioration in physical functioning and fatigue (EORTC QLQ-C30) and lymphoma symptoms (FACT-Lym LymS)	Up to approximately 65 months
Percentage of Participants with Adverse Events (AEs)	From randomization to the end of study (up to approximately 65 months)
Complete response (CR) rate	At the end of treatment (up to approximately 65 months)
Objective response rate (ORR)	At treatment completion or discontinuation (up to approximately 65 months)
Overall survival (OS)	From randomization to death from any cause (up to approximately 65 months)
Duration of response (DOR)	From the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 65 months)
Duration of complete response (DOCR)	From the first occurrence of a documented complete response (CR) to disease progression or death, whichever occurs first (up to approximately 65 months)
Disease-free survival (DFS)	From a documented CR at the end of treatment to disease progression or death, whichever occurs first (up to approximately 65 months)

Trial Locations

Locations (274)

Alaska Oncology & Hematology, LLC; 🇺🇸 Anchorage, Alaska, United States

Kaiser Permanente - Anaheim (E. La Palma); 🇺🇸 Anaheim, California, United States

University of California, San Francisco-Fresno; 🇺🇸 Clovis, California, United States

City of Hope National Medical Center; 🇺🇸 Duarte, California, United States

City of Hope - Lennar Foundation Cancer Center; 🇺🇸 Irvine, California, United States

Scripps Clinic Torrey Pines; 🇺🇸 La Jolla, California, United States

Valkyrie Clinical Trials; 🇺🇸 Los Angeles, California, United States

UCLA Jonsson Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

Kaiser Permanente - Oakland; 🇺🇸 Oakland, California, United States

Kaiser Permanente - Roseville; 🇺🇸 Roseville, California, United States

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