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

Conditions: Large B-Cell Lymphoma

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).


Eligibility criteria:
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