A Trial of Polatuzumab Vedotin, Obinutuzumab and Glofitamab As a Peri-CAR-T Cell Treatment Strategy in Large B-cell Lymphoma

Inclusion Criteria: * Histologically proven CD20+ LBCL (with CD20 positivity at any timepoint) including diffuse large B cell lymphoma, high grade B cell lymphoma with MYC, BCL2 and/or BCL6 (double/triple hit lymphoma), high grade B cell lymphoma not otherwise specified (NOS), primary mediastinal B-cell lymphoma or transformed follicular lymphoma. * Part 1: Relapsed or refractory disease and eligible for CAR T-cell therapy in the UK and in need of systemic bridging in the opinion of the local investigator. * Part 2: Failed to achieve CMR (Deauville score 1-3) on PET scan 1-month post CAR-T or progressed at any point post CAR-T (patients in part 2 may have been previously enrolled in Part 1 and responded to Pola-Glofit bridging or be de novo patients who are naïve to this combination) * At least one measurable target lesion * Patient has recent archival biopsy tissue available or is willing to undergo a new biopsy. * ECOG performance status: * Part 1: ECOG PS 0/1 * Part 2: ECOG PS 0-2 * Life expectancy of ≥ 12 weeks * Adequate haematological status. * Adequate liver and renal function * Negative test for hepatitis B, hepatitis C, HIV and SARS-CoV-2 Exclusion Criteria: * Patients with known active infection * Current ≥ Grade 2 peripheral neuropathy * History of confirmed progressive multifocal leukoencephalopathy * Current evidence of CNS lymphoma * Patients with another invasive malignancy in the last 2 years * Significant history of cardiovascular disease * Active autoimmune disease or immune deficiency * Severe neurological disorder * Uncontrolled tumour-related pain * Uncontrolled pleural effusion, pericardial effusion, or ascites * Treatment with other standard anti-cancer radiotherapy/chemotherapy including investigational therapy and targeted therapy within 4 weeks prior to cycle 1 day 1 * Prior solid organ transplantation * Prior allogeneic stem cell transplant * Autologous SCT within 100 days prior to cycle 1 day 1 * Any history of immune related ≥ Grade 3 adverse events * Ongoing corticosteroid use \> 25 mg/day of prednisone or equivalent within 4 weeks prior to study treatment * Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment * Administration of a live, attenuated vaccine within 4 weeks prior to cycle 1 day 1 * History of severe allergic anaphylactic reactions to chimeric or humanised monoclonal antibodies or recombinant antibody-related fusion proteins. * Known hypersensitivity to Chinese hamster ovary cell products or to any component of the obinutuzumab, polatuzumab vedotin and/or glofitamab formulation. * Known or suspected history of HLH