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