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) includingdiffuse 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 inthe UK and in need of systemic bridging in the opinion of the localinvestigator.

• Part 2: Failed to achieve CMR (Deauville score 1-3) on PET scan 1-month postCAR-T or progressed at any point post CAR-T (patients in part 2 may have beenpreviously enrolled in Part 1 and responded to Pola-Glofit bridging or be denovo 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 newbiopsy.

• 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 includinginvestigational 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 weeksprior to study treatment

• Treatment with systemic immunosuppressive medication within 2 weeks prior toinitiation 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 humanisedmonoclonal antibodies or recombinant antibody-related fusion proteins.

• Known hypersensitivity to Chinese hamster ovary cell products or to any component ofthe obinutuzumab, polatuzumab vedotin and/or glofitamab formulation.

• Known or suspected history of HLH