Radiotherapy in Combination With Glofitamab in Relapsed/Refractory Diffuse Large B Cell Lymphoma

The goal of this clinical trial is to see if a new combination of standard of care radiotherapy treatment prior to administering the study drugs obinutuzumab and glofitamab in relapsed/refractory Diffuse Large B Cell Lymphoma patients is effective. The main question it aims to answer is: If you are able to tolerate the study treatments, and whether your cancer responds to the study treatment, compared with other reported studies of standard care treatments. Participants will have three parts they need to complete over a 5 year period. * Screening period over a 28 day period * Treatment period - Radiotherapy followed by 12 treatment cycles every three weeks (total time approx. 37 weeks) * Follow up, up to 4 years. Additional PET imaging studies will be performed in a cohort of patients (up to 6) who are willing to undergo infusions of 89Zr-Df-Crefmirlimab and 18F-Granzyme B for evaluation of the impact of radiotherapy plus glofitamab with relapsed diffuse large B-cell lymphoma.

Inclusion Criteria: 1. Age 18 years. 2. Histologically proven relapsed/refractory CD20+ve DLBCL or a recognised subtype, including follicular large B-cell lymphoma and high grade B-cell lymphoma. 3. Prior systemic treatment: ≥2 lines OR after 1 line AND autologous stem cell transplant/CAR-T ineligible 4. Eastern Collaborative Oncology Group (ECOG) performance status 0 to 2. 5. Measurable FDG avid disease on baseline PET/CT scan 6. At least one site of active, PET positive disease that can be safely irradiated. Patients with disease only in previously irradiated sites that cannot be safely irradiated again due to tissue tolerance will be excluded. 7. Adequate bone marrow function including: * Haemoglobin \>8.0 g/dL * White cell count (WCC) ≥2000/μL * Neutrophils \>1.0 x 109/L * Platelets \>75 x 109/L at the time of study entry, unless attributed to lymphoma. Red cell transfusion is permitted. 8. Adequate renal function with serum creatinine ≤1.5 x ULN or creatinine clearance (CrCl) ≥ 45mL/min (using Cockcroft-Gault formula, Modification of Diet in Renal Disease Study Equation, 24hr urine collection, eGFR or a formal nuclear medicine technique) unless attributed to lymphoma (e.g. ureteric obstruction). 9. Adequate hepatic function with AST/ALT ≤3x ULN and total bilirubin ≤1.5 x ULN (except subjects with Gilbert syndrome, who can have a total bilirubin ≤3 mg/dL or ≤51.3 μmol/L) unless attributed to lymphoma (e.g. liver infiltration or biliary obstruction). 10. Adequate left ventricular ejection fraction of \>40% as demonstrated on a Gated Cardiac Blood Pool Scan or echocardiogram. 11. Life expectancy \> 3 months. 12. Patients of childbearing potential willing to adhere to the following contraceptive precautions: For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating eggs, as defined below: Women must remain abstinent or use contraceptive methods with a failure rate of \