Cluster of Differentiation Antigen 19/22(CD19/22) CAR T Cells (AUTO3) for the Treatment of Diffuse Large B Cell Lymphoma

Inclusion Criteria: 1. Male or female, aged ≥18 years. 2. Willing and able to give written, informed consent. 3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1. 4. Histologically confirmed DLBCL and large B cell lymphoma subsets, including: Phase I and Phase II Cohort 1: 1. DLBCL, not otherwise specified (NOS), per World Health Organisation classification and DLBCL with MYC oncogene (MYC) and B cell lymphoma 2 (BCL2) gene and/or B cell lymphoma 6 (BCL6) gene rearrangements (double/triple hit). 2. Transformed DLBCL from follicular lymphoma (FL). 3. High-grade B cell lymphoma with MYC expression (excluding Burkitt's lymphoma) Phase I and Phase II Cohort 2. 4. Transformed DLBCL from other indolent lymphomas (excluding Richter's transformation). 5. Primary mediastinal large B cell lymphoma. 5. Chemotherapy-refractory disease, defined as one or more of the following: 1. Stable disease (≤12 months) or progressive disease as best response to most recent chemotherapy containing regimen. Refractory disease after frontline chemo-immunotherapy is allowed. 2. Disease progression or recurrence in ≤12 months of prior autologous haematopoietic stem cell transplantation (ASCT). OR 6. Relapse after ≥two lines of therapy or after ASCT. At a minimum: 1. Patients must have received rituximab or another anti-cluster of differentiation antigen 20 (CD20) monoclonal antibody (unless Investigator determines that tumour is CD20-negative) and an anthracycline-containing chemotherapy regimen. 2. Patients must have either failed ASCT, or be ineligible for or not consenting to ASCT. 3. Patients with transformed DLBCL must have received at least one line of therapy after transformation to DLBCL. 7. Positron emission tomography-positive disease per Lugano classification. 8. For females of childbearing potential, a negative serum or urine pregnancy test must be documented at screening, prior to pre-conditioning and confirmed before receiving the first dose of study treatment. For females who are not postmenopausal or surgically sterile, highly effective methods of contraception must be used during the treatment period and for at least 12 months after the last dose of study treatment. 9. For males, it must be agreed that that two acceptable methods of contraception are used. 10. Adequate renal, hepatic, pulmonary, and cardiac function defined as: 1. Creatinine clearance ≥40 cc/min. 2. Serum alanine aminotransferase / aspartate aminotransferase ≤2.5 x upper limit of normal (ULN). 3. Total bilirubin ≤1.5 x ULN, except in subjects with Gilbert's syndrome. 4. Left ventricular ejection fraction (LVEF) ≥50% (by echocardiogram \[ECHO\] or Multiple gated acquisition scan \[MUGA\]) unless the institutional lower limit of normal is lower. 5. Baseline oxygen saturation \>92% on room air and ≤Grade 1 dyspnoea. 11. Patient has adequate bone marrow (BM) function without requiring ongoing blood product or granulocyte-colony stimulating factor support and meets the following criteria: 1. Absolute neutrophil count ≥1.0 × 10\^9/L. 2. Absolute lymphocyte count ≥0.3 × 10\^9/L (at enrolment and prior to leukapheresis). 3. Haemoglobin ≥80 g/L. 4. Platelets ≥75 × 10\^9/L 12. No contra-indications for leukapheresis. Exclusion Criteria: 1. Prior allogeneic haematopoietic stem cell transplant. 2. Females who are pregnant or lactating. 3. History or presence of clinically relevant CNS pathology such as epilepsy, paresis, aphasia, stroke within prior 3 months, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, uncontrolled mental illness, or psychosis. 4. Patients with active CNS involvement by malignancy. Patients with history of central nervous system (CNS) involvement with malignancy may be eligible if CNS disease has been effectively treated and provided treatment was at least 4 weeks prior to enrolment (at least 8 weeks prior to AUTO3 infusion). 5. Clinically significant, uncontrolled heart disease or a recent (within 12 months) cardiac event. 1. Uncontrolled cardiac arrhythmia (patients with rate-controlled atrial fibrillation are not excluded). 2. Evidence of pericardial effusion 6. Patients with a history (within 3 months) or evidence of deep vein thrombosis or pulmonary embolism requiring ongoing therapeutic anticoagulation at the time of pre-conditioning. 7. Patients with active gastrointestinal bleeding. 8. Patients with any major surgical intervention in the last 3 months. 9. Active bacterial, viral or fungal infection requiring systemic treatment. Active or latent hepatitis B infection or hepatitis C infection. Testing positive for human immunodeficiency virus, human T cell lymphotropic virus (HTLV1 and 2) or syphilis. 10. History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 24 months. 11. Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the CNS. 12. Evidence of active pneumonitis on chest computed tomography (CT) scan at screening or history of drug-induced pneumonitis, idiopathic pulmonary fibrosis, organising pneumonia, or idiopathic pneumonitis. 13. History of other malignant neoplasms unless disease free for at least 24 months (carcinoma in situ, non-melanoma skin cancer, breast or prostate cancer on hormonal therapy allowed). 14. Prior treatment with PD1, programmed cell death ligand 1 (PD-L1), or cytotoxic T lymphocyte-associated protein-4-targeted therapy, or tumour necrosis factor (TNF) receptor superfamily agonists within 6 weeks prior to AUTO3 infusion. 15. Prior treatment with investigational or approved gene therapy or cell therapy products until a dose level has treated at least three patients and has been declared safe. 16. Prior CD19 or CD22 targeted therapy. 17. The following medications are excluded: 1. Steroids: Therapeutic doses of corticosteroids within 7 days of leukapheresis or 72 hours prior to AUTO3 administration. However, physiological replacement, topical, and inhaled steroids are permitted. 2. Immunosuppression: Immunosuppressive medication must be stopped ≥2 weeks prior to leukapheresis or AUTO3 infusion. 3. Cytotoxic chemotherapies within 2 weeks of AUTO3 infusion and 1 week prior to leukapheresis (2 weeks for lymphodepleting chemotherapy). 4. Antibody therapy use including anti-CD20 therapy within 2 weeks prior to AUTO3 infusion, or 5 half-lives of the respective antibody, whichever is shorter. 5. Granulocyte-colony stimulating factor less than 10 days prior to leukapheresis. 6. Live vaccine ≤4 weeks prior to enrolment. 7. Prophylactic intrathecal therapy: Methotrexate within 4 weeks and other intrathecal chemotherapy (e.g. Ara-C) within 2 weeks prior to starting pre-conditioning chemotherapy. 18. Prior limited radiation therapy within 4 weeks of AUTO3 infusion or within 24 weeks for definitive radiation to chest. 19. Research participants receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy. 20. Known allergy to albumin, dimethyl sulphoxide (DMSO), cyclophosphamide or fludarabine, pembrolizumab or tocilizumab. 21. Any contraindications to receive anti-PD1 antibody pembrolizumab will be excluded from cohorts requiring administration of pembrolizumab. 22. Patients, who in the opinion of the Investigator, may not be able to understand or comply with the safety monitoring requirements of the study. 23. Any other condition that in the Investigator's opinion would make the patient unsuitable for the clinical trial. Phase I outpatient cohort: 24. Subjects who do not have caregiver support (in line with institutional outpatient transplant guidelines) for outpatient/ambulatory care setting. 25. Subjects who are staying greater than 60 minutes (or whatever is permissible per institutional outpatient transplant guidelines) from the clinical trial site at the time of treatment. For AUTO3 Infusion: Patients meeting any of the following exclusion criteria must not be treated with AUTO3 or have treatment delayed until they no longer meet these criteria: 1. Severe intercurrent infection. 2. Requirement for supplementary oxygen or active pulmonary infiltrates. 3. Clinical deterioration of organ function (renal and hepatic) exceeding the criteria set at study entry.