Response-adaptive to Epcoritamab In First Relapse: Study to Evaluate the Efficacy of Eptoritamab in Patients With Relapse/Refractory Large B Cell Lymphoma

Inclusion Criteria: 1. Written informed consent must be obtained before any study-specific assessment is performed. 2. Age \>18 years 3. Patients with Relapse/Refractory histologically confirmed LBCL, including, Diffuse Large B Cell Lymphoma (DLBCL); Primary Mediastinal Large B Cell Lymphoma (PMBCL), High-grade B-cell lymphoma (HGBCL); and grade 3B Follicular Lymphoma. Relapsed disease is defined as complete remission to first line therapy followed by a recurrence of the disease after a minimum of 6 months of completion of first-line therapy. A biopsy at the time of relapse is recommended but not mandatory. Refractory disease is defined as no objective response to first line therapy (biopsy not mandatory if diagnostic sample available). Four groups of patients are eligible: * PD as best response to first line therapy. * SD as best response after at least 4 cycles of first line therapy. * PR as best response after at least 6 cycles of first line therapy. * CR and disease recurrence within \< 6 months from the completion of first-line therapy. 4. Patients must have received adequate first-line therapy including at a minimum: an anti-CD20 monoclonal antibody (rituximab or obinutuzumab), and CHOP (cyclophosphamide, hydroxydaunomycin, oncovin, and prednisone) or CHOP-like chemotherapy. 5. At the investigator's discretion, the patient should not be a candidate for 1st relapse CAR-T therapy or unwilling to receive CAR-T therapy. 6. Patients must be autologous stem cell transplantation (ASCT)-ineligible: Age ≥65 and/or HTC-CI ≥3 or or unwilling to receive transplant. 7. PET positive disease. 8. Performance status according to Eastern Cooperative Oncology Group (ECOG) 0 to 2. 9. Patients meeting with the following hematology values: * Hemoglobin ≥8 g/dl (transfusion support permitted but not within 7 days of screening lab collection) * Absolute neutrophil count (ANC) ≥ 1/109/L (growth factor support allowed in case of bone marrow involvement). * Absolute lymphocyte count ≥ 0.1/109/L, * Platelet count ≥ 70/109/L (unless secondary to bone marrow involvement, OR ≥50x/109/L if documented bone marrow involvement). Platelet transfusions permitted but not within 7 days of screening lab collection. 10. Female patients of child-bearing potential must have a negative urine or serum pregnancy test at screening and agree to use highly effective methods of contraception (e.g., established use of oral, injected or implanted combined (estradiol and progesterone containing) hormonal contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS) upon enrollment according to the recommendations provided by Clinical Trial Facilitation Group (CTFG), during the treatment period and for 4 months after the last dose of study medication. Moreover, the patient must agree to ongoing pregnancy testing during the course of the study, and after study therapy has ended. This applies even if the patient practices complete and continued sexual abstinence. Women not of childbearing potential are defined as: premenarchal; postmenopausal (greater than 50 years of age with amenorrhea for at least 12 months or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone (FSH) level greater than 40 IU per L or milli-International unit (mIU) per mL); permanently sterilized (e.g., bilateral tubal occlusion \[which includes tubal ligation procedures as consistent with local regulations\], hysterectomy, bilateral salpingectomy, bilateral oophorectomy); or otherwise be incapable of pregnancy. 11. Male patients must use a reliable method of contraception (if sexually active with a female of child-bearing potential) upon enrollment according to the recommendations provided by CTFG, during the treatment period, and for 4 months following the last dose of investigational drug or agreement to remain abstinent. Agreement to refrain from donating blood or sperm during the study participation and for 4 months after the last dose of study medication. 12. Women must agree not to donate blood or oocytes during the course of the study and for 4 months after the last dose of study medication. Restrictions concerning blood donation apply as well to females who are not of childbearing potential. Men must also not donate sperm during the trial and for 4 months after receiving the last dose of study drug. 13. Females of childbearing potential must refrain from breastfeeding during the course of the study and for 4 months after the last dose of study medication. 14. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. 15. Not included in other clinical trial or treated with an experimental drug. Exclusion Criteria: 1. Patients who received more than one prior line of systemic therapy 2. Patients with detectable Central Nervous System (CNS) lymphoma 3. Significant organ function impairment: * creatinine clearance calculated by Cockcroft-Gault ≤ 45 ml/min * direct bilirubin level \< 2 x ULN (except in patients with Gilbert's syndrome), * alanine transaminase (ALT) and aspartate aminotransferase (AST) \>3 × ULN or \>5 × ULN in cases of documented liver involvement. * clinically relevant pleural effusion, * left ventricular ejection fraction (LVEF) ≤ 45% 4. Serious accompanying disorder leading to impaired organ function causing significant clinical problems and reduced life expectancy of less than 3 months. 5. Have a history of deep venous thrombosis/embolism, threatening thromboembolism or known thrombophilia or are at a high risk for a thromboembolic event in the opinion of the investigator and who are not willing/able to take venous thromboembolic event prophylaxis during the entire treatment period 6. Known clinically significant cardiac disease, including: * Onset of unstable angina pectoris within 6 months of signing the patient informed consent form. * Acute myocardial infarc