Epcoritamab (Epcor)-Containing Combination Salvage Therapy Followed by ASCT & Epcor Consolidation in Patients With Relapsed LBCL

Inclusion Criteria:

1. Age 18 years or older

2. Confirmed diagnosis of DLBCL, Not-otherwise specified (NOS), Transformation ofindolent B-cell lymphoma, High-grade B-cell lymphoma (HGBCL), NOS, Diffuse-large BCL (DLBCL)/ High-grade B-cell lymphoma (HGBL) with MYC and BCL2 rearrangements orFollicular large B-cell lymphoma according to World Health Organization (WHO) 2016or 2022 criteria that has relapsed or progressed after one line ofchemoimmunotherapy

3. Transplant eligible according to local assessment

4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

5. Measurable disease on computed tomography (CT) scan, defined as a nodal site greaterthan 1.5cm in longest axis or an extranodal site greater than 1.0cm in longest axisAND baseline fluorodeoxyglucose (FDG) positron emission tomography (PET) scans mustdemonstrate positive lesion compatible with CT defined anatomical tumour sites

6. Histological confirmation of tumour CD20 positivity, analysed byimmunohistochemistry, on a pre-enrolment tissue sample performed after most recentprior therapy

7. Adequate renal function

• Creatinine clearance greater than 45mL per min (Cockcroft Gault formula)

8. Adequate hepatic function:

• Aspartate transaminase (AST) and alanine transaminase (ALT) less than or equalto 3x Upper Limit of Normal (ULN)

• Bilirubin less than or equal to 1.5x Upper Limit of Normal (ULN) or less thanor equal to 3 if documented liver involvement and/or Gilbert's disease.

9. Adequate haematologic function:

• Haemoglobin greater than or equal to 90g/L (transfusion support permitted)

• Absolute neutrophil count greater than or equal to 1.0 x 109 per L; growthfactor support allowed in case of bone marrow involvement

• Platelet count greater than 75 x 109 per L or greater than or equal to 50 x 109per L if documented marrow involvement

10. Able to take oral medications

11. Adequate washout of prior therapies:

• At least 4 weeks since last dose of immunochemotherapy, radio-conjugated ortoxin-conjugated compound, or other investigational anti-cancer therapy

• At least 6 weeks since chimeric antigen-receptor T-cell therapy

12. Resolution of toxicities from prior therapy to a grade that does not contraindicatetrial participation in the opinion of the investigator

13. If receiving glucocorticoid treatment at screening, treatment must be tapered downand administered with a maximum of 25 mg daily in the last 14 days before the firstdose of Epcoritamab

14. Before the first dose of Epcoritamab, during the trial and for 12 months after lastadministration of Epcoritamab, a woman must be either:

15. Not of childbearing potential, defined as: premenarchal; postmenopausal (greater than 45 years of age with amenorrhea for at least 12 months or any agewith 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 tuballigation procedures as consistent with local regulations], hysterectomy,bilateral salpingectomy, bilateral oophorectomy); or otherwise be incapable ofpregnancy

16. Of childbearing potential and practicing a highly effective method of birthcontrol (as defined by the European Clinical Trial Facilitation Group)consistent with local regulations regarding the use of birth control methodsfor patients participating in clinical trials: e.g., established use of oral,injected or implanted combined (estradiol and progesterone containing) hormonalcontraception; placement of an intrauterine device (IUD) or intrauterine system (IUS); male partner sterilization (the vasectomized partner should be the solepartner for that patient); true abstinence (when this is in line with thepreferred and usual lifestyle of the patient) * If the childbearing potentialchanges after start of the trial (e.g., woman who is not heterosexually activebecomes active, premenarchal woman experiences menarche) a woman must begin ahighly effective method of birth control, as described under 16b

17. A man who is sexually active with a woman of childbearing potential must agree touse a barrier method of birth control (that is the use of condom) during the trialand for 12 months after receiving the last dose of Epcoritamab

18. Women must agree not to donate eggs (ova, oocytes) for the purposes of assistedreproduction during the trial and for 12 months after receiving the last dose ofEpcoritamab. Men must also not donate sperm during the trial and for 12 months afterreceiving the last dose of Epcoritamab

19. The patient understands the purpose of the trial and procedures required for thetrial and is capable of giving signed informed consent which includes compliancewith the requirements (no medical or psychiatric reason precluding participation)and restrictions listed in the informed consent form (ICF) and in this protocol

Exclusion Criteria:

1. Diagnosis of primary Central Nervous System (CNS) lymphoma

2. Active secondary CNS involvement of lymphoma at time of screening

• A prior history of secondary CNS lymphoma is allowed provided that it has beensuccessfully treated and there are no features of recurrence.

3. Prior autologous stem cell transplant

4. Known past or current malignancy other than inclusion diagnosis, except for:

5. Cervical carcinoma of Stage 1B or less.

6. Non-invasive basal cell or squamous cell skin carcinoma.

7. Non-invasive, superficial bladder cancer.

8. Prostate cancer with a current Prostate Specific Agent (PSA) level less than 0.1 ng per mL e. indolent lymphoma

9. Indolent lymphoma

10. Other malignancy that has been treated with curative intent and has remained inremission for 2 years

11. Any prior therapy with a bispecific antibody targeting CD3 and CD20

12. Uncontrolled systemic infection

13. Known HIV infection

14. Known active hepatitis B or C infection based on criteria below:

• Hepatitis B virus (HBV): Patients with positive HbsAg are excluded. Patientswith positive hepatitis B core antibody (antiHBc) and negative HbsAg requirenegative hepatitis B polymerase chain reaction (PCR) before enrolment and mustbe treated with antiviral therapy. Patients who are hepatitis B PCR positivewill be excluded.

• Hepatitis C virus (HCV): If positive hepatitis C antibody, patient will need tohave a negative hepatitis C ribonucleic acid (RNA) before enrolment. Patientswho are hepatitis C RNA positive will be excluded.

9. Seizure disorder, unless seizure-free for 12 months on established anticonvulsanttherapy without the requirement for modification to anticonvulsants within the prior 12 months

10. Known clinically significant cardiac disease, including:

11. Onset of unstable angina pectoris within 6 months of signing the patientinformed consent form (PICF)

12. Acute myocardial infarction within 6 months of signing the PICF

13. Congestive heart failure (grade III or IV as classified by the New York HeartAssociation

14. Decreased ejection fraction of less than 45%

15. Confirmed history or current autoimmune disease requiring permanentimmunosuppressive therapy. Low-dose prednisolone (less than or equal to 10mg/day orequivalent) for rheumatoid arthritis or similar conditions is allowed.

16. Exposed to live or live attenuated vaccine within 4 weeks prior to signing PICF

17. Women who are pregnant or lactating.

18. Patient has any condition for which, in the opinion of the investigator,participation would not be in the best interest of the patient (e.g., compromise thewell-being) or that could prevent, limit, or confound the protocol-specifiedassessments

19. Known hypersensitivity or adverse reaction to rituximab, tocilizumab or any elementsof DHAOx

20. Presence of any psychological, familial, sociological or geographical conditionpotentially hampering compliance with the study protocol and follow-up schedule.This condition must be discussed with the patient prior to signing consent andregistration in the trial