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 of indolent 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 or Follicular large B-cell lymphoma according to World Health Organization (WHO) 2016 or 2022 criteria that has relapsed or progressed after one line of chemoimmunotherapy
• •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 greater than 1.5cm in longest axis or an extranodal site greater than 1.0cm in longest axis AND baseline fluorodeoxyglucose (FDG) positron emission tomography (PET) scans must demonstrate positive lesion compatible with CT defined anatomical tumour sites
• •6. Histological confirmation of tumour CD20 positivity, analysed by immunohistochemistry, on a pre-enrolment tissue sample performed after most recent prior 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 equal to 3x Upper Limit of Normal (ULN)
• •* Bilirubin less than or equal to 1.5x Upper Limit of Normal (ULN) or less than or 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; growth factor 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 109 per 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 or toxin-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 contraindicate trial participation in the opinion of the investigator
• •13. If receiving glucocorticoid treatment at screening, treatment must be tapered down and administered with a maximum of 25 mg daily in the last 14 days before the first dose of Epcoritamab
• •14. Before the first dose of Epcoritamab, during the trial and for 12 months after last administration of Epcoritamab, a woman must be either:
• •1. Not of childbearing potential, defined as: premenarchal; postmenopausal (greater than 45 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
• •2. Of childbearing potential and practicing a highly effective method of birth control (as defined by the European Clinical Trial Facilitation Group) consistent with local regulations regarding the use of birth control methods for patients participating in clinical trials: 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); male partner sterilization (the vasectomized partner should be the sole partner for that patient); true abstinence (when this is in line with the preferred and usual lifestyle of the patient) \* If the childbearing potential changes after start of the trial (e.g., woman who is not heterosexually active becomes active, premenarchal woman experiences menarche) a woman must begin a highly effective method of birth control, as described under 16b
• •15. A man who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control (that is the use of condom) during the trial and for 12 months after receiving the last dose of Epcoritamab
• •16. Women must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the trial and for 12 months after receiving the last dose of Epcoritamab. Men must also not donate sperm during the trial and for 12 months after receiving the last dose of Epcoritamab
• •17. The patient understands the purpose of the trial and procedures required for the trial and is capable of giving signed informed consent which includes compliance with the requirements (no medical or psychiatric reason precluding participation) and restrictions listed in the informed consent form (ICF) and in this protocol