| Eligibility |
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
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 been
successfully 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:
1. Cervical carcinoma of Stage 1B or less.
2. Non-invasive basal cell or squamous cell skin carcinoma.
3. Non-invasive, superficial bladder cancer.
4. Prostate cancer with a current Prostate Specific Agent (PSA) level less than 0.1
ng per mL e. indolent lymphoma
5. Indolent lymphoma
6. Other malignancy that has been treated with curative intent and has remained in
remission for 2 years
5. Any prior therapy with a bispecific antibody targeting CD3 and CD20
6. Uncontrolled systemic infection
7. Known HIV infection
8. Known active hepatitis B or C infection based on criteria below:
- Hepatitis B virus (HBV): Patients with positive HbsAg are excluded. Patients with
positive hepatitis B core antibody (antiHBc) and negative HbsAg require negative
hepatitis B polymerase chain reaction (PCR) before enrolment and must be treated
with antiviral therapy. Patients who are hepatitis B PCR positive will be
excluded.
- Hepatitis C virus (HCV): If positive hepatitis C antibody, patient will need to
have a negative hepatitis C ribonucleic acid (RNA) before enrolment. Patients who
are hepatitis C RNA positive will be excluded.
9. Seizure disorder, unless seizure-free for 12 months on established anticonvulsant
therapy without the requirement for modification to anticonvulsants within the prior
12 months
10. Known clinically significant cardiac disease, including:
1. Onset of unstable angina pectoris within 6 months of signing the patient informed
consent form (PICF)
2. Acute myocardial infarction within 6 months of signing the PICF
3. Congestive heart failure (grade III or IV as classified by the New York Heart
Association
4. Decreased ejection fraction of less than 45%
11. Confirmed history or current autoimmune disease requiring permanent immunosuppressive
therapy. Low-dose prednisolone (less than or equal to 10mg/day or equivalent) for
rheumatoid arthritis or similar conditions is allowed.
12. Exposed to live or live attenuated vaccine within 4 weeks prior to signing PICF
13. Women who are pregnant or lactating.
14. 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 the well-being) or
that could prevent, limit, or confound the protocol-specified assessments
15. Known hypersensitivity or adverse reaction to rituximab, tocilizumab or any elements
of DHAOx
16. Presence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule. This
condition must be discussed with the patient prior to signing consent and registration
in the trial
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