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

Launched by AUSTRALASIAN LEUKAEMIA AND LYMPHOMA GROUP · Feb 28, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for patients with relapsed or difficult-to-treat aggressive B-cell lymphomas, such as Diffuse Large B-cell Lymphoma (DLBCL). The trial is testing a medication called Epcoritamab, which will be combined with a standard chemotherapy regimen and followed by a procedure called autologous stem cell transplantation (ASCT). The main goals are to see if adding Epcoritamab can help more patients achieve complete remission (where the cancer is no longer detectable) before the transplant, and to evaluate the safety and effectiveness of continuing Epcoritamab after the transplant.

To participate in this trial, candidates must be at least 18 years old and have a confirmed diagnosis of one of the specified types of lymphoma that has not responded to previous treatment. They should also meet certain health criteria, such as having measurable disease and adequate organ function. If they join, participants will undergo three phases: receiving Epcoritamab with chemotherapy, then having the stem cell transplant, and finally continuing Epcoritamab for additional cycles. It’s important for potential participants to discuss with their doctors if this trial is the right option for them, considering their specific health conditions and treatment history.

Gender

ALL

Eligibility criteria

• 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