This is a phase II study designed to evaluate the toxicity and efficacy of the combination of loncastuximab tesirine and epcoritamab in patients with relapsed/refractory aggressive B-cell lymphoma. Chimeric antigen receptor (CAR)-T cell naive patients who have failed first-line therapy and patients who have received CAR-T cells as second-line therapy and experienced CAR-T failure will be eligible for inclusion.
Subjects with histologically confirmed relapsed/refractory DLBCL based on pathology report (WHO 2022 criteria)
DLBCL (de novo or transformed)
High-grade B-cell lymphoma with MYC and BCL2 rearrangements
High-grade B-cell lymphoma, not otherwise specified (NOS)
Any prior lymphoma-directed treatment, except for first-line anti-CD20-/anthracycline-containing chemoimmunotherapy or second line CAR-T cell therapy. Particularly, patients previously treated with loncastuximab tesirine and any CD3xCD20 bispecific antibody therapy are not eligible.
Patients with late relapse (>12 months) after first-line immunochemotherapy considered HDCT/ASCT eligible as assessed by the local investigator.
Known central nervous system (CNS) involvement.
Diagnosed or treated for any malignancy other than r/r DLBCL, HGBL or FL grade 3B within the last 3 years, except for adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, non-invasive basal cell or squamous cell skin carcinoma, adequately treated carcinoma in situ without evidence of disease, localized prostate cancer, post-radical prostatectomy with non-rising prostate-specific antigen levels < 0.1 ng/mL, cervical carcinoma of stage 1B or less, non-invasive, superficial bladder cancer or any curable cancer with a CR of > 2 years duration.
Single group
Loncastuximab Tesirine and Epcoritamab
DrugLoncastuximab tesirine: Loncastuximab tesirine 150 µg/kg iv for 2 cycles followed by 75 µg/kg iv on day 1 of each 21-day cycle in responding patients for 4 cycles subsequently (max. 6 cycles). Epcoritamab: Step-up dosing for epcoritamab sc will be performed, consisting of a 0.16 mg sc priming dose on day 1 of cycle 1 (day 8 of cycle 1 for loncastuximab tesirine), followed by a 0.8 mg sc dose on day 8, and full dosing with 48 mg sc on day 15. Starting from day 15, epcoritamab will be administered weekly during cycle 2-3, then once every 2 weeks during cycle 4-9, and once every 4 weeks from cycle 10 until cycle 13 (max. 13 cycles).
Best overall response rate (BORR)
BORR defined as the proportion of patients with r/r DLBCL, HGBL and FL grade 3B who achieve a complete or partial remission as best response up to 12-months of study treatment according to the 2014 Lugano criteria.
Progression-free survival (PFS)
2-year progression-free survival (PFS) with a 95% confidence interval. PFS is defined as time from the first dose of study drug until one of the following events occurs, whichever is first: Disease progression, Relapse or Death due to any cause. Patients who have not experienced an event at the time of analysis will be censored at the most recent date of disease assessment.
Overall survival (OS)
2-year overall survival (OS) defined as the time from the first dose of study drug to death of any cause. Patients who have not experienced an event at the time of analysis will be censored at the last date known to be alive.
Complete response (CR) rate
Complete response (CR) rate measured as the number of complete remissions as best response (achieved up to 12 months) divided by the number of patients treated with at least one dose of study drug.
Partial response (PR) rate
Partial response (PR) rate measured as the number of partial remissions as best response (achieved up to 12 months) divided by the number of patients treated with at least one dose of study drug.
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