phase II, response-adaptive, open-label, multicenter study aiming to include 80 patients in 78 months. Patients will receive 3 cycles of epcoritamab monotherapy and, since cycle 4, they can continue with epcoritamab monotherapy until cycle 12 or change to combination therapy (epcoritamab + tafasitamab + lenalidomide) until cycle 15. Patients will be followed up to 5 years.
Written informed consent must be obtained before any study-specific assessment is performed.
Age >18 years
Patients with Relapse/Refractory histologically confirmed LBCL, including, Diffuse Large B Cell Lymphoma (DLBCL); Primary Mediastinal Large B Cell Lymphoma (PMBCL), High-grade B-cell lymphoma (HGBCL); and grade 3B Follicular Lymphoma.
PD as best response to first line therapy.
Patients who received more than one prior line of systemic therapy
Patients with detectable Central Nervous System (CNS) lymphoma
creatinine clearance calculated by Cockcroft-Gault ≤ 45 ml/min
direct bilirubin level < 2 x ULN (except in patients with Gilbert's syndrome),
Parallel
Epcoritamab
DrugPatients will receive 12 cycles of Epcoritamab monotherapy.
Epcoritamab, tafasitamab and lenalidomide
DrugPatients will receive 3 cycles of Epcoritamab monotherapy and then 12 cycles of Epcoritamab, Tafasitamab and Lenalidomide.
Efficacy of Epcoritamab monotherapy
The efficacy of Epcoritamab monotherapy will be centrally evaluated by the best CRR at any moment since initiation. The CRR will be assessed by PET-CT according to Lugano Classification and is defined as the proportion of patients who achieve a best response of complete response (CR) at any moment since initiation of Epcoritamab first administration.
Efficacy of Epcoritamab monotherapy after 3 cycles
The efficacy of Epcoritamab monotherapy will be centrally evaluated by the best CRR, defined as the proportion of patients who achieve a best response of CR after 3 cycles of Epcoritamab administration.
Efficacy of Epcoritamab monotherapy and combination therapy by CRR
The efficacy of Epcoritamab monotherapy and combination therapy with tafasitamab-lenalidomide will be evaluated by local investigators and central evaluation as per CRR (locally evaluated for Epcoritamab monotherapy; local and central evaluation for combination therapy).
Evaluation of MRD
The efficacy of Epcoritamab monotherapy and combination therapy will be evaluated by MRD (positive or negative) from ctDNA samples immediately before initiation of C3, C4, C7, C10, C12, C13, C15, End of Treatment (EoT) and cycles 18/24 (epcoritamab monotherapy) or cycles 21/27 (combination therapy).
Evaluation of patients with negative MRD by PFS
The PFS of patients with negative MRD at Visit 3 (V3) (immediately before administrating C3 of Epcoritamab monotherapy).
Response of patients stopping treatment by PFS
To compare the PFS of patients stopping therapy after 1 year of treatment (CR by PET-CT and negative MRD) with the groups of patients who continue monotherapy or receive combination.
Correlation between biomarkers and study treatment by ORR
Correlation between biomarkers and study treatment efficacy determined by ORR.
Efficacy of Epcoritamab monotherapy and combination therapy in patients reintroducing treatment by DoR
Efficacy of Epcoritamab or Epcoritamab/Tafasitamab by DoR in patients reintroducing the study treatment with a MRD positive result.
MRD negativity
Median duration of molecular response (MRD negativity).
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Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
Lead sponsor
AbbVie
Collaborator
Incyte Corporation
Collaborator
Evidenze CRO
Collaborator
