A Phase 2 interventional study of Epcoritamab and Epcoritamab, tafasitamab and lenalidomide in Large B Cell Lymphoma, sponsored by Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea. Recruiting at 19 sites in Spain. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-29.
Sponsored by Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea · Phase 2, Interventional, and Treatment
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.
Epcoritamab is a full-length bispecific IgG1 antibody directed against two proteins, CD3 on the T lymphocyte and CD20 on the lymphoma cell. This antibody redirects and activates T cells, generating an immune synapse that eventually eliminates malignant cells expressing CD20.
Previous studies have demonstrated that Epcoritamab has potent antitumor activity as a monotherapy agent, with a favorable and manageable safety profile.
Since its efficacy is so favorable it is reasonable to think that it could be an excellent option for first-relapse patients. However, to date, there is no data on this therapy's usefulness as second-line treatment. Therefore we intend to evaluate the efficacy of Epcoritamab as a treatment option for patients with first-relapse LBCL.
The purpose of this study is to determine the efficacy of Epcoritamab as second line treatment for LBCL patients. On the basis of the clinical experience, it is hypothesized that Epcoritamab would provide a better complete response rate (CRR) in comparison to Platinum-based immunochemotherapy (CRR=25%), Polatuzumab-Bendamustin Rituximab (CRR=40%) and Tafasitamab-Lenalidomide (CRR=43%).
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.
Relapsed disease is defined as complete remission to first line therapy followed by a recurrence of the disease after a minimum of 6 months of completion of first-line therapy. A biopsy at the time of relapse is recommended but not mandatory.
Refractory disease is defined as no objective response to first line therapy (biopsy not mandatory if diagnostic sample available). Four groups of patients are eligible:
Patients meeting with the following hematology values:
Female patients of child-bearing potential must have a negative urine or serum pregnancy test at screening and agree to use highly effective methods of contraception (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) upon enrollment according to the recommendations provided by Clinical Trial Facilitation Group (CTFG), during the treatment period and for 4 months after the last dose of study medication. Moreover, the patient must agree to ongoing pregnancy testing during the course of the study, and after study therapy has ended. This applies even if the patient practices complete and continued sexual abstinence.
Women not of childbearing potential are defined as: premenarchal; postmenopausal (greater than 50 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.
Exclusion Criteria:
Significant organ function impairment:
Known clinically significant cardiac disease, including:
History of HIV infection or acute or chronic active hepatitis B or C infection.
Epcoritamab in monotherapy will be administred until cycle 12.
Drug: Epcoritamab
3 cycles of Epcoritamab in monotherapy will be administred and then Epcoritamab will be administred with Tafasitamab and Lenalidomide from cycle 4 until cycle 15.
Drug: Epcoritamab, tafasitamab and lenalidomide
Patients will receive 12 cycles of Epcoritamab monotherapy.
Patients 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.
Time frame: Cycle 3, cycle 4, cycle 7, cycle 10, cycle 13 (for combination therapy) and EoT (28 days after last administration of investigational product) visits. Each cycle is 28 days.
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.
Time frame: At the end of cycle 3 (each cycle is 28 days)
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).
Time frame: Cycle 3, cycle 4, cycle 7, cycle 10, cycle 13 (for combination therapy) and EoT (28 days after last administration of investigational product) visits. Each cycle is 28 days.
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).
Time frame: Cycles 3, 4, 7, 10, 12, 13, 15 (each cycle is 28 days), EoT (28 days after last administration of Study drug) and cycles 18 and 24 (epcoritamab monotherapy) or cycles 21 and 27 (combination therapy) visits (each cycle is 28 days).
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).
Time frame: At cycle 3 visit (each cycle is 28 days).
Safety and tolerability
The safety and tolerability of Epcoritamab monotherapy and combination therapy are evaluated as follows: * Type, frequency, and severity of adverse events (AEs). * Type, frequency, and severity of Adverse events of special interest (AESIs): Cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), clinical tumor lysis syndrome (CTLS) and other safety topics of interest (tumour flare reaction, prolonged cytopenia, serious infections and second primary malignancies). * Incidence, severity, and treatment.
Time frame: Baseline, during all the cycles day 1 visit (each cycle is 28 days) and at EoT (28 days afert las administration of Study drug).
Efficacy of Epcoritamab Monotherapy and Combination therapy by ORR
The efficacy of Epcoritamab monotherapy and combination therapy with tafasitamab-lenalidomide will be evaluated by local investigators and central evaluation as per ORR at any time.
Time frame: Cycle 3, cycle 4, cycle 7, cycle 10, cycle 13 (for combination therapy) and EoT (28 days after last administration of investigational product) visits. Each cycle is 28 days
Efficacy of Epcoritamab Monotherapy and combination therapy by DoR
The efficacy of Epcoritamab monotherapy and combination therapy with tafasitamab-lenalidomide will be evaluated by local investigators and central evaluation as per DoR at any time.
Time frame: Cycle 3, cycle 4, cycle 7, cycle 10, cycle 13 (for combination therapy) and EoT (28 days after last administration of investigational product) visits. Each cycle is 28 days
Efficacy of Epcoritamab monotherapy and combination therapy by DoCR
The efficacy of Epcoritamab monotherapy and combination therapy with tafasitamab-lenalidomide will be evaluated by local investigators and central evaluation as per DoCR at any time.
Time frame: Cycle 3, cycle 4, cycle 7, cycle 10, cycle 13 (for combination therapy) and EoT (28 days after last administration of investigational product) visits. Each cycle is 28 days
Efficacy of Epcoritamab monotherapy and combination therapy by EFS
The efficacy of Epcoritamab monotherapy and combination therapy with tafasitamab-lenalidomide will be evaluated by local investigators and central evaluation as per Event-free survival (EFS) at any time.
Time frame: Cycle 3, cycle 4, cycle 7, cycle 10, cycle 13 (for combination therapy) and EoT (28 days after last administration of investigational product) visits. Each cycle is 28 days
Efficacy of Epcoritamab monotherapy and combination therapy by PFS
The efficacy of Epcoritamab monotherapy and combination therapy with tafasitamab-lenalidomide will be evaluated by local investigators and central evaluation as per PFS at any time.
Time frame: Cycle 3, cycle 4, cycle 7, cycle 10, cycle 13 (for combination therapy) and EoT (28 days after last administration of investigational product) visits. Each cycle is 28 days
Efficacy of Epcoritamab montherapy and combination therapy by OS
The efficacy of Epcoritamab monotherapy and combination therapy with tafasitamab-lenalidomide will be evaluated by local investigators and central evaluation as per OS at any time.
Time frame: Cycle 3, cycle 4, cycle 7, cycle 10, cycle 13 (for combination therapy) and EoT (28 days after last administration of investigational product) visits. Each cycle is 28 days
Evaluation of patients with negative MRD by OS
The OS of patients with negative MRD at Visit 3 (V3) (immediately before administrating C3 of Epcoritamab monotherapy).
Time frame: At cycle 3 visit (each cycle is 28 days).
Evaluation of patients with negative MRD by DoR
The DoR of patients with negative MRD at Visit 3 (V3) (immediately before administrating C3 of Epcoritamab monotherapy).
Time frame: At cycle 3 visit (each cycle is 28 days).
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.
Time frame: At EoT visit (28 days after last administration of Study drug) for monotherapy and at C13 visit for combination therapy (each cycle is 28 days).
Correlation between biomarkers and study treatment by ORR
Correlation between biomarkers and study treatment efficacy determined by ORR.
Time frame: Cycles 3, 4, 7, 10, 12, 13, 15 (each cycle is 28 days), EoT (28 days after last administration of Study drug) and cycles 18 and 24 (epcoritamab monotherapy) or cycles 21 and 27 (combination therapy) visits (each cycle is 28 days).
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.
Time frame: After reintroduction of study treatment due to MRD positive result, on cycles 13, 16, 19, 22, 25, 28 visits (each cycle is 28 days).
MRD negativity
Median duration of molecular response (MRD negativity).
Time frame: through study completion, an average of 5 years
Correlation between tumor volume and efficacy
Correlation between Total Metabolic Tumor Volume (centrally evaluated) and study treatment efficacy determined by PFS and OS.
Time frame: Cycle 3, cycle 4, cycle 7, cycle 10, cycle 13 (for combination therapy) and EoT (28 days after last administration of investigational product) visits. Each cycle is 28 days.
ctDNA levels
Descriptive analysis of dynamic changes in ctDNA levels
Time frame: Cycles 3, 4, 7, 10, 12, 13, 15 (each cycle is 28 days), EoT (28 days after last administration of Study drug) and cycles 18 and 24 (epcoritamab monotherapy) or cycles 21 and 27 (combination therapy) visits (each cycle is 28 days).
Correlation between lymphocyte subsets and efficacy
Correlation between lymphocyte subsets and study treatment efficacy determined by ORR, CRR, DoR, PFS and OS and safety determined by type, frequency, and severity of adverse events.
Time frame: Through study completion, an average of 5 years.
Response of patients stopping treatment
To compare the DoR 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.
Time frame: At EoT visit (28 days after last administration of Study drug) for monotherapy and at C13 visit for combination therapy (each cycle is 28 days).
Correlation between biomarkers and study treatment efficacy by CRR
Correlation between biomarkers and study treatment efficacy determined by CRR.
Time frame: Cycles 3, 4, 7, 10, 12, 13, 15 (each cycle is 28 days), EoT (28 days after last administration of Study drug) and cycles 18 and 24 (epcoritamab monotherapy) or cycles 21 and 27 (combination therapy) visits (each cycle is 28 days).
Correlation between biomarkers and study treatment efficacy DoR
Correlation between biomarkers and study treatment efficacy determined by DoR, PFS and OS.
Time frame: Cycles 3, 4, 7, 10, 12, 13, 15 (each cycle is 28 days), EoT (28 days after last administration of Study drug) and cycles 18 and 24 (epcoritamab monotherapy) or cycles 21 and 27 (combination therapy) visits (each cycle is 28 days).
Correlation between biomarkers and study treatment efficacy by PFS
Correlation between biomarkers and study treatment efficacy determined by PFS.
Time frame: Cycles 3, 4, 7, 10, 12, 13, 15 (each cycle is 28 days), EoT (28 days after last administration of Study drug) and cycles 18 and 24 (epcoritamab monotherapy) or cycles 21 and 27 (combination therapy) visits (each cycle is 28 days).
Correlation between biomarkers and study treatment efficacy by OS
Correlation between biomarkers and study treatment efficacy determined by OS.
Time frame: Cycles 3, 4, 7, 10, 12, 13, 15 (each cycle is 28 days), EoT (28 days after last administration of Study drug) and cycles 18 and 24 (epcoritamab monotherapy) or cycles 21 and 27 (combination therapy) visits (each cycle is 28 days).
Efficacy of Epcoritamab monotherapy and combination therapy in patients reintroducing treatment by PFS
Efficacy of Epcoritamab or Epcoritamab/Tafasitamab by PFS in patients reintroducing the study treatment with a MRD positive result.
Time frame: After reintroduction of study treatment due to MRD positive result, on cycles 13, 16, 19, 22, 25, 28 visits (each cycle is 28 days)
Efficacy of Epcoritamab monotherapy and combination therapy in patients reintroducing treatment by OS
Efficacy of Epcoritamab or Epcoritamab/Tafasitamab by OS in patients reintroducing the study treatment with a MRD positive result.
Time frame: After reintroduction of study treatment due to MRD positive result, on cycles 13, 16, 19, 22, 25, 28 visits (each cycle is 28 days)
Plan to share: Yes — Data obtained through this study may be provided to qualified researchers with academic interest in hematology diseases. All individual data collected during the trial will be available. Data shared will be coded, with no PHI included. Study protocol, statistical analysis plan, informed consent form and clinical study report will be also available. Information will be available beginning 6 months after final publication with no end date established. Approval of the request and execution of all applicable agreements are prerequisites to the sharing of data with the requesting party. Data requests can be submitted starting 6 months after article publication. Access to trial IPD can be requested by qualified researchers and will be provided following review and approval of a research and execution of a Data Sharing Agreement (DSA). For more information or to submit a request, please contact to GELTAMO though the web page: https://www.geltamo.com/contacto
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