Response-adaptive to Epcoritamab In First Relapse: Study to Evaluate the Efficacy of Eptoritamab in Patients With Relapse/Refractory Large B Cell Lymphoma

NCT07126236 | Recruiting Phase 2

• 2 other identifiers: REPIFIR-AGR-GEL-232024-514440-86-00
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 15

Brief Summary

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.

Conditions

Large B Cell Lymphoma

Keywords

lymphoma; geltamo; DIFFUSE LARGE B-CELL LYMPHOMA; DLBCL; RELAPSE; epcoritamab; tafasitamab; lenalidomide

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

Secondary Outcomes (13)

• Efficacy of Epcoritamab monotherapy after 3 cycles

  At the end of cycle 3 (each cycle is 28 days)

• Efficacy of Epcoritamab monotherapy and combination therapy by CRR

  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

  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

  At cycle 3 visit (each cycle is 28 days).

• Safety and tolerability

  Baseline, during all the cycles day 1 visit (each cycle is 28 days) and at EoT (28 days afert las administration of Study drug).

Other Outcomes (14)

• Response of patients stopping treatment by PFS

  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

  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

  After reintroduction of study treatment due to MRD positive result, on cycles 13, 16, 19, 22, 25, 28 visits (each cycle is 28 days).

Study Arms (2)

EPCO monotherapy

EXPERIMENTAL

Epcoritamab in monotherapy will be administred until cycle 12.

Drug: Epcoritamab

Combination therapy

EXPERIMENTAL

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

Interventions

Epcoritamab DRUG

Patients will receive 12 cycles of Epcoritamab monotherapy.

EPCO monotherapy

Epcoritamab, tafasitamab and lenalidomide DRUG

Patients will receive 3 cycles of Epcoritamab monotherapy and then 12 cycles of Epcoritamab, Tafasitamab and Lenalidomide.

Combination therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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:
• PD as best response to first line therapy.
• SD as best response after at least 4 cycles of first line therapy.
• PR as best response after at least 6 cycles of first line therapy.
• CR and disease recurrence within \< 6 months from the completion of first-line therapy.
• Patients must have received adequate first-line therapy including at a minimum: an anti-CD20 monoclonal antibody (rituximab or obinutuzumab), and CHOP (cyclophosphamide, hydroxydaunomycin, oncovin, and prednisone) or CHOP-like chemotherapy.
• At the investigator's discretion, the patient should not be a candidate for 1st relapse CAR-T therapy or unwilling to receive CAR-T therapy.
• Patients must be autologous stem cell transplantation (ASCT)-ineligible: Age ≥65 and/or HTC-CI ≥3 or or unwilling to receive transplant.
• PET positive disease.
• Performance status according to Eastern Cooperative Oncology Group (ECOG) 0 to 2.
• Patients meeting with the following hematology values:

You may not qualify if:

• Patients who received more than one prior line of systemic therapy
• Patients with detectable Central Nervous System (CNS) lymphoma
• Significant organ function impairment:
• creatinine clearance calculated by Cockcroft-Gault ≤ 45 ml/min
• direct bilirubin level \< 2 x ULN (except in patients with Gilbert's syndrome),
• alanine transaminase (ALT) and aspartate aminotransferase (AST) \>3 × ULN or \>5 × ULN in cases of documented liver involvement.
• clinically relevant pleural effusion,
• left ventricular ejection fraction (LVEF) ≤ 45%
• Serious accompanying disorder leading to impaired organ function causing significant clinical problems and reduced life expectancy of less than 3 months.
• Have a history of deep venous thrombosis/embolism, threatening thromboembolism or known thrombophilia or are at a high risk for a thromboembolic event in the opinion of the investigator and who are not willing/able to take venous thromboembolic event prophylaxis during the entire treatment period
• Known clinically significant cardiac disease, including:
• Onset of unstable angina pectoris within 6 months of signing the patient informed consent form.
• Acute myocardial infarction within 6 months of signing the patient informed consent form.
• Congestive heart failure (grade III or IV as classified by the New York Heart Association.
• Left ventricular ejection fraction ≤45%.

Sponsors & Collaborators

• Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea: lead
• AbbVie: collaborator
• Incyte Corporation: collaborator
• Evidenze Health España (CRO): collaborator

Study Sites (15)

Hospital Universitario Miguel Servet

Zaragoza, Aragon, 50009, Spain

NOT YET RECRUITING

Hospital Universitario de Burgos

Burgos, Castille and León, 09006, Spain

NOT YET RECRUITING

ICO Badalona

Badalona, Catalonia, 08916, Spain

NOT YET RECRUITING

Hospital Universitari Vall d'Hebrón

Barcelona, Catalonia, 08035, Spain

NOT YET RECRUITING

Hospital San Pedro de Alcántara

Cáceres, Extremadura, 10003, Spain

NOT YET RECRUITING

Hospital General Universitario Gregorio Marañón

Madrid, Madrid, 28007, Spain

RECRUITING

Hospital Universitario Infanta Leonor

Madrid, Madrid, 28031, Spain

NOT YET RECRUITING

Hospital Universitario Fundación Jiménez Díaz

Madrid, Madrid, 28040, Spain

NOT YET RECRUITING

Hospital Virgen de la Arrixaca

El Palmar, Murcia, 30120, Spain

NOT YET RECRUITING

Hospital Universitario Costa del Sol

Marbella, Málaga, 29603, Spain

NOT YET RECRUITING

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, 33011, Spain

NOT YET RECRUITING

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Tenerife, 38320, Spain

NOT YET RECRUITING

Hospital Universitario Dr. Peset

Valencia, Valencia, 46017, Spain

NOT YET RECRUITING

Hospital Universitario y Politécnico La Fe

Valencia, Valencia, 46024, Spain

NOT YET RECRUITING

Hospital Universitario de Basurto

Bilbao, Vizcaya, 48013, Spain

NOT YET RECRUITING

Related Links

• GELTAMO web page

MeSH Terms

Conditions

Lymphoma; Lymphoma, Large B-Cell, Diffuse; Recurrence

Interventions

tafasitamab; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Mariana Bastos-Oreiro

  Hospital General Universitario Gregorio Marañón

  PRINCIPAL INVESTIGATOR

• Pau Abrisqueta

  Hospital Universitari Vall d'Hebrón

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Auxi Moreno

CONTACT

+34 683 636 850; amoreno@geltamo.com

Ana María Méndez

CONTACT

+34 942 203 450; administracion@geltamo.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2025
• First Posted: August 17, 2025
• Study Start: August 4, 2025
• Primary Completion (Estimated): December 1, 2031
• Study Completion (Estimated): December 1, 2031
• Last Updated: August 17, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

ES (15)