Epcoritamab Plus Lenalidomide in Relapsed/Refractory Large B-cell Lymphoma After Second-Line CAR T-cell Therapy

NCT07814001 | Not Yet Recruiting Phase 2

• 1 other identifier: BiFAST
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 15

Brief Summary

The goal of this Phase 2, open-label, multicenter clinical trial is to assess the efficacy and safety of accelerated ramp-up and fixed-dose subcutaneous epcoritamab combined with lenalidomide in adults with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) following progression after second-line CAR T-cell therapy. The main question it aims to answer is : \- What is the overall response rate (ORR) after Cycle 2, or at premature treatment discontinuation (PTD), according to the 2014 Lugano Response Criteria? Participants will:

• Receive subcutaneous epcoritamab administered according to an accelerated ramp-up schedule followed by fixed dosing, in combination with lenalidomide.
• Undergo clinical evaluations, laboratory assessments, and PET-CT imaging to determine disease status based on the 2014 Lugano Response Criteria.
• Continue study therapy for up to 48 weeks.
• Enter a follow-up period of at least 24 months after the last dose to monitor long-term outcomes and safety. Approximately 55 adults will be enrolled across multiple centers in France. Eligible individuals must have R/R LBCL, including diffuse large B-cell lymphoma and other eligible LBCL subtypes, with progressive metabolic disease documented by PET-CT at least 1 month after second-line CAR T-cell therapy. The overall study duration is expected to be approximately 5 years.

Conditions

Refractory Diffuse Large B-Cell Lymphoma (DLBCL); Refractory Large B-cell Lymphoma (LBCL); Refractory T-cell/Histiocyte-rich Large B-cell Lymphoma; Refractory Transformed Follicular Lymphoma; Refractory High-Grade B-Cell Lymphoma; Refractory Follicular Lymphoma Grade 3B

Keywords

Post CAR T cells therapy

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Overall response rate (ORR), defined as the proportion of participants achieving a complete response (CR) or partial response (PR) according to the 2014 Lugano Response Criteria following treatment with accelerated ramp-up dosing and fixed-dose epcoritamab in combination with lenalidomide.

  At the end of Cycle 2 (each cycle is 28 days) or until premature treatment discontinuation (PTD) from any cause, whichever occurs first, assessed up to 56 days

Secondary Outcomes (10)

• Best Overall Response Rate (Best ORR)

  From Cycle 1 through the end of Cycle 8 (each cycle is 28 days) or until premature treatment discontinuation (PTD) from any cause, whichever occurs first, assessed up to 224 days.

• Complete Metabolic Response (CMR) Rate

  At Cycles 1, 2, 5, 8, and 12 (each cycle is 28 days), assessed up to 336 days.

• Duration of Response (DoR)

  From the date of first documented partial or complete response until the date of first documented disease progression, relapse, or death from any cause, whichever occurs first, assessed up to 54 months ( end of follow-up).

• Progression-Free Survival (PFS)

  From date of Cycle 1 (each cycle is 28 days)until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 54 months

• Overall Survival (OS)

  From Cycle 1 ( 28 days) until date of death, or until end of follow-up (up to 54 months)

Study Arms (1)

Epcoritamab plus Lenalidomide

EXPERIMENTAL

All enrolled participants will be included in a single cohort. No comparator group will be included.

Drug: Epcoritamab; Drug: Lenalidomide

Interventions

Epcoritamab DRUG

Epcoritamab will be administered subcutaneously in combination with lenalidomide. During Cycle 1, participants will receive an accelerated ramp-up dosing schedule consisting of 0.16 mg on Day 1, 0.8 mg on Day 3, and 48 mg on Days 8, 15, and 22. During Cycle 2, participants will receive 48 mg once weekly on Days 1, 8, 15, and 22. During the consolidation phase (Cycles 3 to 12), participants will receive 48 mg subcutaneously on Day 1 of each 28-day cycle.

Also known as: DuoBody-CD3xCD20

Epcoritamab plus Lenalidomide

Lenalidomide DRUG

Lenalidomide will be administered orally in combination with epcoritamab from Cycles 2 through 12. Lenalidomide will be given once daily on Days 1 to 21 of each 28-day cycle, followed by a 7-day rest period (Days 22 to 28). The starting dose will be 20 mg for participants with creatinine clearance (CrCL) ≥60 mL/min and 10 mg for participants with CrCL between 30 and \<60 mL/min, according to the study protocol.

Epcoritamab plus Lenalidomide

Eligibility Criteria

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

You may qualify if:

• Participant (or their legally acceptable representative / trusted person) who understand and voluntarily signs and dates an informed consent form prior to any study-specific assessments/procedures being conducted
• Aged ≥ 18 years at the time of signing the informed consent form (ICF) with no upper age limit
• Diagnosis at relapse/progression post CAR T-cells of LBCL (de novo or histologically transformed from follicular lymphoma) with histologically confirmed CD20+ disease, inclusive of the following according to WHO 2022 classification and documented in pathology report:
• Diffuse large B-cell lymphoma (DLBCL), NOS
• Large B-cell lymphoma (LBCL)
• T-cell/histiocyte-rich large B-cell lymphoma
• Transformed follicular lymphoma
• DLBCL/High-grade B cell lymphoma with MYC and BCL-2 translocations per WHO 2022.
• High-grade B-cell lymphoma, NOS
• Follicular lymphoma Grade 3B
• Note: The following, non-exhaustive list of histologies excluded from enrollment: patients with CLL, Richter's, indolent non-Hodgkin lymphoma, transformed WM, transformed MZL and Burkitt lymphoma
• Participant must have no prior treatment with epcoritamab or any other bispecific antibody targeting CD3 and CD20
• Relapsing or refractory after two systemic lines of treatment including CAR T-cells therapy (Note: bridging therapy is not considered as a line of treatment)
• R/R status will be determined by a PET scan performed approximately 1 month after CAR T cells infusion or on subsequent PET scans
• Note: Participant who received a combination of CAR T-cells therapy and immunomodulatory drugs (IMids) as second line are not eligible

You may not qualify if:

• Previously known CD20 negative status, excepted if a new biopsy or cytometry analysis proving a CD20 positive status is available before enrollment
• Prior solid organ transplantation
• Prior allogeneic SCT
• Autologous SCT within 100 days prior to epcoritamab infusion
• Known or current central nervous system or meningeal involvement by lymphoma
• Current or past history of Progressive Multifocal Leukoencephalopathy (PML)
• Current or past history of aphasia, delirium, dementia, cerebellar disease, cognitive disorder, epilepsy under treatment, CNS vasculitis, neurodegenerative disease or dysarthria
• History of cerebrovascular ischemia / hemorrhage with sequelae
• Any serious psychiatric illness that would prevent the participant from signing the informed consent form
• Patients with known active infection, or reactivation of a latent infection, whether bacterial, viral (including, but not limited to symptomatic SARS CoV-2 infection), fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics (for IV antibiotics this pertains to completion of last course of antibiotic treatment) within 1 week prior epcoritamab first injection Note: positive PCR EBV related to lymphoma could be enrolled
• Known positive HTLV1 serology
• Active Hepatitis C Virus (HCV) infection (RNA PCR-positive). Participants who received treatment for HCV infection that was intended to eradicate the virus may participate if hepatitis C RNA levels are undetectable,
• Active Hepatitis B Virus (HBV) infection (DNA PCR-positive).
• LVEF \< 45% as determined by echocardiography or multiple uptake gated acquisition (MUGA) scan
• Any serious active disease or co-morbid medical condition (such as New York Heart Association Class III or IV cardiac disease, severe arrhythmia, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or pulmonary disease (including uncontrolled obstructive pulmonary disease and history of bronchospasm or other according to investigator's decision)

Sponsors & Collaborators

• The Lymphoma Academic Research Organisation: lead
• AbbVie: collaborator

Study Sites (15)

Hopital Henri Mondor

Créteil, 94010, France

Location

Chu Dijon Bourgogne

Dijon, 21000, France

Location

Chu de Lille - Hopital Claude Huriez

Lille, 59037, France

Location

CHU de Limoges - Hopital Dupuytren

Limoges, 87042, France

Location

Centre Léon Berard

Lyon, 69373, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

CHU de Montpellier

Montpellier, 34925, France

Location

CHU de Nantes

Nantes, 44093, France

Location

Hopital Necker

Paris, 75743, France

Location

CHU de Bordeaux - Hopital Haut-Leveque

Pessac, 33604, France

Location

CHU Lyon Sud

Pierre-Bénite, 69495, France

Location

CHU de Poitiers - Hopital de la Miletrie

Poitiers, 86021, France

Location

CHU Pontchaillou

Rennes, 35033, France

Location

IUCT Oncopole

Toulouse, 31059, France

Location

CHRU Nancy - Hopital Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Lenalidomide

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

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

Central Study Contacts

Stéphanie Doyen

CONTACT

+33 4 27 01 27 36; stephanie.doyen@lysarc.org

Nina Pronina

CONTACT

+33 (0)4 87 91 94 69; nina.pronina@lysarc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2026
• First Posted: September 10, 2026
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): May 1, 2031
• Last Updated: September 10, 2026

Record last verified: 2026-09

Locations

FR (15)