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

8 de setembro de 2026 atualizado por: The Lymphoma Academic Research Organisation

A Phase II Trial Evaluating Fixed Dose and Faster Ramp-up of Epcoritamab With Lenalidomide for 3L Relapse/Refractory Large B-cell Lymphoma After CAR T-cells Therapy in 2nd Line

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.

Visão geral do estudo

Status

Ainda não está recrutando

Condições

Intervenção / Tratamento

Tipo de estudo

Intervencional

Inscrição (Estimado)

55

Estágio

  • Fase 2

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Estude backup de contato

Locais de estudo

  • França
      • Créteil, França, 94010
        • Hopital Henri Mondor
        • Contato:
      • Dijon, França, 21000
        • CHU Dijon Bourgogne
        • Contato:
      • Lille, França, 59037
        • CHU de Lille - Hôpital Claude Huriez
        • Contato:
      • Limoges, França, 87042
        • CHU de Limoges - Hopital Dupuytren
        • Contato:
      • Lyon, França, 69373
      • Marseille, França, 13273
        • Institut Paoli Calmettes
        • Contato:
      • Montpellier, França, 34925
      • Nantes, França, 44093
      • Paris, França, 75743
        • Hopital Necker
        • Contato:
      • Pessac, França, 33604
      • Pierre-Bénite, França, 69495
      • Poitiers, França, 86021
        • CHU DE POITIERS - Hôpital de la Milétrie
        • Contato:
      • Rennes, França, 35033
      • Toulouse, França, 31059
      • Vandœuvre-lès-Nancy, França, 54511
        • CHRU Nancy - hôpital Brabois
        • Contato:

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

  • Adulto
  • Adulto mais velho

Aceita Voluntários Saudáveis

Não

Descrição

Inclusion Criteria:

  1. 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
  2. Aged ≥ 18 years at the time of signing the informed consent form (ICF) with no upper age limit

  3. 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

  4. Participant must have no prior treatment with epcoritamab or any other bispecific antibody targeting CD3 and CD20

  5. 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

  6. ECOG performance status 0 to 2

  7. Presence of disease specific criteria allowing response evaluation:

    • Bi-dimensionally measurable disease defined by at least one lymph node > 15 mm or extranodal lesion > 10mm
    • At least one hypermetabolic lesion demonstrated by 18FDG PET-CT (PET0)

  8. Adequate hematopoietic function at screening as follows (unless cytopenia is clearly due to bone marrow involvement, or hypersplenism):

    • Hemoglobin level > 8g/dL without RBC transfusion performed within 7 days before epcoritamab infusion
    • ANC ≥ 1 G/L (except if related to lymphoma involvement, ANC must be > 0.5 G/L)
    • Platelets ≥ 50 G/L without platelet transfusion performed within 7 days before epcoritamab (except if related to lymphoma, hypersplenism, platelets must be > 30 G/L)
  9. Adequate renal function (calculated MDRD or Cockcroft-Gault): Creatinine Clearance ≥ 40 ml/min

  10. Adequate liver function:

    • Total bilirubin ≤ 1.5 x ULN
    • Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 3 x ULN Note: Patients with documented history of Gilbert's Syndrome and in whom total bilirubin elevations are

    accompanied by elevated indirect bilirubin are eligible

  11. No persistent CAR-T neurotoxicity symptoms (regardless of grade)
  12. Other adverse events from prior anti-cancer therapy must have resolved to Grade ≤ 1 (excepted the events previously described in criteria 8 to 11)
  13. Negative HIV test at screening, with the following exception: Individuals with a positive HIV test at screening are eligible provided they are stable on antiretroviral therapy for at least 4 weeks, have a CD4 count ≥ 200/uL, have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months.

  14. Participant must not have documented refractoriness to IMids and must be suitable for treatment with lenalidomide in the opinion of the investigator.

    Note: Refractoriness to IMids is defined as:

    • Best response to prior IMids regimen of SD or PD, OR
    • Progressive disease within 6 months of completion of prior IMids regimen
  15. Participant must not have had lenalidomide exposure within 12 months prior to screening.
  16. Participant must be willing to take aspirin prophylaxis or prophylactic anticoagulation for thromboembolic event (or per local guidelines for lenalidomide administration).
  17. Participant must be able to swallow capsules and must not have any disease significantly affecting gastrointestinal function (e.g., resection of the stomach or small bowel, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction).

  18. Women of childbearing potential (WOCBP):

    • should have a negative result for pregnancy test (minimum sensitivity of 25mIU/mL, urine or serum) at screening
    • should agree to use at least one efficient method of birth control from 4 weeks prior to study treatment initiation, during study treatment administration and until 4 weeks after the last dose of lenalidomide and until
  19. Men of reproductive potential should agree to use an acceptable method of birth control (condom) and must agree not to donate sperm during treatment and for 7 days after the last dose of lenalidomide and until 12 months after the last dose of epcoritamab

Exclusion Criteria:

  1. Previously known CD20 negative status, excepted if a new biopsy or cytometry analysis proving a CD20 positive status is available before enrollment
  2. Prior solid organ transplantation
  3. Prior allogeneic SCT
  4. Autologous SCT within 100 days prior to epcoritamab infusion
  5. Known or current central nervous system or meningeal involvement by lymphoma
  6. Current or past history of Progressive Multifocal Leukoencephalopathy (PML)
  7. Current or past history of aphasia, delirium, dementia, cerebellar disease, cognitive disorder, epilepsy under treatment, CNS vasculitis, neurodegenerative disease or dysarthria
  8. History of cerebrovascular ischemia / hemorrhage with sequelae
  9. Any serious psychiatric illness that would prevent the participant from signing the informed consent form
  10. 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
  11. Known positive HTLV1 serology
  12. 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,
  13. Active Hepatitis B Virus (HBV) infection (DNA PCR-positive).
  14. LVEF < 45% as determined by echocardiography or multiple uptake gated acquisition (MUGA) scan
  15. 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)
  16. Uncontrolled cirrhosis
  17. Major surgery or significant traumatic injury < 28 days prior to the epcoritamab infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment
  18. Received systemic immunosuppressive medications (including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) with the exception ofcorticosteroid treatment < 25 mg/day prednisone or equivalent within 2 weeks prior to epcoritamab first infusion. Inhaled and topical steroids are permitted.
  19. Active malignancy other than the one treated in this Study.

  20. Prior history of malignancies unless the participant has been free of the disease (in CR) for ≥ 2 years. However, participants with the following history/concurrent conditions are allowed:

    1. Non-invasive basal cell or epidermoid carcinoma
    2. In situ carcinoma of the cervix
    3. In situ carcinoma of the breast
    4. Incidental histologic finding of prostate cancer (T1a or T1b) using the tumor, nodes, metastasis [TNM] clinical staging system Note: Woman with adjuvant endocrine therapy (i.e., hormonotherapy) after breast cancer treatment can be enrolled if hormonotherapy was started for ≥ 2 years
  21. Known or suspected hypersensitivity to the active substance or to any of the excipients.

  22. Prior treatment within 4 weeks or five half-lives of the drug, whichever is shorter, before epcoritamab infusion with: - standard radiotherapy

    • any chemotherapeutic agent or treatment with any other investigational anti-cancer agents (defined as treatment for which there is currently no regulatory authority approved indication)
    • systemic immunotherapeutic agents, including, but not limited to, radio-immunoconjugates, antibody-drug conjugates, immune/cytokines and monoclonal antibodies (e.g., anti-CTLA4, anti-PD1 and anti-PDL1) 23. Pregnant, planning to become pregnant or lactating or breastfeeding woman of childbearing potential
  23. Pregnant, planning to become pregnant or lactating or breastfeeding woman of childbearing potential
  24. Any significant medical conditions, or laboratory abnormality or psychiatric illness likely to interfere with participation in this clinical study (according to the investigator's decision)
  25. Participant deprived of his/her liberty by a judicial or administrative decision
  26. Participant hospitalized without consent
  27. Adult participant under legal protection

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: N / D
  • Modelo Intervencional: Atribuição de grupo único
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: Epcoritamab plus Lenalidomide
All enrolled participants will be included in a single cohort. No comparator group will be included.
Medicamento: Epcoritamab
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.
Outros nomes:
  • DuoBody-CD3xCD20
Medicamento: Lenalidomide
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.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Overall Response Rate (ORR)
Prazo: 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
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

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Best Overall Response Rate (Best ORR)
Prazo: 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.
Best overall response rate (Best ORR), defined as the proportion of participants achieving a complete response (CR) or partial response (PR) as their best overall response according to the 2014 Lugano Response Criteria during study treatment.
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
Prazo: At Cycles 1, 2, 5, 8, and 12 (each cycle is 28 days), assessed up to 336 days.
Proportion of participants achieving a complete metabolic response (CMR) according to the 2014 Lugano Response Criteria.
At Cycles 1, 2, 5, 8, and 12 (each cycle is 28 days), assessed up to 336 days.
Duration of Response (DoR)
Prazo: 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).
Duration of response (DoR), defined as the time from the first documented complete metabolic response (CMR) or partial metabolic response (PMR) according to the 2014 Lugano Response Criteria until the first documented disease progression, relapse, or death from any cause.
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)
Prazo: 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
Progression-free survival (PFS), defined as the time from the first dose of study treatment to the first documented disease progression according to the 2014 Lugano Response Criteria or death from any cause, whichever occurs first.
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)
Prazo: From Cycle 1 ( 28 days) until date of death, or until end of follow-up (up to 54 months)
Overall survival (OS), defined as the time from the first dose of study treatment until death from any cause.
From Cycle 1 ( 28 days) until date of death, or until end of follow-up (up to 54 months)
Incidence of Tumor Lysis Syndrome (TLS)
Prazo: From Cycle 1 until Cycle 12 ( each cycle is 28 days) or until the date of the permanent treatment discontinuation (PTD) or date of death from any cause, whichever occurs first. Assessed up to 336 days.
Number and proportion of participants experiencing tumor lysis syndrome (TLS), graded according to the protocol-specified toxicity criteria.
From Cycle 1 until Cycle 12 ( each cycle is 28 days) or until the date of the permanent treatment discontinuation (PTD) or date of death from any cause, whichever occurs first. Assessed up to 336 days.
Incidence of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)
Prazo: From Cycle 1 until Cycle 12 ( each cycle is 28 days) or until the date of the permanent treatment discontinuation (PTD) from any cause, whichever occurs first. Assessed up to 336 days
Number and proportion of participants experiencing ICANS.
From Cycle 1 until Cycle 12 ( each cycle is 28 days) or until the date of the permanent treatment discontinuation (PTD) from any cause, whichever occurs first. Assessed up to 336 days
Incidence of Cytokine Release Syndrome (CRS)
Prazo: From Cycle 1 until Cycle 12 ( each cycle is 28 days) or until the date of the permanent treatment discontinuation (PTD) from any cause, whichever occurs first. Assessed up to 336 days
Number and proportion of participants experiencing cytokine release syndrome (CRS).
From Cycle 1 until Cycle 12 ( each cycle is 28 days) or until the date of the permanent treatment discontinuation (PTD) from any cause, whichever occurs first. Assessed up to 336 days
Incidence of Cytopenias
Prazo: From Cycle 1 until Cycle 12 ( each cycle is 28 days) or until the date of the permanent treatment discontinuation (PTD) from any cause, whichever occurs first. Assessed up to 336 days
Number and proportion of participants experiencing treatment-emergent cytopenias.
From Cycle 1 until Cycle 12 ( each cycle is 28 days) or until the date of the permanent treatment discontinuation (PTD) from any cause, whichever occurs first. Assessed up to 336 days
Incidence of Infections
Prazo: From Cycle 1 until Cycle 12 ( each cycle is 28 days) or until the date of the permanent treatment discontinuation (PTD) from any cause, whichever occurs first. Assessed up to 336 days
Number and proportion of participants experiencing treatment-emergent infections.
From Cycle 1 until Cycle 12 ( each cycle is 28 days) or until the date of the permanent treatment discontinuation (PTD) from any cause, whichever occurs first. Assessed up to 336 days

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

The Lymphoma Academic Research Organisation

Colaboradores

AbbVie

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Estimado)

1 de dezembro de 2026

Conclusão Primária (Estimado)

1 de julho de 2028

Conclusão do estudo (Estimado)

1 de maio de 2031

Datas de inscrição no estudo

Enviado pela primeira vez

19 de agosto de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

8 de setembro de 2026

Primeira postagem (Real)

10 de setembro de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

10 de setembro de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

8 de setembro de 2026

Última verificação

1 de setembro de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • BiFAST

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Não

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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