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

8 settembre 2026 aggiornato da: 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.

Panoramica dello studio

Stato

Non ancora reclutamento

Condizioni

Intervento / Trattamento

Tipo di studio

Interventistico

Iscrizione (Stimato)

55

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Backup dei contatti dello studio

Luoghi di studio

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

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Adulto
  • Adulto più anziano

Accetta volontari sani

No

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: N / A
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Epcoritamab plus Lenalidomide
All enrolled participants will be included in a single cohort. No comparator group will be included.
Droga: 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.
Altri nomi:
  • DuoBody-CD3xCD20
Droga: 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.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Overall Response Rate (ORR)
Lasso di tempo: 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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Best Overall Response Rate (Best ORR)
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

The Lymphoma Academic Research Organisation

Collaboratori

AbbVie

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

1 dicembre 2026

Completamento primario (Stimato)

1 luglio 2028

Completamento dello studio (Stimato)

1 maggio 2031

Date di iscrizione allo studio

Primo inviato

19 agosto 2026

Primo inviato che soddisfa i criteri di controllo qualità

8 settembre 2026

Primo Inserito (Effettivo)

10 settembre 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

10 settembre 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

8 settembre 2026

Ultimo verificato

1 settembre 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • BiFAST

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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