Ensaio de Segurança e Eficácia de Combinações de Epcoritamab em Indivíduos com Linfoma Não-Hodgkin de Células B (B-NHL) (EPCORE™ NHL-2)
Um estudo aberto de fase 1b/2 para avaliar a segurança e a eficácia preliminar do epcoritamab (GEN3013; DuoBody®-CD3xCD20) em combinação com outros agentes em indivíduos com linfoma não Hodgkin de células B (NHL B)
The purpose of this trial is to measure the safety and effectiveness of epcoritamab (EPKINLY™), either by itself or together with other therapies, when treating participants with B-cell non-Hodgkin Lymphoma (B-NHL). The aim of the first part of the trial is to identify the most appropriate dose of epcoritamab, and the aim of the second part of the trial is to assess the selected epcoritamab dose in a larger group of participants with B-NHL. All participants in this trial will receive either epcoritamab alone, or epcoritamab combined with another standard treatment regimen, with a total of 10 different treatment arms being studied.
Trial details include:
- The treatment duration for each participant depends upon which arm of treatment they are assigned to.
- The visit frequency for each participant depends upon which arm of treatment they are assigned to, but will be weekly to start for all participants, then will decrease to either: every 2 weeks, or every 3 weeks, or every 4 weeks, or every 8 weeks.
- All participants will receive active drug; no one will be given placebo.
Participants who receive treatment with epcoritamab will have it injected right under the skin. Participants will receive a different regimen of epcoritamab depending upon which arm of treatment they are assigned.
Participants who receive standard treatments will have intravenous (IV) infusions and/or oral administration of those treatments. Participants will receive a different standard treatment regimen depending upon which arm of treatment they are assigned.
Visão geral do estudo
Status
Intervenção / Tratamento
- Medicamento: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
- Biológico: Epcoritamab
- Biológico: Epcoritamab
- Biológico: Epcoritamab
- Biológico: Epcoritamab
- Biológico: Epcoritamab
- Biológico: Epcoritamab
- Biológico: Epcoritamab
- Biológico: Epcoritamab
- Biológico: Epcoritamab
- Medicamento: Rituximab and Lenalidomide
- Medicamento: rituximab and bendamustine
- Medicamento: rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin
- Medicamento: gemcitabine and oxaliplatin
- Medicamento: rituximab and lenalidomide
- Medicamento: rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone
- Medicamento: Lenalidomide
- Medicamento: rituximab, ifosfamide, carboplatin, and etoposide phosphate
Descrição detalhada
A Phase 1b/2, open-label, multinational, interventional trial to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics/biomarkers, immunogenicity, and preliminary efficacy of epcoritamab in combination with other standard of care (SOC) agents in participants with B-NHL.
All participants in the trial will receive epcoritamab, as monotherapy or in combination. The following regimens will be investigated:
- Arm 1: epcoritamab + rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in participants with previously untreated diffuse large B-cell lymphoma (DLBCL)
- Arm 2: epcoritamab + rituximab and lenalidomide (R2) in participants with relapsed/refractory (R/R) follicular lymphoma (FL)
- Arm 3: epcoritamab + rituximab and bendamustine (BR) in participants with previously untreated FL
- Arm 4: epcoritamab + rituximab, cytarabine, dexamethasone, and oxaliplatin/ carboplatin (R-DHAX/C) in participants with R/R DLBCL eligible for autologous stem cell transplant (ASCT)
- Arm 5: epcoritamab + gemcitabine and oxaliplatin (GemOx) in participants with R/R DLBCL ineligible for ASCT due to age, performance status (PS), or comorbidity
- Arm 6: epcoritamab + R2 in participants with previously untreated FL
- Arm 7: epcoritamab maintenance in participants with FL who achieve a complete response (CR) or a partial response (PR) following first or second line SOC treatment
- Arm 8: epcoritamab + reduced dose of R-CHOP (R mini-CHOP) in participants with previously untreated DLBCL who are ineligible to receive full-dose anthracycline
- Arm 9: epcoritamab + lenalidomide for second-line treatment in participants with R/R FL who progressed within 24 months of initiation of first-line anti-CD20-containing immunochemotherapy
- Arm 10: epcoritamab + rituximab, ifosfamide, carboplatin, and etoposide phosphate (R-ICE) in participants with R/R DLBCL eligible for ASCT
The trial consists of two parts: Part 1 ('Dose Escalation') and Part 2 ('Dose Expansion'). The primary objective of Part 1 is safety, and it includes Arm 1-5 and Arm 10. Part 2 includes all 10 arms (Arm 1-10) and the primary goal of all arms, except Arm 7, is preliminary efficacy. For Arm 7, the primary goal is safety. Participants in Arm 1-5 and Arm 10 can only participate in either Part 1 or Part 2. Dose Limiting Toxicities (DLTs) will be assessed in Part 1 and for a selected number of participants in Arm 8 during a 28-day period (safety run-in). The arms are conducted in parallel.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 2
- Fase 1
Acesso expandido
Contactos e Locais
Locais de estudo
-
-
-
Heidelberg, Austrália, VIC 3084
- Austin Health
-
Nedlands, Austrália, 6009
- Linear Clinical Research Limited
-
-
-
-
-
Bruges, Bélgica, 8000
- AZ Sint-Jan
-
Ghent, Bélgica, 9000
- Universitair Ziekenhuis Gent
-
Yvoir, Bélgica, 5530
- CHU UCL Namur Site Godinne
-
-
-
-
-
Aarhus, Dinamarca
- Århus Hospital
-
Copenhagen, Dinamarca, 2100
- Rigshospitalet
-
Odense, Dinamarca
- Odense University Hospital
-
Vejle, Dinamarca
- Vejle Sygehus
-
-
-
-
-
Barcelona, Espanha, 8035
- Hospital Universitari Vall d'Hebron
-
Barcelona, Espanha, 08908
- ICO l Hospitalet
-
Madrid, Espanha, 28046
- Hospital Universitario La Paz
-
Madrid, Espanha, 28040
- Hospital Universitario Fundacion Jimenez Diaz
-
Salamanca, Espanha, 37007
- Hospital Universitario de Salamanca
-
-
-
-
Alabama
-
Birmingham, Alabama, Estados Unidos, 35294
- University of Alabama at Birmingham
-
-
California
-
Los Angeles, California, Estados Unidos, 90048
- Cedars-Sinai Medical Center
-
Los Angeles, California, Estados Unidos, 90095
- David Geffen School of Medicine at UCLA
-
San Francisco, California, Estados Unidos, 94143
- University of California San Francisco
-
-
Massachusetts
-
Boston, Massachusetts, Estados Unidos, 02215
- Dana Farber Cancer Institute
-
-
Michigan
-
Ann Arbor, Michigan, Estados Unidos, 48109
- University of Michigan Comprehensive Cancer Center Michigan Medicine
-
-
New Jersey
-
Hackensack, New Jersey, Estados Unidos, 07601
- Hackensack University Medical Center
-
-
New York
-
New York, New York, Estados Unidos, 10029
- Mount Sinai
-
New York, New York, Estados Unidos, 10065
- Memorial Sloan Kettering CC
-
-
North Carolina
-
Charlotte, North Carolina, Estados Unidos, 28204
- Levine Cancer Center
-
-
Texas
-
Dallas, Texas, Estados Unidos, 75390
- Southwestern Medical Center
-
-
-
-
-
Kuopio, Finlândia, 70210
- Kuopio University Hospital
-
Lahti, Finlândia, 15850
- HUS Cancer Center
-
-
-
-
-
Lille, França, 59037
- Hopital Claude Huriez - CHRU Lille
-
Marseille, França, 13005
- Hôpital de la Timone
-
Paris, França, 75475
- Hôpital Saint-Louis
-
Pierre-Bénite, França, 69495
- Centre Hospitalier Lyon Sud
-
-
-
-
-
Amsterdam, Holanda, 1105 AZ
- Amsterdam UMC, Locatie VUMC
-
Groningen, Holanda, 9713
- Universitair Medisch Centrum Groningen (UMCG)
-
Leiden, Holanda, 2333 ZA
- Leids Universitair Medisch Centrum
-
Maastricht, Holanda, 6229 HX
- Maastricht University Medical Center
-
Rotterdam, Holanda
- Erasmus Medisch Centrum
-
Utrecht, Holanda, 3584
- UMC Utrecht
-
-
-
-
-
Bergamo, Itália, 24127
- Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)
-
Bologna, Itália
- Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS
-
Candiolo, Itália, 10060
- Fondazione del Piemonte per l Oncologia Istituto di Candiolo IRCCS
-
Meldola, Itália, 47014
- IRCCS Istituto Scientifico Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST
-
Milan, Itália, 20122
- Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
-
Pavia, Itália, 27100
- Fondazione IRCCS Policlinico San Matteo
-
Reggio Emilia, Itália, 42123
- Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio Emilia
-
-
-
-
-
Oslo, Noruega, 310
- Oslo Universitetssykehus HF, Radiumhospitalet
-
-
-
-
-
Manchester, Reino Unido
- The Christie Hospital
-
Newcastle upon Tyne, Reino Unido, NE7 7D
- Freeman Hospital
-
Plymouth, Reino Unido, PL6 8DH
- Derriford Hospital
-
-
-
-
-
Borås, Suécia
- Södra Älvsborgs Sjukhus
-
Gothenburg, Suécia, 413 45
- Sahlgrenska Sjukhuset
-
Lund, Suécia
- Skånes Universitetssjukhus
-
Solna, Suécia
- Karolinska Universitetssjukhuset
-
Uppsala, Suécia
- Akademiska Sjukhuset
-
-
-
-
-
Hradec Králové, Tcheca
- Fakultni nemocnice Hradec Kralove
-
Ostrava - Poruba, Tcheca
- Fakultni nemocnice Ostrava
-
Prague, Tcheca, 15006
- Fakultni nemocnice v Motole
-
Prague, Tcheca
- Vseobecna Fakultni Nemocnice
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Key Inclusion Criteria
- Measurable disease defined as ≥1 measurable nodal lesion (long axis >1.5 cm and short axis >1.0 cm) or ≥1 measurable extra-nodal lesion (long axis >1.0 cm) on computed tomography (CT) or magnetic resonance imaging (MRI). Applies to all arms except arm 7.
- Eastern Cooperative Oncology Group (ECOG) PS score of 0, 1 or 2
- Acceptable organ function at screening
- CD20-positive non-Hodgkin lymphoma (NHL) at most recent representative tumor biopsy
- If of childbearing potential participant must practicing a highly effective method of birth control
- A man who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control
Arm 1:
- Newly diagnosed DLBCL
- DLBCL, not otherwise specified (NOS)
- "Double-hit" or "triple-hit" DLBCL
- FL Grade 3B
Arm 2: R/R FL
Arm 3: Newly diagnosed, previously untreated FL grade 1-3A
Arm 4:
- Documented R/R DLBCL and eligible for HDT-ASCT
- DLBCL, NOS
- "Double-hit" or "triple-hit" DLBCL
- FL Grade 3B
Arm 5:
- Documented R/R DLBCL and ineligible for HDT-ASCT
- DLBCL, NOS
- "Double-hit" or "triple-hit" DLBCL
- FL Grade 3B
Arm 6: Newly diagnosed, previously untreated FL grade 1-3A
Arm 7:
- FL Grade 1-3A
- If PR or CR per Lugano criteria following first-line or second-line treatment with SOC regimen, and last dose of SOC within 6 months prior to enrollment.
Arm 8:
- Newly diagnosed DLBCL who are not fit to receive full-dose anthracycline
- T-cell/histiocyte rich DLBCL
- "Double-hit" or "triple-hit" DLBCL
- FL Grade 3B
Arm 9:
- R/R FL
- Progressed within 24 months of initiating first-line treatment
Arm 10:
- Documented R/R DLBCL and eligible for HDT-ASCT
- DLBCL, NOS
- "Double-hit" or "triple-hit" DLBCL
- FL Grade 3B
Key Exclusion Criteria
- Chemotherapy, radiation therapy, or major surgery within 4 weeks prior to the first dose of epcoritamab
- Any prior treatment with a bispecific antibody targeting CD3 and CD20.
- Treatment with CAR-T therapy within 100 days prior to first dose of epcoritamab
- Clinically significant cardiovascular disease
- Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
- CNS lymphoma or known CNS involvement by lymphoma at screening as confirmed by MRI/CT scan of the brain and, if clinically indicated, by lumbar puncture
- Positive tests for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
- Known history of seropositivity of human immunodeficiency virus (HIV)
- Active tuberculosis or history of completed treatment for active tuberculosis within the past 12 months
- Neuropathy > grade 1
- Receiving immunostimulatory agent
- Prior allogeneic HSCT
- Current seizure disorder requiring anti-epileptic therapy
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: Arm 1 - Epcoritamab + R-CHOP
In participants with previously untreated DLBCL. |
6 cycles (21-day cycles)
Outros nomes:
Every week in cycle 1-4, every 3 weeks in cycle 5 and 6, followed by every 4 weeks in cycle 7 for a total of 1 year.
Outros nomes:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Outros nomes:
Every week in cycles 1 and 2, then every 3 weeks in cycles 3 to 6 and then every 4 weeks for cycles 7 and 8.
Outros nomes:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Outros nomes:
Eligible participants will receive subcutaneous (SC) epcoritamab in 28-day cycles. Fixed-treatment epcoritamab will be administered following a 2-Set Up Dosing regimen in Cycle 1. There will be 2 cohorts, 2a and 2b with different dosing schedules. Cohort 2a will be dosed weekly (QW) in Cycles 1-3, once every 2 weeks (Q2W) in Cycles 4-9, and once every 4 weeks (Q4W) in Cycle 10 and beyond for up to 2 years. In cohort 2b, an alternate dosing schedule for epcoritamab will be explored: epcoritamab administered QW for Cycles 1-2 only, then Q4W in Cycle 3 and beyond for up to 2 years.
Outros nomes:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Outros nomes:
|
|
Experimental: Arm 2 - Epcoritamab + R2
In participants with R/R FL. |
Every week in cycle 1-4, every 3 weeks in cycle 5 and 6, followed by every 4 weeks in cycle 7 for a total of 1 year.
Outros nomes:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Outros nomes:
Every week in cycles 1 and 2, then every 3 weeks in cycles 3 to 6 and then every 4 weeks for cycles 7 and 8.
Outros nomes:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Outros nomes:
Eligible participants will receive subcutaneous (SC) epcoritamab in 28-day cycles. Fixed-treatment epcoritamab will be administered following a 2-Set Up Dosing regimen in Cycle 1. There will be 2 cohorts, 2a and 2b with different dosing schedules. Cohort 2a will be dosed weekly (QW) in Cycles 1-3, once every 2 weeks (Q2W) in Cycles 4-9, and once every 4 weeks (Q4W) in Cycle 10 and beyond for up to 2 years. In cohort 2b, an alternate dosing schedule for epcoritamab will be explored: epcoritamab administered QW for Cycles 1-2 only, then Q4W in Cycle 3 and beyond for up to 2 years.
Outros nomes:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Outros nomes:
Rituximab 375 milligrams per meter squared (mg/m^2) will be administered intravenously QW in Cycle 1 and Q4W in Cycles 2-5. Lenalidomide 20 mg will be administered orally daily for 21 days for 12 cycles.
Outros nomes:
|
|
Experimental: Arm 3 - Epcoritamab + BR
In participants with previously untreated FL. |
Every week in cycle 1-4, every 3 weeks in cycle 5 and 6, followed by every 4 weeks in cycle 7 for a total of 1 year.
Outros nomes:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Outros nomes:
Every week in cycles 1 and 2, then every 3 weeks in cycles 3 to 6 and then every 4 weeks for cycles 7 and 8.
Outros nomes:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Outros nomes:
Eligible participants will receive subcutaneous (SC) epcoritamab in 28-day cycles. Fixed-treatment epcoritamab will be administered following a 2-Set Up Dosing regimen in Cycle 1. There will be 2 cohorts, 2a and 2b with different dosing schedules. Cohort 2a will be dosed weekly (QW) in Cycles 1-3, once every 2 weeks (Q2W) in Cycles 4-9, and once every 4 weeks (Q4W) in Cycle 10 and beyond for up to 2 years. In cohort 2b, an alternate dosing schedule for epcoritamab will be explored: epcoritamab administered QW for Cycles 1-2 only, then Q4W in Cycle 3 and beyond for up to 2 years.
Outros nomes:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Outros nomes:
6 cycles (28-day cycles)
Outros nomes:
|
|
Experimental: Arm 4 - Epcoritamab + R-DHAX/C
In participants with R/R DLBCL eligible for ASCT. |
Every week in cycle 1-4, every 3 weeks in cycle 5 and 6, followed by every 4 weeks in cycle 7 for a total of 1 year.
Outros nomes:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Outros nomes:
Every week in cycles 1 and 2, then every 3 weeks in cycles 3 to 6 and then every 4 weeks for cycles 7 and 8.
Outros nomes:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Outros nomes:
Eligible participants will receive subcutaneous (SC) epcoritamab in 28-day cycles. Fixed-treatment epcoritamab will be administered following a 2-Set Up Dosing regimen in Cycle 1. There will be 2 cohorts, 2a and 2b with different dosing schedules. Cohort 2a will be dosed weekly (QW) in Cycles 1-3, once every 2 weeks (Q2W) in Cycles 4-9, and once every 4 weeks (Q4W) in Cycle 10 and beyond for up to 2 years. In cohort 2b, an alternate dosing schedule for epcoritamab will be explored: epcoritamab administered QW for Cycles 1-2 only, then Q4W in Cycle 3 and beyond for up to 2 years.
Outros nomes:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Outros nomes:
3 cycles (21-day cycles)
Outros nomes:
|
|
Experimental: Arm 5 - Epcoritamab + GemOx
In participants with R/R DLBCL ineligible ASCT. |
Every week in cycle 1-4, every 3 weeks in cycle 5 and 6, followed by every 4 weeks in cycle 7 for a total of 1 year.
Outros nomes:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Outros nomes:
Every week in cycles 1 and 2, then every 3 weeks in cycles 3 to 6 and then every 4 weeks for cycles 7 and 8.
Outros nomes:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Outros nomes:
Eligible participants will receive subcutaneous (SC) epcoritamab in 28-day cycles. Fixed-treatment epcoritamab will be administered following a 2-Set Up Dosing regimen in Cycle 1. There will be 2 cohorts, 2a and 2b with different dosing schedules. Cohort 2a will be dosed weekly (QW) in Cycles 1-3, once every 2 weeks (Q2W) in Cycles 4-9, and once every 4 weeks (Q4W) in Cycle 10 and beyond for up to 2 years. In cohort 2b, an alternate dosing schedule for epcoritamab will be explored: epcoritamab administered QW for Cycles 1-2 only, then Q4W in Cycle 3 and beyond for up to 2 years.
Outros nomes:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Outros nomes:
4 cycles (28-day cycles)
Outros nomes:
|
|
Experimental: Arm 6 - Epcoritamab + R2
In participants with previously untreated FL. |
Every week in cycle 1-4, every 3 weeks in cycle 5 and 6, followed by every 4 weeks in cycle 7 for a total of 1 year.
Outros nomes:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Outros nomes:
Every week in cycles 1 and 2, then every 3 weeks in cycles 3 to 6 and then every 4 weeks for cycles 7 and 8.
Outros nomes:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Outros nomes:
Eligible participants will receive subcutaneous (SC) epcoritamab in 28-day cycles. Fixed-treatment epcoritamab will be administered following a 2-Set Up Dosing regimen in Cycle 1. There will be 2 cohorts, 2a and 2b with different dosing schedules. Cohort 2a will be dosed weekly (QW) in Cycles 1-3, once every 2 weeks (Q2W) in Cycles 4-9, and once every 4 weeks (Q4W) in Cycle 10 and beyond for up to 2 years. In cohort 2b, an alternate dosing schedule for epcoritamab will be explored: epcoritamab administered QW for Cycles 1-2 only, then Q4W in Cycle 3 and beyond for up to 2 years.
Outros nomes:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Outros nomes:
rituximab 6 cycles and lenalidomide 12 cycles (28-day cycles)
Outros nomes:
|
|
Experimental: Arm 7 - Epcoritamab maintenance
In participants with FL who achieved a CR or PR after receiving SOC treatment in 1L or 2L. |
Every week in cycle 1-4, every 3 weeks in cycle 5 and 6, followed by every 4 weeks in cycle 7 for a total of 1 year.
Outros nomes:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Outros nomes:
Every week in cycles 1 and 2, then every 3 weeks in cycles 3 to 6 and then every 4 weeks for cycles 7 and 8.
Outros nomes:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Outros nomes:
Eligible participants will receive subcutaneous (SC) epcoritamab in 28-day cycles. Fixed-treatment epcoritamab will be administered following a 2-Set Up Dosing regimen in Cycle 1. There will be 2 cohorts, 2a and 2b with different dosing schedules. Cohort 2a will be dosed weekly (QW) in Cycles 1-3, once every 2 weeks (Q2W) in Cycles 4-9, and once every 4 weeks (Q4W) in Cycle 10 and beyond for up to 2 years. In cohort 2b, an alternate dosing schedule for epcoritamab will be explored: epcoritamab administered QW for Cycles 1-2 only, then Q4W in Cycle 3 and beyond for up to 2 years.
Outros nomes:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Outros nomes:
|
|
Experimental: Arm 8 - Epcoritamab + R mini-CHOP
In participants with previously untreated DLBCL who are ineligible to receive full-dose anthracycline. |
Every week in cycle 1-4, every 3 weeks in cycle 5 and 6, followed by every 4 weeks in cycle 7 for a total of 1 year.
Outros nomes:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Outros nomes:
Every week in cycles 1 and 2, then every 3 weeks in cycles 3 to 6 and then every 4 weeks for cycles 7 and 8.
Outros nomes:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Outros nomes:
Eligible participants will receive subcutaneous (SC) epcoritamab in 28-day cycles. Fixed-treatment epcoritamab will be administered following a 2-Set Up Dosing regimen in Cycle 1. There will be 2 cohorts, 2a and 2b with different dosing schedules. Cohort 2a will be dosed weekly (QW) in Cycles 1-3, once every 2 weeks (Q2W) in Cycles 4-9, and once every 4 weeks (Q4W) in Cycle 10 and beyond for up to 2 years. In cohort 2b, an alternate dosing schedule for epcoritamab will be explored: epcoritamab administered QW for Cycles 1-2 only, then Q4W in Cycle 3 and beyond for up to 2 years.
Outros nomes:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Outros nomes:
6 cycles (21-day cycles)
Outros nomes:
|
|
Experimental: Arm 9 - Epcoritamab + Lenalidomide
In participants with R/R FL who progressed within 24 months of initiation of first-line anti-CD20-containing immunochemotherapy. |
Every week in cycle 1-4, every 3 weeks in cycle 5 and 6, followed by every 4 weeks in cycle 7 for a total of 1 year.
Outros nomes:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Outros nomes:
Every week in cycles 1 and 2, then every 3 weeks in cycles 3 to 6 and then every 4 weeks for cycles 7 and 8.
Outros nomes:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Outros nomes:
Eligible participants will receive subcutaneous (SC) epcoritamab in 28-day cycles. Fixed-treatment epcoritamab will be administered following a 2-Set Up Dosing regimen in Cycle 1. There will be 2 cohorts, 2a and 2b with different dosing schedules. Cohort 2a will be dosed weekly (QW) in Cycles 1-3, once every 2 weeks (Q2W) in Cycles 4-9, and once every 4 weeks (Q4W) in Cycle 10 and beyond for up to 2 years. In cohort 2b, an alternate dosing schedule for epcoritamab will be explored: epcoritamab administered QW for Cycles 1-2 only, then Q4W in Cycle 3 and beyond for up to 2 years.
Outros nomes:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Outros nomes:
12 cycles (28-day cycles) |
|
Experimental: Arm 10 - Epcoritamab + R-ICE
In participants with R/R DLBCL eligible for ASCT. |
Every week in cycle 1-4, every 3 weeks in cycle 5 and 6, followed by every 4 weeks in cycle 7 for a total of 1 year.
Outros nomes:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Outros nomes:
Every week in cycles 1 and 2, then every 3 weeks in cycles 3 to 6 and then every 4 weeks for cycles 7 and 8.
Outros nomes:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Outros nomes:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Outros nomes:
Eligible participants will receive subcutaneous (SC) epcoritamab in 28-day cycles. Fixed-treatment epcoritamab will be administered following a 2-Set Up Dosing regimen in Cycle 1. There will be 2 cohorts, 2a and 2b with different dosing schedules. Cohort 2a will be dosed weekly (QW) in Cycles 1-3, once every 2 weeks (Q2W) in Cycles 4-9, and once every 4 weeks (Q4W) in Cycle 10 and beyond for up to 2 years. In cohort 2b, an alternate dosing schedule for epcoritamab will be explored: epcoritamab administered QW for Cycles 1-2 only, then Q4W in Cycle 3 and beyond for up to 2 years.
Outros nomes:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Outros nomes:
3 cycles (21-day cycles)
Outros nomes:
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Part 1: Number of Participants With Dose limiting Toxicities (DLTs)
Prazo: During the first cycle (Cycle length= 28 days) in each cohort
|
DLT events are defined as clinically significant adverse events (AEs) or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications as assessed per Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria version 5.0. |
During the first cycle (Cycle length= 28 days) in each cohort
|
|
Part 1 and Part 2 (Arms 1-5, 7 and 10): Number of Participants With Adverse Events (AEs)
Prazo: From first dose of drug until either 60 days after last dose, date participant withdraws consent, date participant starts a new systemic anticancer therapy, or date participant dies, whichever occurs first (up to approximately 3 years)
|
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign. (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. |
From first dose of drug until either 60 days after last dose, date participant withdraws consent, date participant starts a new systemic anticancer therapy, or date participant dies, whichever occurs first (up to approximately 3 years)
|
|
Part 2 (Except Arm 7): Overall Response Rate (ORR)
Prazo: Up to 3 years
|
ORR is defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on Lugano criteria. |
Up to 3 years
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Parte 1 e 2: Depuração (CL) de Epcoritamab
Prazo: Pré-dose e pós-dose em vários momentos até a descontinuação do tratamento (até 3 anos)
|
Pré-dose e pós-dose em vários momentos até a descontinuação do tratamento (até 3 anos)
|
|
|
Parte 1 e 2: Concentração Plasmática Máxima (Pico) (Cmax) de Epcoritamab
Prazo: Pré-dose e pós-dose em vários momentos até a descontinuação do tratamento (até 3 anos)
|
Pré-dose e pós-dose em vários momentos até a descontinuação do tratamento (até 3 anos)
|
|
|
Parte 1 e 2: Tempo para atingir Cmax (Tmax) de Epcoritamab
Prazo: Pré-dose e pós-dose em vários momentos até a descontinuação do tratamento (até 3 anos)
|
Pré-dose e pós-dose em vários momentos até a descontinuação do tratamento (até 3 anos)
|
|
|
Parte 1 e 2: Meia-vida de eliminação terminal (t 1/2) de Epcoritamab
Prazo: Pré-dose e pós-dose em vários momentos até a descontinuação do tratamento (até 3 anos)
|
Pré-dose e pós-dose em vários momentos até a descontinuação do tratamento (até 3 anos)
|
|
|
Parte 1 e 2: Número de participantes com anticorpos antidrogas (ADAs) para Epcoritamab
Prazo: Até 3 anos
|
Até 3 anos
|
|
|
Parte 1 e 2: Duração da negatividade da doença residual mínima (DRM)
Prazo: Até 3 anos
|
Até 3 anos
|
|
|
Parte 2 (Braço 7): Porcentagem de participantes que converteram de positividade MRD para negatividade MRD
Prazo: Até 3 anos
|
Até 3 anos
|
|
|
Parte 2 (Exceto Grupo 7): Porcentagem de Participantes com Resposta Completa (CR) nos Grupos 1 a 10
Prazo: Até 3 anos
|
Até 3 anos
|
|
|
Parte 1 e 2: Área sob a curva de concentração-tempo (AUC) de Epcoritamab
Prazo: Presos e pós -Dose em vários pontos de tempo até a descontinuação do tratamento (até 3 anos)
|
Presos e pós -Dose em vários pontos de tempo até a descontinuação do tratamento (até 3 anos)
|
|
|
Part 1 and 2: Number of Immune Cell Populations
Prazo: Up to 2 years
|
Immune cell populations in peripheral blood and tumor biopsies will be assessed. |
Up to 2 years
|
|
Part 1 and 2: Percentage of Immune Cell Populations
Prazo: Up to 2 years
|
Immune cell populations in peripheral blood and tumor biopsies will be assessed. |
Up to 2 years
|
|
Part 1 and 2: Change From Baseline in Cytokine Levels up to Cycle 3
Prazo: Up to Cycle 3 (cycle length = 21 days for Arms 1, 4, 8 and 10; cycle length = 28 days for Arms 2, 3, 5, 6 and 9; cycle length = 28 days (Cycle 1) and 56 days (Cycles 2, 3) for Arm 7)
|
Change in cytokine levels in peripheral blood samples will be assessed. |
Up to Cycle 3 (cycle length = 21 days for Arms 1, 4, 8 and 10; cycle length = 28 days for Arms 2, 3, 5, 6 and 9; cycle length = 28 days (Cycle 1) and 56 days (Cycles 2, 3) for Arm 7)
|
|
Part 1 and 2: Change From Baseline in Circulating Tumor Deoxyribonucleic Acid (DNA) Level up to End of Treatment (up to 2 Years)
Prazo: Up to 2 years
|
Change in circulating tumor DNA levels will be assessed. |
Up to 2 years
|
|
Part 1: ORR
Prazo: Up to 3 years
|
ORR is defined as the percentage of participants achieving CR or PR based on Lugano criteria. |
Up to 3 years
|
|
Part 1 and 2: Duration of Response (DOR)
Prazo: Up to 3 years
|
DOR: the time from the first documentation of objective tumor response (CR or PR) to the date of first PD or death, whichever occurs earlier, based on Lugano criteria. |
Up to 3 years
|
|
Part 1 and 2: Time to Response (TTR)
Prazo: Up to 3 years
|
TTR is defined as the time from Day 1 of Cycle 1 to first documentation of objective tumor response (CR or PR). |
Up to 3 years
|
|
Part 1 and 2: Progression Free Survival (PFS)
Prazo: Up to 3 years
|
PFS is defined as the time from Day 1 of Cycle 1 to first documented PD or death due to any cause, whichever occurs earlier, based on Lugano criteria. |
Up to 3 years
|
|
Part 1 and 2: Overall Survival (OS)
Prazo: Up to 3 years
|
OS is defined as the time from the date of first dose, to the date of death due to any cause. |
Up to 3 years
|
|
Part 1 and 2: Time to Next Anti-lymphoma Therapy (TTNT)
Prazo: Up to 3 years
|
TTNT is defined as the time from Day 1 of Cycle 1 to first documented administration of subsequent anti-lymphoma therapy. |
Up to 3 years
|
|
Part 1 and 2: Percentage of Participants With Minimal Residual Disease (MRD) Negativity
Prazo: Up to 3 years
|
It is defined as the percentage of participants with at least 1 MRD negative result. |
Up to 3 years
|
|
Part 2 (Arm 7): Percentage of Participants With CR
Prazo: Week 24, Week 48, and Week 96
|
It is defined as the percentage of participants who remain in complete remission or converting to complete remission after first trial drug administration. |
Week 24, Week 48, and Week 96
|
|
Part 1 and 2: Time to Complete Response (TTCR)
Prazo: Up to 3 years
|
TTCR is defined as the time from first trial drug administration to the date of first documented complete response post-treatment. |
Up to 3 years
|
|
Part 1 and 2: Duration of Complete Response (DoCR)
Prazo: Up to 3 years
|
DoCR is defined as the time from the first documentation of CR to the date of PD or death, whichever occurs first based on Lugano criteria. |
Up to 3 years
|
|
Part 2: Number of Participants with AEs (Except Arm 7)
Prazo: From first dose of drug until either 60 days after last dose, date participant withdraws consent, date participant starts a new systemic anticancer therapy, or date participant dies, whichever occurs first (up to approximately 3 years)
|
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign. (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. |
From first dose of drug until either 60 days after last dose, date participant withdraws consent, date participant starts a new systemic anticancer therapy, or date participant dies, whichever occurs first (up to approximately 3 years)
|
Colaboradores e Investigadores
Publicações e links úteis
Publicações Gerais
- Brody JD, Jorgensen J, Belada D, Costello R, Trneny M, Vitolo U, Lewis DJ, Karimi YH, Sureda A, Andre M, Wahlin BE, Lugtenburg PJ, Jiang T, Karagoz K, Steele AJ, Abbas A, Wang L, Risum M, Cordoba R. Epcoritamab plus GemOx in transplant-ineligible relapsed/refractory DLBCL: results from the EPCORE NHL-2 trial. Blood. 2025 Apr 10;145(15):1621-1631. doi: 10.1182/blood.2024026830.
- Falchi L, Sureda A, Leppa S, Vermaat JSP, Nijland M, Christensen JH, de Vos S, Holte H, Merryman RW, Lugtenburg PJ, Abrisqueta P, Linton KM, Sunkersett G, Hoehn D, Rana A, Abbas A, Marek J, Hao Y, Steele AJ, Morehouse C, Hutchings M, Belada D. Fixed-duration epcoritamab plus R2 drives favorable outcomes in relapsed or refractory follicular lymphoma. Blood. 2025 Nov 27;146(22):2629-2640. doi: 10.1182/blood.2025029909.
- Falchi L, Vermaat JSP, Brody JD, Leslie L, Offner F, Christensen JH, Nijland M, Belada D, Wahlin BE, Drott K, Gomez Prieto P, Kopeckova K, Garcia-Sancho AM, Mei JP, Altintas I, Risum M, Reilly A, Zou J, Abrisqueta P. Epcoritamab with rituximab and lenalidomide as first-line treatment for follicular lymphoma (EPCORE NHL-2): an open-label, multicentre, phase 1/2 b trial. Lancet Haematol. 2026 Sep;13(9):e614-e625. doi: 10.1016/S2352-3026(26)00198-5.
- Falchi L, Offner F, de Vos S, Brody JD, Morillo D, Linton K, Snauwaert S, Roost Clausen M, Karimi YH, Thieblemont C, Vitolo U, Leslie LA, Narkhede MS, Cordoba R, Oki T, Wielgos-Bonvallet M, Khoshdeli M, Hao Y, Archer K, Risum M, Belada D. Fixed-duration epcoritamab plus R-CHOP in newly diagnosed LBCL with IPI score 3-5: results from the EPCORE NHL-2 trial. Blood. 2026 Aug 11:blood.2026033839. doi: 10.1182/blood.2026033839. Online ahead of print.
- Abrisqueta P, Karimi YH, Morillo D, Cordoba R, Phillips T, De Vos S, Nijland M, Offner F, Andersson PO, Brody J, Cheah CY, Prieto PG, Hellstrom M, Jorgensen JM, Lewis D, Linton KM, Musuraca G, Wang L, Marek J, Osei-Bonsu K, Risum M, Falchi L. Epcoritamab plus rituximab, dexamethasone, cytarabine, oxaliplatin/carboplatin induces deep and durable responses in transplant-eligible patients with relapsed or refractory diffuse large B-cell lymphoma: results from the EPCORE NHL-2 trial. Haematologica. 2026 Oct 1;111(10):3346-3357. doi: 10.3324/haematol.2025.300086. Epub 2026 Mar 5.
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Neoplasias
- Doenças do sistema imunológico
- Neoplasias por Tipo Histológico
- Doenças Linfáticas
- Distúrbios Linfoproliferativos
- Distúrbios imunoproliferativos
- Linfoma Não-Hodgkin
- Linfoma de Células B
- Linfoma
- Doenças hemic e linfáticas
- Linfoma de Células B Grandes Difuso
- Linfoma Folicular
- Aminoácidos, peptídeos e proteínas
- Proteínas
- Produtos químicos orgânicos
- Compostos heterocíclicos, 1 anel
- Compostos heterocíclicos
- Benzimidazóis
- Compostos heterocíclicos, 2 anel
- Compostos heterocíclicos, anel fundido
- Ácidos nucleicos, nucleotídeos e nucleosídeos
- Hidrocarbonetos
- Hidrocarbonetos, cíclicos
- Carboidratos
- Ácidos, acíclico
- Ácidos carboxílicos
- Alcalóides
- Hidrocarbonetos aromáticos policíclicos
- Hidrocarbonetos, aromáticos
- Compostos policíclicos
- Glicosídeos
- Piperidinas
- Indoles
- Anticorpos, monoclonais
- Anticorpos
- Imunoglobulinas
- Imunoproteínas
- Proteínas sanguíneas
- Globulinas de soro
- Globulins
- Complexos de coordenação
- Desoxicitidina
- Citidina
- Nucleosídeos de pirimidina
- Pirimidinas
- Pregada
- Pregnas
- Esteróides
- Compostos de anel fundido
- Esteróides, fluorados
- Mustarazas de fosforamida
- Compostos de mostarda de nitrogênio
- Compostos de mostarda
- Hidrocarbonetos, halogenados
- Fosforamidas
- Compostos organofosforos
- Nucleosídeos
- Pregadienetriols
- PregadaDiols
- Alcalóides de Vinca
- Alcalóides de triptamina de secologanin
- Alcalóides indol
- Indolizidinas
- Indolizinas
- Arabinonucleosides
- Antraciclinas
- Nafthacenos
- Aminoglicosídeos
- Butyrates
- Anticorpos, monoclonais, derivados de murinos
- Daunorubicina
- Oxazinas
- Ftalimidas
- Ácidos ftaléticos
- Ácidos, carbocíclicos
- Piperidones
- Isoindoles
- Lenalidomida
- Oxaliplatina
- Cloridrato de Bendamustina
- Rituximabe
- Gemcitabina
- Dexametasona
- Prednisona
- Ciclofosfamida
- Citarabina
- Carboplatina
- Doxorrubicina
- Vincristina
- Ifosfamida
- fosfato de etoposídeo
- Protocolo R-Chop
Outros números de identificação do estudo
- GCT3013-02
- 2020-000845-15 (Número EudraCT)
- NL74222.056.20 (Identificador de registro: CCMO)
- 283235 (Outro identificador: IRAS ID; UK Research Summaries Database)
- RECF4377 (Outro identificador: The French National Cancer Institute)
- 2023 (Concessão/Contrato do NIH dos EUA)
- 2023-504805-35-00 (Ctis)
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
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 .