Исследование безопасности и эффективности комбинаций эпкоритамаба у субъектов с В-клеточной неходжкинской лимфомой (В-НХЛ) (EPCORE™ NHL-2)
Открытое исследование фазы 1b/2 для оценки безопасности и предварительной эффективности эпкоритамаба (GEN3013; DuoBody®-CD3xCD20) в комбинации с другими агентами у субъектов с В-клеточной неходжкинской лимфомой (В-НХЛ)
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.
Обзор исследования
Статус
Вмешательство/лечение
- Лекарство: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
- Биологический: Epcoritamab
- Биологический: Epcoritamab
- Биологический: Epcoritamab
- Биологический: Epcoritamab
- Биологический: Epcoritamab
- Биологический: Epcoritamab
- Биологический: Epcoritamab
- Биологический: Epcoritamab
- Биологический: Epcoritamab
- Лекарство: Rituximab and Lenalidomide
- Лекарство: rituximab and bendamustine
- Лекарство: rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin
- Лекарство: gemcitabine and oxaliplatin
- Лекарство: rituximab and lenalidomide
- Лекарство: rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone
- Лекарство: Lenalidomide
- Лекарство: rituximab, ifosfamide, carboplatin, and etoposide phosphate
Подробное описание
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.
Тип исследования
Регистрация (Действительный)
Фаза
- Фаза 2
- Фаза 1
Расширенный доступ
Контакты и местонахождение
Места учебы
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Heidelberg, Австралия, VIC 3084
- Austin Health
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Nedlands, Австралия, 6009
- Linear Clinical Research Limited
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Bruges, Бельгия, 8000
- AZ Sint-Jan
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Ghent, Бельгия, 9000
- Universitair Ziekenhuis Gent
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Yvoir, Бельгия, 5530
- CHU UCL Namur Site Godinne
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Aarhus, Дания
- Århus Hospital
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Copenhagen, Дания, 2100
- Rigshospitalet
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Odense, Дания
- Odense University Hospital
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Vejle, Дания
- Vejle Sygehus
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Barcelona, Испания, 8035
- Hospital Universitari Vall d'Hebron
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Barcelona, Испания, 08908
- ICO l Hospitalet
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Madrid, Испания, 28046
- Hospital Universitario La Paz
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Madrid, Испания, 28040
- Hospital Universitario Fundacion Jimenez Diaz
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Salamanca, Испания, 37007
- Hospital Universitario de Salamanca
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Bergamo, Италия, 24127
- Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)
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Bologna, Италия
- Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS
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Candiolo, Италия, 10060
- Fondazione del Piemonte per l Oncologia Istituto di Candiolo IRCCS
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Meldola, Италия, 47014
- IRCCS Istituto Scientifico Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST
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Milan, Италия, 20122
- Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
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Pavia, Италия, 27100
- Fondazione IRCCS Policlinico San Matteo
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Reggio Emilia, Италия, 42123
- Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio Emilia
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Amsterdam, Нидерланды, 1105 AZ
- Amsterdam UMC, Locatie VUMC
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Groningen, Нидерланды, 9713
- Universitair Medisch Centrum Groningen (UMCG)
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Leiden, Нидерланды, 2333 ZA
- Leids Universitair Medisch Centrum
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Maastricht, Нидерланды, 6229 HX
- Maastricht University Medical Center
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Rotterdam, Нидерланды
- Erasmus Medisch Centrum
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Utrecht, Нидерланды, 3584
- UMC Utrecht
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Oslo, Норвегия, 310
- Oslo Universitetssykehus HF, Radiumhospitalet
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Manchester, Соединенное Королевство
- The Christie Hospital
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Newcastle upon Tyne, Соединенное Королевство, NE7 7D
- Freeman Hospital
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Plymouth, Соединенное Королевство, PL6 8DH
- Derriford Hospital
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Alabama
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Birmingham, Alabama, Соединенные Штаты, 35294
- University of Alabama at Birmingham
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California
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Los Angeles, California, Соединенные Штаты, 90048
- Cedars-Sinai Medical Center
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Los Angeles, California, Соединенные Штаты, 90095
- David Geffen School of Medicine at UCLA
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San Francisco, California, Соединенные Штаты, 94143
- University of California San Francisco
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Massachusetts
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Boston, Massachusetts, Соединенные Штаты, 02215
- Dana Farber Cancer Institute
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Michigan
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Ann Arbor, Michigan, Соединенные Штаты, 48109
- University of Michigan Comprehensive Cancer Center Michigan Medicine
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New Jersey
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Hackensack, New Jersey, Соединенные Штаты, 07601
- Hackensack University Medical Center
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New York
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New York, New York, Соединенные Штаты, 10029
- Mount Sinai
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New York, New York, Соединенные Штаты, 10065
- Memorial Sloan Kettering CC
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North Carolina
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Charlotte, North Carolina, Соединенные Штаты, 28204
- Levine Cancer Center
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Texas
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Dallas, Texas, Соединенные Штаты, 75390
- Southwestern Medical Center
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Kuopio, Финляндия, 70210
- Kuopio University Hospital
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Lahti, Финляндия, 15850
- HUS Cancer Center
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Lille, Франция, 59037
- Hopital Claude Huriez - CHRU Lille
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Marseille, Франция, 13005
- Hôpital de la Timone
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Paris, Франция, 75475
- Hôpital Saint-Louis
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Pierre-Bénite, Франция, 69495
- Centre Hospitalier Lyon Sud
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Hradec Králové, Чехия
- Fakultni nemocnice Hradec Kralove
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Ostrava - Poruba, Чехия
- Fakultni nemocnice Ostrava
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Prague, Чехия, 15006
- Fakultni nemocnice v Motole
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Prague, Чехия
- Vseobecna Fakultni Nemocnice
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Borås, Швеция
- Södra Älvsborgs Sjukhus
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Gothenburg, Швеция, 413 45
- Sahlgrenska Sjukhuset
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Lund, Швеция
- Skånes Universitetssjukhus
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Solna, Швеция
- Karolinska Universitetssjukhuset
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Uppsala, Швеция
- Akademiska Sjukhuset
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Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
Принимает здоровых добровольцев
Полы, имеющие право на обучение
Описание
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.
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Нерандомизированный
- Интервенционная модель: Параллельное назначение
- Маскировка: Нет (открытая этикетка)
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
|---|---|
|
Экспериментальный: Arm 1 - Epcoritamab + R-CHOP
In participants with previously untreated DLBCL. |
6 cycles (21-day cycles)
Другие имена:
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.
Другие имена:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Другие имена:
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.
Другие имена:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Другие имена:
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.
Другие имена:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Другие имена:
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Экспериментальный: 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.
Другие имена:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Другие имена:
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.
Другие имена:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Другие имена:
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.
Другие имена:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Другие имена:
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.
Другие имена:
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Экспериментальный: 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.
Другие имена:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Другие имена:
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.
Другие имена:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Другие имена:
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.
Другие имена:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Другие имена:
6 cycles (28-day cycles)
Другие имена:
|
|
Экспериментальный: 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.
Другие имена:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Другие имена:
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.
Другие имена:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Другие имена:
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.
Другие имена:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Другие имена:
3 cycles (21-day cycles)
Другие имена:
|
|
Экспериментальный: 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.
Другие имена:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Другие имена:
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.
Другие имена:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Другие имена:
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.
Другие имена:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Другие имена:
4 cycles (28-day cycles)
Другие имена:
|
|
Экспериментальный: 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.
Другие имена:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Другие имена:
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.
Другие имена:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Другие имена:
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.
Другие имена:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Другие имена:
rituximab 6 cycles and lenalidomide 12 cycles (28-day cycles)
Другие имена:
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Экспериментальный: 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.
Другие имена:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Другие имена:
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.
Другие имена:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Другие имена:
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.
Другие имена:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Другие имена:
|
|
Экспериментальный: 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.
Другие имена:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Другие имена:
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.
Другие имена:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Другие имена:
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.
Другие имена:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Другие имена:
6 cycles (21-day cycles)
Другие имена:
|
|
Экспериментальный: 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.
Другие имена:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Другие имена:
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.
Другие имена:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Другие имена:
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.
Другие имена:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Другие имена:
12 cycles (28-day cycles) |
|
Экспериментальный: 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.
Другие имена:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Другие имена:
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.
Другие имена:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Другие имена:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Другие имена:
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.
Другие имена:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Другие имена:
3 cycles (21-day cycles)
Другие имена:
|
Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Part 1: Number of Participants With Dose limiting Toxicities (DLTs)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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
|
Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Часть 1 и 2: Клиренс (CL) эпкоритамаба
Временное ограничение: Предварительное и постдозовое введение в несколько моментов времени до прекращения лечения (до 3 лет)
|
Предварительное и постдозовое введение в несколько моментов времени до прекращения лечения (до 3 лет)
|
|
|
Часть 1 и 2: Максимальная (пиковая) концентрация в плазме (Cmax) эпкоритамаба
Временное ограничение: Предварительное и постдозовое введение в несколько моментов времени до прекращения лечения (до 3 лет)
|
Предварительное и постдозовое введение в несколько моментов времени до прекращения лечения (до 3 лет)
|
|
|
Часть 1 и 2: Время достижения Cmax (Tmax) эпкоритамаба
Временное ограничение: Предварительное и постдозовое введение в несколько моментов времени до прекращения лечения (до 3 лет)
|
Предварительное и постдозовое введение в несколько моментов времени до прекращения лечения (до 3 лет)
|
|
|
Часть 1 и 2: Терминальный период полувыведения (t 1/2) эпкоритамаба
Временное ограничение: Предварительное и постдозовое введение в несколько моментов времени до прекращения лечения (до 3 лет)
|
Предварительное и постдозовое введение в несколько моментов времени до прекращения лечения (до 3 лет)
|
|
|
Часть 1 и 2: Количество участников с антилекарственными антителами (ADA) к эпкоритамабу
Временное ограничение: До 3 лет
|
До 3 лет
|
|
|
Часть 1 и 2: продолжительность отрицательного результата минимальной остаточной болезни (MRD)
Временное ограничение: До 3 лет
|
До 3 лет
|
|
|
Часть 2 (группа 7): процент участников, у которых MRD-положительный статус был изменен на MRD-отрицательный
Временное ограничение: До 3 лет
|
До 3 лет
|
|
|
Часть 2 (кроме группы 7): процент участников с полным ответом (ПО) в группах с 1 по 10
Временное ограничение: До 3 лет
|
До 3 лет
|
|
|
Часть 1 и 2: площадь под кривой концентрации (AUC) Epcoritamab
Временное ограничение: Предыдущий и постдоза в несколько времени до тех пор, пока не прекращается лечение (до 3 лет)
|
Предыдущий и постдоза в несколько времени до тех пор, пока не прекращается лечение (до 3 лет)
|
|
|
Part 1 and 2: Number of Immune Cell Populations
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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)
Временное ограничение: Up to 2 years
|
Change in circulating tumor DNA levels will be assessed. |
Up to 2 years
|
|
Part 1: ORR
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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)
|
Соавторы и исследователи
Публикации и полезные ссылки
Общие публикации
- 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.
Полезные ссылки
Даты записи исследования
Изучение основных дат
Начало исследования (Действительный)
Первичное завершение (Оцененный)
Завершение исследования (Оцененный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
- Новообразования
- Заболевания иммунной системы
- Новообразования по гистологическому типу
- Лимфатические заболевания
- Лимфопролиферативные заболевания
- Иммунопролиферативные заболевания
- Лимфома, неходжкинская
- Лимфома, В-клеточная
- Лимфома
- Гемики и лимфатические заболевания
- Лимфома, крупная В-клеточная, диффузная
- Лимфома, фолликулярная
- Аминокислоты, пептиды и белки
- Белки
- Органические химические вещества
- Гетероциклические соединения, 1-кольцо
- Гетероциклические соединения
- Бензимидазолы
- Гетероциклические соединения, 2-кольцо
- Гетероциклические соединения, слитое кольцо
- Нуклеиновые кислоты, нуклеотиды и нуклеозиды
- Углеводороды
- Углеводороды, циклические
- Углеводы
- Кислоты, ациклические
- Карбоновые кислоты
- Алкалоиды
- Полициклические ароматические углеводороды
- Углеводороды, ароматные
- Полициклические соединения
- Гликозиды
- Пиперидины
- Индолы
- Антитела, моноклональные
- Антитела
- Иммуноглобулины
- Иммунопротеины
- Белки крови
- Сывороточные глобулины
- Глобулины
- Координационные комплексы
- Дезоксицитидин
- Цитидин
- Пиримидиновые нуклеозиды
- Пиримидины
- Беременные
- Беременные
- Стероиды
- Соединения слитого кольца
- Стероиды, фторированные
- Фосфорамид горчицы
- Азотные соединения горчицы
- Горчичные соединения
- Углеводороды, галогенированные
- Фосфорамиды
- Соединения органофосфора
- Нуклеозиды
- Bergyadienetriols
- Беременные
- VINCA ALKALOIDS
- Секологические триптаминовые алкалоиды
- Индольные алкалоиды
- Индолизидины
- Индолизины
- Арабинонуклеозиды
- Антрациклины
- Нафтацены
- Аминогликозиды
- Бутират
- Антитела, моноклональные, происходящие из мыши
- Даунорубицин
- Оксазины
- Фталимиды
- Фталевые кислоты
- Кислоты, карбоциклический
- Пиперидоны
- Изондолы
- Леналидомид
- Оксалиплатин
- Бендамустин гидрохлорид
- Ритуксимаб
- Гемцитабин
- Дексаметазон
- Преднизолон
- Циклофосфамид
- Цитарабин
- Карбоплатин
- Доксорубицин
- Винкристин
- Ифосфамид
- этопозид фосфат
- Протокол R-Chop
Другие идентификационные номера исследования
- GCT3013-02
- 2020-000845-15 (Номер EudraCT)
- NL74222.056.20 (Идентификатор реестра: CCMO)
- 283235 (Другой идентификатор: IRAS ID; UK Research Summaries Database)
- RECF4377 (Другой идентификатор: The French National Cancer Institute)
- 2023 (Грант/контракт NIH США)
- 2023-504805-35-00 (Ктис)
Планирование данных отдельных участников (IPD)
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Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .