Sikkerheds- og effektivitetsforsøg med Epcoritamab-kombinationer hos forsøgspersoner med B-celle non-Hodgkin-lymfom (B-NHL) (EPCORE™ NHL-2)
Et fase 1b/2, åbent studie for at vurdere sikkerheden og den foreløbige effektivitet af Epcoritamab (GEN3013; DuoBody®-CD3xCD20) i kombination med andre midler hos forsøgspersoner med B-celle non-Hodgkin lymfom (B-NHL)
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.
Studieoversigt
Status
Betingelser
Intervention / Behandling
- Medicin: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
- Biologisk: Epcoritamab
- Biologisk: Epcoritamab
- Biologisk: Epcoritamab
- Biologisk: Epcoritamab
- Biologisk: Epcoritamab
- Biologisk: Epcoritamab
- Biologisk: Epcoritamab
- Biologisk: Epcoritamab
- Biologisk: Epcoritamab
- Medicin: Rituximab and Lenalidomide
- Medicin: rituximab and bendamustine
- Medicin: rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin
- Medicin: gemcitabine and oxaliplatin
- Medicin: rituximab and lenalidomide
- Medicin: rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone
- Medicin: Lenalidomide
- Medicin: rituximab, ifosfamide, carboplatin, and etoposide phosphate
Detaljeret beskrivelse
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.
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 2
- Fase 1
Udvidet adgang
Kontakter og lokationer
Studiesteder
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Heidelberg, Australien, VIC 3084
- Austin Health
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Nedlands, Australien, 6009
- Linear Clinical Research Limited
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Bruges, Belgien, 8000
- AZ Sint-Jan
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Ghent, Belgien, 9000
- Universitair Ziekenhuis Gent
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Yvoir, Belgien, 5530
- CHU UCL Namur Site Godinne
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Aarhus, Danmark
- Århus Hospital
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Copenhagen, Danmark, 2100
- Rigshospitalet
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Odense, Danmark
- Odense University Hospital
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Vejle, Danmark
- Vejle Sygehus
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Manchester, Det Forenede Kongerige
- The Christie Hospital
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Newcastle upon Tyne, Det Forenede Kongerige, NE7 7D
- Freeman Hospital
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Plymouth, Det Forenede Kongerige, PL6 8DH
- Derriford Hospital
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Kuopio, Finland, 70210
- Kuopio University Hospital
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Lahti, Finland, 15850
- HUS Cancer Center
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Alabama
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Birmingham, Alabama, Forenede Stater, 35294
- University of Alabama at Birmingham
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California
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Los Angeles, California, Forenede Stater, 90048
- Cedars-Sinai Medical Center
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Los Angeles, California, Forenede Stater, 90095
- David Geffen School of Medicine at UCLA
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San Francisco, California, Forenede Stater, 94143
- University of California San Francisco
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Massachusetts
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Boston, Massachusetts, Forenede Stater, 02215
- Dana Farber Cancer Institute
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Michigan
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Ann Arbor, Michigan, Forenede Stater, 48109
- University of Michigan Comprehensive Cancer Center Michigan Medicine
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New Jersey
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Hackensack, New Jersey, Forenede Stater, 07601
- Hackensack University Medical Center
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New York
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New York, New York, Forenede Stater, 10029
- Mount Sinai
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New York, New York, Forenede Stater, 10065
- Memorial Sloan Kettering CC
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North Carolina
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Charlotte, North Carolina, Forenede Stater, 28204
- Levine Cancer Center
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Texas
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Dallas, Texas, Forenede Stater, 75390
- Southwestern Medical Center
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Lille, Frankrig, 59037
- Hopital Claude Huriez - CHRU Lille
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Marseille, Frankrig, 13005
- Hôpital de la Timone
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Paris, Frankrig, 75475
- Hôpital Saint-Louis
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Pierre-Bénite, Frankrig, 69495
- Centre Hospitalier Lyon Sud
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Amsterdam, Holland, 1105 AZ
- Amsterdam UMC, Locatie VUMC
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Groningen, Holland, 9713
- Universitair Medisch Centrum Groningen (UMCG)
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Leiden, Holland, 2333 ZA
- Leids Universitair Medisch Centrum
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Maastricht, Holland, 6229 HX
- Maastricht University Medical Center
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Rotterdam, Holland
- Erasmus Medisch Centrum
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Utrecht, Holland, 3584
- UMC Utrecht
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Bergamo, Italien, 24127
- Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)
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Bologna, Italien
- Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS
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Candiolo, Italien, 10060
- Fondazione del Piemonte per l Oncologia Istituto di Candiolo IRCCS
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Meldola, Italien, 47014
- IRCCS Istituto Scientifico Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST
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Milan, Italien, 20122
- Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
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Pavia, Italien, 27100
- Fondazione IRCCS Policlinico San Matteo
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Reggio Emilia, Italien, 42123
- Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio Emilia
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Oslo, Norge, 310
- Oslo Universitetssykehus HF, Radiumhospitalet
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Barcelona, Spanien, 8035
- Hospital Universitari Vall d'Hebron
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Barcelona, Spanien, 08908
- ICO l Hospitalet
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Madrid, Spanien, 28046
- Hospital Universitario La Paz
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Madrid, Spanien, 28040
- Hospital Universitario Fundacion Jimenez Diaz
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Salamanca, Spanien, 37007
- Hospital Universitario de Salamanca
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Borås, Sverige
- Södra Älvsborgs Sjukhus
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Gothenburg, Sverige, 413 45
- Sahlgrenska Sjukhuset
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Lund, Sverige
- Skånes Universitetssjukhus
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Solna, Sverige
- Karolinska Universitetssjukhuset
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Uppsala, Sverige
- Akademiska Sjukhuset
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Hradec Králové, Tjekkiet
- Fakultni nemocnice Hradec Kralove
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Ostrava - Poruba, Tjekkiet
- Fakultni nemocnice Ostrava
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Prague, Tjekkiet, 15006
- Fakultni nemocnice v Motole
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Prague, Tjekkiet
- Vseobecna Fakultni Nemocnice
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
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Eksperimentel: Arm 1 - Epcoritamab + R-CHOP
In participants with previously untreated DLBCL. |
6 cycles (21-day cycles)
Andre navne:
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.
Andre navne:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Andre navne:
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.
Andre navne:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Andre navne:
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.
Andre navne:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Andre navne:
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Eksperimentel: 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.
Andre navne:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Andre navne:
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.
Andre navne:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Andre navne:
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.
Andre navne:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Andre navne:
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.
Andre navne:
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Eksperimentel: 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.
Andre navne:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Andre navne:
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.
Andre navne:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Andre navne:
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.
Andre navne:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Andre navne:
6 cycles (28-day cycles)
Andre navne:
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Eksperimentel: 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.
Andre navne:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Andre navne:
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.
Andre navne:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Andre navne:
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.
Andre navne:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Andre navne:
3 cycles (21-day cycles)
Andre navne:
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Eksperimentel: 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.
Andre navne:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Andre navne:
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.
Andre navne:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Andre navne:
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.
Andre navne:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Andre navne:
4 cycles (28-day cycles)
Andre navne:
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Eksperimentel: 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.
Andre navne:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Andre navne:
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.
Andre navne:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Andre navne:
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.
Andre navne:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Andre navne:
rituximab 6 cycles and lenalidomide 12 cycles (28-day cycles)
Andre navne:
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Eksperimentel: 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.
Andre navne:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Andre navne:
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.
Andre navne:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Andre navne:
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.
Andre navne:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Andre navne:
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Eksperimentel: 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.
Andre navne:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Andre navne:
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.
Andre navne:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Andre navne:
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.
Andre navne:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Andre navne:
6 cycles (21-day cycles)
Andre navne:
|
|
Eksperimentel: 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.
Andre navne:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Andre navne:
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.
Andre navne:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Andre navne:
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.
Andre navne:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Andre navne:
12 cycles (28-day cycles) |
|
Eksperimentel: 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.
Andre navne:
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
Andre navne:
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.
Andre navne:
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
Andre navne:
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
Andre navne:
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.
Andre navne:
Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.
Andre navne:
3 cycles (21-day cycles)
Andre navne:
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Part 1: Number of Participants With Dose limiting Toxicities (DLTs)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Del 1 og 2: Clearance (CL) af Epcoritamab
Tidsramme: Før- og efterdosis på flere tidspunkter indtil behandlingsophør (op til 3 år)
|
Før- og efterdosis på flere tidspunkter indtil behandlingsophør (op til 3 år)
|
|
|
Del 1 og 2: Maksimal (Peak) Plasma Koncentration (Cmax) af Epcoritamab
Tidsramme: Før- og efterdosis på flere tidspunkter indtil behandlingsophør (op til 3 år)
|
Før- og efterdosis på flere tidspunkter indtil behandlingsophør (op til 3 år)
|
|
|
Del 1 og 2: Tid til at nå Cmax (Tmax) for Epcoritamab
Tidsramme: Før- og efterdosis på flere tidspunkter indtil behandlingsophør (op til 3 år)
|
Før- og efterdosis på flere tidspunkter indtil behandlingsophør (op til 3 år)
|
|
|
Del 1 og 2: Terminal eliminationshalveringstid (t 1/2) af Epcoritamab
Tidsramme: Før- og efterdosis på flere tidspunkter indtil behandlingsophør (op til 3 år)
|
Før- og efterdosis på flere tidspunkter indtil behandlingsophør (op til 3 år)
|
|
|
Del 1 og 2: Antal deltagere med antistof antistoffer (ADA'er) mod Epcoritamab
Tidsramme: Op til 3 år
|
Op til 3 år
|
|
|
Del 1 og 2: Varighed af minimal residual disease (MRD) negativitet
Tidsramme: Op til 3 år
|
Op til 3 år
|
|
|
Del 2 (arm 7): Procentdel af deltagere, der konverterede fra MRD-positivitet til MRD-negativitet
Tidsramme: Op til 3 år
|
Op til 3 år
|
|
|
Del 2 (undtagen arm 7): Procentdel af deltagere med komplet respons (CR) i arm 1 til 10
Tidsramme: Op til 3 år
|
Op til 3 år
|
|
|
Del 1 og 2: Område under koncentrationstidskurven (AUC) af epcoritamab
Tidsramme: Predose og postdosis på flere tidspunkter, indtil behandling af behandlingen (op til 3 år)
|
Predose og postdosis på flere tidspunkter, indtil behandling af behandlingen (op til 3 år)
|
|
|
Part 1 and 2: Number of Immune Cell Populations
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: Up to 2 years
|
Change in circulating tumor DNA levels will be assessed. |
Up to 2 years
|
|
Part 1: ORR
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
|
Samarbejdspartnere og efterforskere
Publikationer og nyttige links
Generelle publikationer
- 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.
Hjælpsomme links
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Neoplasmer
- Sygdomme i immunsystemet
- Neoplasmer efter histologisk type
- Lymfesygdomme
- Lymfoproliferative lidelser
- Immunproliferative lidelser
- Lymfom, Non-Hodgkin
- Lymfom, B-celle
- Lymfom
- Hemiske og lymfatiske sygdomme
- Lymfom, stor B-celle, diffus
- Lymfom, follikulært
- Aminosyrer, peptider og proteiner
- Proteiner
- Organiske kemikalier
- Heterocykliske forbindelser, 1-ring
- Heterocykliske forbindelser
- Benzimidazoler
- Heterocykliske forbindelser, 2-ring
- Heterocykliske forbindelser, smeltet ring
- Nukleinsyrer, nukleotider og nukleosider
- Kulbrinter
- Kulbrinter, cyklisk
- Kulhydrater
- Syrer, acyklisk
- Carboxylsyrer
- Alkaloider
- Polycykliske aromatiske kulbrinter
- Kulbrinter, aromatisk
- Polycykliske forbindelser
- Glycosider
- Piperidiner
- Indoler
- Antistoffer, monoklonal
- Antistoffer
- Immunoglobuliner
- Immunoproteiner
- Blodproteiner
- Serum globuliner
- Globuliner
- Koordinationskomplekser
- Deoxycytidin
- Cytidin
- Pyrimidin -nukleosider
- Pyrimidiner
- Gravidier
- Graviditet
- Steroider
- SMUSED-RING-forbindelser
- Steroider, fluoreret
- Fosforamid -sennep
- Nitrogen sennepsforbindelser
- Sennepsforbindelser
- Kulbrinter, halogeneret
- Phosphoramider
- Organophosphorforbindelser
- Nukleosider
- Gravideretrioler
- Gravideretioler
- Vinca alkaloider
- Secologanin tryptamin alkaloider
- Indole alkaloider
- Indolizidiner
- Indolizines
- Arabinonucleosider
- Anthracycliner
- Naphthacenes
- Aminoglycosider
- Butyrater
- Antistoffer, monoklonal, murint afledt
- Daunorubicin
- Oxaziner
- Phthalimider
- Phthalinsyrer
- Syrer, carbocykliske
- Piperidones
- Isoindoler
- Lenalidomid
- Oxaliplatin
- Bendamustine hydrochlorid
- Rituximab
- Gemcitabin
- Dexamethason
- Prednison
- Cyclofosfamid
- Cytarabin
- Carboplatin
- Doxorubicin
- Vincristine
- Ifosfamid
- Etoposidphosphat
- R-CHOP-protokol
Andre undersøgelses-id-numre
- GCT3013-02
- 2020-000845-15 (EudraCT nummer)
- NL74222.056.20 (Registry Identifier: CCMO)
- 283235 (Anden identifikator: IRAS ID; UK Research Summaries Database)
- RECF4377 (Anden identifikator: The French National Cancer Institute)
- 2023 (U.S. NIH-bevilling/kontrakt)
- 2023-504805-35-00 (Ctis)
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