First-in-Human (FIH) Trial in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma
EPCORE™ NHL-1
A Phase 1/2, Open-label Safety Trial of GEN3013 in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma
5 other identifiers
interventional
666
15 countries
85
Brief Summary
The purpose of this trial is to measure the following in participants with relapsed and/or refractory B-cell lymphoma who receive epcoritamab, an antibody also known as EPKINLY™ and GEN3013 (DuoBody®-CD3xCD20):
- The dose schedule for epcoritamab
- The side effects seen with epcoritamab
- What the body does with epcoritamab once it is administered
- What epcoritamab does to the body once it is administered
- How well epcoritamab works against relapsed and/or refractory B-cell lymphoma The trial consists of 3 parts:
- a dose-escalation part (Phase 1, first-in-human \[FIH\])
- an expansion part (Phase 2a)
- a dose-optimization part (OPT) (Phase 2a) The trial time for each participant depends on which trial part the participant enters:
- For the dose-escalation part, each participant will be in the trial for approximately 1 year, which is made up of 21 days of screening, 6 months of treatment (the total time of treatment may be different for each participant), and 6 months of follow-up (the total time of follow-up may be different for each participant).
- For the expansion and dose-OPT parts, each participant will be in the trial for approximately 1.5 years, which is made up of 21 days of screening, 1 year of treatment (the total time of treatment may be different for each participant), and 6 months of follow-up (the total time of follow-up may be different for each participant). Participation in the study will require visits to the sites. During the first month, participants must visit every day or every few days, depending on which trial part the participant enters. After that, participants must visit weekly, every other week, once a month, and once every 2 months, as trial participation ends. All participants will receive active drug, and no participants will be given placebo.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jun 2018
Longer than P75 for phase_1
85 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 7, 2018
CompletedStudy Start
First participant enrolled
June 26, 2018
CompletedFirst Posted
Study publicly available on registry
August 10, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 1, 2029
May 5, 2026
May 1, 2026
10.5 years
June 7, 2018
May 4, 2026
Conditions
Outcome Measures
Primary Outcomes (4)
Dose-Escalation: Dose Limiting Toxicity (DLT)
To determine the MTD and/or RP2D to be studied in the Expansion part. DLT will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.
During the first cycle (28 days)
Dose-Escalation: Number of Participants with Adverse Events (AEs)
An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.
From first dose until the end of the safety follow-up period (Up to 1 year)
Expansion: Overall Response Rate (ORR)
ORR is defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on Lugano criteria.
Up to 1.5 years
Dose-OPT DLBCL, FL and MCL: Percentage of Participants with =>Grade 2 Cytokine Release Syndrome (CRS) Events and All Grade CRS Events
CRS will be graded based on American Society for Transplantation and Cellular Therapy (ASTCT) criteria.
From first dose until 7 days after second full dose (Day 28 for DLBCL; Day 35 for FL; Day 28-35 for MCL)
Secondary Outcomes (35)
Dose-Escalation: Number of Participants with Anti-lymphoma Activity of Epcoritamab
Up to 1 year
Dose-Escalation: Duration of Response (DOR)
Up to 1 year
Expansion: DOR
Up to 1.5 years
Expansion Part: Changes in Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym)
Up to 1.5 year
Dose-OPT DLBCL and FL: Percentage of Participants with >=Grade 2 CRS Events and All Grade CRS Events Following First Full Dose
Up to 1.5 years
- +30 more secondary outcomes
Study Arms (1)
Epcoritamab
EXPERIMENTALEpcoritamab will be administered by subcutaneous injections in cycles of 28 days.
Interventions
Administered as specified in the treatment arm.
Eligibility Criteria
You may qualify if:
- Documented CD20+ mature B-cell neoplasm
- DLBCL - de novo or transformed
- HGBCL
- PMBCL
- MCL
- SLL
- MZL (nodal, extranodal or mucosa associated)
- Relapsed and/or refractory disease following treatment with an anti-CD20 monoclonal antibody (e.g. rituximab) potentially in combination with chemotherapy and/or relapsed after autologous stem cell rescue.
- Eastern Cooperative Oncology Group (ECOG) performance status 0,1 or 2.
- Participants must have measurable disease by computed tomography (CT), magnetic resonance imaging (MRI) or Positron emission tomography-Computed tomography (PET-CT) scan
- Acceptable renal function.
- Acceptable liver function.
- Documented CD20 positive mature B cell neoplasm or CD20+ MCL.
- DLBCL, de novo or transformed (including double hit or triple hit).
- PMBCL
- +8 more criteria
You may not qualify if:
- Primary central nervous system (CNS) lymphoma or CNS involvement by lymphoma at screening.
- Aspartate aminotransferase (AST), and/or alanine transaminase (ALT) \>3 × upper limit of normal.
- Total bilirubin \>1.5 × upper limit of normal, unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin.
- Estimated Creatinine clearance (CrCl) \<45 milliliters (mL)/min.
- Known clinically significant cardiovascular disease.
- Ongoing active bacterial, viral, fungal, mycobacterial, parasitic, or other infection requiring systemic treatment (excluding prophylactic treatment). Past coronavirus disease 2019 (COVID-19) infection may be a risk factor.
- Confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy.
- Seizure disorder requiring therapy (such as steroids or anti-epileptics).
- Any prior therapy with an investigational bispecific antibody targeting CD3 and CD20.
- Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 30 days prior to first epcoritamab administration.
- Eligible for curative intensive salvage therapy followed by high dose chemotherapy with HSCT rescue.
- Autologous HSCT within 100 days prior to first epcoritamab administration, or any prior allogeneic HSCT or solid organ transplantation.
- Active hepatitis B (deoxyribonucleic acid \[DNA\] polymerase chain reaction \[PCR\]-positive) or hepatitis C (ribonucleic acid \[RNA\] PCR-positive infection). Participants with evidence of prior hepatitis B (HBV) but who are PCR-negative are permitted in
- Known human immunodeficiency virus (HIV) infection.
- Exposed to live or live attenuated vaccine within 4 weeks prior to signing Informed consent form (ICF).
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (85)
Arizona Mayo Clinic
Phoenix, Arizona, 85054, United States
University of California at San Francisco
San Francisco, California, 94117, United States
Colorado Blood Cancer Institute
Denver, Colorado, 80218, United States
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612, United States
University of Iowa Hospital and Clinics
Iowa City, Iowa, 52242, United States
Ochsner Medical Center
New Orleans, Louisiana, 70121, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48334, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Hackensack Meridian Health
Hackensack, New Jersey, 07601, United States
The Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
OHSU Knight Cancer Institute
Portland, Oregon, 97210, United States
Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
Rhode Island Hospital
Providence, Rhode Island, 02903, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
UT Southwestern
Dallas, Texas, 75390, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
Monash Health
Clayton, Australia
Concord Hospital
Concord, Australia
St. Vincent Hospital
Fitzroy, Australia
Royal Brisbane and Women's Hospital
Herston, Australia
Royal Hobart Hospital RHH
Hobart, Australia
St. George Hospital
Kogarah, Australia
Cabrini Hospital
Malvern, Australia
Sir Charles Gairdner Hospital
Nedlands, Australia
Gold Coast Hospital
Southport, Australia
Westmead Hospital
Sydney, Australia
Tom Baker Cancer Care
Calgary, Canada
Toronto-Sunnybrook Regional Cancer Ctr
Toronto, Canada
Rigshospitalet
Copenhagen, Denmark
Odense University Hospital
Odense, 5000 C, Denmark
Vejle Hospital
Vejle, Denmark
Helsinki University Hospital
Helsinki, Finland
Kuopio University Hospital
Kuopio, Finland
Tampere University Hospital
Tampere, Finland
Hopital Henri Mondor
Créteil, France
CHU Montpellier
Montpellier, France
Hospital Saint-Louis
Paris, France
Hospices Civils de Lyon Centre Hospitalier Lyon Sud
Pierre-Bénite, France
Centre Henri Becquerel
Rouen, France
CHU de Tours-Hopital Bretonneau
Tours, France
Charite - Universitaetsmedizin Berlin
Berlin, Germany
Klinik fur Innere Medizin Hamatologie and Onkologie
Berlin, Germany
Universitaetsklinikum Koeln
Cologne, Germany
Universitaetsklinikum Essen
Essen, Germany
Johannes Gutenberg University
Mainz, Germany
Der Universität Munchen Medizinische Klinik III LMU
München, Germany
Ao Ss Antonio E Biagio Alessandria
Alessandria, Italy
Policlinico S. Orsola-Ematologia LA Seragnoli
Bologna, Italy
Istituto di Candiolo- Fondazione del Piemonte per l'Oncologia
Candiolo, Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola, Italy
IRCCS Ospedale San Raffaele
Milan, Italy
VU University Medical Center
Amsterdam, Netherlands
Maastricht University Medical Center
Maastricht, 6229 HX, Netherlands
Erasmus MC Cancer Institute
Rotterdam, Netherlands
Universitair Medisch Centrum Utrecht
Utrecht, Netherlands
Szpital Uniwersytecki nr 2 im dr. Jana Biziela
Bydgoszcz, Poland
Uniwersyteckie Centrum Kliniczne
Gdansk, Poland
Pratia-McM
Krakow, Poland
Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka
Słupsk, Poland
Maria Sklodowska-Curie Memorial Cancer Center and Institute
Warsaw, Poland
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego
Wroclaw, Poland
National University Hospital
Singapore, Singapore
Singapore General Hospital
Singapore, Singapore
Dong-A University Hospital
Busan, South Korea
Keimyung University Dongsan Medical Center
Daegu, South Korea
National Cancer Center
Goyang-si, South Korea
Chonbuk National University Hospital
Jeonju, South Korea
Seoul National University Bundang Hospital
Seongnam-si, South Korea
Asan Medical Center
Seoul, South Korea
Samsung Medical Center
Seoul, South Korea
Seoul National University Hospital
Seoul, South Korea
Severance Hospital, Yonsei University
Seoul, South Korea
Clinica Universidad de Navarra
Pamplona, Navarre, 31008, Spain
Hospital Germans Trias i Pujol
Badalona, Spain
Hospital Universitario Vall dHebron
Barcelona, Spain
Institut Catala de Oncologia
Barcelona, Spain
Hospital Universitario Fundacin Jimnez Daz
Madrid, Spain
Skåne University Hospital
Lund, Sweden
Karolinska University Hospital Huddinge
Stockholm, Sweden
Akademiska sjukhuset Uppsala University Hospital
Uppsala, Sweden
The Christie NHS Foundation Trust
Manchester, United Kingdom
Plymouth University School of Medicine- Derriford Hospital
Plymouth, United Kingdom
University Hospital Southampton NHS Foundation Trust
Southampton, United Kingdom
Royal Marsden NHS Foundation Trust
Sutton, United Kingdom
Related Publications (6)
Thieblemont C, Phillips T, Ghesquieres H, Cheah CY, Clausen MR, Cunningham D, Do YR, Feldman T, Gasiorowski R, Jurczak W, Kim TM, Lewis DJ, van der Poel M, Poon ML, Cota Stirner M, Kilavuz N, Chiu C, Chen M, Sacchi M, Elliott B, Ahmadi T, Hutchings M, Lugtenburg PJ. Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial. J Clin Oncol. 2023 Apr 20;41(12):2238-2247. doi: 10.1200/JCO.22.01725. Epub 2022 Dec 22.
PMID: 36548927RESULTLinton KM, Vitolo U, Jurczak W, Lugtenburg PJ, Gyan E, Sureda A, Christensen JH, Hess B, Tilly H, Cordoba R, Lewis DJ, Okada C, Hutchings M, Clausen MR, Sancho JM, Cochrane T, Leppa S, Chamuleau MED, Gernhardt D, Altintas I, Liu Y, Ahmadi T, Dinh MH, Hoehn D, Favaro E, Elliott B, Thieblemont C, Vose JM. Epcoritamab monotherapy in patients with relapsed or refractory follicular lymphoma (EPCORE NHL-1): a phase 2 cohort of a single-arm, multicentre study. Lancet Haematol. 2024 Aug;11(8):e593-e605. doi: 10.1016/S2352-3026(24)00166-2. Epub 2024 Jun 15.
PMID: 38889737RESULTDanilov AV, Kambhampati Thiruvengadam S, Linton K, Cumings K, Chirikov V, Mutebi A, Bains Chawla S, Chhibber A, Rivas Navarro F, Marques Goncalves F, Wang A, Ding Z, Alshreef A, Favaro E, Hoehn D, Sureda A. Indirect comparison of epcoritamab vs chemoimmunotherapy, mosunetuzumab, or odronextamab in follicular lymphoma. Blood Adv. 2025 Aug 12;9(15):3754-3765. doi: 10.1182/bloodadvances.2024015274.
PMID: 40472301DERIVEDThieblemont C, Karimi YH, Ghesquieres H, Cheah CY, Clausen MR, Cunningham D, Jurczak W, Do YR, Gasiorowski R, Lewis DJ, Kim TM, van der Poel M, Poon ML, Feldman T, Linton KM, Sureda A, Hutchings M, Dinh MH, Kilavuz N, Soong D, Mark T, Sacchi M, Phillips T, Lugtenburg PJ. Epcoritamab in relapsed/refractory large B-cell lymphoma: 2-year follow-up from the pivotal EPCORE NHL-1 trial. Leukemia. 2024 Dec;38(12):2653-2662. doi: 10.1038/s41375-024-02410-8. Epub 2024 Sep 25.
PMID: 39322711DERIVEDPhillips T, Lugtenburg P, Kalsekar A, Mutebi A, Wang A, Blaedel J, Kosa K, Martin S, Sacchi M, Kilavuz N, Thieblemont C. Improvements in Patient-Reported Outcomes in Relapsed or Refractory Large B-Cell Lymphoma Patients Treated With Epcoritamab. Clin Lymphoma Myeloma Leuk. 2024 Mar;24(3):e78-e87.e2. doi: 10.1016/j.clml.2023.11.005. Epub 2023 Nov 27.
PMID: 38151388DERIVEDHutchings M, Mous R, Clausen MR, Johnson P, Linton KM, Chamuleau MED, Lewis DJ, Sureda Balari A, Cunningham D, Oliveri RS, Elliott B, DeMarco D, Azaryan A, Chiu C, Li T, Chen KM, Ahmadi T, Lugtenburg PJ. Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. Lancet. 2021 Sep 25;398(10306):1157-1169. doi: 10.1016/S0140-6736(21)00889-8. Epub 2021 Sep 8.
PMID: 34508654DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Study Official
Genmab
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
June 7, 2018
First Posted
August 10, 2018
Study Start
June 26, 2018
Primary Completion (Estimated)
January 1, 2029
Study Completion (Estimated)
January 1, 2029
Last Updated
May 5, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will not share