Clinical trial • Phase I/II • Oncology

EPCORITAMAB for B-cell lymphoma | Non-Hodgkin B-cell lymphoma

Phase I/II trial of EPCORITAMAB for B-cell lymphoma | Non-Hodgkin B-cell lymphoma. open-label, adaptive. 312 participants.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
B-cell lymphoma | Non-Hodgkin B-cell lymphoma
Trial Stage
Phase I/II
Drug Modality
Bispecific antibody
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
08-01-2024
First CTIS Authorization Date
07-02-2024

Trial design

open-label, adaptive Phase I/II trial in Italy, France, Finland and others.

Open Label
Yes
Adaptive
True, design includes dose-escalation to determine MTD and RP2D, expansion cohorts for efficacy assessment, and an optimization part to evaluate alternative priming/intermediate dose regimens intended to reduce CRS risk; includes planned PK, interim safety assessments and dose-limiting toxicity evaluations.
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
312

Eligibility

Recruits 312 Vulnerable population selected in the CTIS record. Only adults are eligible (minimum age 18 years; for expansion in some countries legal age 21 is required). Informed consent is required; multiple subject information and informed consent form (L1_SIS and ICF) documents are listed (country/language-specific versions, including documents titled 'Pregnant Partner' and 'Waiver for Knowledge'). No assent process for minors is described in the available trial data..

Vulnerable Population
Vulnerable population selected in the CTIS record. Only adults are eligible (minimum age 18 years; for expansion in some countries legal age 21 is required). Informed consent is required; multiple subject information and informed consent form (L1_SIS and ICF) documents are listed (country/language-specific versions, including documents titled 'Pregnant Partner' and 'Waiver for Knowledge'). No assent process for minors is described in the available trial data.

Inclusion criteria

  • {"criterion_text":"- 1. Patient must be 18 years of age or older (for expansion: In countries where the legal age is 21 years of age; only patients 21 years of age or older are eligible)\n- 2. Documented CD20+ mature non-Hodgkin B-cell lymphoma according to WHO classification\n- 3. Relapsed, progressive and/or refractory disease (Cheson et al., 2007) following treatment with an anti-CD20 monoclonal antibody\n- 4. Patients must have received at least 2 prior lines of therapy\n- 5. Patients must have measurable disease by imaging\n- 6. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2. For MCL: ECOG PS <2 required for participation.\n- 7. For the optimization part, patients must have R/R DLBCL, or FL grades 1-3A, or MCL (according to cohort)."}

Exclusion criteria

  • {"criterion_text":"- 1. Primary central nervous system (CNS) lymphoma or known CNS involvement by lymphoma\n- 2. AST, and/or ALT > 3 x upper limit of normal\n- 3. Total bilirubin > 1.5 x upper limit of normal\n- 4. Creatinine clearance < 45 mL/min\n- 5. Known clinically significant cardiac disease, including: a. Onset of unstable angina pectoris within 6 months of signing ICF b. Acute myocardial infarction within 6 months of signing ICF c. Congestive heart failure (grade III or IV as classified by the New York Heart Association and/or known decrease ejection fraction of < 45%\n- 6. Ongoing active bacterial, viral, fungal, mycobacterial, parasitic, or other infection requiring systemic treatment (excluding prophylactic treatment) at the time of enrolment or within the previous 2 weeks prior to the first dose of epcoritamab, including COVID-19 infection.\n- 7. Eligible for curative salvage therapy with high dose therapy followed by stem cell rescue\n- 8. Active hepatitis B (DNA PCR-positive) or hepatitis C (RNA PCR positive infection). Subjects with evidence of prior HBV but who are PCRnegative are permitted in the trial but should receive prophylactic antiviral therapy.\n- 9. Known human immunodeficiency virus (HIV) infection.\n- 10. Exposed to live or live attenuated vaccine within 4 weeks prior to signing ICF\n- 11. Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 30 days prior to first GEN3013 administration\n- 12. Autologous HSCT within 100 days prior to first GEN3013 administration, or any prior allogeneic HSCT or solid organ transplantation\n- 13. Contraindication to all uric acid lowering agents"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Escalation End Points: - Dose limiting toxicity - Adverse events\n- Expansion End Points: - Overall response rate (ORR) determined by Lugano criteria as assessed by independent review committee (IRC)\n- Optimization End Points: - Adverse events; Rating of ≥ Grade 2 CRS events","definition_or_measurement_approach":"Escalation: DLT and adverse events (safety reporting). Expansion: ORR determined by Lugano criteria assessed by an independent review committee (IRC). Optimization: adverse events with specific assessment of Grade ≥2 CRS events (CRS grading as per protocol)."}

Secondary endpoints

  • {"endpoint_text":"- Escalation End Points: - Cytokine measures - Laboratory parameters (biochemistry, hematology including immunophenotyping for absolute T-cell and B-cell counts as well as Tcell activation and exhaustion markers) - PK parameters (clearance, volume of distribution and area-under-the concentration- time curve (AUC0-Clast and AUC0-∞), maximum concentration (Cmax), time of Cmax (Tmax), pre dose values, and halflife)\n- Escalation End Points: - Immunogenicity of GEN3013 - Anti-lymphoma activity, i.e. resolution of constitutional symptoms, reduction in tumor size, objective and best response - Duration of response - Progression free survival - Time to next anti-lymphoma therapy - Overall survival\n- Expansion/Optimization: - Duration of response (DOR) determined by Lugano criteria - Complete response (CR) rate determined by Lugano criteria - Duration of CR (DoCR) by Lugano criteria - Progression-free survival (PFS) determined by Lugano criteria - Time to response (TTR) determined by Lugano criteria\n- Expansion/Optimization: - Objective and best response rate determined by LYRIC; PFS, DOR, DoCR, TTR, OS determined by LYRIC\n- Expansion/Optimization: - Time to next (anti-lymphoma) therapy (TTNT) - Rate of MRD negativity - Safety (adverse events, laboratory parameters, hospitalizations, and cytokine measures)\n- Expansion/Optimization: - PK parameters and incidence of ADAs to GEN3013 - Changes in lymphoma symptoms measured by FACT-Lym\n- Expansion/Optimization: - Rate of ≥ Grade 2 CRS events and all grade CRS events following first full dose and overall","definition_or_measurement_approach":"Includes cytokine assays, laboratory tests, PK parameter calculations (AUC, Cmax, Tmax, clearance, half-life), immunogenicity assays (ADA), efficacy assessments by Lugano and LYRIC criteria (by IRC and investigator), MRD assessment, survival endpoints (DOR, PFS, OS), PROs via FACT-Lym, and CRS grading (≥ Grade 2 events) as specified in protocol."}

Recruitment

Planned Sample Size
312
Recruitment Window Months
120
Consent Approach
Informed consent obtained from adult participants. Age eligibility: ≥18 years (expansion cohorts in some countries require ≥21 years). Multiple country- and language-specific subject information and informed consent form documents are listed (L1_SIS and ICF files in EN, IT, FR, FI, DE, NL, PL, SE etc.). Additional ICF material referenced includes 'Pregnant Partner' information and a 'Waiver for Knowledge' document in some jurisdictions. No assent process for minors is described in available documents.

Geography

Total Number Of Sites
41
Total Number Of Participants
395

Italy

Earliest CTIS Part Ii Submission Date
22-01-2024
Latest Decision Or Authorization Date
24-02-2026
Processing Time Days
764
Number Of Sites
5
Number Of Participants
42

Sites

Site Name
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Department Name
Onco-hematology
Contact Person Name
Pierluigi Zinzani
Contact Person Email
pierluigi.zinzani@unibo.it
Site Name
Istituto Di Candiolo Fondazione Del Piemonte Per Loncologia IRCCS
Department Name
Onco-hematology
Contact Person Name
Umberto Vitolo
Contact Person Email
umberto.vitolo@ircc.it
Site Name
Ospedale San Raffaele S.r.l.
Department Name
Onco-Hematology - Lymphoma Unit
Contact Person Name
Andrés José Maria Ferreri
Contact Person Email
ferreri.andres@hsr.it
Site Name
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
Department Name
Hematology
Contact Person Name
Gerardo Musuraca
Contact Person Email
gerardo.musuraca@irst.emr.it
Site Name
Azienda Ospedaliera Nazionale Ss Antonio E Biagio E C Arrigo Alessandria
Department Name
Hematology
Contact Person Name
Manuela Zanni
Contact Person Email
manuela.zanni@ospedale.al.it

France

Earliest CTIS Part Ii Submission Date
22-01-2024
Latest Decision Or Authorization Date
23-02-2026
Processing Time Days
763
Number Of Sites
5
Number Of Participants
61

Sites

Site Name
Assistance Publique Hopitaux De Paris (Creteil Cedex)
Department Name
Unite Hemopathies Lymphoïdes
Contact Person Name
Corinne HAIOUN
Contact Person Email
corinne.haioun@aphp.fr
Site Name
Assistance Publique Hopitaux De Paris (Paris Cedex 10)
Department Name
Service Hematologie-Oncologie
Contact Person Name
Catherine THIEBLEMONT
Contact Person Email
catherine.thieblemont@aphp.fr
Site Name
Centre Hospitalier Regional Universitaire De Tours
Department Name
Centre Henri S. Kaplan / Hematologie et Therapie Cellulaire
Contact Person Name
Emmanuel GYAN
Contact Person Email
emmanuel.gyan@univ-tours.fr
Site Name
Hospices Civils De Lyon
Department Name
Service d’Hematologie Clinique
Contact Person Name
Herve GHESQUIERES
Contact Person Email
herve.ghesquieres@chu-lyon.fr
Site Name
Centre Henri Becquerel
Department Name
Service Hematologie
Contact Person Name
Herve TILLY
Contact Person Email
herve.tilly@chb.unicancer.fr

Finland

Earliest CTIS Part Ii Submission Date
22-01-2024
Latest Decision Or Authorization Date
24-02-2026
Processing Time Days
764
Number Of Sites
3
Number Of Participants
10

Sites

Site Name
HUS-Yhtymae
Department Name
Department of Oncology
Contact Person Name
Sirpa Leppa
Contact Person Email
sirpa.leppa@hus.fi
Site Name
Tampere University Hospital
Department Name
Department of Oncology
Contact Person Name
Marjukka Pollari
Contact Person Email
marjukka.pollari@pirha.fi
Site Name
Kuopio University Hospital
Department Name
Department of Oncology
Contact Person Name
Outi Kuittinen
Contact Person Email
outi.kuittinen@kuh.fi

Netherlands

Earliest CTIS Part Ii Submission Date
22-01-2024
Latest Decision Or Authorization Date
24-02-2026
Processing Time Days
764
Number Of Sites
4
Number Of Participants
68

Sites

Site Name
University Hospital Maastricht
Department Name
Hematology
Contact Person Name
Marjolein van der Poel
Contact Person Email
marjolein.vander.poel@mumc.nl
Site Name
Universitair Medisch Centrum Utrecht
Department Name
Hematology
Contact Person Name
Rimke Oostvogels
Contact Person Email
r.oostvogels@umcutrecht.nl
Site Name
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Department Name
Hematology
Contact Person Name
Pieternella Lugtenburg
Contact Person Email
p.lugtenburg@erasmusmc.nl
Site Name
Amsterdam UMC
Department Name
Hematology
Contact Person Name
Martine Chamuleau
Contact Person Email
m.chamuleau@vumc.nl

Denmark

Earliest CTIS Part Ii Submission Date
22-01-2024
Latest Decision Or Authorization Date
23-02-2026
Processing Time Days
763
Number Of Sites
3
Number Of Participants
59

Sites

Site Name
Lillebaelt Hospital
Department Name
Department of Hematology
Contact Person Name
Michael Roost Clausen
Contact Person Email
michael.roost.clausen@rsyd.dk
Site Name
Odense University Hospital
Department Name
Haematological Research Unit
Contact Person Name
Jacob Haaber
Contact Person Email
jacob.h.christensen@rsyd.dk
Site Name
Rigshospitalet
Department Name
Department of Hematology
Contact Person Name
Martin Hutchings
Contact Person Email
Martin.Hutchings@regionh.dk

Sweden

Earliest CTIS Part Ii Submission Date
22-01-2024
Latest Decision Or Authorization Date
24-02-2026
Processing Time Days
764
Number Of Sites
3
Number Of Participants
22

Sites

Site Name
Region Skane Skanes Universitetssjukhus
Department Name
Hematology/Oncology/Radiology
Contact Person Name
Mats Jerkeman
Contact Person Email
mats.jerkeman@med.lu.se
Site Name
Karolinska University Hospital
Department Name
Hematology Clinic
Contact Person Name
Kristina Sonnevi
Site Name
Uppsala University Hospital
Department Name
Hematology/Oncology Clinic
Contact Person Name
Ingrid Glimelius
Contact Person Email
ingrid.glimelius@igp.uu.se

Germany

Earliest CTIS Part Ii Submission Date
22-01-2024
Latest Decision Or Authorization Date
25-02-2026
Processing Time Days
765
Number Of Sites
6
Number Of Participants
16

Sites

Site Name
University Hospital Cologne AöR
Department Name
Studienzentrum der Klinik I für Innere Medizin (CTU Cologne)Universitätsklinikum Köln AöR
Contact Person Name
Jan-Michel Heger
Contact Person Email
jan-michel.heger@uk-koeln.de
Site Name
Universitaetsklinikum Essen AöR
Department Name
Klinik für Hämatologie und Stammzelltransplantation
Contact Person Name
Bastian von Tresckow
Contact Person Email
bastian.vontreskow@uk-essen.de
Site Name
Klinikum der Universitaet Muenchen AöR
Department Name
Medizinische Klinik und Poliklinik III
Contact Person Name
Martin Heinz Dreyling
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie (CBF)
Contact Person Name
Corinna Leng
Contact Person Email
corinna.leng@charite.de
Site Name
Vivantes Netzwerk fuer Gesundheit GmbH
Department Name
Haematologie und Onkologie
Contact Person Name
Christian Scholz
Contact Person Email
christian.scholz@vivantes.de
Site Name
Johannes Gutenberg University Mainz
Department Name
III Med. Hämatologie/Onkologie
Contact Person Name
Georg Hess
Contact Person Email
georg.hess@unimedizin-mainz.de

Poland

Earliest CTIS Part Ii Submission Date
22-01-2024
Latest Decision Or Authorization Date
26-02-2026
Processing Time Days
766
Number Of Sites
7
Number Of Participants
60

Sites

Site Name
Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu
Department Name
Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku
Contact Person Name
Tomasz Wróbel
Contact Person Email
twrobel@usk.wroc.pl
Site Name
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Department Name
Klinika Nowotworów Układu Chłonnego
Contact Person Name
Joanna Romejko-Jarosińska
Site Name
Szpital Uniwersytecki Nr 2 Im Dr Jana Biziela W Bydgoszczy
Department Name
Klinika Hematologii
Contact Person Name
Jarosław Czyż
Site Name
SZPITAL NA KLINACH Grupa Neo Hospital
Contact Person Name
Wojciech Jurczak
Contact Person Email
wojciech.jurczak@pratia.com
Site Name
Uniwersyteckie Centrum Kliniczne
Department Name
Ośrodek Badań Klinicznych Wczesnych Faz
Contact Person Name
Jan Zaucha
Contact Person Email
jzaucha@gumed.edu.pl
Site Name
Pratia S.A.
Department Name
Pratia MCM Krakow
Contact Person Name
Wojciech Jurczak
Contact Person Email
wojciech.jurczak@pratia.com
Site Name
Wojewodzki Szpital Specjalistyczny Im. Janusza Korczaka W Slupsku Sp. z o.o.
Department Name
Oddział Hematologiczny/Transplantacji Szpiku
Contact Person Name
Wojciech Homenda
Contact Person Email
wojhom@sl.home.pl

Spain

Earliest CTIS Part Ii Submission Date
22-01-2024
Latest Decision Or Authorization Date
25-02-2026
Processing Time Days
765
Number Of Sites
5
Number Of Participants
57

Sites

Site Name
Hospital Universitario Fundacion Jimenez Diaz
Department Name
Hematology
Contact Person Name
Daniel Morillo Gile
Contact Person Email
dmorillo@startmadrid.com
Site Name
Clinica Universidad De Navarra
Department Name
Hematology
Contact Person Name
Miguel Angel Canales
Contact Person Email
macanales@unav.es
Site Name
Institut Catala D'oncologia
Department Name
Hematology
Contact Person Name
Ana Maria Sureda Balari
Contact Person Email
asureda@iconcologia.net
Site Name
Hospital Germans Trias I Pujol
Department Name
Hematology
Contact Person Name
Juan Manuel Sancho
Contact Person Email
jsancho@iconcologia.net
Site Name
Fir Huvh Fundacio Institut De Recerca Hospital Universitari Vall De Hebron
Department Name
Hematology
Contact Person Name
Pau Abrisqueta
Contact Person Email
pabrisqueta@vhebron.net

Sponsor

Primary sponsor

Full Name
Genmab A/S
Organisation Type
Pharmaceutical company
Country Of Registered Address
Denmark

Contract research organisations

Name
Icon (Lr) Limited
Responsibilities
data entry
Name
Clinipace Inc.
Responsibilities
Programming and statistics; additional responsibilities (codes 6 and 7)
Name
Syneos Health Netherlands B.V.
Responsibilities
Multiple operational sponsor duties (management/operational roles listed under several duty codes)
Name
Covance Caps Limited
Responsibilities
Management of safety database and AE reporting

Third parties

  • {"country":"Ireland","full_name":"Icon (Lr) Limited","duties_or_roles":"data entry","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Canada","full_name":"Cellcarta Biosciences Inc.","duties_or_roles":"handling biomarker analysis and biomarker testing","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Roche Molecular Systems Inc.","duties_or_roles":"Biomarker analysis and DNA sequencing","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"(duty code 4) (specific duty text not provided)","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Belgium","full_name":"International Drug Development Institute","duties_or_roles":"duties codes 6 and 7 (specific duty text not provided)","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Clinipace Inc.","duties_or_roles":"Programming and statistics; duties codes 6 and 7 (additional duties listed)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Expansion ePRO/eCOA, Escalation central ECG","organisation_type":"Pharmaceutical company"}
  • {"country":"Netherlands","full_name":"Pharma Bio-Research Group","duties_or_roles":"Handling of bionanalysis","organisation_type":"Pharmaceutical company"}
  • {"country":"France","full_name":"Pixilib","duties_or_roles":"Calculation of Total Metabolic Tumor Volume - TMTV","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Covance Caps Limited","duties_or_roles":"Managment of safety database and AE reporting","organisation_type":"Pharmaceutical company"}
  • {"country":"Netherlands","full_name":"Syneos Health Netherlands B.V.","duties_or_roles":"Multiple sponsor duties (codes 1,2,5,8,11,12) – roles include project management and operational trial activities (specific text not provided)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Adaptive Biotechnologies Corp.","duties_or_roles":"handling biomarker analysis and biomarker testing","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"duty code 13 (specific duty text not provided)","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
Epcoritamab
Active Substance
EPCORITAMAB
Modality
Bispecific antibody
Routes Of Administration
Subcutaneous use
Route
Subcutaneous
Authorisation Status
Authorised
Orphan Designation
Yes

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