Safety and Efficacy Trial of Epcoritamab Combinations in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL)

NCT04663347 | Active Not Recruiting Phase 1 DMC FDA Drug

• 6 other identifiers: GCT3013-022023-504805-35-002020-000845-15NL74222.056.20283235RECF4377
• Study Type: interventional
• Target: 543
• Locations: 13 countries
• Sites: 57

Brief Summary

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.

Conditions

Diffuse Large B-Cell Lymphoma; Follicular Lymphoma

Keywords

DuoBody®; monoclonal antibodies; anti-CD3; anti-CD20

Outcome Measures

Primary Outcomes (3)

• Part 1: Number of Participants With Dose limiting Toxicities (DLTs)

  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)

  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)

  ORR is defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on Lugano criteria.

  Up to 3 years

Secondary Outcomes (24)

• Part 1 and 2: Clearance (CL) of Epcoritamab

  Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)

• Part 1 and 2: Area Under the Concentration-Time Curve (AUC) of Epcoritamab

  Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)

• Part 1 and 2: Maximum (Peak) Plasma Concentration (Cmax) of Epcoritamab

  Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)

• Part 1 and 2: Time to Reach Cmax (Tmax) of Epcoritamab

  Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)

• Part 1 and 2: Terminal Elimination Half-Life (t 1/2) of Epcoritamab

  Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)

Study Arms (10)

Arm 1 - Epcoritamab + R-CHOP

EXPERIMENTAL

In participants with previously untreated DLBCL.

Drug: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; Biological: Epcoritamab

Arm 2 - Epcoritamab + R2

EXPERIMENTAL

In participants with R/R FL.

Biological: Epcoritamab; Drug: Rituximab and Lenalidomide

Arm 3 - Epcoritamab + BR

EXPERIMENTAL

In participants with previously untreated FL.

Drug: rituximab and bendamustine; Biological: Epcoritamab

Arm 4 - Epcoritamab + R-DHAX/C

EXPERIMENTAL

In participants with R/R DLBCL eligible for ASCT.

Drug: rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin; Biological: Epcoritamab

Arm 5 - Epcoritamab + GemOx

EXPERIMENTAL

In participants with R/R DLBCL ineligible ASCT.

Drug: gemcitabine and oxaliplatin; Biological: Epcoritamab

Arm 6 - Epcoritamab + R2

EXPERIMENTAL

In participants with previously untreated FL.

Drug: rituximab and lenalidomide; Biological: Epcoritamab

Arm 7 - Epcoritamab maintenance

EXPERIMENTAL

In participants with FL who achieved a CR or PR after receiving SOC treatment in 1L or 2L.

Biological: Epcoritamab

Arm 8 - Epcoritamab + R mini-CHOP

EXPERIMENTAL

In participants with previously untreated DLBCL who are ineligible to receive full-dose anthracycline.

Drug: rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone; Biological: Epcoritamab

Arm 9 - Epcoritamab + Lenalidomide

EXPERIMENTAL

In participants with R/R FL who progressed within 24 months of initiation of first-line anti-CD20-containing immunochemotherapy.

Drug: Lenalidomide; Biological: Epcoritamab

Arm 10 - Epcoritamab + R-ICE

EXPERIMENTAL

In participants with R/R DLBCL eligible for ASCT.

Drug: rituximab, ifosfamide, carboplatin, and etoposide phosphate; Biological: Epcoritamab

Interventions

rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone DRUG

6 cycles (21-day cycles)

Also known as: R-CHOP

Arm 1 - Epcoritamab + R-CHOP

rituximab and bendamustine DRUG

6 cycles (28-day cycles)

Also known as: BR

Arm 3 - Epcoritamab + BR

rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone DRUG

6 cycles (21-day cycles)

Also known as: R mini-CHOP

Arm 8 - Epcoritamab + R mini-CHOP

Lenalidomide DRUG

12 cycles (28-day cycles)

Arm 9 - Epcoritamab + Lenalidomide

gemcitabine and oxaliplatin DRUG

4 cycles (28-day cycles)

Also known as: GemOx

Arm 5 - Epcoritamab + GemOx

rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin DRUG

3 cycles (21-day cycles)

Also known as: R-DHAX/C

Arm 4 - Epcoritamab + R-DHAX/C

rituximab, ifosfamide, carboplatin, and etoposide phosphate DRUG

3 cycles (21-day cycles)

Also known as: R-ICE

Arm 10 - Epcoritamab + R-ICE

Epcoritamab BIOLOGICAL

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.

Also known as: GEN3013, DuoBody®-CD3xCD20, EPKINLY™

Arm 1 - Epcoritamab + R-CHOP

Rituximab and Lenalidomide DRUG

rituximab 6 cycles and lenalidomide 12 cycles (28-day cycles)

Also known as: R2

Arm 6 - Epcoritamab + R2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AbbVie: collaborator
• Genmab: lead

Study Sites (57)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

David Geffen School of Medicine at UCLA

Los Angeles, California, 90095, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan Comprehensive Cancer Center Michigan Medicine

Ann Arbor, Michigan, 48109, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Mount Sinai

New York, New York, 10029, United States

Location

Memorial Sloan Kettering CC

New York, New York, 10065, United States

Location

Levine Cancer Center

Charlotte, North Carolina, 28204, United States

Location

Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Austin Health

Heidelberg, VIC 3084, Australia

Location

Linear Clinical Research Limited

Nedlands, 6009, Australia

Location

AZ Sint-Jan

Bruges, 8000, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

CHU UCL Namur Site Godinne

Yvoir, 5530, Belgium

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, Czechia

Location

Fakultni nemocnice Ostrava

Ostrava - Poruba, Czechia

Location

Fakultni nemocnice v Motole

Prague, 15006, Czechia

Location

Vseobecna Fakultni Nemocnice

Prague, Czechia

Location

Århus Hospital

Aarhus, Denmark

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Odense University Hospital

Odense, Denmark

Location

Vejle Sygehus

Vejle, Denmark

Location

Kuopio University Hospital

Kuopio, 70210, Finland

Location

HUS Cancer Center

Lahti, 15850, Finland

Location

Hopital Claude Huriez - CHRU Lille

Lille, 59037, France

Location

Hôpital de la Timone

Marseille, 13005, France

Location

Hôpital Saint-Louis

Paris, 75475, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)

Bergamo, 24127, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS

Bologna, Italy

Location

Fondazione del Piemonte per l Oncologia Istituto di Candiolo IRCCS

Candiolo, 10060, Italy

Location

IRCCS Istituto Scientifico Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST

Meldola, 47014, Italy

Location

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio Emilia

Reggio Emilia, 42123, Italy

Location

Amsterdam UMC, Locatie VUMC

Amsterdam, 1105 AZ, Netherlands

Location

Universitair Medisch Centrum Groningen (UMCG)

Groningen, 9713, Netherlands

Location

Leids Universitair Medisch Centrum

Leiden, 2333 ZA, Netherlands

Location

Maastricht University Medical Center

Maastricht, 6229 HX, Netherlands

Location

Erasmus Medisch Centrum

Rotterdam, Netherlands

Location

UMC Utrecht

Utrecht, 3584, Netherlands

Location

Oslo Universitetssykehus HF, Radiumhospitalet

Oslo, 310, Norway

Location

ICO l Hospitalet

Barcelona, 08908, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 8035, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Södra Älvsborgs Sjukhus

Borås, Sweden

Location

Sahlgrenska Sjukhuset

Gothenburg, 413 45, Sweden

Location

Skånes Universitetssjukhus

Lund, Sweden

Location

Karolinska Universitetssjukhuset

Solna, Sweden

Location

Akademiska Sjukhuset

Uppsala, Sweden

Location

The Christie Hospital

Manchester, United Kingdom

Location

Freeman Hospital

Newcastle upon Tyne, NE7 7D, United Kingdom

Location

Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 40920572 DERIVED

• 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.

  PMID: 39792928 DERIVED

Related Links

• Patient website: Recruiting clinical sites in Finland

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular

Interventions

Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone; R-CHOP protocol; Lenalidomide; Bendamustine Hydrochloride; Cytarabine; Dexamethasone; Oxaliplatin; Carboplatin; Gemcitabine; Ifosfamide; etoposide phosphate

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Isoindoles; Butyrates; Acids, Acyclic; Benzimidazoles; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pregnadienetriols; Steroids, Fluorinated; Coordination Complexes; Deoxycytidine; Oxazines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: October 27, 2020
• First Posted: December 11, 2020
• Study Start: November 3, 2020
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: May 5, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (4); CZ (4); FR (4); ES (5); NO (1); BE (3); IT (7); SE (5); GB (3); NL (6); FI (2); US (11); AU (2)