Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome

Last updated: June 2, 2025
Sponsor: Genmab
Overall Status: Active - Recruiting

Phase

1/2

Condition

Leukemia

Lymphocytic Leukemia, Chronic

Leukemia (Pediatric)

Treatment

Epcoritamab

Lenalidomide

Pirtobrutinib

Clinical Study ID

NCT04623541
GCT3013-03
RECF-005228
NL74221.056.20
MOH_2023-04-02_012496
1006575
2020-000848-57
2023-504828-25-00
  • Ages > 18
  • All Genders

Study Summary

The study is a global, multi-center safety and efficacy trial of epcoritamab, an antibody also known as EPKINLY™ and GEN3013 (DuoBody®-CD3xCD20). Epcoritamab will be tested either in

Relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) as:

  • Monotherapy, or

  • Combination therapy:

    • epcoritamab + venetoclax

    • epcoritamab + pirtobrutinib

Treatment-naïve (TN) high risk (HR) (CLL):

• epcoritamab + pirtobrutinib

Combination therapy for Richter's Syndrome (RS):

  • epcoritamab + lenalidomide

  • epcoritamab + R-CHOP (i.e., rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine [Oncovin®] and prednisone).

The study includes participants with R/R or TN HR CLL/small lymphocytic lymphoma (SLL) and participants with RS.

The trial consists of two parts, a dose-escalation phase (phase Ib) and an expansion phase (phase II). Participants with RS are only included in the expansion phase.

Epcoritamab will be injected subcutaneously (under the skin). Standard-of-care and combination treatments (venetoclax, pirtobrutinib, lenalidomide, and R-CHOP) will be given either orally (by mouth) or intravenously (in a vein).

Study details include:

  • Study duration will be up to 5 years after the last participant's first treatment in the trial.

  • The treatment duration for each participant will be between 12 months (1 year) and 24 months (2 years), depending upon the treatment arm assigned.

  • The visit frequency will be either weekly, every other week, or monthly, depending upon the part of the study.

All participants will receive active drug; no one will be given placebo.

Eligibility Criteria

Inclusion

Key Inclusion Criteria

  1. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.

  2. Evidence of CD20 positivity in a sample representative of the disease at Screening.

  3. Acceptable hematology parameters and organ function based on baseline bloodwork.

  4. Life expectancy >3 months on standard of care (SOC) for CLL, >3 months for RS.

  5. For R/R CLL arms - Must have active CLL/SLL disease requiring treatment per iwCLL 2018 criteria.

  6. For R/R CLL monotherapy arms - Received at least 2 prior lines of systemic anti-neoplastic therapy including a Bruton's tyrosine kinase (BTK) inhibitor or at least 1 prior line of systemic antineoplastic therapy, including treatment with (or intolerance of) a covalent BTK inhibitor (cBTKi) and a B-cell lymphoma 2 (BCL-2) inhibitor.

  7. For all RS arms - Have tumor biopsy-proven CD20+ Diffuse large B-cell Lymphoma (DLBCL) and a clinical history of CLL/SLL.

  8. For all RS arms - Must have measurable disease by fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) or magnetic resonance imaging (MRI) scan.

  9. For all RS arms - Must provide mandatory formalin-fixed, paraffin-embedded (FFPE) tumor biopsy sample.

  10. For RS - monotherapy arm: Deemed as ineligible for chemoimmunotherapy at investigator's discretion or participant who refuses to receive intensive chemotherapy

  11. For RS - lenalidomide combination therapy arm

  • Deemed as ineligible for chemoimmunotherapy at the investigator's discretion, or participant who refuses to receive intensive chemotherapy.

  • Eligible for treatment with lenalidomide.

  • Must be willing to use contraception and adhere to the Lenalidomide Pregnancy Risk Minimization Plan

  • A woman must agree not to breastfeed a child during treatment and for at least 28 days after discontinuation from study.

  1. For RS - R-CHOP combination Therapy Arm -
  • Eligible for treatment with R-CHOP.

  • Females of childbearing potential must use highly effective contraceptive measures while taking R-CHOP and for 12 months after stopping treatment.

  • A woman must agree not to breastfeed a child during treatment or until 12 months after last treatment.

  1. For R/R CLL - venetoclax combination Therapy arm - after receiving at least 1 prior line of systemic antineoplastic therapy.
  • Presence of measurable disease.

  • Must take prophylaxis for tumor lysis syndrome (TLS).

  1. For R/R CLL pirtobrutinib combination Therapy arm:
  • Must have active CLL/SLL disease requiring treatment per iwCLL 2018 criteria.

  • Presence of measurable disease.

  • Previous treatment with at least one and a maximum 3 prior lines of therapy including a cBTKi.

  • Diagnosis of CLL/SLL that met published iwCLL criteria.

  1. Participants with TN HR CLL - Pirtobrutinib Combination Therapy Expansion:
  • Diagnosis of CLL/SLL that met published iwCLL criteria 2018.

  • Must have active CLL/SLL disease that needs treatment per iwCLL

  • Must take prophylaxis for TLS based on their TLS risk evaluation upon initiation of trial drug.

  • Must have one or more high-risk features.

  • Presence of measurable disease.

Key Exclusion Criteria

  1. Received prior treatment with a CD3×CD20 bispecific antibody.

  2. Received any prior allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation.

  3. Received chimeric antigen receptor (CAR) T-cell therapy within 100 days or an investigational drug within 4 weeks, prior to first dose of trial drug.

  4. Autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy.

  5. Received vaccination with live vaccines within 28 days.

  6. Clinically significant cardiac disease.

  7. Known current malignancy other than inclusion diagnosis.

  8. Has had major surgery within 4 weeks.

  9. Known history of human immunodeficiency virus (HIV).

  10. For R/R CLL arms - Any history of RS or evidence indicating a potential Richter's transformation.

  11. For R/R CLL - Venetoclax Combination Therapy arm: received venetoclax within 24 months prior to beginning venetoclax ramp-up for this trial or has progressed on venetoclax treatment.

  12. For all RS arms - Diagnosis of Richter's syndrome not of the DLBCL subtype such as Hodgkin's lymphoma, prolymphocytic leukemia.

  13. RS - Lenalidomide Combination Therapy and RS Monotherapy Arms - received more than 2 prior lines of therapy for RS.

  14. R/R CLL - Pirtobrutinib Combination Therapy Arm - Prior exposure to a non-covalent (reversible) BTK inhibitor or a BTK degrader.

  15. Pirtobrutinib Combination Therapy Expansion Arms:

  • History of bleeding disorders or participants requiring therapeutic anticoagulation with warfarin or another vitamin K antagonist

  • Require continuous treatment with or have received strong cytochrome P450 (CYP) 3A inhibitors or strong/moderate CYP3A inducers within 4 to 5 half-lives or 14 days prior to the first dose of pirtobrutinib.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Design

Total Participants: 424
Treatment Group(s): 5
Primary Treatment: Epcoritamab
Phase: 1/2
Study Start date:
November 25, 2020
Estimated Completion Date:
August 31, 2029

Study Description

The purpose of the dose-escalation phase of the trial is to determine the recommended phase 2 dose (RP2D) and the maximum tolerated dose (MTD; if reached) as well as establish the safety profile of epcoritamab monotherapy and epcoritamab + venetoclax in participants with R/R CLL.

The purpose of the expansion phase is to assess and evaluate the preliminary efficacy, safety and tolerability profiles of epcoritamab monotherapy, epcoritamab + venetoclax and epcoritamab + pirtobrutinib at the RP2D for participants with R/R CLL, TN HR CLL and SLL. Along with this, epcoritamab monotherapy, epcoritamab + lenalidomide and epcoritamab + R-CHOP will be evaluated in participants with RS to assess their efficacy, safety and tolerability profiles.

The purpose of safety run-in phase for pirtobrutinib combination therapy is to evaluate the safety and tolerability profiles of pirtobrutinib in combination with epcoritamab.

Connect with a study center

  • St George Hospital

    Kogarah, New South Wales 2217
    Australia

    Site Not Available

  • St. George Hospital

    Kogarah, New South Wales
    Australia

    Active - Recruiting

  • Flinders Medical Centre

    Bedford Park, South Australia 5042
    Australia

    Active - Recruiting

  • Barwon Health

    Geelong, Victoria
    Australia

    Active - Recruiting

  • University Hospital of Geelong

    Geelong, Victoria 3220
    Australia

    Active - Recruiting

  • Alfred Health

    Melbourne, Victoria 3004
    Australia

    Active - Recruiting

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria 3000
    Australia

    Active - Recruiting

  • AZ Sint-Jan

    Bruges, 8000
    Belgium

    Active - Recruiting

  • Universitair Ziekenhuis Gent

    Gent, 9000
    Belgium

    Active - Recruiting

  • UZ Leuven

    Leuven, 3000
    Belgium

    Active - Recruiting

  • Vseobecna Fakultni Nemocnice

    Praha, Nové Město 128 08
    Czechia

    Active - Recruiting

  • Fakultni nemocnice Hradec Kralove

    Hradec Králové, Nový Hradec Králové 500 05
    Czechia

    Active - Recruiting

  • Fakultni Nemocnice Ostrava

    Ostrava, Poruba
    Czechia

    Active - Recruiting

  • Fakultni nemocnice Brno

    Brno, 625 00
    Czechia

    Active - Recruiting

  • Fakultni nemocnice Olomouc

    Olomouc, 779 00
    Czechia

    Active - Recruiting

  • Rigshospitalet

    København, Hovedstaden 2100
    Denmark

    Active - Recruiting

  • Aalborg University Hospital

    Aalborg, 9100
    Denmark

    Active - Recruiting

  • Odense University Hospital

    Odense, 5000
    Denmark

    Active - Recruiting

  • Roskilde Sygehus

    Roskilde, 4000
    Denmark

    Active - Recruiting

  • Vejle Sygehus

    Vejle, 7100
    Denmark

    Active - Recruiting

  • Århus University Hospital

    Århus, 8000
    Denmark

    Active - Recruiting

  • CHU de Montpellier Hôpital Saint Eloi

    Montpellier, Cedex 5 34090
    France

    Active - Recruiting

  • CHU Hôpital Haut-Lévêque Bordeaux

    Pessac, Gironde 33404
    France

    Active - Recruiting

  • CHU Hôpital de Brabois Nancy

    Vandœuvre-lès-Nancy, Meurthe et Moselle 54500
    France

    Active - Recruiting

  • Hopital Saint Eloi

    Montpellier, Occitania 34090
    France

    Active - Recruiting

  • Hôpital Privé du Confluent

    Nantes, Pays de la Loire 44000
    France

    Active - Recruiting

  • CHU Clermont Ferrand

    Clermont Ferrand cedex, Puy de Dome 63000
    France

    Active - Recruiting

  • Groupe Hospitalier Pitie-Salpetriere

    Paris, 75013
    France

    Active - Recruiting

  • Hôpital Saint-Louis

    Paris, 75010
    France

    Active - Recruiting

  • Hôpital Universitaire Pitié-Salpêtrière

    Paris, 75013
    France

    Active - Recruiting

  • CHU de Bordeaux - Hôpital Haut-Lévêque

    Pessac, 33604
    France

    Active - Recruiting

  • CHU de Nancy - Hôpital de Brabois Adultes

    Vandœuvre-lès-Nancy, 54500
    France

    Active - Recruiting

  • Universitaetsklinikum Ulm

    Ulm, Baden Wuerttemberg 89070
    Germany

    Active - Recruiting

  • Universitaetsklinikum Schleswig-Holstein- Karl-Lennart-Krebscentrum

    Kiel, 24105
    Germany

    Active - Recruiting

  • Universitaetsklinikum Koeln

    Koeln, 50937
    Germany

    Active - Recruiting

  • University of Cologne

    Köln,
    Germany

    Site Not Available

  • Bnai Zion Medical Center

    Haifa,
    Israel

    Active - Recruiting

  • Hadassah University Hospital - Ein Kerem

    Jerusalem,
    Israel

    Active - Recruiting

  • Rabin Medical Center-Beilinson Campus

    Petah Tikva, 4941492
    Israel

    Active - Recruiting

  • Chaim Sheba Medical Center

    Ramat Gan,
    Israel

    Active - Recruiting

  • Tel Aviv Sourasky Medical Center

    Tel Aviv-Yafo,
    Israel

    Active - Recruiting

  • Istituto di Candiolo

    Torino, Candiolo 10060
    Italy

    Active - Recruiting

  • AOU Arcispedale Sant'Anna

    Ferrara, Cona 44124
    Italy

    Active - Recruiting

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

    Meldola, Forli - Cesena 47014
    Italy

    Active - Recruiting

  • IRCCS Policlinico Universitario Agostino Gemelli

    Roma, Lazio 00136
    Italy

    Active - Recruiting

  • AOU Policlinico Sant'Orsola Malpighi IRCCS

    Bologna, 00161
    Italy

    Active - Recruiting

  • Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)

    Brescia,
    Italy

    Active - Recruiting

  • Ospedale San Raffaele

    Milano, 20132
    Italy

    Active - Recruiting

  • Ospedale Maggiore di Novara

    Novara, 28100
    Italy

    Active - Recruiting

  • AOU Policlinico Umberto I

    Roma, 00161
    Italy

    Active - Recruiting

  • Fondazione Policlinico Universitario Agostino Gemelli IRCCS

    Roma, 00168
    Italy

    Active - Recruiting

  • AOU Città della Salute e della Scienza di Torino

    Torino, 10126
    Italy

    Active - Recruiting

  • Maastricht University Medical Center

    Maastricht, Limburg 6229 HX
    Netherlands

    Active - Recruiting

  • Albert Schweitzer Ziekenhuis, Dordwijk

    Dordrecht, South Holland 3318 AT
    Netherlands

    Active - Recruiting

  • Amsterdam UMC

    Amsterdam, 1105 AZ
    Netherlands

    Active - Recruiting

  • Universitair Medisch Centrum Groningen

    Groningen, 9713 GZ
    Netherlands

    Active - Recruiting

  • UMC Utrecht

    Utrecht, 3584 CX
    Netherlands

    Active - Recruiting

  • Universitair Medisch Centrum Utrecht

    Utrecht, 3584 CX
    Netherlands

    Active - Recruiting

  • Pratia Medical Center Katowice (Centrum Medyczne Pratia Katowice)

    Katowice,
    Poland

    Active - Recruiting

  • Pratia Malopolskie Medical Center Krakow (Pratia Małopolskie Centrum Medyczne Krakow)

    Kraków,
    Poland

    Active - Recruiting

  • Aidport sp z o.o.

    Skorzewo,
    Poland

    Active - Recruiting

  • ICO Badalona - Hospital Universitario Germans Trias Pujol

    Badalona, Barcelona
    Spain

    Active - Recruiting

  • AOC Arcispedale Saint'Anna

    Coaña, Ferarra
    Spain

    Active - Recruiting

  • Hospital Clinico Universitario de Valencia

    Valencia, València 46010
    Spain

    Active - Recruiting

  • Hospital Clinic de Barcelona

    Barcelona, 08036
    Spain

    Active - Recruiting

  • Hospital de la Santa Creu i Sant Pau

    Barcelona,
    Spain

    Active - Recruiting

  • Hospital Universitario Fundacion Jiménez Díaz

    Madrid, 28040
    Spain

    Active - Recruiting

  • Hospital Universitario Ramón y Cajal

    Madrid, 28034
    Spain

    Active - Recruiting

  • Hospital Universitario Virgen Macarena

    Sevilla,
    Spain

    Active - Recruiting

  • Royal Cornwall Hospital

    Truro, Cornwall TR1 3LJ
    United Kingdom

    Site Not Available

  • Nottingham University Hospitals City Campus

    Nottingham, Nottinghamshire
    United Kingdom

    Site Not Available

  • St. James s University Hospital

    Leeds, West Yorkshire
    United Kingdom

    Active - Recruiting

  • Barts Hospital

    London, EC1A 7BE
    United Kingdom

    Active - Recruiting

  • O'Neal Comprehensive Cancer Center at University of Alabama at Birmingham

    Birmingham, Alabama 35233
    United States

    Active - Recruiting

  • University of Alabama

    Tuscaloosa, Alabama 35487
    United States

    Site Not Available

  • University of California Davis Medical Center Sacramento

    California, California 95817
    United States

    Active - Recruiting

  • University of California Davis Medical Center Sacramento

    California City, California 95817
    United States

    Site Not Available

  • City of Hope

    Duarte, California 91010
    United States

    Active - Recruiting

  • City of Hope National Medical Center

    Duarte, California 91010
    United States

    Active - Recruiting

  • Cedars-Sinai Medical Center

    Los Angeles, California 90048
    United States

    Site Not Available

  • David Geffen School of Medicine

    Los Angeles, California 90095
    United States

    Active - Recruiting

  • Stanford Cancer Center

    Palo Alto, California 94305
    United States

    Active - Recruiting

  • Stanford University School of Medicine

    Stanford, California 94305
    United States

    Site Not Available

  • Memorial Healthcare System

    Hollywood, Florida 33021
    United States

    Site Not Available

  • Mount Sinai Comprehensive Cancer Center

    Miami Beach, Florida 33140
    United States

    Active - Recruiting

  • Memorial Healthcare System

    Pembroke Pines, Florida 33024
    United States

    Active - Recruiting

  • National Institutes of Health

    Bethesda, Maryland 20892
    United States

    Active - Recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts 02114
    United States

    Active - Recruiting

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan 48190
    United States

    Active - Recruiting

  • Henry Ford Medical Group

    Detroit, Michigan 48202
    United States

    Active - Recruiting

  • Hackensack Meridian Hospital

    Hackensack, New Jersey 07601
    United States

    Active - Recruiting

  • Duke University Medical Center

    Durham, New York 27710
    United States

    Active - Recruiting

  • Northwell Health Cancer Institute

    Lake Success, New York 11043
    United States

    Active - Recruiting

  • Columbia University Herbert Irving Comprehensive Cancer Center

    New York, New York 10032
    United States

    Active - Recruiting

  • Columbia University Hervert Irving Comprehensive Cancer Center

    New York, New York 10032
    United States

    Active - Recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York 10065
    United States

    Active - Recruiting

  • University of Cincinnati

    Cincinnati, Ohio 45221
    United States

    Site Not Available

  • James Cancer Hospital

    Columbus, Ohio 43210
    United States

    Active - Recruiting

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio 43210
    United States

    Active - Recruiting

  • The Ohio State University Comprehensive Cancer Center

    Columbus, Ohio 43210
    United States

    Active - Recruiting

  • University of Pennsylvania

    Philadelphia, Pennsylvania 19104
    United States

    Active - Recruiting

  • University of Pennsylvania School of medicine

    Philadelphia, Pennsylvania 19104
    United States

    Active - Recruiting

  • The University of Texas Southwestern Medical Centre

    Dallas, Texas 75390
    United States

    Active - Recruiting

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas 77030
    United States

    Active - Recruiting

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington 98109
    United States

    Active - Recruiting

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