Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome
EPCORE™ CLL-1
A Phase 1b/2, Open-Label, Safety and Efficacy Study of Epcoritamab (GEN3013; DuoBody®-CD3xCD20) in Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome
7 other identifiers
interventional
195
12 countries
83
Brief 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 In Non-United States (US) Participants Only: 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 (non-US participants only)/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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Nov 2020
Longer than P75 for phase_1
83 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
October 27, 2020
CompletedFirst Posted
Study publicly available on registry
November 10, 2020
CompletedStudy Start
First participant enrolled
November 25, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 1, 2028
May 5, 2026
May 1, 2026
7 years
October 27, 2020
May 4, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Dose Escalation Phase and Safety Run-in (R/R CLL arm): Number of Participants with Dose Limiting Toxicities (DLTs)
DLT events were 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 for low dose cohorts (Cycle length = 28 days) and for high dose cohorts (Cycle length = 35 days)
Dose Escalation Phase and Safety Run-in: Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Up to 5 years
Dose Escalation Phase: Number of Participants with Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and Clinical Tumor Lysis Syndrome (CTLS)
CRS and ICANS will be graded based on American Society for Transplantation and Cellular Therapy (ASTCT) criteria. CTLS will be graded according to Cairo-Bishop criteria.
Up to 5 years
Expansion Phase: Overall Response Rate (ORR)
R/R CLL participants will be assessed according to International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria and the RS participants according to Lugano criteria. ORR based on the Lugano criteria is defined as the percentage of participants who achieve a response of PR or complete remission (CR), prior to initiation of subsequent therapy. The ORR based on the iwCLL criteria is defined as the percentage of participants who achieve a response of PR, CR with incomplete bone marrow recovery (CRi), or CR, prior to the initiation of subsequent therapy.
Up to 5 years
Secondary Outcomes (20)
Expansion Phase: Number of Participants with TEAEs and SAEs
Up to 5 years
Dose Escalation Phase and Safety Run-in: ORR (for R/R CLL Participants)
Up to 5 years
Both Phases and Safety Run-in: Duration of Response (DOR)
Up to 5 years
Both Phases and Safety Run-in: Number of Participants with CR/CRi
Up to 5 years
Both Phases and Safety Run-in: Time to Response (TTR)
Up to 5 years
- +15 more secondary outcomes
Study Arms (7)
Epcoritamab in R/R CLL/SLL
EXPERIMENTALIn both study phases. Participants in the expansion phase will be treated at the RP2D defined in the dose-escalation phase.
Epcoritamab in RS
EXPERIMENTALOnly in expansion phase.
Epcoritamab + Venetoclax in R/R CLL/SLL
EXPERIMENTALIn both study phases. Participants in the expansion phase will be treated at the RP2D defined in the dose-escalation phase.
Epcoritamab + Lenalidomide in RS
EXPERIMENTALOnly in expansion phase.
Epcoritamab + R-CHOP in RS
EXPERIMENTALOnly in expansion phase.
Epcoritamab + Pirtobrutinib in R/R CLL, TN HR CLL (Non-US Participants Only) and SLL
EXPERIMENTALSafety run-in and expansion phases.
Fixed Duration Epcoritamab in R/R CLL/SLL
EXPERIMENTALOnly in expansion phase.
Interventions
R-CHOP will be administered intravenously (prednisone may be administered orally) in cycles of 21 days.
Venetoclax tablets will be administered orally once daily during the 5-week ramp up period in cycles of 28 or 35 days each.
Lenalidomide capsules will be administered once daily for 21 days in each cycle of 28 days.
Pirtobrutinib tablets will be administered in cycles of 28 days.
Epcoritamab will be administered subcutaneously in cycles of 28 days, (except Cycle 1 for high-dose cohorts = 35 days).
Eligibility Criteria
You may qualify if:
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
- Evidence of CD20 positivity in a sample representative of the disease at Screening.
- Acceptable hematology parameters and organ function based on baseline bloodwork.
- Life expectancy \>3 months on standard of care (SOC) for CLL, \>3 months for RS.
- For R/R CLL arms - Must have active CLL/SLL disease requiring treatment per iwCLL 2018 criteria.
- 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.
- For all RS arms - Have tumor biopsy-proven CD20+ Diffuse large B-cell Lymphoma (DLBCL) and a clinical history of CLL/SLL.
- 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.
- For all RS arms - Must provide mandatory formalin-fixed, paraffin-embedded (FFPE) tumor biopsy sample.
- For RS - monotherapy arm: Deemed as ineligible for chemoimmunotherapy at investigator's discretion or participant who refuses to receive intensive chemotherapy
- 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.
- +18 more criteria
You may not qualify if:
- Received prior treatment with a CD3×CD20 bispecific antibody.
- Received any prior allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation.
- 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.
- Autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy.
- Received vaccination with live vaccines within 28 days.
- Clinically significant cardiac disease.
- Has had major surgery within 4 weeks.
- Known history of human immunodeficiency virus (HIV).
- For R/R CLL arms - Any history of RS or evidence indicating a potential Richter's transformation.
- 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.
- For all RS arms - Diagnosis of Richter's syndrome not of the DLBCL subtype such as Hodgkin's lymphoma, prolymphocytic leukemia.
- RS - Lenalidomide Combination Therapy and RS Monotherapy Arms - received more than 2 prior lines of therapy for RS.
- R/R CLL - Pirtobrutinib Combination Therapy Arm - Prior exposure to a non-covalent (reversible) BTK inhibitor or a BTK degrader.
- Pirtobrutinib Combination Therapy Expansion Arms:
- History of bleeding disorders or participants requiring therapeutic anticoagulation with warfarin or another vitamin K antagonist
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Genmablead
- AbbViecollaborator
- Eli Lilly and Companycollaborator
Study Sites (83)
O'Neal Comprehensive Cancer Center at University of Alabama at Birmingham
Birmingham, Alabama, 35233, United States
University of California Davis Medical Center Sacramento
California City, California, 95817, United States
City of Hope National Medical Center
Duarte, California, 91010, United States
Cedars-Sinai Medical Center
Los Angeles, California, 90048, United States
David Geffen School of Medicine
Los Angeles, California, 90095, United States
Stanford Cancer Center
Palo Alto, California, 94305, United States
Mount Sinai Comprehensive Cancer Center
Miami Beach, Florida, 33140, United States
Memorial Healthcare System
Pembroke Pines, Florida, 33024, United States
National Institutes of Health
Bethesda, Maryland, 20892, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48190, United States
Henry Ford Medical Group
Detroit, Michigan, 48202, United States
Hackensack Meridian Hospital
Hackensack, New Jersey, 07601, United States
Northwell Health Cancer Institute
Lake Success, New York, 11043, United States
Columbia University Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Duke University Medical Center
Durham, North Carolina, 27708, United States
University of Cincinnati
Cincinnati, Ohio, 45221, United States
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Pennsylvania School of medicine
Philadelphia, Pennsylvania, 19104, United States
The University of Texas Southwestern Medical Centre
Dallas, Texas, 75390, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
St. George Hospital
Kogarah, New South Wales, Australia
Flinders Medical Centre
Bedford Park, South Australia, 5042, Australia
Barwon Health
Geelong, Victoria, Australia
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000, Australia
Alfred Health
Melbourne, Victoria, 3004, Australia
AZ Sint-Jan
Bruges, 8000, Belgium
Universitair Ziekenhuis Gent
Ghent, 9000, Belgium
UZ Leuven
Leuven, 3000, Belgium
Vseobecna Fakultni Nemocnice
Prague, Nové Město, 128 08, Czechia
Fakultni nemocnice Hradec Kralove
Hradec Králové, Nový Hradec Králové, 500 05, Czechia
Fakultni Nemocnice Ostrava
Ostrava, Poruba, Czechia
Fakultni nemocnice Brno
Brno, 625 00, Czechia
Fakultni nemocnice Olomouc
Olomouc, 779 00, Czechia
Rigshospitalet
Copenhagen, Capital Region, 2100, Denmark
Aalborg University Hospital
Aalborg, 9100, Denmark
Århus University Hospital
Aarhus, 8000, Denmark
Odense University Hospital
Odense, 5000, Denmark
Roskilde Sygehus
Roskilde, 4000, Denmark
Vejle Sygehus
Vejle, 7100, Denmark
CHU de Montpellier Hôpital Saint Eloi
Montpellier, Cedex 5, 34090, France
CHU Hôpital Haut-Lévêque Bordeaux
Pessac, Gironde, 33404, France
CHU Hôpital de Brabois Nancy
Vandœuvre-lès-Nancy, Meurthe Et Moselle, 54500, France
Hôpital Privé du Confluent
Nantes, Pays de la Loire Region, 44000, France
CHU Clermont Ferrand
Clermont-Ferrand, Puy De Dome, 63000, France
Hôpital Saint-Louis
Paris, 75010, France
Hôpital Universitaire Pitié-Salpêtrière
Paris, 75013, France
Universitaetsklinikum Ulm
Ulm, Baden-Wurttemberg, 89070, Germany
Universitaetsklinikum Koeln
Cologne, 50937, Germany
Universitaetsklinikum Schleswig-Holstein- Karl-Lennart-Krebscentrum
Kiel, 24105, Germany
Bnai Zion Medical Center
Haifa, Israel
Hadassah University Hospital - Ein Kerem
Jerusalem, Israel
Rabin Medical Center-Beilinson Campus
Petah Tikva, 4941492, Israel
Chaim Sheba Medical Center
Ramat Gan, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, Israel
Istituto di Candiolo
Torino, Candiolo, 10060, Italy
AOU Arcispedale Sant'Anna
Ferrara, Cona, 44124, Italy
IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST
Meldola, Forli - Cesena, 47014, Italy
IRCCS Policlinico Universitario Agostino Gemelli
Rome, Lazio, 00136, Italy
AOU Policlinico Sant'Orsola Malpighi IRCCS
Bologna, 00161, Italy
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
Brescia, Italy
Ospedale San Raffaele
Milan, 20132, Italy
Ospedale Maggiore di Novara
Novara, 28100, Italy
AOU Policlinico Umberto I
Roma, 00161, Italy
AOU Città della Salute e della Scienza di Torino
Torino, 10126, Italy
Maastricht University Medical Center
Maastricht, Limburg, 6229 HX, Netherlands
Albert Schweitzer Ziekenhuis, Dordwijk
Dordrecht, South Holland, 3318 AT, Netherlands
Amsterdam UMC
Amsterdam, 1105 AZ, Netherlands
Universitair Medisch Centrum Groningen
Groningen, 9713 GZ, Netherlands
Universitair Medisch Centrum Utrecht
Utrecht, 3584 CX, Netherlands
Pratia Medical Center Katowice (Centrum Medyczne Pratia Katowice)
Katowice, Poland
Pratia Malopolskie Medical Center Krakow (Pratia Małopolskie Centrum Medyczne Krakow)
Krakow, Poland
Aidport sp z o.o.
Skorzewo, Poland
ICO Badalona - Hospital Universitario Germans Trias Pujol
Badalona, Barcelona, Spain
AOC Arcispedale Saint'Anna
Coaña, Ferarra, Spain
Hospital Clinico Universitario de Valencia
Valencia, València, 46010, Spain
Hospital Clinic de Barcelona
Barcelona, 08036, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain
Hospital Universitario Ramón y Cajal
Madrid, 28034, Spain
Hospital Universitario Fundacion Jiménez Díaz
Madrid, 28040, Spain
Hospital Universitario Virgen Macarena
Seville, Spain
Related Publications (1)
Kater AP, Janssens A, Eradat H, Offner F, Sandoval-Sus JD, Shadman M, Poulsen CB, Christensen JH, Thompson MC, Guan M, Steele AJ, Rios M, Holst Morch M, Oki T, Valentin R, Bellido M, Eichhorst B. Epcoritamab monotherapy for Richter transformation (EPCORE CLL-1): findings from a single-arm, multicentre, open-label, phase 1b/2 trial. Lancet Haematol. 2026 Jan;13(1):e8-e21. doi: 10.1016/S2352-3026(25)00327-8. Epub 2025 Dec 8.
PMID: 41380698DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
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
November 10, 2020
Study Start
November 25, 2020
Primary Completion (Estimated)
December 1, 2027
Study Completion (Estimated)
February 1, 2028
Last Updated
May 5, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will not share