Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome
- Conditions
- Relapsed/Refractory Chronic Lymphocytic LeukemiaSmall Lymphocytic LymphomaRichter's SyndromeTreatment-naïve High Risk Chronic Lymphocytic Leukemia
- Interventions
- Drug: rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone
- Registration Number
- NCT04623541
- Lead Sponsor
- Genmab
- 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
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.
- Detailed 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 424
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Epcoritamab in R/R CLL/SLL Epcoritamab In both study phases. Participants in the expansion phase will be treated at the RP2D defined in the dose-escalation phase. Epcoritamab in RS Epcoritamab Only in expansion phase. Epcoritamab + Venetoclax in R/R CLL/SLL Epcoritamab In both study phases. Participants in the expansion phase will be treated at the RP2D defined in the dose-escalation phase. Epcoritamab + Venetoclax in R/R CLL/SLL Venetoclax In both study phases. Participants in the expansion phase will be treated at the RP2D defined in the dose-escalation phase. Epcoritamab + Lenalidomide in RS Epcoritamab Only in expansion phase. Epcoritamab + Lenalidomide in RS Lenalidomide Only in expansion phase. Epcoritamab + R-CHOP in RS Epcoritamab Only in expansion phase. Epcoritamab + R-CHOP in RS rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone Only in expansion phase. Epcoritamab + Pirtobrutinib in R/R CLL, TN HR CLL and SLL Epcoritamab Safety run-in and expansion phases. Epcoritamab + Pirtobrutinib in R/R CLL, TN HR CLL and SLL Pirtobrutinib Safety run-in and expansion phases. Fixed Duration Epcoritamab in R/R CLL/SLL Epcoritamab Only in expansion phase.
- Primary Outcome Measures
Name Time Method Dose Escalation Phase and Safety Run-in (R/R CLL arm): Number of Participants with Dose Limiting Toxicities (DLTs) During the first cycle for low dose cohorts (Cycle length = 28 days) and for high dose cohorts (Cycle length = 35 days) 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.
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) Up to 5 years 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.
Expansion Phase: Overall Response Rate (ORR) Up to 5 years 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.
- Secondary Outcome Measures
Name Time Method 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 The ORR is defined as the percentage of participants who achieve a response of PR, CRi, or CR, prior to the initiation of subsequent therapy as assessed by iwCLL criteria.
Both Phases and Safety Run-in: Duration of Response (DOR) Up to 5 years DOR is defined among responders, as the time from the initial documentation of response to the date of disease progression or death, whichever occurs earlier.
Both Phases and Safety Run-in: Number of Participants with CR/CRi Up to 5 years CR and CRi for R/R CLL participants will be assessed according to iwCLL criteria and CR for the RS participants, according to Lugano criteria.
Both Phases and Safety Run-in: Time to Response (TTR) Up to 5 years TTR is defined among responders, as the time between first dose of any study drug and the initial documentation of response.
Both Phases and Safety Run-in: Progression Free Survival (PFS) Up to 5 years PFS is defined as the time from the first dosing date of any study drug and the date of disease progression or death, whichever occurs earlier.
Both Phases and Safety Run-in: Overall Survival (OS) Up to 5 years OS is defined as the time from the first dosing date of any study drug and the date of death due to any cause.
Both Phase and Safety Run-in: Time to Next Systemic Anti-cancer Therapy (TTNT) Up to 5 years TTNT is defined as the time from the first dosing date of any study drug to the first documented administration of subsequent systemic anticancer therapy.
Both Phases and Safety Run-in: Area Under the Concentration-time Curve (AUC) in Epcoritamab Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days), up to 5 years Both Phases and Safety Run-in: Maximum (Peak) Plasma Concentration (Cmax) in Epcoritamab Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days), up to 5 years Both Phases: Pre-dose (Trough) Concentrations (Cthrough) in Epcoritamab Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days), up to 5 years Both Phases and Safety Run-in: Time to Reach Cmax (Tmax) in Epcoritamab Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days), up to 5 years Both Phases and Safety Run-in: Elimination Half-life (T1/2) in Epcoritamab Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days), up to 5 years Both Phases and Safety Run-in: Total Body Clearance of Drug From Plasma (CL) in Epcoritamab Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days), up to 5 years Both Phases: Lymphoid Cells for Immunophenotyping Up to 5 years Evaluation of B cells, T cells and their activation
Expansion Phase: Number of Participants with CRS, ICANS and CTLS Up to 5 years CRS and ICANS will be graded based on ASTCT criteria. CTLS will be graded according to Cairo-Bishop criteria.
Expansion Phase and Safety Run-in : Percentage of Participants with Minimal Residual Disease (MRD) Negativity Up to 5 years MRD negativity rate, is defined as the proportion of participants with at least 1 undetectable MRD result according to the specific threshold, prior to initiation of subsequent therapy.
Both Phases and Safety Run-in: Number of Participants with Anti-drug Antibodies (ADA) to Epcoritamab Up to 5 years Expansion Phase: Number of Participants with PR Up to 5 years Both Phases and Safety Run-in: Duration of MRD Negativity Up to 5 years The time from first achieving MRD negativity after start of treatment to the MRD conversion to positive.
Trial Locations
- Locations (77)
CHU de Montpellier Hôpital Saint Eloi
🇫🇷Montpellier, Cedex 5, France
O'Neal Comprehensive Cancer Center at University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of California Davis Medical Center Sacramento
🇺🇸California City, California, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
David Geffen School of Medicine
🇺🇸Los Angeles, California, United States
Stanford Cancer Center
🇺🇸Palo Alto, California, United States
Mount Sinai Comprehensive Cancer Center
🇺🇸Miami Beach, Florida, United States
Memorial Healthcare System
🇺🇸Pembroke Pines, Florida, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Henry Ford Medical Group
🇺🇸Detroit, Michigan, United States
Hackensack Meridian Hospital
🇺🇸Hackensack, New Jersey, United States
Northwell Health Cancer Institute
🇺🇸Lake Success, New York, United States
Columbia University Herbert Irving Comprehensive Cancer Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
James Cancer Hospital
🇺🇸Columbus, Ohio, United States
University of Pennsylvania School of medicine
🇺🇸Philadelphia, Pennsylvania, United States
The University of Texas Southwestern Medical Centre
🇺🇸Dallas, Texas, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
St. George Hospital
🇦🇺Kogarah, New South Wales, Australia
Barwon Health
🇦🇺Geelong, Victoria, Australia
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Alfred Health
🇦🇺Melbourne, Victoria, Australia
AZ Sint-Jan
🇧🇪Bruges, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
Vseobecna Fakultni Nemocnice
🇨🇿Praha, Nové Město, Czechia
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Králové, Nový Hradec Králové, Czechia
Fakultni Nemocnice Ostrava
🇨🇿Ostrava, Poruba, Czechia
Fakultni nemocnice Brno
🇨🇿Brno, Czechia
Fakultni nemocnice Olomouc
🇨🇿Olomouc, Czechia
Rigshospitalet
🇩🇰København, Hovedstaden, Denmark
Aalborg University Hospital
🇩🇰Aalborg, Denmark
Odense University Hospital
🇩🇰Odense, Denmark
Roskilde Sygehus
🇩🇰Roskilde, Denmark
Vejle Sygehus
🇩🇰Vejle, Denmark
Århus University Hospital
🇩🇰Århus, Denmark
CHU Hôpital Haut-Lévêque Bordeaux
🇫🇷Pessac, Gironde, France
CHU Hôpital de Brabois Nancy
🇫🇷Vandœuvre-lès-Nancy, Meurthe Et Moselle, France
Hôpital Privé du Confluent
🇫🇷Nantes, Pays De La Loire, France
CHU Clermont Ferrand
🇫🇷Clermont Ferrand cedex, Puy De Dome, France
Hôpital Saint-Louis
🇫🇷Paris, France
Hôpital Universitaire Pitié-Salpêtrière
🇫🇷Paris, France
Universitaetsklinikum Schleswig-Holstein- Karl-Lennart-Krebscentrum
🇩🇪Kiel, Germany
Universitaetsklinikum Koeln
🇩🇪Koeln, Germany
Bnai Zion Medical Center
🇮🇱Haifa, Israel
Hadassah University Hospital - Ein Kerem
🇮🇱Jerusalem, Israel
Rabin Medical Center-Beilinson Campus
🇮🇱Petah Tikva, Israel
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv-Yafo, Israel
IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST
🇮🇹Meldola, Forli - Cesena, Italy
IRCCS Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Lazio, Italy
AOU Policlinico Sant'Orsola Malpighi IRCCS
🇮🇹Bologna, Italy
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
🇮🇹Brescia, Italy
Ospedale San Raffaele
🇮🇹Milano, Italy
Ospedale Maggiore di Novara
🇮🇹Novara, Italy
AOU Policlinico Umberto I
🇮🇹Roma, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹Roma, Italy
Maastricht University Medical Center
🇳🇱Maastricht, Limburg, Netherlands
Albert Schweitzer Ziekenhuis, Dordwijk
🇳🇱Dordrecht, South Holland, Netherlands
Amsterdam UMC
🇳🇱Amsterdam, Netherlands
Universitair Medisch Centrum Groningen
🇳🇱Groningen, Netherlands
Universitair Medisch Centrum Utrecht
🇳🇱Utrecht, Netherlands
ICO Badalona - Hospital Universitario Germans Trias Pujol
🇪🇸Badalona, Barcelona, Spain
AOC Arcispedale Saint'Anna
🇪🇸Coaña, Ferarra, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, València, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Universitario Fundacion Jiménez Díaz
🇪🇸Madrid, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Royal Cornwall Hospital
🇬🇧Truro, Cornwall, United Kingdom
Nottingham University Hospitals City Campus
🇬🇧Nottingham, Nottinghamshire, United Kingdom
St. James s University Hospital
🇬🇧Leeds, West Yorkshire, United Kingdom
Barts Hospital
🇬🇧London, United Kingdom