A Phase 3 Trial of Epcoritamab vs Investigator's Choice Chemotherapy in R/R DLBCL
- Conditions
- Diffuse Large B-cell Lymphoma
- Interventions
- Drug: Investigator's Choice Chemotherapy
- Registration Number
- NCT04628494
- Lead Sponsor
- Genmab
- Brief Summary
The purpose of this trial is to find out if epcoritamab, also known as EPKINLY™ and GEN3013, is safe and works well as treatment for patients with diffuse large B-cell lymphoma (DLBCL) that are not responding to treatment, have grown in size, or have come back following treatment with at least 1 prior systemic cancer therapy. All participants in this trial will be randomly assigned to receive either epcoritamab or a pre-specified investigator's choice (standard of care) chemotherapy (either rituximab + gemcitabine + oxaliplatin \[R-GemOx\], or bendamustine + rituximab \[BR\]). Participants must have failed or be ineligible to receive an autologous stem cell transplant (ASCT).
Epcoritamab will be injected under the skin. Investigator's choice chemotherapy will be given intravenously.
Trial details include:
* The trial duration will be up to 5 years after last participant is randomized.
* All trial participants have a 21-day screening period, a treatment period, and a follow-up period that continues until death.
* The estimated trial duration for an individual subject depends upon the treatment arm assigned:
* Participants who receive epcoritamab will have 28-day treatment cycles. Epcoritamab will be given once weekly for the first 3 months, then every other week for 6 months, then every 28 days until lymphoma progression or unacceptable adverse events.
* Participants who receive investigator's choice (standard of care) chemotherapy will receive treatments either:
* R-GemOx: On Day 1 (or Day 1 \& Day 2), and Day 15 (or Day 15 \& Day 16) every 28 days, for up to 4 months; or
* BR: On Day 1 and Day 2 every 3 weeks for up to 4.5 months.
- Detailed Description
The trial is an open label, multi-center, global phase-3 randomized trial of epcoritamab. The goal of this randomized trial is to evaluate the efficacy of epcoritamab (GEN3013, DuoBody®-CD3xCD20) compared to investigator's choice of chemotherapy, in patients with relapsed, refractory DLBCL who have failed or are ineligible for high-dose chemotherapy and autologous stem cell transplant (HDT-ASCT). No change in chemotherapy is permitted for participants during the treatment phase of the trial.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 552
-
Relapsed or refractory disease and previously treated with at least 1 line of systemic antineoplastic therapy including anti-CD20 mAb-containing combination chemotherapy since lymphoma diagnosis
-
One of the confirmed histologies below with CD20-positivity:
- DLBCL, NOS, including de novo or histologically transformed from FL
- "Double-hit" or "triple-hit" DLBCL (technically classified in WHO 2016 as HGBCL, with MYC and BCL2 and/or BCL6 translocations), including de novo or histologically transformed from FL
- FL Grade 3B
- T-cell/histiocyte-rich large B-cell lymphoma
-
ECOG PS score of 0-2
-
Failed previous HDT-ASCT or not eligible for HDT-ASCT at screening
-
Patients must have detectable disease by PET scan and measurable by CT scan or MRI
-
Acceptable renal and liver function
-
Life expectancy >2 months on SOC treatment
Main
- Primary Central Nervous System (CNS) tumor or known CNS involvement
- Any prior therapy with a bispecific antibody targeting CD3 and CD20
- Major surgery within 4 weeks prior to randomization
- Chemotherapy and other non-investigational antineoplastic agents (except CD20 mAbs) within 4 weeks or 5 half-lives (whichever is shorter) prior to randomization
- Any investigational drug within 4 weeks or 5 half-lives, whichever is longer, prior to randomization
- ASCT within 100 days of randomization
- Treatment with CAR-T therapy within 100 days prior to randomization
- Seizure disorder requiring anti-epileptic therapy
- Clinically significant cardiac disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Investigator's choice of chemotherapy Investigator's Choice Chemotherapy R-GemOx will be administrated in Cycles of 28 days until maximum cycles completion or any of the discontinuation criteria is met BR will be administrated in Cycles of 21 days until maximum cycles completion or any of the discontinuation criteria is met Epcoritamab (GEN3013; DuoBody®CD3xCD20) Epcoritamab Epcoritamab will be administered in Cycles of 28 days until any of the discontinuation criteria is met
- Primary Outcome Measures
Name Time Method Overall Survival (OS) throughout the study and up to 5 years following the last patient first dose OS is calculated as the time from first dose to death date or last date known to be alive.
- Secondary Outcome Measures
Name Time Method Complete Response (CR) throughout the study and up to 5 years following the last patient first dose CR rate is calculated as the proportion of subjects achieving a complete response. Response is determined by the Lugano criteria and LYRIC.
Duration of Response (DOR) throughout the study and up to 5 years following the last patient first dose DOR is calculated as the time from initial response (CR or PR) to date of progression or death, whichever is earlier. Response and progression are determined by the Lugano criteria and LYRIC.
Time to Response (TTR) throughout the study and up to 5 years following the last patient first dose TTR is calculated as the time from randomization to date of initial response (CR or PR) among responders only. Response is determined by the Lugano criteria and LYRIC.
Progression Free Survival (PFS) throughout the study and up to 5 years following the last patient first dose PFS is calculated as the time from randomization to the date of disease progression or death, whichever is earlier. Progression is determined by the Lugano criteria and LYRIC.
Incidence and severity of adverse events (AEs) throughout the study and up to 5 years following the last patient first dose identify patterns of incidence in adverse events, with particular emphasis on pre-defined adverse events of special interest
Anti-epcoritamab antibody response throughout the study and up to 5 years following the last patient first dose calculate incidence of antibody response to epcoritamab in relation to dosing
Incidence and severity of changes in laboratory values throughout the study and up to 5 years following the last patient first dose Clinical laboratory parameters assessed: hematology, chemistry, coagulation, tumor lysis, immunoglobulins, and urinalyses
Incidence of dose interruptions and delays throughout the study and up to 5 years following the last patient first dose calculate incidence and present the occurrence of dose modifying toxicities by cycles and overall
Overall Response Rate (ORR) throughout the study and up to 5 years following the last patient first dose ORR is calculated as the proportion of subjects achieving a complete response or partial response. Response is determined by the Lugano criteria and LYRIC.
Rate and duration of minimal residual disease (MRD) negative status up to 5 years after randomization of the last patient Compare other measures of efficacy to SOC - MRD negativity rate, defined as the proportion of subjects who have at least one negative MRD sample at any time point prior to start of subsequent anti-lymphoma therapy
Time to next anti-lymphoma therapy (TTNT) throughout the study and up to 5 years following the last patient first dose TTNT is calculated as the time from randomization to date of initiation of new anti-lymphoma therapy.
Changes in lymphoma symptoms as measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) throughout the study and up to 5 years following the last patient first dose monitor change from baseline in health-related quality of life over time and in relation to treatment
Trial Locations
- Locations (208)
CHU de LIMOGES
🇫🇷Limoges, France
Centre Léon Bérard
🇫🇷Lyon, France
Hopital de la Conception APHM
🇫🇷Marseille, France
CHU de Nantes - Hôtel Dieu
🇫🇷Nantes, France
Centre Antoine Lacassagne
🇫🇷Nice, France
Clinique Victor Hugo
🇫🇷Paris, France
Hôpital Saint-Louis
🇫🇷Paris, France
CHU de Bordeaux Hôpital Haut-Lévêque
🇫🇷Pessac, France
Centre Hospitalier Lyon Sud
🇫🇷Pierre-Bénite, France
CHU de Poitiers - Hôpital la Milétrie
🇫🇷Poitiers, France
Centre Hospitalier Rene Dubos
🇫🇷Pontoise, France
Ch Cornouaille
🇫🇷Quimper, France
Centre Henri Becquerel
🇫🇷Rouen, France
CHRU Tours Hôpital Bretonneau
🇫🇷Tours, France
Uniklinik Köln, Klinik I für Innere Medizin, CIO Gebäude 70, 5.094
🇩🇪Cologne, Germany
Universitaetsklinikum Essen
🇩🇪Essen, Germany
Universitätsklinikum Schleswig-Holstein Medizinische Klinik II Hämatologie und Onkologie
🇩🇪Kiel, Germany
Universitätsklinikum Würzburg
🇩🇪Würzburg, Germany
National Institute of Oncology
🇭🇺Budapest, Hungary
Semmelweis Egyetem Belgyógyászati és Onkológiai Klinika
🇭🇺Budapest, Hungary
Debreceni Egyetem Klinikai Kozpont, Belgyogyaszati Klinika, Hematologia
🇭🇺Debrecen, Hungary
Belgyógyászati osztály Markhot Ferenc Kórház
🇭🇺Eger, Hungary
Petz Aladar Egyetemi Oktato Korhaz
🇭🇺Győr, Hungary
Josa Andras Teaching Hospital, Hematology Dept
🇭🇺Nyiregyhaza, Hungary
University of Pecs 1st. Internal medicine Clinic Dept. Hematology
🇭🇺Pécs, Hungary
Szegedi Tudományegyetem II. sz. Belgyogyaszat, Hematologia
🇭🇺Szeged, Hungary
Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
🇭🇺Szekesfehervar, Hungary
Bnai Zion Medical Center
🇮🇱Haifa, Israel
Rambam Health Care Center
🇮🇱Haifa, Israel
UZ Brussel
🇧🇪Jette, Belgium
Hôpital de Jolimont
🇧🇪La Louvière, Belgium
Universitair Ziekenhuis gasthuisberg Leuven
🇧🇪Leuven, Belgium
AZ Nikolaas- Verenigde Ziekenhuizen van Waas en Durme
🇧🇪Sint-Niklaas, Belgium
AZ Turnhout, Campus Sint-Elisabeth
🇧🇪Turnhout, Belgium
CHU de Quebec-Universite Laval
🇨🇦Québec City, Canada
Guangdong Provincial Peoples Hospital
🇨🇳Guangdong, China
Guangxi Medical University Affiliated Tumor Hospital
🇨🇳Guangxi, China
Hunan Cancer Hospital
🇨🇳Hunan, China
Shengjing Hospital of China Medical University
🇨🇳Shenyang, China
Shenzhen Peoples Hospital
🇨🇳Shenzhen, China
The First Affiliated Hospital of Soochow University
🇨🇳Suzhou, China
Groupe Hospitalier de La Rochelle
🇫🇷La Rochelle, France
Community Cancer Trials of Utah
🇺🇸Ogden, Utah, United States
LDS Hospital
🇺🇸Salt Lake City, Utah, United States
Erasmus MC
🇳🇱Rotterdam, Netherlands
Franciscus Gasthuis And Vlietland
🇳🇱Rotterdam, Netherlands
Oslo University Hospital location Radium hospital
🇳🇴Oslo, Norway
St. Olavs Hospital HF
🇳🇴Trondheim, Norway
Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii
🇵🇱Gdańsk, Poland
Pratia Onkologia Katowice
🇵🇱Katowice, Poland
Pratia MCM Kraków
🇵🇱Kraków, Poland
Centrum Medyczne Pratia Poznan
🇵🇱Skorzewo, Poland
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
🇵🇱Wrocław, Poland
Instytut Centrum Zdrowia Matki Polki
🇵🇱Łódź, Poland
Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii
🇵🇱Łódź, Poland
State Autonomous Institution of Healthcare Republican Clinical Oncological Dispensary of the Ministr
🇷🇺Kazan, Russian Federation
State Budgetary Institution of Healthcare Leningrad Regional Clinical Hospital
🇷🇺Leningrad, Russian Federation
Federal State Budgetary Institution of Science
🇷🇺Moscow, Russian Federation
Federal State Budgetary Institution
🇷🇺Moscow, Russian Federation
State Budgetary Institution of Healthcare of Nizhniy Novgorod region, 1st inpatient facility, 5th fl
🇷🇺Nizhny Novgorod, Russian Federation
Federal State Budgetary Institution V.A. Almazov National Medical Research Center of the Ministry of
🇷🇺Saint Petersburg, Russian Federation
Hadassah University Hospital
🇮🇱Jerusalem, Israel
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Sourasky Medical Center
🇮🇱Tel Aviv, Israel
IRCCS Istituto Tumori Giovanni Paolo II Bari
🇮🇹Bari, Italy
Azienda Socio Sanitaria Territoriale Sette Laghi (Presidio Ospedale di Circolo e Fondazione Macchi)
🇮🇹Bergamo, Italy
Clinical Trials and Research Centre
🇸🇬Singapore, Singapore
Hospita Universitario Puerta Del Mar
🇪🇸Cadiz, Spain
Hospital San Pedro de Alcántara
🇪🇸Cáceres, Spain
Hospital Universitario Reina Sofía
🇪🇸Córdoba, Spain
Hospital Arnau de Vilanova
🇪🇸Lleida, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Md Anderson Cancer Center
🇪🇸Madrid, Spain
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Hospital Universitario Marqués de Valdecilla
🇪🇸Santander, Spain
Hospital Universitario Virgen De Valme
🇪🇸Sevilla, Spain
Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Karolinska university Hospital
🇸🇪Stockholm, Sweden
Iqvia Tibbi Istatistik
🇹🇷Istanbul, Turkey
Istanbul University Cerrahpasa - Cerrahpasa Tip Fakultesi
🇹🇷Istanbul, Turkey
Istanbul University Medical Faculty
🇹🇷Istanbul, Turkey
Dokuz Eylul University Medical Faculty
🇹🇷İzmir, Turkey
Ege University Medical Faculty
🇹🇷İzmir, Turkey
Tekirdag Namik Kemal University
🇹🇷Tekirdağ, Turkey
Karadeniz Technical University
🇹🇷Trabzon, Turkey
Admiraal de Ruyter Ziekenhuis
🇳🇱Goes, Netherlands
Bravis Ziekenhuis
🇳🇱Roosendaal, Netherlands
Kyoto University Medical Hospital
🇯🇵Kyoto, Japan
Indiana Blood and Marrow Transplantation
🇺🇸Indianapolis, Indiana, United States
Community Health Network Cancer Center North
🇺🇸Indianapolis, Indiana, United States
University of Kentucky Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
Henry Ford Health System
🇺🇸Jackson, Michigan, United States
MMCORC Attn Delaney Anderson
🇺🇸Saint Louis Park, Minnesota, United States
MD Anderson Cancer Center at Cooper
🇺🇸Camden, New Jersey, United States
Wake Forest Baptist Health
🇺🇸Winston-Salem, North Carolina, United States
The Christ Hospital Cancer Center
🇺🇸Cincinnati, Ohio, United States
TriHealth Cancer Institute- Good Samaritan Hospital
🇺🇸Cincinnati, Ohio, United States
Brooke Army Medical Center
🇺🇸Fort Sam Houston, Texas, United States
Virginia Commonwealth University (VCU) Massey Cancer Center
🇺🇸Richmond, Virginia, United States
North Star Lodge Cancer Center
🇺🇸Yakima, Washington, United States
Waukesha Memorial Hospital
🇺🇸Waukesha, Wisconsin, United States
Flinders Medical Centre
🇦🇺Bedford Park, Australia
Concord Repatriation General Hospital
🇦🇺Concord, Australia
Peninsula Private Hospital Clinical Trials Unit
🇦🇺Frankston, Australia
Icon Cancer Centre Corporate Office
🇦🇺South Brisbane, Australia
Calvary Mater Newcastle
🇦🇺Waratah, Australia
Westmead Hospital
🇦🇺Westmead, Australia
Ordensklinikum Linz Barmherzige Schwestern
🇦🇹Linz, Austria
Ordensklinikum Linz GmbH Elisabethinen
🇦🇹Linz, Austria
Uniklinikum Salzburg, Universitätsklinik für Innere Medizin III der PMU
🇦🇹Salzburg, Austria
ZNA Middelheim
🇧🇪Antwerp, Belgium
AZ Sint-Jan
🇧🇪Brugge, Belgium
Institut Jules Bordet
🇧🇪Brussels, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
Affiliated Hospital of Hebei University
🇨🇳Baoding, China
Beijing Cancer Hospital
🇨🇳Beijing, China
Beijing Tongren Hospital, Capital Medical University
🇨🇳Beijing, China
The First Hospital of Jilin University
🇨🇳Changchun, China
West China Hospital, Sichuan University
🇨🇳Chengdu, China
The Second Hospital of Dalian Medical University
🇨🇳Dalian, China
The First Affiliated Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, China
Hubei Cancer Hospital
🇨🇳Hubei, China
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, China
Qingdao Central Hospital
🇨🇳Qingdao, China
Shanxi Provincial Cancer Hospital
🇨🇳Shanxi, China
Tianjin Medical University Cancer Institute and Hospital
🇨🇳Tianjin, China
EC of Union Hospital Tongji Medical College Huazhong University of Science and Technology
🇨🇳Wuhan, China
Yantai Yuhuangding Hospital
🇨🇳Yantai, China
Henan Cancer Hospital
🇨🇳Zhengzhou, China
The Second Affiliated Hospital Zhejiang University School of Medicine
🇨🇳Zhenjiang, China
Aalborg Universitetshospital
🇩🇰Aalborg, Denmark
Aarhus University Hospital, Department of Hematology, Clinical Research Unit C116
🇩🇰Aarhus, Denmark
Clinical Research Unit, Roskilde Sygehus
🇩🇰Roskilde, Denmark
Vejle Hospital
🇩🇰Vejle, Denmark
HUS Cancer Center/ Clinical Trial Unit
🇫🇮Helsinki, Finland
Oulu university hospital, Department of hematology
🇫🇮Oulu, Finland
Audrey ALEME
🇫🇷Amiens, France
Centre Hospitalier de la Côte Basque
🇫🇷Bayonne, France
CHRU de Brest - Hospital Morvan
🇫🇷Brest, France
CHU Caen - IHBN
🇫🇷Caen, France
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
🇮🇹Brescia, Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.)
🇮🇹Meldola, Italy
Istituto Oncologico Europeo
🇮🇹Milan, Italy
San Raffaele Hospital
🇮🇹Milan, Italy
Azienda Ospedaliero - Universitaria Maggiore delle Carita SCDU Ematologia building C
🇮🇹Novara, Italy
Fondazione IRCCS Policlinico San matteo
🇮🇹Pavia, Italy
Ospedale Santa Maria delle Croci
🇮🇹Ravenna, Italy
Azienda Ospedaliera Universitaria Policlinico Umberto I Università di Roma La Sapienza, Dip Med Tra
🇮🇹Rome, Italy
IRCCS Ospedale Casa Sollievo della Sofferenza
🇮🇹San Giovanni Rotondo, Italy
Azienda Sanitaria Universitaria Giuliano Isontina (ASU GI) Ospedale Maggiore di Trieste
🇮🇹Trieste, Italy
SC di Ematologia - AON SS Antonio e Biagio e Cesare Arrigo
🇮🇹Venezia, Italy
Kyushu University Hospital
🇯🇵Fukuoka, Japan
Fukushima Medical University Hospital
🇯🇵Fukushima, Japan
Chugoku Central Hospital
🇯🇵Fukuyama, Japan
Hokkaido University Hospital
🇯🇵Hokkaido, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa, Japan
Matsuyama Red Cross Hospital
🇯🇵Matsuyama, Japan
Mie University Hospital
🇯🇵Mie, Japan
Japanese Red Cross Nagoya Daini Hospital
🇯🇵Nagoya, Japan
NHO Nagoya Medical Center
🇯🇵Nagoya, Japan
Okayama University Hospital
🇯🇵Okayama, Japan
Tohoku University Hospital
🇯🇵Sendai, Japan
Keio University Hospital
🇯🇵Tokyo, Japan
National Cancer Center Hospital
🇯🇵Tokyo, Japan
Tokai University Hospital
🇯🇵Tokyo, Japan
Fujita Health University Hospital
🇯🇵Toyoake, Japan
Yamagata University Hospital
🇯🇵Yamagata, Japan
Kindai University Hospital
🇯🇵Ōsaka-sayama, Japan
Dong-A University Hospital
🇰🇷Busan, Korea, Republic of
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Pusan National University Hosptial
🇰🇷Busan, Korea, Republic of
Keimyung University Dongsan Hospital
🇰🇷Daegu, Korea, Republic of
Chonbuk National University Hospital
🇰🇷Geumam, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea Seoul St. Marys Hospital
🇰🇷Seoul, Korea, Republic of
Ulsan University Hospital
🇰🇷Ulsan, Korea, Republic of
Rijnstate Arnhem
🇳🇱Arnhem, Netherlands
Amphia Ziekenhuis, Interne Geneeskunde, Oncologie. Route 43
🇳🇱Breda, Netherlands
Albert Schweitzer Ziekenhuis
🇳🇱Dordrecht, Netherlands
National University Hospital
🇸🇬Kent Ridge, Singapore
National Cancer Centre Singapore
🇸🇬Singapore, Singapore
ICO Badalona - Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Spain
ICO l'Hospitalet - Hospital Duran i Reynals
🇪🇸Barcelona, Spain
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Tri-Service General Hospital
🇨🇳Taipei, Taiwan
Ankara University Medical Faculty
🇹🇷Ankara, Turkey
Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi
🇹🇷Ankara, Turkey
Gazi University Medical Faculty
🇹🇷Ankara, Turkey
Amerikan Hospital
🇹🇷Istanbul, Turkey
Haematology - University Hospitals Birmingham NHS Foundation Trust
🇬🇧Birmingham, United Kingdom
Guys and St Thomas NHS Foundation Trust
🇬🇧London, United Kingdom
Hammersmith Hospital
🇬🇧London, United Kingdom
Norfolk and Norwich University Hospitals NHS Foundation Trust
🇬🇧Norwich, United Kingdom
Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, United Kingdom
Derriford Hospital
🇬🇧Plymouth, United Kingdom
University Hospital Southampton
🇬🇧Southampton, United Kingdom
Royal Marsden NHS Foundation Trust (Sutton)
🇬🇧Sutton, United Kingdom
Royal Cornwall Hospital
🇬🇧Truro, United Kingdom