Clinical trial NCT04628494: A Phase 3 Trial of Epcoritamab vs Investigator's Choice Chemotherapy in R/R DLBCL
Official title: A Randomized, Open-Label, Phase 3 Trial of Epcoritamab vs Investigator's Choice Chemotherapy in Relapsed/Refractory Diffuse Large B-cell Lymphoma (R/R DLBCL)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Diffuse Large B-cell Lymphoma
Keywords: double-hit DLBCL
triple-hit DLBCL
follicular grade 3B
transformed DLBCL
T-cell histiocytes-rich large B cell lymphoma
Lead sponsor: Genmab
Sponsor class: INDUSTRY
Collaborators: name: AbbVie
First posted: 2020-11-13
Enrollment: 552
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Main Inclusion Criteria:

1. 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
2. One of the confirmed histologies below with CD20-positivity:

   1. DLBCL, NOS, including de novo or histologically transformed from FL
   2. "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
   3. FL Grade 3B
   4. T-cell/histiocyte-rich large B-cell lymphoma
3. ECOG PS score of 0-2
4. Failed previous HDT-ASCT or not eligible for HDT-ASCT at screening
5. Patients must have detectable disease by PET scan and measurable by CT scan or MRI
6. Acceptable renal and liver function
7. Life expectancy \>2 months on SOC treatment

Main Exclusion Criteria:

1. Primary Central Nervous System (CNS) tumor or known CNS involvement
2. Any prior therapy with a bispecific antibody targeting CD3 and CD20
3. Major surgery within 4 weeks prior to randomization
4. Chemotherapy and other non-investigational antineoplastic agents (except CD20 mAbs) within 4 weeks or 5 half-lives (whichever is shorter) prior to randomization
5. Any investigational drug within 4 weeks or 5 half-lives, whichever is longer, prior to randomization
6. ASCT within 100 days of randomization
7. Treatment with CAR-T therapy within 100 days prior to randomization
8. Seizure disorder requiring anti-epileptic therapy
9. Clinically significant cardiac disease

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: throughout the study and up to 5 years following the last patient first dose
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: throughout the study and up to 5 years following the last patient first dose
measure: Overall Response Rate (ORR)
timeFrame: throughout the study and up to 5 years following the last patient first dose
measure: Complete Response (CR)
timeFrame: throughout the study and up to 5 years following the last patient first dose
measure: Duration of Response (DOR)
timeFrame: throughout the study and up to 5 years following the last patient first dose
measure: Time to Response (TTR)
timeFrame: throughout the study and up to 5 years following the last patient first dose
measure: Rate and duration of minimal residual disease (MRD) negative status
timeFrame: up to 5 years after randomization of the last patient
measure: Time to next anti-lymphoma therapy (TTNT)
timeFrame: throughout the study and up to 5 years following the last patient first dose
measure: Incidence and severity of adverse events (AEs)
timeFrame: throughout the study and up to 5 years following the last patient first dose
measure: Incidence and severity of changes in laboratory values
timeFrame: throughout the study and up to 5 years following the last patient first dose
measure: Incidence of dose interruptions and delays
timeFrame: throughout the study and up to 5 years following the last patient first dose
measure: Anti-epcoritamab antibody response
timeFrame: throughout the study and up to 5 years following the last patient first dose
measure: Changes in lymphoma symptoms as measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym)
timeFrame: throughout the study and up to 5 years following the last patient first dose
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana Blood and Marrow Transplantation
state: Indiana
city: Indianapolis
country: United States
facility: Community Health Network Cancer Center North
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky Markey Cancer Center
state: Kentucky
city: Jackson
country: United States
facility: Henry Ford Health System
state: Michigan
city: Saint Louis Park
country: United States
facility: MMCORC Attn Delaney Anderson
state: Minnesota
city: Camden
country: United States
facility: MD Anderson Cancer Center at Cooper
state: New Jersey
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Cincinnati
country: United States
facility: The Christ Hospital Cancer Center
state: Ohio
city: Cincinnati
country: United States
facility: TriHealth Cancer Institute- Good Samaritan Hospital
state: Ohio
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Ogden
country: United States
facility: Community Cancer Trials of Utah
state: Utah
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University (VCU) Massey Cancer Center
state: Virginia
city: Yakima
country: United States
facility: North Star Lodge Cancer Center
state: Washington
city: Waukesha
country: United States
facility: Waukesha Memorial Hospital
state: Wisconsin
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
city: Frankston
country: Australia
facility: Peninsula Private Hospital Clinical Trials Unit
city: South Brisbane
country: Australia
facility: Icon Cancer Centre Corporate Office
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
city: Westmead
country: Australia
facility: Westmead Hospital
city: Linz
country: Austria
facility: Ordensklinikum Linz Barmherzige Schwestern
city: Linz
country: Austria
facility: Ordensklinikum Linz GmbH Elisabethinen
city: Salzburg
country: Austria
facility: Uniklinikum Salzburg, Universitätsklinik für Innere Medizin III der PMU
city: Antwerp
country: Belgium
facility: ZNA Middelheim
city: Brugge
country: Belgium
facility: AZ Sint-Jan
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Jette
country: Belgium
facility: UZ Brussel
city: La Louvière
country: Belgium
facility: Hôpital de Jolimont
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis gasthuisberg Leuven
city: Sint-Niklaas
country: Belgium
facility: AZ Nikolaas- Verenigde Ziekenhuizen van Waas en Durme
city: Turnhout
country: Belgium
facility: AZ Turnhout, Campus Sint-Elisabeth
city: Québec City
country: Canada
facility: CHU de Quebec-Universite Laval
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Beijing Tongren Hospital, Capital Medical University
city: Changchun
country: China
facility: The First Hospital of Jilin University
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Dalian
country: China
facility: The Second Hospital of Dalian Medical University
city: Guangdong
country: China
facility: Guangdong Provincial Peoples Hospital
city: Guangxi
country: China
facility: Guangxi Medical University Affiliated Tumor Hospital
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
city: Hubei
country: China
facility: Hubei Cancer Hospital
city: Hunan
country: China
facility: Hunan Cancer Hospital
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
city: Qingdao
country: China
facility: Qingdao Central Hospital
city: Shanxi
country: China
facility: Shanxi Provincial Cancer Hospital
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
city: Shenzhen
country: China
facility: Shenzhen Peoples Hospital
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
city: Wuhan
country: China
facility: EC of Union Hospital Tongji Medical College Huazhong University of Science and Technology
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Zhenjiang
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital, Department of Hematology, Clinical Research Unit C116
city: Roskilde
country: Denmark
facility: Clinical Research Unit, Roskilde Sygehus
city: Vejle
country: Denmark
facility: Vejle Hospital
city: Helsinki
country: Finland
facility: HUS Cancer Center/ Clinical Trial Unit
city: Oulu
country: Finland
facility: Oulu university hospital, Department of hematology
city: Amiens
country: France
facility: Audrey ALEME
city: Bayonne
country: France
facility: Centre Hospitalier de la Côte Basque
city: Brest
country: France
facility: CHRU de Brest - Hospital Morvan
city: Caen
country: France
facility: CHU Caen - IHBN
city: La Rochelle
country: France
facility: Groupe Hospitalier de La Rochelle
city: Limoges
country: France
facility: CHU de LIMOGES
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Hopital de la Conception APHM
city: Nantes
country: France
facility: CHU de Nantes - Hôtel Dieu
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Clinique Victor Hugo
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Pessac
country: France
facility: CHU de Bordeaux Hôpital Haut-Lévêque
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Poitiers
country: France
facility: CHU de Poitiers - Hôpital la Milétrie
city: Pontoise
country: France
facility: Centre Hospitalier Rene Dubos
city: Quimper
country: France
facility: Ch Cornouaille
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Tours
country: France
facility: CHRU Tours Hôpital Bretonneau
city: Cologne
country: Germany
facility: Uniklinik Köln, Klinik I für Innere Medizin, CIO Gebäude 70, 5.094
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein Medizinische Klinik II Hämatologie und Onkologie
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
city: Budapest
country: Hungary
facility: National Institute of Oncology
city: Budapest
country: Hungary
facility: Semmelweis Egyetem Belgyógyászati és Onkológiai Klinika
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont, Belgyogyaszati Klinika, Hematologia
city: Eger
country: Hungary
facility: Belgyógyászati osztály Markhot Ferenc Kórház
city: Győr
country: Hungary
facility: Petz Aladar Egyetemi Oktato Korhaz
city: Nyiregyhaza
country: Hungary
facility: Josa Andras Teaching Hospital, Hematology Dept
city: Pécs
country: Hungary
facility: University of Pecs 1st. Internal medicine Clinic Dept. Hematology
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem II. sz. Belgyogyaszat, Hematologia
city: Szekesfehervar
country: Hungary
facility: Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
city: Bari
country: Italy
facility: IRCCS Istituto Tumori Giovanni Paolo II Bari
city: Bergamo
country: Italy
facility: Azienda Socio Sanitaria Territoriale Sette Laghi (Presidio Ospedale di Circolo e Fondazione Macchi)
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.)
city: Milan
country: Italy
facility: Istituto Oncologico Europeo
city: Milan
country: Italy
facility: San Raffaele Hospital
city: Novara
country: Italy
facility: Azienda Ospedaliero - Universitaria Maggiore delle Carita SCDU Ematologia building C
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San matteo
city: Ravenna
country: Italy
facility: Ospedale Santa Maria delle Croci
city: Rome
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Umberto I Università di Roma La Sapienza, Dip Med Tra
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Ospedale Casa Sollievo della Sofferenza
city: Trieste
country: Italy
facility: Azienda Sanitaria Universitaria Giuliano Isontina (ASU GI) Ospedale Maggiore di Trieste
city: Venezia
country: Italy
facility: SC di Ematologia - AON SS Antonio e Biagio e Cesare Arrigo
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Fukushima
country: Japan
facility: Fukushima Medical University Hospital
city: Fukuyama
country: Japan
facility: Chugoku Central Hospital
city: Hokkaido
country: Japan
facility: Hokkaido University Hospital
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Kyoto
country: Japan
facility: Kyoto University Medical Hospital
city: Matsuyama
country: Japan
facility: Matsuyama Red Cross Hospital
city: Mie
country: Japan
facility: Mie University Hospital
city: Nagoya
country: Japan
facility: Japanese Red Cross Nagoya Daini Hospital
city: Nagoya
country: Japan
facility: NHO Nagoya Medical Center
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Sendai
country: Japan
facility: Tohoku University Hospital
city: Tokyo
country: Japan
facility: Keio University Hospital
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: Tokai University Hospital
city: Toyoake
country: Japan
facility: Fujita Health University Hospital
city: Yamagata
country: Japan
facility: Yamagata University Hospital
city: Ōsaka-sayama
country: Japan
facility: Kindai University Hospital
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National University Hosptial
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
city: Geumam
country: Korea, Republic of
facility: Chonbuk National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St. Marys Hospital
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Arnhem
country: Netherlands
facility: Rijnstate Arnhem
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis, Interne Geneeskunde, Oncologie. Route 43
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis
city: Goes
country: Netherlands
facility: Admiraal de Ruyter Ziekenhuis
city: Roosendaal
country: Netherlands
facility: Bravis Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Rotterdam
country: Netherlands
facility: Franciscus Gasthuis And Vlietland
city: Oslo
country: Norway
facility: Oslo University Hospital location Radium hospital
city: Trondheim
country: Norway
facility: St. Olavs Hospital HF
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii
city: Katowice
country: Poland
facility: Pratia Onkologia Katowice
city: Kraków
country: Poland
facility: Pratia MCM Kraków
city: Skorzewo
country: Poland
facility: Centrum Medyczne Pratia Poznan
city: Wrocław
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
city: Łódź
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki
city: Łódź
country: Poland
facility: Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii
city: Kazan
country: Russian Federation
facility: State Autonomous Institution of Healthcare Republican Clinical Oncological Dispensary of the Ministr
city: Leningrad
country: Russian Federation
facility: State Budgetary Institution of Healthcare Leningrad Regional Clinical Hospital
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Institution of Science
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Institution
city: Nizhny Novgorod
country: Russian Federation
facility: State Budgetary Institution of Healthcare of Nizhniy Novgorod region, 1st inpatient facility, 5th fl
city: Saint Petersburg
country: Russian Federation
facility: Federal State Budgetary Institution V.A. Almazov National Medical Research Center of the Ministry of
city: Kent Ridge
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: Clinical Trials and Research Centre
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: Badalona
country: Spain
facility: ICO Badalona - Hospital Universitari Germans Trias i Pujol
city: Barcelona
country: Spain
facility: ICO l'Hospitalet - Hospital Duran i Reynals
city: Cadiz
country: Spain
facility: Hospita Universitario Puerta Del Mar
city: Cáceres,
country: Spain
facility: Hospital San Pedro de Alcántara
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcántara
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Lleida
country: Spain
facility: Hospital Arnau de Vilanova
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Md Anderson Cancer Center
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen De Valme
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Stockholm
country: Sweden
facility: Karolinska university Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty
city: Ankara
country: Turkey
facility: Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi
city: Ankara
country: Turkey
facility: Gazi University Medical Faculty
city: Istanbul
country: Turkey
facility: Amerikan Hospital
city: Istanbul
country: Turkey
facility: Iqvia Tibbi Istatistik
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa - Cerrahpasa Tip Fakultesi
city: Istanbul
country: Turkey
facility: Istanbul University Medical Faculty
city: İzmir
country: Turkey
facility: Dokuz Eylul University Medical Faculty
city: İzmir
country: Turkey
facility: Ege University Medical Faculty
city: Tekirdağ
country: Turkey
facility: Tekirdag Namik Kemal University
city: Trabzon
country: Turkey
facility: Karadeniz Technical University
city: Birmingham
country: United Kingdom
facility: Haematology - University Hospitals Birmingham NHS Foundation Trust
city: London
country: United Kingdom
facility: Guys and St Thomas NHS Foundation Trust
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospitals NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Southampton
country: United Kingdom
facility: University Hospital Southampton
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust (Sutton)
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
Study officials:
References: