A Phase 3 Trial of Epcoritamab vs Investigator's Choice Chemotherapy in R/R DLBCL

Diffuse Large B-cell Lymphoma Clinical Trial

— EPCORE DLBCL-1  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04628494
• Other study ID #: GCT3013-05
• Secondary ID: 2020-003016-27jR
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 13, 2021
• Est. completion date: April 2028

Study information

• Verified date: June 2024
• Source: Genmab
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

• 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 552
• Est. completion date: April 2028
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diffuse Large B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Biological:
• Epcoritamab
Following mandatory pre-medication subject will be administered epcoritamab as a subcutaneous injection.

Drug:
• Investigator's Choice Chemotherapy
Following mandatory pre-medication subject will be administered intravenously either BR or R-GemOx.

Locations

Country	Name	City	State
Australia	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
Austria	Ordensklinikum Linz Barmherzige Schwestern	Linz
Austria	Ordensklinikum Linz GmbH Elisabethinen	Linz
Austria	Uniklinikum Salzburg, Universitätsklinik für Innere Medizin III der PMU	Salzburg
Belgium	ZNA Middelheim	Antwerp
Belgium	AZ Sint-Jan	Brugge
Belgium	Institut Jules Bordet	Brussels
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	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
Canada	CHU de Quebec-Universite Laval	Québec City
China	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	Guangdong Provincial Peoples Hospital	Guangdong
China	Guangxi Medical University Affiliated Tumor Hospital	Guangxi
China	The First Affiliated Hospital, Zhejiang University School of Medicine	Hangzhou
China	Hubei Cancer Hospital	Hubei
China	Hunan Cancer Hospital	Hunan
China	The First Affiliated Hospital of Nanchang University	Nanchang
China	Qingdao Central Hospital	Qingdao
China	Shanxi Provincial Cancer Hospital	Shanxi
China	Shengjing Hospital of China Medical University	Shenyang
China	Shenzhen Peoples Hospital	Shenzhen
China	The First Affiliated Hospital of Soochow University	Suzhou
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
Denmark	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
Finland	HUS Cancer Center/ Clinical Trial Unit	Helsinki
Finland	Oulu university hospital, Department of hematology	Oulu
France	Audrey ALEME	Amiens
France	Centre Hospitalier de la Côte Basque	Bayonne
France	CHRU de Brest - Hospital Morvan	Brest
France	CHU Caen - IHBN	Caen
France	Groupe Hospitalier de La Rochelle	La Rochelle
France	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
Germany	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
Hungary	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	Gyor
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
Israel	Bnai Zion Medical Center	Haifa
Israel	Rambam Health Care Center	Haifa
Israel	Hadassah University Hospital	Jerusalem
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Sourasky Medical Center	Tel Aviv
Italy	IRCCS Istituto Tumori Giovanni Paolo II Bari	Bari
Italy	Azienda Socio Sanitaria Territoriale Sette Laghi (Presidio Ospedale di Circolo e Fondazione Macchi)	Bergamo
Italy	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	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
Japan	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	Kyoto University Medical Hospital	Kyoto
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	Kindai University Hospital	Osaka-sayama
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
Korea, Republic of	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	Ulsan University Hospital	Ulsan
Netherlands	Rijnstate Arnhem	Arnhem
Netherlands	Amphia Ziekenhuis, Interne Geneeskunde, Oncologie. Route 43	Breda
Netherlands	Albert Schweitzer Ziekenhuis	Dordrecht
Netherlands	Admiraal de Ruyter Ziekenhuis	Goes
Netherlands	Bravis Ziekenhuis	Roosendaal
Netherlands	Erasmus MC	Rotterdam
Netherlands	Franciscus Gasthuis And Vlietland	Rotterdam
Norway	Oslo University Hospital location Radium hospital	Oslo
Norway	St. Olavs Hospital HF	Trondheim
Poland	Pratia Onkologia Katowice	Katowice
Poland	Pratia MCM Kraków	Kraków
Poland	Instytut Centrum Zdrowia Matki Polki	Lódz
Poland	Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii	Lódz
Poland	Centrum Medyczne Pratia Poznan	Skorzewo
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu	Wroclaw
Russian Federation	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	Moscow
Russian Federation	Federal State Budgetary Institution of Science	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
Singapore	National University Hospital	Kent Ridge
Singapore	Clinical Trials and Research Centre	Singapore
Singapore	National Cancer Centre Singapore	Singapore
Spain	ICO Badalona - Hospital Universitari Germans Trias i Pujol	Badalona
Spain	ICO l'Hospitalet - Hospital Duran i Reynals	Barcelona
Spain	Hospital San Pedro de Alcántara	Cáceres
Spain	Hospital San Pedro de Alcántara	Cáceres,
Spain	Hospita Universitario Puerta Del Mar	Cadiz
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
Sweden	Karolinska university Hospital	Stockholm
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Tri-Service General Hospital	Taipei
Turkey	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	Iqvia Tibbi Istatistik	Istanbul
Turkey	Istanbul University Cerrahpasa - Cerrahpasa Tip Fakultesi	Istanbul
Turkey	Istanbul University Medical Faculty	Istanbul
Turkey	Dokuz Eylul University Medical Faculty	Izmir
Turkey	Ege University Medical Faculty	Izmir
Turkey	Tekirdag Namik Kemal University	Tekirdag
Turkey	Karadeniz Technical University	Trabzon
United Kingdom	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 States	TriHealth Cancer Institute- Good Samaritan Hospital	Cincinnati	Ohio
United States	Community Health Network Cancer Center North	Indianapolis	Indiana
United States	Indiana Blood and Marrow Transplantation	Indianapolis	Indiana
United States	Henry Ford Health System	Jackson	Michigan
United States	LDS Hospital	Salt Lake City	Utah
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Genmab	AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  China,  Denmark,  Finland,  France,  Germany,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Norway,  Poland,  Russian Federation,  Singapore,  Spain,  Sweden,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	OS is calculated as the time from first dose to death date or last date known to be alive.	throughout the study and up to 5 years following the last patient first dose
Secondary	Progression Free Survival (PFS)	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.	throughout the study and up to 5 years following the last patient first dose
Secondary	Overall Response Rate (ORR)	ORR is calculated as the proportion of subjects achieving a complete response or partial response. Response is determined by the Lugano criteria and LYRIC.	throughout the study and up to 5 years following the last patient first dose
Secondary	Complete Response (CR)	CR rate is calculated as the proportion of subjects achieving a complete response. Response is determined by the Lugano criteria and LYRIC.	throughout the study and up to 5 years following the last patient first dose
Secondary	Duration of Response (DOR)	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.	throughout the study and up to 5 years following the last patient first dose
Secondary	Time to Response (TTR)	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.	throughout the study and up to 5 years following the last patient first dose
Secondary	Rate and duration of minimal residual disease (MRD) negative status	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	up to 5 years after randomization of the last patient
Secondary	Time to next anti-lymphoma therapy (TTNT)	TTNT is calculated as the time from randomization to date of initiation of new anti-lymphoma therapy.	throughout the study and up to 5 years following the last patient first dose
Secondary	Incidence and severity of adverse events (AEs)	identify patterns of incidence in adverse events, with particular emphasis on pre-defined adverse events of special interest	throughout the study and up to 5 years following the last patient first dose
Secondary	Incidence and severity of changes in laboratory values	Clinical laboratory parameters assessed: hematology, chemistry, coagulation, tumor lysis, immunoglobulins, and urinalyses	throughout the study and up to 5 years following the last patient first dose
Secondary	Incidence of dose interruptions and delays	calculate incidence and present the occurrence of dose modifying toxicities by cycles and overall	throughout the study and up to 5 years following the last patient first dose
Secondary	Anti-epcoritamab antibody response	calculate incidence of antibody response to epcoritamab in relation to dosing	throughout the study and up to 5 years following the last patient first dose
Secondary	Changes in lymphoma symptoms as measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym)	monitor change from baseline in health-related quality of life over time and in relation to treatment	throughout the study and up to 5 years following the last patient first dose