History of Changes for Study: NCT03625037

Version	Submitted Date	Changes
1	August 9, 2018	None (earliest Version on record)
2	August 14, 2018	Study Status
3	September 13, 2018	Study Status and Contacts/Locations
4	September 27, 2018	Contacts/Locations and Study Status
5	January 7, 2019	Contacts/Locations, Study Status and Eligibility
6	January 14, 2019	Contacts/Locations and Study Status
7	February 26, 2019	Contacts/Locations and Study Status
8	April 12, 2019	Study Status and Contacts/Locations
9	July 19, 2019	Study Status and Contacts/Locations
10	August 20, 2020	Contacts/Locations, Arms and Interventions, Outcome Measures, Study Design, Study Description, Study Status, Eligibility and Sponsor/Collaborators
11	January 8, 2021	Contacts/Locations, Study Status and Study Design
12	February 11, 2021	Contacts/Locations, Study Status, Study Identification, Eligibility and Study Design
13	July 27, 2021	Study Status and Contacts/Locations
14	June 17, 2022	Outcome Measures, Contacts/Locations, Arms and Interventions, Study Status, Study Description, Eligibility and Study Identification
15	October 18, 2022	Outcome Measures, Study Description, Study Status, Study Identification, Contacts/Locations, Eligibility and Study Design
16	February 7, 2023	Study Status
17	February 23, 2023	Study Status
18	March 27, 2023	Outcome Measures, Study Status, Study Identification, Study Description, Eligibility and Conditions
19	May 25, 2023	Study Status, References, Arms and Interventions and Study Description
20	May 30, 2023	Study Status and Study Identification
21	June 27, 2023	Study Status, Contacts/Locations and Study Design
22	August 7, 2023	Contacts/Locations, Study Status and Study Identification
23	January 2, 2024	Study Status
24	February 14, 2024	Outcome Measures, Contacts/Locations, Study Description, Study Status, Eligibility, Arms and Interventions, Study Design and Conditions
25	March 4, 2024	Study Status and Study Identification
26	March 25, 2024	Recruitment Status, Study Status, Contacts/Locations and Study Design
27	April 4, 2024	Study Status
28	May 6, 2024	Study Status and Study Identification

Brief Summary:

The trial is a global, multi-center safety trial of Epcoritamab, an antibody also known as GEN3013 (DuoBody®-CD3xCD20). The trial consists of three parts: a dose-escalation part (Phase 1, first-in-human (FIH)), an expansion part (Phase 2a) and a dose optimization part (Phase 2a)

Detailed Description:

The purpose of the dose-escalation part of the trial is to determine the maximum tolerated dose (MTD) and the recommended Phase-2 dose (RP2D), as well as to establish the safety profile of epcoritamab in patients with relapsed, progressive or refractory B-Cell Lymphoma.

In the expansion part, additional patients will be treated with epcoritamab, at the RP2D and the purpose is to further explore and determine the safety and efficacy of epcoritamab.

The dose optimization part will evaluate alternative priming and intermediate dose regimens of epcoritamab. All patients will receive Epcoritamab at the already established full dose.

Outcome Measures


Primary Outcome Measures:
1.	Escalation part: Incidence of Dose Limiting Toxicities (DLTs) [ Time Frame: Assessed during the first cycle (28 days) in each cohort. ] To determine the RP2D and the MTD, if reached.
2.	Escalation part: Incidence and severity of Adverse Events (AEs) [ Time Frame: From first dose until the end of the safety follow-up period (4 weeks after last dose) ] Treatment-emergent AEs (TEAEs)
3.	Expansion part: Objective Response Rate (ORR) [ Time Frame: From first dose until up to 1 year after the last participant's first dose ] Defined as proportion of participants who have a partial or complete response (PR or CR) following treatment with epcoritamab. Determined by the Lugano response criteria, assessed by the Independent Review Committee (IRC).
4.	Optimization Part: • Determine whether an alternative priming/intermediate dose regimen may reduce CRS risk [ Time Frame: per subject 5 weeks after the first dose of Epcoritamab. per cohort 5 weeks after the last dosed patient in a cohort first dose of Epcoritamab ] Rate of ≥ Grade 2 CRS events and all grade CRS events from first dose of epcoritamab through 7 days following administration of the second full dose of epcoritamab
Secondary Outcome Measures:
1.	Both parts: Area-under-the-concentration-time curve from Time 0 to Time of last dose (AUClast) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
2.	Both parts: AUC from Time 0 to Infinity (AUCinf) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year. ]
3.	Both parts: Maximum (peak) plasma concentration (Cmax) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
4.	Both parts: Time to reach Cmax (Tmax) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
5.	Both parts: Pre-dose (trough) concentrations (Cthrough) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
6.	Both parts: Total body clearance of drug from the plasma (CL) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
7.	Both parts: Volume of distribution (Vd) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
8.	Both parts: Elimination half-life (t 1/2) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
9.	Both parts: Incidence of anti-drug antibodies (ADA) [ Time Frame: From first dose until up to 1 year after the last participant's first dose ]
10.	Escalation part: ORR [ Time Frame: From first dose until up to 1 year after the last participant's first dose ] Defined as proportion of participants who have a PR or CR following treatment with epcoritamab. Determined by the Lugano response criteria.
11.	Escalation phase: PR [ Time Frame: From first dose until up to 1 year after the last participant's first dose ] Determined by the Lugano response criteria.
12.	Expansion part: Time to Response (TTR) [ Time Frame: From first dose until up to 1 year after the last participant's first dose ] Defined as time to first documentation of objective tumor response (PR or better). Determined by the Lugano and LYRIC response criteria, assessed by the IRC.
13.	Both parts: Duration of Response (DOR) [ Time Frame: From first dose until up to 1 year after the last participant's first dose ] Defined as time from first documentation of response (CR or PR) to the date of progression of disease (PD) or death, whichever occurs earlier. Determined by the Lugano response criteria (both parts) and by the LYRIC response criteria (expansion part). Response/disease progression in the expansion part is reviewed by the IRC.
14.	Both parts: CR rate [ Time Frame: From first dose until up to 1 year after the last participant's first dose ] Defined as proportion of participants with CR. Determined by the Lugano response criteria (both parts) and by the LYRIC response criteria (expansion part). Response/disease progression in expansion part is reviewed by the IRC.
15.	Expansion part: Duration of CR (DoCR) [ Time Frame: From first dose until up to 1 year after the last participant's first dose ] Defined as time from first documentation of CR to the date of PD or death, whichever occurs earlier. Determined by the Lugano and LYRIC response criteria, assessed by the IRC.
16.	Both parts: Progression Free Survival (PFS) [ Time Frame: From first dose until up to 1 year after the last participant's first dose ] Defined as time to first documented PD or death due to any cause. Determined by the Lugano response criteria (both parts) and by the LYRIC response criteria (expansion part). Response/disease progression in the expansion part is reviewed by the IRC.
17.	Both parts: Time to next anti-lymphoma therapy (TTNT) [ Time Frame: From first dose until up to 1 year after the last participant's first dose ] Calculated as time to date of initiation of new anti-lymphoma therapy.
18.	Both parts: Overall Survival (OS) [ Time Frame: From first dose until up to 1 year after the last participant's first dose ] Defined as time to death.
19.	Expansion part: Rate and duration of Minimal Residual Disease (MRD) negative status [ Time Frame: From first dose until up to 1 year after the last participant's first dose ] Rate is defined as proportion of participants with at least one MRD- sample. Duration is defined as the number of days from the first documentation of MRD- to the date of MRD status change (not MRD-).
20.	Expansion part: Incidence and severity of AEs [ Time Frame: From first dose until the end of the safety follow-up period (60 days after last dose) ] TEAEs
21.	Expansion part: Number of participants with clinically significant shifts from baseline in clinical laboratory parameters [ Time Frame: From first dose until the end of the safety follow-up period (60 days after last dose) ] Clinical laboratory parameters assessed: biochemistry, hematology including immunophenotyping).
22.	Expansion part: Changes in lymphoma symptoms as measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) [ Time Frame: From first dose until up to 1 year after the last participant's first dose ] Monitor change from baseline in health-related quality of life over time and in relation to treatment.
23.	Optimization Part: To evaluate safety and tolerability of alternative priming/intermediate dosing regimens [ Time Frame: 5 weeks after last patient dosed per cohort ] Rate of ≥ Grade 2 CRS events and all grade CRS events following first full dose Rate of ≥ Grade 2 CRS events and all grade CRS events overall Safety i.e., rate of DLTs [as applicable], rate of adverse events
24.	Optimization Part: Establish PK and pharmacodynamic profile after single and multiple doses [ Time Frame: Ongoing throughout optimization part Conduct ] PK paramters (predose and half life)
25.	Optimization Part: Evaluate immunogenicity [ Time Frame: Ongoing throughout optimization part Conduct ] Immunogenicity of epcoritamab
26.	Optimization Part: Evaluate clinical efficacy as determined by Lugano criteria [ Time Frame: Ongoing throughout optimization part Conduct and up to 1 year after LPFD ] ORR, CR, DOR, DoCR, PFS, TTNT, OS, MRD rate
27.	Optimization Part: Exploratory Objective: • To evaluate pharmacodynamic markers linked to the mechanism of action of epcoritamab [ Time Frame: Ongoing throughout optimization part Conduct and up to 1 year after LPFD ] Pharmacodynamic markers in blood samples

Minimum Age:

18 Years

Maximum Age:

Sex:

All

Gender Based:

Accepts Healthy Volunteers:

Criteria:

Main Inclusion Criteria Escalation Part (recruitment completed)

Documented CD20+ mature B-cell neoplasm
1. Diffuse large B-cell lymphoma - de novo or transformed
2. High-grade B-cell lymphoma
3. Primary mediastinal large B-cell lymphoma
4. Follicular lymphoma
5. Mantle cell lymphoma
6. Small lymphocytic lymphoma
7. Marginal zone lymphoma (nodal, extranodal or mucosa associated)
Relapsed, progressive and/or refractory disease following treatment with an anti-CD20 monoclonal antibody (e.g. rituximab) potentially in combination with chemotherapy and/or relapsed after autologous stem cell rescue.
ECOG performance status 0,1 or 2
Patients must have measurable disease by CT, MRI or PET-CT scan
Acceptable renal function
Acceptable liver function

Main Inclusion Criteria Expansion and Optimization Parts

Documented CD20 positive mature B cell neoplasm or CD20+ MCL
Diffuse large B cell lymphoma, de novo or transformed (including double hit or triple hit)
Primary mediastinal large B cell lymphoma
Follicular lymphoma grade 3B
Histologic confirmed follicular lymphoma
Marginal zone lymphomas
Small lymphocytic lymphoma
Mantle Cell Lymphoma (prior BTKi or intolerant to BTKi)
At least 2 therapies including an anti CD20 monoclonal antibody containing chemotherapy combination regimen
Either failed prior autologous hematopoietic stem cell transplantation or ineligible for autologous stem cell transplantation due to age or comorbidities
At least 1 measurable site of disease based on CT, MRI or PET-CT scan with involvement of 2 or more clearly demarcated lesions and or nodes

NOTE: Other protocol defined Inclusion criteria may apply.

Main Exclusion Criteria Escalation, Expansion and Optimization Parts

Primary central nervous system (CNS) lymphoma or CNS involvement by lymphoma at screening
Known past or current malignancy other than inclusion diagnosis
AST, and/or ALT >3 × upper limit of normal
Total bilirubin >1.5 × upper limit of normal, unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin
Estimated CrCl <45 mL/min
Known clinically significant cardiovascular disease
Ongoing active bacterial, viral, fungal, mycobacterial, parasitic, or other infection requiring systemic treatment (excluding prophylactic treatment). Past COVID-19 infection may be a risk factor
Confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy
Seizure disorder requiring therapy (such as steroids or anti-epileptics)
Any prior therapy with an investigational bispecific antibody targeting CD3 and CD20
Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 30 days prior to first epcoritamab administration
Eligible for curative intensive salvage therapy followed by high dose chemotherapy with HSCT rescue
Autologous HSCT within 100 days prior to first epcoritamab administration, or any prior allogeneic HSCT or solid organ transplantation
Active hepatitis B (DNA PCR-positive) or hepatitis C (RNA PCR-positive infection). Subjects with evidence of prior HBV but who are PCR-negative are permitted in
Known human immunodeficiency virus (HIV) infection
Exposed to live or live attenuated vaccine within 4 weeks prior to signing ICF
Pregnancy or breast feeding
Patient is known or suspected of not being able to comply with the study protocol or has any condition for which, participation would not be in the best interest of the patient
Contraindication to all uric acid lowering agents

Central Contact Person:

Genmab Trial Information
Telephone: +45 70202728
Email: clinicaltrials@genmab.com

Study Officials:

Pieternella Lugtenburg, MD, PhD
Principal Investigator
Erasmus MC University Medical Center Rotterdam

Locations:

United States, Arizona

Arizona Mayo Clinic
[Recruiting]
Phoenix, Arizona, United States, 85054

United States, California

University of California at San Francisco
[Recruiting]
San Francisco, California, United States, 94117

United States, Colorado

Colorado Blood Cancer Institute
[Recruiting]
Denver, Colorado, United States, 80218

United States, Florida

H. Lee Moffitt Cancer Center and Research Institute
[Recruiting]
Tampa, Florida, United States, 33612

United States, Georgia

Northside Hospital- The Blood Marrow Transplant Group
[Withdrawn]
Atlanta, Georgia, United States, 30309

United States, Iowa

University of Iowa Hospital and Clinics
[Recruiting]
Iowa City, Iowa, United States, 52242

United States, Louisiana

Ochsner Medical Center
[Recruiting]
New Orleans, Louisiana, United States, 70121

United States, Michigan

University of Michigan
[Recruiting]
Ann Arbor, Michigan, United States, 48109

Barbara Ann Karmanos Cancer Institute
[Recruiting]
Detroit, Michigan, United States, 48334

United States, Nebraska

University of Nebraska Medical Center
[Recruiting]
Omaha, Nebraska, United States, 68198

United States, New Jersey

Hackensack Meridian Health
[Recruiting]
Hackensack, New Jersey, United States, 07601

United States, North Carolina

Levine Cancer institute/ Atrium Health
[Withdrawn]
Charlotte, North Carolina, United States, 28204

United States, Ohio

The Cleveland Clinic Foundation
[Recruiting]
Cleveland, Ohio, United States, 44195

United States, Oregon

OHSU Knight Cancer Institute
[Recruiting]
Portland, Oregon, United States, 97210

United States, Pennsylvania

Hillman Cancer Center
[Recruiting]
Pittsburgh, Pennsylvania, United States, 15232

United States, Rhode Island

Rhode Island Hospital
[Recruiting]
Providence, Rhode Island, United States, 02903

United States, South Carolina

Medical University of South Carolina
[Recruiting]
Charleston, South Carolina, United States, 29425

Prisma Health- Upstate
[Recruiting]
Greenville, South Carolina, United States, 29605

United States, Texas

UT Southwestern
[Recruiting]
Dallas, Texas, United States, 75390

MD Anderson Cancer Center
[Recruiting]
Houston, Texas, United States, 77030

United States, Wisconsin

University of Wisconsin Carbone Cancer Center
[Withdrawn]
Madison, Wisconsin, United States, 53705

Australia

Monash Health
[Recruiting]
Clayton, Australia

Concord Hospital
[Recruiting]
Concord, Australia

St. Vincent Hospital
[Recruiting]
Fitzroy, Australia

Integrated Clinical Oncology Network Pty Ltd (ICON)
[Recruiting]
Herston, Australia

Royal Hobart Hospital RHH
[Recruiting]
Hobart, Australia

St. George Hospital
[Recruiting]
Kogarah, Australia

Cabrini Hospital
[Recruiting]
Malvern, Australia

Sir Charles Gairdner Hospital
[Recruiting]
Nedlands, Australia

Gold Coast Hospital
[Recruiting]
Southport, Australia

St George Hospital
[Recruiting]
Sydney, Australia

Canada

Tom Baker Cancer Care
[Recruiting]
Calgary, Canada

Toronto-Sunnybrook Regional Cancer Ctr
[Recruiting]
Toronto, Canada

Denmark

Rigshospitalet
[Recruiting]
Copenhagen, Denmark

Odense University Hospital
[Recruiting]
Odense, Denmark, 5000 C

Vejle Hospital
[Recruiting]
Vejle, Denmark

Finland

Helsinki University Hospital
[Recruiting]
Helsinki, Finland

Kuopio University Hospital
[Recruiting]
Kuopio, Finland

Tampere University Hospital
[Recruiting]
Tampere, Finland

France

Hopital Henri Mondor
[Recruiting]
Créteil, France

Hopital Huriez-CHRU Lille
[Recruiting]
Lille, France

CHU Montpellier
[Recruiting]
Montpellier, France

Hospital Saint-Louis
[Recruiting]
Paris, France

Hospices Civils de Lyon Centre Hospitalier Lyon Sud
[Recruiting]
Pierre-Bénite, France

Centre Henri Becquerel
[Recruiting]
Rouen cedex, France

CHU de Tours-Hopital Bretonneau
[Recruiting]
Tours, France

Institut Gustave Roussy
[Recruiting]
Villejuif, France

Germany

Charite - Universitaetsmedizin Berlin
[Recruiting]
Berlin, Germany

Klinik fur Innere Medizin Hamatologie and Onkologie
[Recruiting]
Berlin, Germany

Universitaetsklinikum Koeln
[Recruiting]
Cologne, Germany

Universitaetsklinikum Essen
[Recruiting]
Essen, Germany

Johannes Gutenberg University
[Recruiting]
Mainz, Germany

Der Universität Munchen Medizinische Klinik III LMU
[Recruiting]
München, Germany

Italy

Ao Ss Antonio E Biagio Alessandria
[Recruiting]
Alessandria, Italy

Policlinico S. Orsola-Ematologia LA Seragnoli
[Recruiting]
Bologna, Italy

Istituto di Candiolo- Fondazione del Piemonte per l'Oncologia
[Recruiting]
Candiolo, Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
[Recruiting]
Meldola, Italy

IRCCS Ospedale San Raffaele
[Recruiting]
Milan, Italy

Korea, Republic of

Dong-A University Hospital
[Recruiting]
Busan, Korea, Republic of

Keimyung University Dongsan Medical Center
[Recruiting]
Daegu, Korea, Republic of

National Cancer Center
[Recruiting]
Goyang-si, Korea, Republic of

Chonbuk National University Hospital
[Recruiting]
Jeonju, Korea, Republic of

Seoul National University Bundang Hospital
[Recruiting]
Seongnam-si, Korea, Republic of

Asan Medical Center
[Recruiting]
Seoul, Korea, Republic of

Samsung Medical Center
[Recruiting]
Seoul, Korea, Republic of

Seoul National University Hospital
[Recruiting]
Seoul, Korea, Republic of

Severance Hospital, Yonsei University
[Recruiting]
Seoul, Korea, Republic of

Netherlands

VU University Medical Center
[Recruiting]
Amsterdam, Netherlands

Maastricht University Medical Center
[Recruiting]
Maastricht, Netherlands, 6229 HX
Contact:Contact: Principal Investigator

Erasmus MC Cancer Institute
[Recruiting]
Rotterdam, Netherlands

Universitair Medisch Centrum Utrecht
[Recruiting]
Utrecht, Netherlands

Poland

Szpital Uniwersytecki nr 2 im dr. Jana Biziela
[Recruiting]
Bydgoszcz, Poland

Uniwersyteckie Centrum Kliniczne
[Recruiting]
Gdańsk, Poland

Pratia-McM
[Recruiting]
Kraków, Poland

Uniwersytet Medyczny w Lublinie
[Withdrawn]
Lublin, Poland

Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka
[Recruiting]
Słupsk, Poland

Maria Sklodowska-Curie Memorial Cancer Center and Institute
[Recruiting]
Warszawa, Poland

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego
[Recruiting]
Wrocław, Poland

Singapore

National University Hospital
[Recruiting]
Singapore, Singapore

Singapore General Hospital
[Recruiting]
Singapore, Singapore

Spain

Hospital Germans Trias i Pujol
[Recruiting]
Badalona, Spain

Hospital Universitario Vall dHebron
[Recruiting]
Barcelona, Spain

Institut Catala de Oncologia
[Recruiting]
Barcelona, Spain

Hospital Universitario Fundacin Jimnez Daz
[Recruiting]
Madrid, Spain

Spain, Navarra

Clinica Universidad de Navarra
[Recruiting]
Pamplona, Navarra, Spain, 31008

Sweden

Skåne University Hospital
[Recruiting]
Lund, Sweden

Karolinska University Hospital Huddinge
[Recruiting]
Stockholm, Sweden

Akademiska sjukhuset Uppsala University Hospital
[Recruiting]
Uppsala, Sweden

United Kingdom

University Hospital of Wales
[Recruiting]
Cardiff, United Kingdom

The Christie NHS Foundation Trust
[Recruiting]
Manchester, United Kingdom

Plymouth University School of Medicine- Derriford Hospital
[Recruiting]
Plymouth, United Kingdom

University Hospital Southampton NHS Foundation Trust
[Recruiting]
Southampton, United Kingdom

Royal Marsden NHS Foundation Trust
[Recruiting]
Sutton, United Kingdom