Epcoritamab: Administered as specified in the treatment arm.
Study summary
The purpose of this trial is to measure the following in participants with relapsed and/or refractory B-cell lymphoma who receive epcoritamab, an antibody also known as EPKINLY™ and GEN3013 (DuoBody®-CD3xCD20):
* The dose schedule for epcoritamab
* The side effects seen with epcoritamab
* What the body does with epcoritamab once it is administered
* What epcoritamab does to the body once it is administered
* How well epcoritamab works against relapsed and/or refractory B-cell lymphoma
The trial consists of 3 parts:
* a dose-escalation part (Phase 1, first-in-human \[FIH\])
* an expansion part (Phase 2a)
* a dose-optimization part (OPT) (Phase 2a)
The trial time for each participant depends on which trial part the participant enters:
* For the dose-escalation part, each participant will be in the trial for approximately 1 year, which is made up of 21 days of screening, 6 months of treatment (the total time of treatment may be different for each participant), and 6 months of follow-up (the total time of follow-up may be different for each participant).
* For the expansion and dose-OPT parts, each participant will be in the trial for approximately 1.5 years, which is made up of 21 days of screening, 1 year of treatment (the total time of treatment may be different for each participant), and 6 months of follow-up (the total time of follow-up may be different for each participant).
Participation in the study will require visits to the sites. During the first month, participants must visit every day or every few days, depending on which trial part the participant enters. After that, participants must visit weekly, every other week, once a month, and once every 2 months, as trial participation ends.
All participants will receive active drug, and no participants will be given placebo.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Main Inclusion Criteria - Escalation Part (recruitment completed)
* Documented CD20+ mature B-cell neoplasm
1. DLBCL - de novo or transformed
2. HGBCL
3. PMBCL
4. FL
5. MCL
6. SLL
7. MZL (nodal, extranodal or mucosa associated)
* Relapsed 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.
* Eastern Cooperative Oncology Group (ECOG) performance status 0,1 or 2.
* Participants must have measurable disease by computed tomography (CT), magnetic resonance imaging (MRI) or Positron emission tomography-Computed tomography (PET-CT) scan
* Acceptable renal function.
* Acceptable liver function.
Main Inclusion Criteria - Expansion \& Dose-OPT Parts
* Documented CD20 positive mature B cell neoplasm or CD20+ MCL.
* DLBCL, de novo or transformed (including double hit or triple hit).
* PMBCL
* FL grade 3B
* Histologic confirmed FL
* MZL
* SLL
* MCL (prior Bruton's tyrosine kinase inhibitor \[BTKi\] 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 (HSCT) 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.
Main Exclusion Criteria - All Parts
* Primary central nervous system (CNS) lymphoma or CNS involvement by lymphoma at screening.
* Known past or current malignancy other than inclusion diagnosis.
* Aspartate aminotransferase (AST), and/or alanine transaminase (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 Creatinine clearance (CrCl) \<45 milliliters (mL)/min.
* Known clinically significant cardiovascular disease.
* Ongoing active bacterial, viral, fungal, mycobacterial, parasitic, or other infection requiring systemic treatment (excluding prophylactic treatment). Past coronavirus disease 2019 (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 (deoxyribonucleic acid \[DNA\] polymerase chain reaction \[PCR\]-positive) or hepatitis C (ribonucleic acid \[RNA\] PCR-positive infection). Participants with evidence of prior hepatitis B (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 Informed consent form (ICF).
* Pregnancy or breast feeding.
* Participant 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 participant.
* Contraindication to all uric acid lowering agents.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Primary outcome measure(s)
Dose-Escalation: Dose Limiting Toxicity (DLT) — During the first cycle (28 days) To determine the MTD and/or RP2D to be studied in the Expansion part. DLT will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.
Dose-Escalation: Number of Participants with Adverse Events (AEs) — From first dose until the end of the safety follow-up period (Up to 1 year) An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.
Expansion: Overall Response Rate (ORR) — Up to 1.5 years ORR is defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on Lugano criteria.
Dose-OPT DLBCL, FL and MCL: Percentage of Participants with =>Grade 2 Cytokine Release Syndrome (CRS) Events and All Grade CRS Events — From first dose until 7 days after second full dose (Day 28 for DLBCL; Day 35 for FL; Day 28-35 for MCL) CRS will be graded based on American Society for Transplantation and Cellular Therapy (ASTCT) criteria.
Trial sites (85)
Facility
City
Region
Status
Arizona Mayo Clinic
Phoenix
Arizona
University of California at San Francisco
San Francisco
California
Colorado Blood Cancer Institute
Denver
Colorado
H. Lee Moffitt Cancer Center and Research Institute
Tampa
Florida
University of Iowa Hospital and Clinics
Iowa City
Iowa
Ochsner Medical Center
New Orleans
Louisiana
University of Michigan
Ann Arbor
Michigan
Barbara Ann Karmanos Cancer Institute
Detroit
Michigan
University of Nebraska Medical Center
Omaha
Nebraska
Hackensack Meridian Health
Hackensack
New Jersey
The Cleveland Clinic Foundation
Cleveland
Ohio
OHSU Knight Cancer Institute
Portland
Oregon
Hillman Cancer Center
Pittsburgh
Pennsylvania
Rhode Island Hospital
Providence
Rhode Island
Medical University of South Carolina
Charleston
South Carolina
UT Southwestern
Dallas
Texas
MD Anderson Cancer Center
Houston
Texas
Monash Health
Clayton
Australia
Concord Hospital
Concord
Australia
St. Vincent Hospital
Fitzroy
Australia
Royal Brisbane and Women's Hospital
Herston
Australia
Royal Hobart Hospital RHH
Hobart
Australia
St. George Hospital
Kogarah
Australia
Cabrini Hospital
Malvern
Australia
Sir Charles Gairdner Hospital
Nedlands
Australia
Gold Coast Hospital
Southport
Australia
Westmead Hospital
Sydney
Australia
Tom Baker Cancer Care
Calgary
Canada
Toronto-Sunnybrook Regional Cancer Ctr
Toronto
Canada
Rigshospitalet
Copenhagen
Denmark
Odense University Hospital
Odense
Denmark
Vejle Hospital
Vejle
Denmark
Helsinki University Hospital
Helsinki
Finland
Kuopio University Hospital
Kuopio
Finland
Tampere University Hospital
Tampere
Finland
Hopital Henri Mondor
Créteil
France
CHU Montpellier
Montpellier
France
Hospital Saint-Louis
Paris
France
Hospices Civils de Lyon Centre Hospitalier Lyon Sud
Pierre-Bénite
France
Centre Henri Becquerel
Rouen
France
+ 45 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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