Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome (EPCORE™ CLL-1)
Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
Details and patient eligibility
About
The study is a global, multi-center safety and efficacy trial of epcoritamab, an antibody also known as EPKINLY™ and GEN3013 (DuoBody®-CD3xCD20). Epcoritamab will either be studied as:
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Monotherapy, or
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Combination therapy:
- epcoritamab + venetoclax
- epcoritamab + lenalidomide
- epcoritamab + R-CHOP (i.e., rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine (Oncovin®) and prednisone).
The study includes patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL)/small lymphocytic lymphoma (SLL) and patients with Richter's Syndrome (RS).
Study participants with R/R CLL/SLL are treated either with epcoritamab as monotherapy or epcoritamab + venetoclax. Study participants with RS are treated either with epcoritamab as monotherapy or epcoritamab + lenalidomide or epcoritamab + R-CHOP. The trial consists of two parts, a dose-escalation phase (phase Ib) and an expansion phase (phase II). Patients with RS are only included in the expansion phase.
Epcoritamab will be injected subcutaneously (under the skin). Standard-of-care and combination treatments (venetoclax, lenalidomide, and R-CHOP) will be given either orally (by mouth) or intravenously (in a vein).
Study details include:
- Study duration will be up to 5 years.
- The treatment duration for each participant will be between 18 months (1.5 years) and 24 months (2 years), depending upon the treatment arm assigned.
- The visit frequency will be either weekly, every other week, or monthly, depending upon the part of the study.
All participants will receive active drug; no one will be given placebo.
Full description
The purpose of the dose-escalation phase of the trial is to determine the recommended phase 2 dose (RP2D) and the maximum tolerated dose (MTD; if reached) as well as establish the safety profile of epcoritamab monotherapy and epcoritamab + venetoclax in participants with R/R CLL.
The purpose of the expansion phase is to assess and evaluate the preliminary efficacy, safety and tolerability profiles of epcoritamab monotherapy and epcoritamab + venetoclax at the RP2D for patients with R/R CLL/SLL. Along with this, epcoritamab monotherapy, epcoritamab + lenalidomide and epcoritamab + R-CHOP will be evaluated in patients with RS to assess their efficacy, safety and tolerability profiles.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Key Inclusion Criteria
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Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
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Evidence of CD20 positivity in a sample representative of the disease at Screening.
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Acceptable hematology parameters and organ function based on baseline bloodwork.
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For R/R CLL arms - Must have active CLL/SLL disease requiring treatment per iwCLL 2018 criteria.
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For R/R CLL arms - Received at least 2 prior lines of systemic anti-neoplastic therapy including a Bruton's tyrosine kinase (BTK) inhibitor.
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For all RS arms - Have tumor biopsy-proven CD20+ Diffuse large B-cell Lymphoma (DLBCL) and a clinical history of CLL/SLL.
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For all RS arms - Must have measurable disease by fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) or magnetic resonance imaging (MRI) scan.
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For all RS arms - Must provide mandatory formalin-fixed, paraffin-embedded (FFPE) tumor biopsy sample.
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Life expectancy >3 months on standard of care (SOC).
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For RS - monotherapy arm: Deemed as ineligible for chemoimmunotherapy at investigator's discretion or participant who refuses to receive intensive chemotherapy
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For RS - lenalidomide combination therapy arm
- Deemed as ineligible for chemoimmunotherapy at the investigator's discretion, or participant who refuses to receive intensive chemotherapy.
- Eligible for treatment with lenalidomide.
- Must be willing to use contraception and adhere to the Lenalidomide Pregnancy Risk Minimization Plan
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For RS - R-CHOP combination Therapy Arm -
- Eligible for treatment with R-CHOP.
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For R/R CLL - venetoclax combination Therapy arm - after receiving at least 1 prior line of systemic antineoplastic therapy.
Key Exclusion Criteria
- Received prior treatment with a CD3×CD20 bispecific antibody.
- Received any prior allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation.
- Received (CAR) T-cell therapy within 100 days or an investigational drug within 4 weeks, prior to first dose of epcoritamab.
- Autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy.
- Received vaccination with live vaccines within 28 days.
- Clinically significant cardiac disease.
- Known current malignancy other than inclusion diagnosis.
- Has had major surgery within 4 weeks.
- Active hepatitis B virus or active hepatitis C.
- Known history of HIV.
- For R/R CLL arms - Any history of RS or evidence indicating a potential Richter's transformation.
- Received venetoclax within 24 months prior to beginning venetoclax ramp-up for this trial and progressed on treatment.
- For all RS arms - Diagnosis of Richter's syndrome not of the DLBCL subtype such as Hodgkin's lymphoma, prolymphocytic leukemia.
- RS - Lenalidomide Combination Therapy and RS Monotherapy Arms - received more than 2 prior lines of therapy for RS.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Trial design
Primary purpose
Allocation
Interventional model
Masking
184 participants in 5 patient groups
Trial contacts and locations
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Central trial contact
Genmab Trial Information
Data sourced from clinicaltrials.gov
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