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 for relapsed/refractory chronic lymphocytic leukemia (R/R CLL):
- epcoritamab + venetoclax
- epcoritamab + pirtobrutinib
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Combination therapy for Richter's Syndrome (RS):
- epcoritamab + lenalidomide
- epcoritamab + R-CHOP (i.e., rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine [Oncovin®] and prednisone).
The study includes participants with R/R CLL/small lymphocytic lymphoma (SLL) and participants with RS.
The trial consists of two parts, a dose-escalation phase (phase Ib) and an expansion phase (phase II). Participants with RS are only included in the expansion phase.
Epcoritamab will be injected subcutaneously (under the skin). Standard-of-care and combination treatments (venetoclax, pirtobrutinib, 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 after the last participant's first treatment in the trial.
- The treatment duration for each participant will be between 12 months (1 year) 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, epcoritamab + venetoclax and epcoritamab + pirtobrutinib at the RP2D for participants with R/R CLL/SLL. Along with this, epcoritamab monotherapy, epcoritamab + lenalidomide and epcoritamab + R-CHOP will be evaluated in participants with RS to assess their efficacy, safety and tolerability profiles.
The purpose of safety run-in phase for pirtobrutinib combination therapy is to evaluate the safety and tolerability profiles of pirtobrutinib in combination with epcoritamab.
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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Life expectancy >3 months on standard of care (SOC) for CLL, >3 months for RS.
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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 monotherapy arm - 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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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
- A woman must agree not to breastfeed a child during treatment and for at least 28 days after discontinuation from study.
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For RS - R-CHOP combination Therapy Arm -
- Eligible for treatment with R-CHOP.
- Females of childbearing potential must use highly effective contraceptive measures while taking R-CHOP and for 12 months after stopping treatment.
- A woman must agree not to breastfeed a child during treatment or until 12 months after last treatment.
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For R/R CLL - venetoclax combination Therapy arm - after receiving at least 1 prior line of systemic antineoplastic therapy.
- Presence of measurable disease (absolute lymphocyte count >5,000/microliter [μL], measurable lymph nodes ≥1.5 centimeters (cm) on imaging, or bone marrow involvement of CLL ≥30%).
- Females of childbearing potential must use highly effective contraceptive measures while taking venetoclax and for 30 days after stopping treatment.
- Must take prophylaxis for tumor lysis syndrome (TLS).
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A woman must agree not to breastfeed a child during treatment and for 4 months after last treatment.
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For R/R CLL pirtobrutinib combination Therapy arm:
- Must have active CLL/SLL disease requiring treatment per iwCLL 2018 criteria.
- Presence of measurable disease (absolute lymphocyte count >5,000/μL, measurable lymph nodes ≥1.5cm on imaging, or bone marrow involvement of CLL ≥30%).
- Previous treatment with at least one and a maximum 3 prior lines of therapy.
- Diagnosis of CLL/SLL that meets published diagnostic criteria.
- Females of childbearing potential must use highly effective contraceptive measures while taking pirtobrutinib and for 5 weeks after the last dose.
- A woman must agree not to breastfeed a child during treatment and until one week after last dose.
- A man who is sexually active with a woman of childbearing potential must use an effective method of contraception during treatment and for 3 months after last dose.
Key Exclusion Criteria
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Received prior treatment with a CD3×CD20 bispecific antibody.
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Received any prior allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation.
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Received chimeric antigen receptor (CAR) T-cell therapy within 100 days or an investigational drug within 4 weeks, prior to first dose of epcoritamab.
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Autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy.
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Received vaccination with live vaccines within 28 days.
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Clinically significant cardiac disease.
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Known current malignancy other than inclusion diagnosis.
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Has had major surgery within 4 weeks.
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Any of the following active infections:
- Hepatitis C
- Human T cell leukemia virus infection
- Active cytomegalovirus (CMV) infection
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Known history of human immunodeficiency virus (HIV).
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For R/R CLL arms - Any history of RS or evidence indicating a potential Richter's transformation. R/R CLL - Pirtobrutinib Combination Therapy Arm - Any history of RS or evidence indicating a potential Richter's transformation.
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Received venetoclax within 24 months prior to beginning venetoclax ramp-up for this trial or progressed on venetoclax treatment.
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For all RS arms - Diagnosis of Richter's syndrome not of the DLBCL subtype such as Hodgkin's lymphoma, prolymphocytic leukemia.
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RS - Lenalidomide Combination Therapy and RS Monotherapy Arms - received more than 2 prior lines of therapy for RS.
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R/R CLL - Pirtobrutinib Combination Therapy Arm - history of bleeding disorders or participants requiring therapeutic anticoagulation with warfarin or another vitamin K antagonist.
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Additional exclusion criteria specific to participants in epcoritamab monotherapy, venetoclax + epcoritamab, R-CHOP + epcoritamab, Pirtobrutinib + epcoritamab arms, participants with paraimmunoblastic transformation, prolymphocytic progression, or accelerated phase CLL.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Trial design
Primary purpose
Allocation
Interventional model
Masking
304 participants in 7 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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