Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome
About the study
Who can take part
INCLUSION CRITERIA
Key Inclusion Criteria
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
- Evidence of CD20 positivity in a sample representative of the disease at Screening.
- Acceptable hematology parameters and organ function based on baseline bloodwork.
- Life expectancy >3 months on standard of care (SOC) for CLL, >3 months for RS.
- For R/R CLL arms - Must have active CLL/SLL disease requiring treatment per iwCLL 2018 criteria.
- 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.
- For all RS arms - Have tumor biopsy-proven CD20+ Diffuse large B-cell Lymphoma (DLBCL) and a clinical history of CLL/SLL.
- 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.
- For all RS arms - Must provide mandatory formalin-fixed, paraffin-embedded (FFPE) tumor biopsy sample.
- For RS - monotherapy arm: Deemed as ineligible for chemoimmunotherapy at investigator's discretion or participant who refuses to receive intensive chemotherapy
- 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.
- 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.
- 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).
- A woman must agree not to breastfeed a child during treatment and for 4 months after last treatment.
- 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.
EXCLUSION CRITERIA
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 chimeric antigen receptor (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.
- Any of the following active infections:
- Hepatitis C
- Human T cell leukemia virus infection
- Active cytomegalovirus (CMV) infection
- Known history of human immunodeficiency virus (HIV).
- 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.
- Received venetoclax within 24 months prior to beginning venetoclax ramp-up for this trial or progressed on venetoclax 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.
- R/R CLL - Pirtobrutinib Combination Therapy Arm - history of bleeding disorders or participants requiring therapeutic anticoagulation with warfarin or another vitamin K antagonist.
16. 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.

Study Locations
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How to Apply
Study Details
Contition
Relapsed/Refractory Chronic Lymphocytic Leukemia,Small Lymphocytic Lymphoma,Richter's Syndrome
Age
18+
Phase
PHASE1/PHASE2
Participants Needed
304
Est. Completion Date
Aug 31, 2029
Treatment Type
INTERVENTIONAL
Sponsor
Genmab
ClinicalTrials.gov NCT Identifier
NCT04623541
Study Number
GCT3013-03
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