Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome

Open to people ages 18 years and up

1. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
2. Evidence of CD20 positivity in a sample representative of the disease at Screening.
3. Acceptable hematology parameters and organ function based on baseline bloodwork.
4. For R/R CLL arms - Must have active CLL/SLL disease requiring treatment per iwCLL 2018 criteria.
5. For R/R CLL arms - Received at least 2 prior lines of systemic anti-neoplastic therapy including a Bruton's tyrosine kinase (BTK) inhibitor.
6. For all RS arms - Have tumor biopsy-proven CD20+ Diffuse large B-cell Lymphoma (DLBCL) and a clinical history of CLL/SLL.
7. 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.
8. For all RS arms - Must provide mandatory formalin-fixed, paraffin-embedded (FFPE) tumor biopsy sample.
9. Life expectancy >3 months on standard of care (SOC).
10. For RS - monotherapy arm: Deemed as ineligible for chemoimmunotherapy at investigator's discretion or participant who refuses to receive intensive chemotherapy
11. 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
12. For RS - R-CHOP combination Therapy Arm -
    • Eligible for treatment with R-CHOP.
13. For R/R CLL - venetoclax combination Therapy arm - after receiving at least 1 prior line of systemic antineoplastic therapy.

1. Received prior treatment with a CD3×CD20 bispecific antibody.
2. Received any prior allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation.
3. Received (CAR) T-cell therapy within 100 days or an investigational drug within 4 weeks, prior to first dose of epcoritamab.
4. Autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy.
5. Received vaccination with live vaccines within 28 days.
6. Clinically significant cardiac disease.
7. Known current malignancy other than inclusion diagnosis.
8. Has had major surgery within 4 weeks.
9. Active hepatitis B virus or active hepatitis C.
10. Known history of HIV.
11. For R/R CLL arms - Any history of RS or evidence indicating a potential Richter's transformation.
12. Received venetoclax within 24 months prior to beginning venetoclax ramp-up for this trial and progressed on treatment.
13. For all RS arms - Diagnosis of Richter's syndrome not of the DLBCL subtype such as Hodgkin's lymphoma, prolymphocytic leukemia.
14. 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.