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 be tested either in

Relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) as:

• Monotherapy, or

• Combination therapy:

  • epcoritamab + venetoclax
  • epcoritamab + pirtobrutinib

In Non-United States (US) Participants Only: Treatment-naïve (TN) high risk (HR) (CLL):

• epcoritamab + pirtobrutinib

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 or TN HR CLL (non-US participants only)/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.