NCT04623541

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

A Phase 1b/2, Open-Label, Safety and Efficacy Study of Epcoritamab (GEN3013; DuoBody®-CD3xCD20) in Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 195 (actual)
• Sponsor: Genmab · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed 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, TN HR CLL (in non-US participants only) and 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.

Conditions

• Relapsed/Refractory Chronic Lymphocytic Leukemia
• Small Lymphocytic Lymphoma
• Richter's Syndrome
• Treatment-naïve High Risk Chronic Lymphocytic Leukemia

Interventions

Type	Name	Description
BIOLOGICAL	Epcoritamab	Epcoritamab will be administered subcutaneously in cycles of 28 days, (except Cycle 1 for high-dose cohorts = 35 days).
BIOLOGICAL	Epcoritamab	Epcoritamab will be administered subcutaneously in cycles of 21 days and 28 days.
DRUG	rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone	R-CHOP will be administered intravenously (prednisone may be administered orally) in cycles of 21 days.
DRUG	Venetoclax	Venetoclax tablets will be administered orally once daily during the 5-week ramp up period in cycles of 28 or 35 days each.
BIOLOGICAL	Epcoritamab	Epcoritamab will be administered subcutaneously in cycles of 28 days.
DRUG	Lenalidomide	Lenalidomide capsules will be administered once daily for 21 days in each cycle of 28 days.
BIOLOGICAL	Epcoritamab	Epcoritamab will be administered subcutaneously in cycles of 28 days.
DRUG	Pirtobrutinib	Pirtobrutinib tablets will be administered in cycles of 28 days.
BIOLOGICAL	Epcoritamab	Epcoritamab will be administered subcutaneously in cycles of 28 days.

Timeline

• Start date: 2020-11-25
• Primary completion: 2027-12-01
• Completion: 2028-02-01
• First posted: 2020-11-10
• Last updated: 2026-04-13

Locations

83 sites across 12 countries: United States, Australia, Belgium, Czechia, Denmark, France, Germany, Israel, Italy, Netherlands, Poland, Spain

Regulatory

• FDA-regulated drug study